Apolipoprotein AI and HDL are reduced in stable cirrhotic patients with adrenal insufficiency: a possible role in glucocorticoid deficiency

Backgrounds and aims: Adrenal insufficiency (AI) has been reported in patients with stable cirrhosis. A lack of substrates has been suggested as a possible contributing pathogenic mechanism leading to glucocorticoid deficiency in these subjects. To better explore this hypothesis, we studied lipoproteins in cirrhotics with and without AI. Methods. A total of 81 cirrhotic patients and 30 normal volunteers were enrolled. The severity of liver disease was graded by Child-Pugh score. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), and apolipoprotein AI (Apo-AI) levels were evaluated. HDL subfractions were measured by gradient gel electrop…

Identification of a novel ANGPTL3 mutation splicing associeted to severe hypobetalipoproteinemia

Introduction. Primary hypobetalipoproteinemia (pHBL) is a monogenic heterogeneous condition inherited as a dominant or recessive trait characterized by total cholesterol (TC) and/or LDL cholesterol (LDL-C) and/or apolipoprotein B (APOB) levels below the 5th percentile of the reference population. Heterozygous APOB gene mutations are responsible for the majority of the dominant pHBL causing the familial hypobetalipoproteinemia (FHBL). Loss-of-function mutations in the PCSK9 gene also cause FHBL. Familial combined hypolipidemia is a recently discovered dyslipidemic phenotype characterized by low levels of TC, triglycerides (TG), LDL-C, and high-density lipoprotein cholesterol (HDL-C). The gen…

COMPOUND HETEROZYGOUS FH AND FDB: IDENTIFICATION OF A SICILIAN FAMILY HARBOURING THE FDB3531 MUTATION AND THE Y398X MUTATION OF THE LDL RECEPTOR GENE.

PREVALENCE OF ANGPTL3 AND APOB GENE MUTATIONS IN SUBJECTS WITH COMBINED HYPOLIPIDEMIA

Introduction. Mutations of the ANGPTL3 gene have been found responsible for a novel form of primary hypobetalipoproteinemia (pHBL), the combined hypolipidemia, characterized by low total cholesterol (TC) and low HDL-cholesterol (HDL-C) levels. The aim of this work is to define the role of ANGPTL3 gene as determinant of the combined hypolipidemia phenotype in two large cohorts of 913 American and Italian subjects with primary hypobetalipoproteinemia (TC <5th percentile). Materials and Methods. The cut-offs adopted to define the combined hypolipidemia phenotype were chosen taking into account the TC and HDL-C levels reported in the ANGPTL3 kindred described to date and are as follows: TC leve…

A NOVEL COMPOUND HETEROZYGOUS MUTATION OF THE LIPOPROTEIN LIPASE GENE IN A NEWBORN WITH CHYLOMICRONEMIA

Automated untargeted stable isotope assisted lipidomics of liver cells on high glucose shows alteration of sphingolipid kinetics

Abstract Untargeted lipidomics is a powerful tool to discover new biomarkers and to understand the physiology and pathology of lipids. The use of stable isotopes as tracers to investigate the kinetics of lipids is another tool able to supply dynamic information on lipid synthesis and catabolism. Coupling the two methodology is then very appealing in the study of lipid metabolism. The main issue to face is to perform thousands of calculations in order to obtain kinetic parameters starting from the MS raw data. An automated computerized routine able to do accomplish such task is presented in this paper. We analyzed the lipid kinetics of palmitic acid (PA) in hepatoma liver cells cultured in v…

Baseline metabolic disturbances and the twenty-five years risk of incident cancer in a Mediterranean population.

Abstract Background and aims Obesity is predictive of metabolic syndrome (metS), type 2 diabetes, cardiovascular (CV) disease and cancer. The aim of the study is to assess the risk of incident cancer connected to obesity and metS in a Mediterranean population characterized by a high prevalence of obesity. Methods and results As many as 1133 subjects were enrolled in two phases and followed for 25 years (859 subjects) or 11 years (274 subjects) and incident cancer was registered in the follow-up period. Anthropometric measures and biochemical parameters were filed at baseline and evaluated as predictors of incident cancer by measuring hazards ratios (HR) using multivariate Cox parametric haz…

Metabolic disturbances and risk of cancer in the 25 years follow-up of the “Ventimiglia Heart Study” epidemiological project

NEXT GENERATION SEQUENCIN: A NEW METHODOLOGICAL APPROACH FOR THE MOLECULAR DIAGNOSIS OF GENETIC DYSLIPIDEMIAS

RT-PCR and in situ hybridization analysis of apolipoprotein H expression in rat normal tissues

In this study, by using different techniques (i.e. Northern blot hybridization, RT-PCR and Southern blot hybridization) on various normal rat tissues, we were able to identify liver, kidney, heart, small intestine, brain, spleen, stomach and prostate as tissues in which the ApoH gene is transcribed. Moreover, for some of these tissues, by in situ hybridization, we found a specific localization of apoH transcripts. For instance epithelial cells of the bile ducts in liver and of the proximal tubules in kidney are the major sites of apoH synthesis. Our data suggest that some of the different physiological roles proposed for apoH could correlate with its direct expression, while others could co…

IDENTIFICATION OF A HETEROZYGOUS COMPOUND INDIVIDUAL WITH AUTOSOMAL DOMINANT HYPERCHOLESTEROLEMIA HARBOURING IN THE LDL-R GENE AND IN THE PCSK9 GENE

Mutation in candidate genes account for a small minority of hypobetalipoproteinemias and NGS analysis support polygenicity in mutation-negative patients

Obesity and the metabolic syndrome in a student cohort from Southern Italy

Abstract Background and aim Cardiovascular (CV) risk factors present in childhood predict future CV events. Few data regarding the metabolic syndrome (MS) prevalence are available in adolescents from Mediterranean areas where obesity is becoming a social emergency. This study presents data of MS prevalence in a student cohort from southern Italy. Methods and results 1629 students between 7 and 14 years of age underwent anthropometric measurements and a blood sample was obtained to assess biochemical parameters. MS risk factors were calculated based on age and gender adjusted percentiles of parameter distributions. MS prevalence rate was 0.022 using paediatric, age-adjusted criteria; the rat…

LA LIPIDOMICA DELLA NON ALCOHOLIC FATTY LIVER DISEASE: ANALISI DELLA CINETICA DELL’ACIDO PALMITICO MEDIANTE L’USO DI UN ISOTOPO STABILE IN UN MODELLO IN VITRO

Interleukin 6 plasma levels predict with high sensitivity and specificity coronary stenosis detected by coronary angiography

SummaryIn recent years new biomarkers able to measure the coronary atherosclerotic burden have been investigated. The aim of the present study was: i) to measure plasma levels of four biomarkers: C reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), 8-isosprostane (8-ISO),in a series of patients undergoing coronary angiography; ii) to assess the power of the biomarkers to predict critical coronary stenosis detected by angiography. The study population consisted of a group of 438 subjects undergoing coronary angiography; 160 patients with 0, 1, 2, or 3 critical vessels were selected, and biomarkers plasma levels were measured in plasma samples o…

Genotypic and phenotypic characterization of patients with autosomal dominant hypercholesterolemia identified in the lipigen centre of Palermo

Whole Cow’s Milk but Not Lactose Can Induce Symptoms in Patients with Self-Reported Milk Intolerance: Evidence of Cow’s Milk Sensitivity in Adults

Background: Lactose intolerance is the most frequent food intolerance, but many subjects with self-reported milk intolerance (SRMI) are asymptomatic at lactose hydrogen breath test (LHBT). The aim of this study was to evaluate the frequency of lactose intolerance in SRMI patients and their clinical characteristics. Methods: In a retrospective study, the clinical records of 314 SRMI patients (259 females, mean age: 39.1 ± 13.5 years) were reviewed; 102 patients with irritable bowel syndrome (IBS) served as controls. In a prospective study, 42 SRMI patients, negatives at the LHBT, underwent a double-blind, placebo-controlled (DBPC) whole cow’s milk challenge. Results: In the retrospective stu…

Clinical and genetic features of 2 patients with severe hypertriglyceridemia due to a mutation in GPIHBP1 gene

Genotypic and phenotypic characterization of patients with autosomal dominant hypercholesterolemia in sicily

Aim: Autosomal dominant hypercholesterolemia (ADH) is an autosomal dominant disorder characterized by high serum low density lipoproteincholesterol (LDL-C) levels. The clinical manifestations of ADH might vary among affected subjects and the phenotype correlates with the severity of mutation and the specific gene involved. The aim of this study was to evaluate the clinical expression and clinical outcomes in a cohort of ADH subjects. Methods: 300 ADH probands with a DUTCH score &gt; 6 were enrolled in this study and the analysis was extended to the family members of these index cases. Anthropometric measures, clinical and biochemical parameters, life style (smoker and/or alcohol habits) and…

LIPIDOMICS OF HUMAN SKIN FIBROBLASTS IN NEIMANN-PICK DISEASE TYPE C

Neimann-Pick Disease type C is a hereditary lysosomal storage disease due to mutations of the NPC1 or NPC2 genes. The products of these genes encodes for components of a lysosomal machinery that transport different kinds of lipids across the lysosomal membrane. The main abnormalities of NPC1 de ciency phenotype is the accumulation of free cholesterol (FC) and sphingolipids (GL) in brain, liver and other organs cells. Neurodegeneration and hepato-splenomegaly are common ndings. The NPC disease, in his severe onset, leads to a precocious exitus, though the inhibition of glyco-SL synthesis by miglustat has shown some clinical bene t. Recently the physiopathological mechanism has been partly el…

Identification of a novel LMF1 nonsense mutation responsible for severe hypertriglyceridemia by targeted next-generation sequencing

Background Severe hypertriglyceridemia (HTG) may result from mutations in genes affecting the intravascular lipolysis of triglyceride (TG)-rich lipoproteins. Objective The aim of this study was to develop a targeted next-generation sequencing panel for the molecular diagnosis of disorders characterized by severe HTG. Methods We developed a targeted customized panel for next-generation sequencing Ion Torrent Personal Genome Machine to capture the coding exons and intron/exon boundaries of 18 genes affecting the main pathways of TG synthesis and metabolism. We sequenced 11 samples of patients with severe HTG (TG&gt;885 mg/dL–10 mmol/L): 4 positive controls in whom pathogenic mutations had pre…

A NOVEL NONSENSE MUTATION IN THE CETP GENE IN ITALIAN HYPERALPHALIPOPROTEINEMIC SUBJECTS

FAMILIAL HYPOBETALIPOPROTEINEMIA DUE TO APOLIPOPROTEIN B GENE MUTATIONS CAUSES INTESTINAL FAT ACCUMULATION AND LIPID MALABSORPTION.

Familial hypobetalipoproteinemia due to apolipoprotein B R463W mutation causes intestinal fat accumulation and low postprandial lipemia

Abstract Objective Familial hypobetalipoproteinemia (FHBL) is characterized by inherited low plasma levels of apolipoprotein B (apoB)-containing lipoproteins. In this paper we investigated whether the already described APOB R463W missense mutation, a FHBL mutation able to impair the activity of microsomal triglyceride transfer protein (MTP), may cause intestinal fat accumulation and reduced postprandial lipemia. Methods Four out of five probands harboring APOB R463W mutation were compared with six healthy controls and six patients with celiac disease (CD). An oral fat load supplemented with retinyl palmitate (RP) was administered and a gastro-duodenal endoscopy with biopsy was performed. Re…

NOVEL NONSENSE MUTATION IN THE CETP GENE IN ITALIAN HYPERALPHALIPOPROTEINEMIC SUBJECTS

Identification Of P.Leu167Del Apoe Gene Mutation By Next Generation Sequencing In A Large Hypercholesterolemic Family

IL GENE PCSK9: UN NUOVO GENE IMPLICATO NEL CONTROLLO DELLA COLESTEROLEMIA

The distribution of cholesterol plasma is regulated by complex interactions between genes and environmental factors. Mutations of PCSK9 gene seem to modulate the levels of LDL-C. Mutations of PCSK9 gene with gain of function are associated to hypercholesterolemia and mutations with loss of function determine hypocholesterolemia.

Searching for wheat plants with low toxicity in celiac disease: Between direct toxicity and immunologic activation.

Abstract Background Natural or induced variations in the noxiousness of gluten proteins for celiac disease (CD) patients are currently being investigated for their potential in breeding wheat crops with reduced toxicity. Aims We evaluated the bread wheat line C173 for its effects on the in vitro -grown duodenal mucosa of CD patients. Methods In vitro -grown duodenal mucosa biopsies of 19 CD patients on a gluten-free diet were exposed to peptic/tryptic-digested prolamins from bread wheat line C173 lacking gliadin–glutenin subunits, analyzed for morphology, cytokine and anti-tTG antibody production, and compared with mucosa biopsies exposed to prolamins from wild-type cv. San Pastore. Results…

Predominance of Type 1 Innate Lymphoid Cells in the Rectal Mucosa of Patients With Non-Celiac Wheat Sensitivity: Reversal After a Wheat-Free Diet.

OBJECTIVES: Non-celiac wheat sensitivity (NCWS) is defined as a reaction to ingested wheat after exclusion of celiac disease and wheat allergy. As its pathogenesis is incompletely understood, we evaluated the inflammatory response in the rectal mucosa of patients with well-defined NCWS. METHODS: The prospective study included 22 patients with irritable bowel syndrome (IBS)-like clinical presentation, diagnosed with NCWS by double-blind placebo-controlled challenge. Eight IBS patients not improving on wheat-free diet were used as controls. Two weeks after oral challenge was performed with 80 grams of wheat daily, cells were isolated from rectal biopsies and thoroughly characterized by fluore…

Frequency and clinical aspects of neurological and psychiatric symptoms in patients with non-celiac wheat sensitivity

Background: Non-Celiac Wheat Sensitivity (NCWS) is characterized by both intestinal and extra-intestinal symptoms. The study aims to investigate the frequency of neuropsychiatric manifestations in NCWS patients and identify their clinical and demographic characteristics. Methods: 278 clinical records of NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge between 2006 and 2020, were retrospectively revised. Fifty-two patients with Celiac Disease (CD) and 54 patients with Irritable Bowel Syndrome (IBS) served as controls. Results: 87% of the NCWS patients had an IBS-like clinical presentation. The NCWS group showed a longer duration of symptoms, a higher frequency of…

SEVERE MALABSORPTION AND DECREASED TRIGLYCERIDE RICH LIPOPROTEINS PRODUCTION IN A PROBAND CARRYING A MUTATION ENCODING FOR A TRUNCATED APOLIPOPROTEIN B100 VARIANT (APO B 34.8).

Myristic acid is associated to low plasma HDL cholesterol levels in a Mediterranean population and increases HDL catabolism by enhancing HDL particles trapping to cell surface proteoglycans in a liver hepatoma cell model

Background: HDL-C plasma levels are modulated by dietary fatty acid (FA), but studies investigating dietary supplementation in FA gave contrasting results. Saturated FA increased HDL-C levels only in some studies. Mono-unsaturated FA exerted a slight effect while poly-unsaturated FA mostly increased plasma HDL-C. Aims: This study presents two aims: i) to investigate the relationship between HDL-C levels and plasma FA composition in a Sicilian population following a "Mediterranean diet", ii) to investigate if FA that resulted correlated with plasma HDL-C levels in the population study and/or very abundant in the plasma were able to affect HDL catabolism in an "in vitro" model of cultured hep…

TERAPIA CON STATINE IN PAZIENTI SICILIANI AFFETTI DA IPERLIPIDEMIA FAMILIARE COMBINATA

Familial combined hyperlipidemia (FCHL) is the most frequent genetic hyperlipidemia. FHCL is associated with high prevalence of cardiovascular disease. In this study we selected 208 patients affected by FHCL and evaluated the efficacy of the lipid-lowering statin therapy using different statins available in the market. The results show that the percent of patients reaching the therapeutic goal ranges from 19.7 % (LDL-C <100 mg/dL) to 50.9% (LDL-C <130 mg/dL) and from 16.9 % (non HDL-C <130 mg/dL) to 46.6 % (non HDL-C <160 mg/dL) according to the different ATPIII-NCEP-guidelines cut offs. In conclusion the statin monotherapy is only partly effective in the management of FCHL therapy

I LIVELLI DI CISTATINA C SONO RIDOTTI NELL’INFARTO MIOCARDIO ACUTO. EFFETTO DEL POLIMORFISMO G73A SUI LIVELLI PLASMATICI.

HYPOBETALIPOPROTEINEMIA AND FATTY LIVER: WHO IS THE CULPRIT

MALABSORPTION OF FAT IN CELIAC DISEASE DURING AN ORAL FAT LOAD. KINETIC STUDY OF CHYLOMICRONS AND REMNANTS AND CORRELATION WITH THE STAGE OF THE DISEASE

Plasma non-cholesterol sterols: a useful diagnostic tool in pediatric hypercholesterolemia.

Current guidelines strongly recommend the identification of genetic forms of hypercholesterolemia (HC) during childhood. The usefulness of non–cholesterol sterols (NCS) in the diagnosis of genetic HC has not been fully explored. Plasma NCS were measured by gas chromatography/mass spectrometry (GC/MS) in 113 children with hypercholesterolemia affected by: autosomal dominant hypercholesterolemia (ADH), familial combined hyperlipidemia (FCHL), polygenic hypercholesterolemia (PHC), and in 79 controls to evaluate: i) plasma NCS profile in different genetic HC and ii) the usefulness of NCS for the diagnosis of HC beyond current clinical criteria. ADH was characterized by raised lathosterol/total …

MOLECULAR CHARACTERIZATION OF PATIENTS WITH AND WITHOUT CORONARY ARTERY DISEASE WITH "EXTREME LDL-C PHENOTYPES"

UNA NUOVA MUTAZIONE DELL’INTRONE 16 (G>A a 2390 -1) DEL RECETTORE DELLE LDL RESPONSABILE DI IPERCOLESTEROLEMIA FAMILIARE. EFFETTI SULLA ESPRESSIONE DELL’mRNA DEL RECETTORE DELLE LDL

PCSK9-D374Y mediated LDL-R degradation can be functionally inhibited by EGF-A and truncated EGF-A peptides: An in vitro study.

Abstract Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low density lipoprotein receptor (LDLR) through the LDLR epidermal growth factor-like repeat A (EGF-A) domain and induces receptor internalization and degradation. PCSK9 has emerged as a novel therapeutic target for hypercholesterolemia. Clinical studies with PCSK9 inhibiting antibodies have demonstrated strong LDL-c lowering effects, but other therapeutic approaches using small molecule inhibitors for targeting PCSK9 functions may offer supplementary therapeutic options. The aim of our study was to evaluate the effect of synthetic EGF-A analogs on mutated (D374Y) PCSK9-D374Y mediated LDLR degradatio…

A NOVEL APOB MUTATION IDENTIFIED BY EXOME SEQUENCING COSEGREGATES WITH STEATOSIS, LIVER CANCER AND HYPOCHOLESTEROLEMIA

Objective. In familial hypobetalipoproteinemia (FHBL), fatty liver is a characteristic feature, and there are several reports of associated cirrhosis and hepatocarcinoma. We investigated a large kindred in which low-density lipoprotein (LDL) cholesterol, fatty liver and hepatocarcinoma displayed an autosomal dominant pattern of inheritance. Approach and Results. The proband was a 25 year-old female with low plasma cholesterol and hepatic steatosis. Low plasma levels of total cholesterol and fatty liver were observed in 10 more family members; 1 member was affected by liver cirrhosis and four more subjects died of either hepatocarcinoma or carcinoma on cirrhosis. To identify the causal mutat…

FAMILIAL LIGAND-DEFECTIVE APOLIPOPROTEIN B: IDENTIFICATION OF A FAMILY HARBOURING THE ARG3531CYS (FDB3531) OF THE APOB GENE

CEREBROTENDINOUS XANTHOMATOSIS: A SICILIAN FAMILY HARBOURING THE R362C MUTATION IN THE STEROL 27-HYDROXYLASE GENE

ΒETA ARRESTIN-2: A NEW “ACTOR” IN THE LDL-R ENDOCYTOSIS?

Duodenal and Rectal Mucosa Inflammation in Patients With Non-celiac Wheat Sensitivity

Background &amp; Aims: Studies of non-celiac gluten or wheat sensitivity (NCGWS) have increased but there are no biomarkers of this disorder. We aimed to evaluate histologic features of colon and rectal tissues from patients with NCGWS. Methods: We performed a prospective study of 78 patients (66 female; mean age, 36.4 years) diagnosed with NCGWS by double-blind wheat challenge at 2 tertiary care centers in Italy, from January 2015 through September 2016. Data were also collected from 55 patients wither either celiac disease or self-reported NCGWS but negative results from the wheat-challenge test (non-NCGWS controls). Duodenal and rectal biopsies were collected and analyzed by immunohistoc…

Metabolomic analysis of plasma from Alzheimer disease patients

Alzheimer Disease is a degenerative disease characterized by progressive impairment of cognitive function. The main feature of AD the generation of an abnormal peptide, beta amyloid 42 (Ab42) from Amyloid Precursor Protein (APP). Ab42 is the main constituent of neurotangles and amyloid plaques, microscopic lesions found in AD patients brain. Ab42 triggers an inflammatory response that is responsible for most of the observed tissue damage. The diagnosis of AD is a complex task, mostly based on imaging techniques and clinical evaluation of the patient’s neurological and cognitive functions. The search for plasma biomarkers able to detect early mild cognitive impairment is one of the recent at…

THE METABOLIC SYNDROME IS A PREDICTOR OF CARDIOVASCULAR EVENTS IN A SICILIAN POPULATION. RESULT OF A 15 YEARS FOLLOW UP

RUOLO DEL POLIMORFISMO ILE148MET DEL GENE PNPLA3 NELLA STEATOSI ASSOCIATA ALLA IPOBETALIPOPROTEINEMIA FAMILIARE

PREVALENCE OF PCSK9 VARIANTS IN A COHORT OF SUBJECTS WITH HYPOCHOLESTEROLEMIA

Low-density lipoproteins generated during an oral fat load in mild hypertriglyceridemic and healthy subjects are smaller, denser, and have an increased low-density lipoprotein receptor binding affinity.

Triglyceride-rich lipoproteins generated during the postprandial phase are atherogenic. Large very low-density lipoproteins (LDLs) or chylomicrons (CMs) are not as atherogenic as their remnants (Rem). Small and dense LDLs are associated with cardiovascular disease. Low-density lipoprotein size is partly under genetic control and is considered as a relatively stable LDL feature. In this article, we present data on retinyl palmitate kinetics correlated with the modification of LDL features in terms of size, density, and in vitro receptor binding affinity after an oral fat load. Six nondiabetic, hypertriglyceridemic (HTG) patients and 6 healthy controls were examined. Low-density lipoprotein s…

IPERCOLESTEROLEMIA AUTOSOMICA DOMINANTE IN SICILIA

ASSOCIATION OF THE PARAOXONASE-1 Q192R POLYMORPHISM WITH CORONARY ARTERY DISEASE IN AMI PATIENTS, NON AMI CAD AND HEALTHY CONTROLS.

A novel nonsense mutation in the cept gene in italian Hyperalphalipoproteinemic subjects

Persistence of Nonceliac Wheat Sensitivity, Based on Long-term Follow-up

We investigated how many patients with a diagnosis of nonceliac wheat sensitivity (NCWS) still experienced wheat sensitivity after a median follow-up time of 99 months. We collected data from 200 participants from a previous study of NCWS, performed between July and December 2016 in Italy; 148 of these individuals were still on a strict wheat- free diet. In total, 175 patients (88%) improved (had fewer symptoms) after a diagnosis of NCWS; 145 of 148 patients who adhered strictly to a gluten-free diet (98%) had reduced symptoms, compared with 30 of 52 patients who did not adhere to a gluten-free diet (58%) (P &lt; .0001). Of the 22 patients who repeated the double-blind, placebo- controlled …

Lack of phenotypic additive effect of familial defective apolipoprotein B3531 in familial hypercholesterolaemia.

Familial defective apolipoprotein (apo) B (FDB) and familial hypercholesterolaemia (FH) are the two common genetic conditions that cause hypercholesterolaemia. R3531C mutation of the APOB gene is a rare cause of FDB. Individuals with both FDB and FH are rare. A 51-year-old man with hypercholesterolaemia (11.4 mmol/L) and his family were studied. Low-density lipoprotein (LDL) receptor (LDLR) and APOB genes were analysed by direct sequencing. LDL of four subjects were studied in a fibroblast LDL receptor-binding displacement assay. We found a mutation of the LDLR gene (p.Y398X) in the proband and in four other family members: the p.R3531C APOB gene mutation was also found in the proband, his …

Gynecological Disorders in Patients with Non-celiac Wheat Sensitivity

Background: Non-celiac wheat sensitivity (NCWS) most frequently presents clinically with irritable bowel syndrome (IBS)-like symptoms, although many extra-intestinal manifestations have also been attributed to it. No studies to date have evaluated the presence and frequency of gynecological symptoms in NCWS. Aim: To evaluate the frequency of gynecological disorders in patients with NCWS. Patients and Methods: Sixty-eight women with NCWS were included in the study. A questionnaire investigating gynecological symptoms and recurrent cystitis was administered, and patients reporting symptoms were then examined by specialists. Three control groups were selected: 52 patients with IBS not related …

Genetic heterogeneity of familial hypercholesterolemia in Sicily

NONSENSE MUTATION IN THE CETP GENE IN ITALIAN HYPERALPHALIPOPROTEINEMIC SUBJECTS.

GLI ACIDI GRASSI SATURI ED INSATURI MODULANO L’UPTAKE DELLE LIPOPROTEINE HDL IN UN MODELLO DI CELLULE EPATICHE IN COLTURA.

DETECTION OF NEW GENES RESPONSIBLE OF FAMILIAL RECESSIVE HYPERCHOLESTEROLEMIA: PRELIMINARY DATA FROM AN EXOME SEQUENCING APPROACH

Prevalence of ANGPTL3 and APOB gene mutations in subjects with combined hypolipidemia.

Objective— Mutations of the ANGPTL3 gene have been associated with a novel form of primary hypobetalipoproteinemia, the combined hypolipidemia (cHLP), characterized by low total cholesterol and low HDL-cholesterol levels. The aim of this work is to define the role of ANGPTL3 gene as determinant of the combined hypolipidemia phenotype in 2 large cohorts of 913 among American and Italian subjects with primary hypobetalipoproteinemia (total cholesterol &lt;5th percentile). Methods and Results— The combined hypolipidemia cut-offs were chosen according to total cholesterol and HDL-cholesterol levels reported in the ANGPTL3 kindred described to date: total cholesterol levels, &lt;2nd percentile …

Erratum: FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer's disease (Analytical and Bioanalytical Chemistry DOI: 10.1007/s00216-015-9229-6)

Erratum to: FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer’s disease

Le ipocolesterolemie primitive

Hypobetalipoproteinemia (HBL) is characterized by cholesterol levels below the 5th percentile of the population distribution. Familial HBL (FHBL) is characterized by an inherited HBL trait within a family. In the last years gene defects underlying some cases of FHBL, but not all, have been identified. The molecular basis of some gene defect and the clinical onset of FHBL are presented in this paper.

Identification of a novel LMF1 nonsense mutation responsible for severe hypertriglyceridemia by targeted next-generation sequencing

Body Mass Index and Associated Clinical Variables in Patients with Non-Celiac Wheat Sensitivity.

Background: Non-Celiac Wheat Sensitivity (NCWS) is still a largely undefined condition, due to the lack of a diagnostic marker. Few data are available about the nutritional characteristics of NCWS patients at diagnosis. Aims: To evaluate the proportion of NCWS patients who were underweight, normal weight, overweight, or obese at diagnosis, and to search for possible correlations between their Body Mass Index (BMI) and other NCWS-related disease characteristics. Patients and Methods: The clinical charts of 145 NCWS patients (125 F, 20 M, mean age 37.1 &plusmn

TNF-α, IL-17, and IL-22 production in the rectal mucosa of nonceliac wheat sensitivity patients: role of adaptive immunity.

In recent years, a new gluten- or wheat-related disease has emerged, a condition labeled "nonceliac gluten sensitivity" (NCGS) or "nonceliac wheat sensitivity" (NCWS). NCWS pathogenesis is still uncertain and attributed to very different mechanisms. We aimed to study the different T-lymphocyte subsets in the rectal mucosa of NCWS patients to demonstrate the possible contribution of adaptative immune response. Twelve patients (11 women, 1 man, age range 23-61 yr, median 32 yr) with a definitive diagnosis of NCWS were recruited at random for the present study. They underwent rectal endoscopy with multiple mucosal biopsies at the end of a double-blind placebo-controlled (DBPC) wheat challenge …

Le LDL generate in fase post-prandiale dopo carico grasso presentano maggiore densita’, minore size e maggiore affinita’ per il recettore

LIPIDOMICS OF FATTY LIVER IN NAFLD AND HCV INFECTION: LIVER SPHYNGOLIPIDS AND FATTY ACIDS

Lipids are used by the liver mainly for energy storage and membrane building, but they also contribute to cell signaling. Fatty liver is characterized by activation of metabolic and inflammatory pathways. In this work differences in lipidomic profiles of sphyngolipids (SL) and fatty acids (FA) have been evaluated in biopsies from 10 NAFLD patients, 22 (14 FL, 8 w/o FL) HCV patients and 13 healthy controls. FL is characterized by increased content of the main FA as myristic, palmitic, oleic, linoleic, saturated and monounsaturated FA in both model. FL of HCV is characterized by a more severe degree of cell damage and fibrosis associated with an increase of palmitoleic acid, long chain SL and…

Contact dermatitis due to nickel allergy in patients suffering from non-celiac wheat sensitivity

Background: Non‐celiac wheat sensitivity (NCWS) is a new clinical entity in the world of gluten‐related diseases. Nickel, the most frequent cause of contact allergy, can be found in wheat and results in systemic nickel allergy syndrome and mimics irritable bowel syndrome (IBS). Objective: To evaluate the frequency of contact dermatitis due to nickel allergy in NCWS patients diagnosed by a double‐blind placebo‐controlled(DBPC)challenge,and to identify the characteristics of NCWS patients with nickel allergy. Methods: We performed a prospective study of 60 patients (54 females, 6 males; mean age 34.1 ± 8.1 years) diagnosed with NCWS from December 2014 to November 2016; 80 age‐ and sex‐matched…

SHORT APOB TRUNCATIONS SHOW IMPAIRE CHYLOMICRON EXPORT AND ENTEROCYTE TRIGLYCERIDE ACCUMULATION. IN VIVO AND IN VITRO EVIDENCE ON A APOB 28.25 STABLE-TRANSFECTED ENTEROCYTE CELL LINE

Autoimmunity Features in Patients With Non-Celiac Wheat Sensitivity.

INTRODUCTION: Nonceliac wheat sensitivity (NCWS) is characterized by intestinal and extraintestinal manifestations consequent to wheat ingestion in subjects without celiac disease and wheat allergy. Few studies investigated the relationship between NCWS and autoimmunity. The aim of this study is to evaluate the frequency of autoimmune diseases (ADs) and autoantibodies in patients with NCWS. METHODS: Ninety-one patients (13 men and 78 women; mean age of 40.9 years) with NCWS, recruited in a single center, were included. Seventy-six healthy blood donors (HBD) and 55 patients with a diagnosis of irritable bowel syndrome (IBS) unrelated to NCWS served as controls. Autoantibodies levels were mea…

LE IPERCOLESTEROLEMIE PRIMITIVE

DeepSRE: Identification of sterol responsive elements and nuclear transcription factors Y proximity in human DNA by Convolutional Neural Network analysis

SREBP1 and 2, are cholesterol sensors able to modulate cholesterol-related gene expression responses. SREBPs binding sites are characterized by the presence of multiple target sequences as SRE, NFY and SP1, that can be arranged differently in different genes, so that it is not easy to identify the binding site on the basis of direct DNA sequence analysis. This paper presents a complete workflow based on a one-dimensional Convolutional Neural Network (CNN) model able to detect putative SREBPs binding sites irrespective of target elements arrangements. The strategy is based on the recognition of SRE linked (less than 250 bp) to NFY sequences according to chromosomal localization derived from …

rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography

Abstract Background and aims Novel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients. Methods and results The patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected,…

FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer's disease

Lipidomic analysis is able to measure simultaneously thousands of compounds belonging to a few lipid classes. In each lipid class, compounds differ only by the acyl radical, ranging between C10:0 (capric acid) and C24:0 (lignoceric acid). Although some metabolites have a peculiar pathological role, more often compounds belonging to a single lipid class exert the same biological effect. Here, we present a lipidomics workflow that extracts the tandem mass spectrometry data from individual files and uses them to group compounds into structurally homogeneous clusters by chemical structure hierarchical clustering analysis (CHCA). The case-to-control peak area ratios of the metabolites are then a…

Wheat consumption leads to immune activation and symptom worsening in patients with familial mediterranean fever : a pilot randomized trial

We have identified a clinical association between self-reported non-celiac wheat sensitivity (NCWS) and Familial Mediterranean Fever (FMF). Objectives: A) To determine whether a 2-week double-blind placebo-controlled (DBPC) cross-over wheat vs. rice challenge exacerbates the clinical manifestations of FMF

Genetic epidemiology of ARH in Sicily

ASSOCIAZIONE DEL POLIMORFISMO Q192R DEL GENE DELLA PARAOXONASI I (PON1) CON LA MALATTIA CORONARICA IN UN CAMPIONE DI PZ CON INFARTO MIOCARDICO, MALATTIA CORONARICA NON INFARTUALE E SOGGETTI NORMALI.

INTERLEUKIN 6 PLASMA LEVELS PREDICT WITH HIGH SENSITIVITY AND SPECIFICITY CORONARY STENOSIS DETECTED BY CORONARY ANGIOGRAPHY

Clinical symptoms in celiac patients on a gluten-free diet.

OBJECTIVE: Persistent villous atrophy in patients with celiac disease (CD) on a gluten-free diet (GFD) is reported with increasing frequency. The aim of this study was to evaluate a possible association between persistent damage of the villi and "atypical" gastrointestinal symptoms in CD patients on a GFD. MATERIAL AND METHODS: Sixty-nine CD patients on a GFD were divided into two groups: Group A included 42 patients (6 M, 36 F, age range 17-62 years) undergoing esophagogastroduodenoscopies (EGDs) due to the presence of symptoms; Group B included 27 control patients (6 M, 21 F, age range 24-71 years) who were asymptomatic at the time of the study. Both groups underwent EGDs and a duodenal h…

Plasma non-cholesterol sterols in primary hypobetalipoproteinemia

Primary hypobetalipoproteinemia (pHBL) is characterized by plasma cholesterol levels ApoB48, and FHBL harbouring as yet unknown molecular defects. Not linked FHBL kindred are not homogeneous in terms of plasma NCS levels. NCS cannot replace genetic HBL analysis.

PREVALENCE OF APOB VARIANTS IN A SAMPLE OF SUBJECTS WITH HYPOCHOLESTEROLEMIA