The pathophysiology of intestinal lipoprotein production

Intestinal lipoprotein production is a multistep process, essential for the absorption of dietary fats and fat-soluble vitamins. Chylomicron assembly begins in the endoplasmic reticulum with the formation of primordial, phospholipids-rich particles that are then transported to the Golgi for secretion. Several classes of transporters play a role in the selective uptake and/or export of lipids through the villus enterocytes. Once secreted in the lymph stream, triglyceride-rich lipoproteins (TRLs) are metabolized by Lipoprotein lipase (LPL), which catalyzes the hydrolysis of triacylglycerols of very low density lipoproteins (VLDLs) and chylomicrons, thereby delivering free fatty acids to various tissues. Genetic mutations in the genes codifying for these proteins are responsible of different inherited disorders affecting chylomicron metabolism. This review focuses on the molecular pathways that modulate the uptake and the transport of lipoproteins of intestinal origin and it will highlight recent findings on TRLs assembly

The management of transitional care of patients affected by phenylketonuria in Italy: Review and expert opinion

Phenylketonuria (PKU) is a metabolic inherited disorder in which transition from infancy to adult care is particularly difficult and not sufficiently regulated. According to the scientific literature, only few medical centers offer healthcare assistance for adult patients with PKU that are therefore still treated in pediatric settings. This generates psychological, emotional, and organizational discomfort among patients, leading them to discontinue the follow-up. European guidelines and national consensus documents underline this unmet need and the lack of practical recommendations for a structured transitional pathway in PKU. The aim of this review and expert opinion is to propose good practices for managing the transition period of PKU patients, based on the literature and the experience of a panel of Italian experts in PKU. The consensus of the experts was obtained through the administration of three rounds of surveys and one structured interview. The result is the first proposal of a pathway for an efficient transition of PKU patients. Key steps of the proposed pathway are the "a priori" planning involving the pediatric and adult teams, the acceptance of the patient and his/her family to the process, the preliminary definition of appropriate spaces in the structure, the organization of meetings with the joint team, and the appointment of a transition coordinator. For the first time, the involvement of decision makers and patient associations is proposed

Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases

Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce HDL increases. Primary forms of HALP are caused by mutations in the genes coding for cholesteryl ester transfer protein (CETP), hepatic lipase (HL), apolipoprotein C-III (apo C-III), scavenger receptor class B type I (SR-BI) and endothelial lipase (EL). However, in the last decades, genome-wide association studies (GWAS) have also suggested a polygenic inheritance of hyperalphalipoproteinemia. Epidemiological studies have suggested that HDL-C is inversely correlated with cardiovascular (CV) risk, but recent Mendelian randomization data have shown a lack of atheroprotective causal effects of HDL-C. This review will focus on primary forms of HALP, the role of polygenic inheritance on HDL-C, associated risk for cardiovascular diseases and possible treatment options

SUPERIOR MESENTERIC VEIN THROMBOSIS AND CYTOMEGAOLOVIRUS: A DIAGNOSTIC DILEMMA, A CASE REPORT AND REVIEW OF THE LITERATURE

Superior mesenteric vein thrombosis (SMVT) is a rare condition, usually caused by infections, intra-abdominal inflammatory diseases, portal hypertension, hypercoagulable states, or contraceptive therapy. Due to its vague symptomatology, SMVT is often diagnosed only after an abdominal contrast-enhanced computed computed tomography (CT) scan. In this article, we present a case of SMVT in a patient with a history of contraceptive drug use and a recent cytomegalovirus infection. A 36-year-old female was admitted to our department with the clinical symptoms of an acute appendicitis. the patient was a smoker and had been using hormonal contraceptive for over a year. surgery was deemed the best course of action. before the operation, blood tests showed a mild lymphocytosis and altered liver enzyme levels, while coagulation values were normal. a contrast-enhanced CT scan revealed a complete superior mesenteric vein thrombosis of bowel ischemia. Anticoagulants were immediately administered. a thrombophilia panel did not highlight any noteworthy elements. Cytomegalovirus (CMV) tests resulted positive

INFLAMMATORY BOWEL DISEASE (IBD) IN PREGNANCY: ANALYSIS OF THE POSSIBLE EFFECTS OF THE DISEASE ON THE FETUS AND THE NEWBORN AND THERAPEUTIC APPROACHES

The Inflammatory Bowel Diseases(IBD), are a group of inflammatory diseases characterized by the presence of chronic inflammation, i the absenc of infectious ethiology. The two most well-known diseases in this group are: Crohn's disease (CD) and Ulcerative Colitis (UC). In cases where iti is not possible to distinguish between CD and UC, it is called Indeterminated Colitis. IBD can affect women pregnant. The causes of IBD are unknown, and the clinical course of the sdisease is characterized by phases of activity and remission. UC is a chronic inflammation of the mucosa of the colon and involving predominantly the left colon and rectum. It is associatred with presence of blood and mucus in the stool, diarrhea and anemia. characteristically, CD involves entire mgastrointestinal tract, from the mouth to the anus. In CD, the inflammatory infiltrate involves the entire intestinal wall. Clinically manifested by abdominal pain, diarrhea, loss of appetite and weight loss. The complications are stenosis, fistulas, abscesses, and perianal involvement. In IBD TNF_alpha and proinflammatory cytokines are overexpressed. The analysis of the scientific literature shows that fertility, in pregant women suffering from IBD, is preserved. It shows slightly reduced for CD and ileo-anal pouch. Women with active disease at the time of conception have an increased risk of spontaneous abortion, preterm birth, with low birth weight and congenital malformations of the fetus. The indications for surgical treatment are the same as for non-pregnant women. The inactive disease or ileo-anal pouch is not a contraindication to spontaneous vaginal delivery, as is happens in the case of active colitis or perirectal fistulas or rectovaginal fistulas. Safe drug during pregnancy are: 5-aminosalicylic acid (5-ASA), steroids, 6-Mercaptopurine (&MP), Atatioprine (AZA) and Infliximab. Contraindicateddrugs are Metrotrexate and Thalidomide. In conclusion, the expectations about pregnancy, in women affected of IBD, is similar to the general population, especiually if the conception occurs in inactive phase of the disease

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 hepatoma cells (HepG2). Results: plasma HDL-C levels in the population correlated negatively with myristic acid (C14:0, β = -0.24, p < 0.01), oleic acid (C18:1n9, β = -0.22, p < 0.01) and cis-11-Eicosenoic (C20:1n9, β = -0.19, p = 0.01) and positively with palmitoleic acid (C16:1, β = +0.19, p = 0.03). HepG2 cells were conditioned with FA before evaluating HDL binding kinetics, and only C14:0 increased HDL binding by a non-saturable pathway. After removal of heparan sulphate proteoglycans (HSPG) by heparinases HDL binding dropped by 29% only in C14:0 conditioned cells (p < 0.05). C14:0 showed also the highest internalization of HDL-derived cholesteryl esters (CE, +32% p = 0.01 vs. non-conditioned cells). Conclusions: C14:0 was correlated with decreased plasma HDL-C levels in a Mediterranean population. C14:0 might reduce HDL-C levels by increasing HDL trapping to cell surface HSPG and CE stripping from bound HDL. Other mechanisms are to be investigated to explain the effects of other FA on HDL metabolism

THE NUCK'S CYST: A DISEASE EASILY CONFUSED FOR INGUINAL HERNIA. A CASE REPORT.

Nuck's canal cyst is a blind end adult residual of the fetal peritoneum. These rare cyst formations are usually found in the inguinal canal and can easily be mistaken for hernia, or enlarged limph nodes. Clinically, a Nuck's canal cyst appears as a painless or moderately painful swelling in inguinal area. We report the case of a 40 years-old woman with a painless swelling in her left inguinal region, believed a groin hernia but diagnosed as a Nuck's canal cyst only after intervention. Intraoperatively, the cyst was opened and sebsequently excised, closing the abdominal wall without the use of any sort of syntetic prostetic material

VALIDATION OF A MODIFIED MODEL OF TNBS-INDUCED COLITIS IN RATS. HOW TO INDUCE A CHEMICAL COLITIS IN RATS.

Background: there are no standard practice in the induction of colitis by 2,4,6-trinitrobenzene sulfonic (TNBS) acid. Usually, the repeated administration of TNBS is preferred, because it will result in a local Th1 response that has the characteristics of Crohn's disease. material and Methods: A total of 30 rats were randomized into two groups, consisting of a saline control group of ten rats and a TNBS groups of 20 rats. After the animals were anesthesized, 0,5 ml of either 0,9 % saline 8controls) or TNBS 50 mg/Kg dissolved in 50% ethanol were instilled into the colon through a rubber catheter. The experiment was repeated weekly for four weeks, then, the rats were killed at day 40, and the distal colon removed. results: At day 40, the bowel wall basically normal in the control group. In the TNBS group, the bowel lumen became narrow with tickened wall, and the mucosal surface presented adherent membrane with brown black, linear ulcers, proliferous lymphocites tissue, inflammatory granulomas and submucosal neutrophil infiltration. The median score of the severity of the colonic damage was 0 in the control group, and 4,75 (range 4-5) in the TNBS group; the mean weight of the rats was 180+35 g in the TNBS group, while it was 215+25 in the control group. Conclusions: The presented experiment is a cost-effective and safe method to induce Crohn-like colonic damage using a lower dose of TNBS, thus avoiding the risk of a massive loss of rats. This model is rather suitable for the assessment of the effects of potential therapeutic agent

NUTRITION IN IBD PATIENT'S: WHAT ARE THE PROSPECTS?

Summary: Inflammatory Bowel Disease (IBD) is a chronic disorder characterized by a relapsing-remitting course, which alternates between active and quiescent states, ultimately impairing a patients quality of life. The two main types of IBD are Crohn's disease (CD) and Ulcerative Colitis (UC). In physiological conditions the gut is costantly exposed to various antigens, commensal microflora and pathogens and the inflammatory response is finely balanced. It is thought that a vast number of environmental risk factors may be implicated in the development of IBD, including smoking factors, dietary factors, psycological stress, use of non-steroidal anti-inflammatory drugs and oral contraceptives, appendicectomy, breastfeeding, as well as infections. Nutritional support, as a primary therapy, has a crucial role in the management of patients with IBD. The gut microbiota is clearly manipulated by dietary components such as n-3 polyunsatured fatty acids (n-3 PUFA) and coniugated linoleic acid (CLA) which favorably reduce endotoxin load via shifts in the composition and metabolic activity of the microbial community. in particular, the beneficial effect of n-3 PUFAs and fermentable fiber, during the remission/quiescent phase of both CD and UC is Highlighted. In fact, PUFAs are associated with a less grade of inflammation since they are metabolized to 3-series prostagliandins and thromboxanes and 5-series leukotrienes and, in addition, exert antiinflammatory effects when compared with their n-6 PUFA counterparts. In similar action to dietary n-3 PUFA, coniugated linoleic acid (CLA) have been reported to ameliorate intestinal inflammation in animal models of IBD. Currently, is still unclear the role of the fibers in helping the remission of the disease. Data about the consumption of fiber are controversial. On one hand, dietary fibers can act as effective prebiotics by altering the intestinal microbial composition and promoting the growth of beneficial bacterial communities within the large intestine. On the other hand, fibers can promote diarrhea, pain and gas aggravating the clinical sate. Cocnclusion: We suggest that the consumption of fermentable fibers may have a good impact on patient's health

Atorvastatin but not pravastatin impairs mitochondrial function in human pancreatic islets and rat β-cells. Direct effect of oxidative stress

Statins are a class of drugs widely prescribed as frontline therapy for lowering plasma LDL-cholesterol in cardiovascular risk prevention. Several clinical reports have recently suggested an increased risk of type 2 diabetes associated with chronic use of these drugs. The pathophysiology of this effect remains to be fully elucidated but impaired β-cell function constitutes a potential mechanism. The aim of this study was to explore the effect of a chronic treatment with lipophilic and hydrophilic statins on β-cell function, using human pancreatic islets and rat insulin-secreting INS-1 cells; we particularly focused on the role of mitochondria and oxidative stress. The present study demonstrates, for the first time, that atorvastatin (lipophilic) but not pravastatin (hydrophilic) affected insulin release and mitochondrial metabolism due to the suppression of antioxidant defense system and induction of ROS production in pancreatic β-cell models. Mevalonate addition and treatment with a specific antioxidant (N-AcetylCysteine) effectively reversed the observed defects. These data demonstrate that mitochondrial oxidative stress is a key element in the pathogenesis of statin-related diabetes and may have clinical relevance to design strategies for prevention or reduction of statin induced β-cell dysfunction and diabetes in patients treated with lipophilic statins