Biomedical subjects

Jaime Poniachik

Publications and source records attributed to Jaime Poniachik.

16 recordsLinked to original sources

PubMed2007

Polyunsaturated fatty acid pattern in liver and erythrocyte phospholipids from obese patients.

OBJECTIVE: Our aim was to study the fatty acid (FA) composition of liver phospholipids and its relation to that in erythrocyte membranes from patients with obese nonalcoholic fatty liver disease (NAFLD), as an indication of lipid metabolism alterations leading to steatosis. RESEARCH METHODS AND PROCEDURES: Eight control subjects who underwent antireflux surgery and 12 obese patients with NAFLD who underwent subtotal gastrectomy with a gastro-jejunal anastomosis in Roux-en-Y were studied. The oxidative stress status of patients was assessed by serum F2-isoprostanes levels (gas chromatography/negative ion chemical ionization tandem mass spectrometry). Analysis of FA composition of liver and erythrocyte phospholipids was carried out by gas-liquid chromatography. RESULTS: Patients with NAFLD showed serum F2-isoprostanes levels 84% higher than controls. Compared with controls, liver phospholipids from obese patients exhibited significantly 1) lower levels of 20:4n-6, 22:5n-3, 22:6n-3 [docosahexaenoic acid (DHA)], total long-chain polyunsaturated FA (LCPUFA), and total n-3 LCPUFA, 2) higher 22:5n-6 [docosapentaenoic acid (DPAn-6)] levels and n-6/n-3 LCPUFA ratios, and 3) comparable levels of n-6 LCPUFA. Levels of DHA and DPAn-6 in liver were positively correlated with those in erythrocytes (r = 0.77 and r = 0.90, respectively; p < 0.0001), whereas DHA and DPAn-6 showed a negative association in both tissues (r = -0.79, p < 0.0001 and r = -0.58, p < 0.01, respectively), associated with lower DHA/DPAn-6 ratios. DISCUSSION: Obese patients with NAFLD showed marked alterations in the polyunsaturated fatty acid pattern of the liver. These changes are significantly correlated with those found in erythrocytes, thus suggesting that erythrocyte FA composition could be a reliable indicator of derangements in liver lipid metabolism in obese patients.

Adult↗

PubMed2006

Insulin resistance and oxidative stress interdependency in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is emerging as a major cause of chronic liver disease in association with the rising prevalence of obesity and type 2 diabetes in the population. Oxidative stress and insulin resistance (IR) are major contributors in the pathogenesis of NAFLD and in the progression from steatosis to steatohepatitis. Recently, Houstis and colleagues reported that reactive oxygen species have a causal role in multiple forms of IR, a phenomenon that can further promote exacerbation of oxidative stress. The improvement of the knowledge of these interrelationships should contribute to elucidate pathogenic pathways and design effective treatments for NAFLD.

Cytokines↗

PubMed2006

Increased production of IL-1alpha and TNF-alpha in lipopolysaccharide-stimulated blood from obese patients with non-alcoholic fatty liver disease.

Enhanced pro-inflammatory cytokine production is considered a pathogenic factor in non-alcoholic fatty liver disease (NAFLD). Peripheral blood production of interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) was studied in relation to the severity of histological changes of the liver in obese NAFLD patients. Basal levels in serum and production of IL-1alpha and TNF-alpha in peripheral blood cell cultures after stimulation with lipopolysaccharide (enzyme-linked immunoabsorbent assays) were measured in 11 patients with steatosis and 15 with steatohepatitis, who underwent gastrectomy with a gastro-jejunal anastomosis in roux and Y, and in 9 controls who underwent anti-reflux surgery. Production of IL-1alpha and TNF-alpha was 122 and 67% higher in patients with steatosis than control values, respectively. In patients with steatohepatitis, IL-1alpha production was 300 and 80% higher and that of TNF-alpha 110 and 26% higher, as compared with controls and steatosis patients, respectively. Production of IL-1alpha was positively correlated with that of TNF-alpha (r=0.78, p<0.0001). IL-1alpha and TNF-alpha production were both positively correlated with the degree of steatosis (r=0.68, p<0.001 and r=0.74, p<0.0001) and steatohepatitis (r=0.77 and r=0.75, p<0.0001) at liver biopsy, and with the homeostasis model assessment index (r=0.73, p<0.0001 and r=0.63, p<0.01), respectively. Basal serum IL-1alpha and TNF-alpha levels were comparable in the three groups studied. It is concluded that elevated production of IL-1alpha and TNF-alpha by in vitro stimulated whole blood cell cultures occurs in NAFLD obese patients, which might play a pathophysiological role upon inflammatory leukocyte infiltration of the liver.

Adult↗

PubMed2006

Relationship between in vivo chlorzoxazone hydroxylation, hepatic cytochrome P450 2E1 content and liver injury in obese non-alcoholic fatty liver disease patients.

The aim of the present study was to test the hypothesis that induction of cytochrome P450 2E1 (CYP2E1) in the liver of patients with non-alcoholic fatty liver disease (NAFLD) is correlated both with the in vivo activity of the cytochrome and with the development of liver injury. For this purpose, the liver content of CYP2E1 was determined by Western blot and the CYP2E1 activity by the in vivo hydroxylation of chlorzoxazone (CLZ). The study groups were obese women with an average body mass index (BMI) of 40.3kg/m(2), who underwent therapeutic gastroplasty or gastrectomy with a gastro-jejunal anastomosis. Further, the hepatic histology was determined to establish the pathological score grouping the subjects into three categories: control, steatosis and steatohepatitis. The liver CYP2E1 content and the CLZ hydroxylation of obese patients with steatosis and, particularly, with steatohepatitis were significantly higher than controls and correlated positively with both the severity of the liver damage. These data provide evidence that CYP2E1 would be involved in the mechanism of liver injury found in obese NAFLD patients. Also, the correlation between liver CYP2E1 content and in vivo CLZ hydroxylation would validate the latter as a reliable indicator of liver injury in NAFLD, thus providing a simple and not invasive method to study these patients.

Journal Article↗

PubMed2005

[Primary sclerosing cholangitis: a twelve-year experience].

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder characterized by progressive inflammation and fibrosis of the biliary tract, evolving to cirrhosis. It is commonly associated with inflammatory bowel disease (IBD). AIM: To communicate the clinical characteristics of patient with PSC seen in two reference centers. PATIENTS AND METHODS: Review of medical records of patients with PSC confirmed by liver biopsies. The clinical picture, laboratory abnormalities, imaging studies and treatment were recorded. RESULTS: Thirty three patients (aged 16 to 73 years, 64% female) were identified. They corresponded to 1.7% of liver biopsies done between 1991-2003. Clinical presentation was a cholestatic picture in 40%, right upper abdominal pain in 36%, a dysenteric syndrome in 9% and varied symptoms in 15%. Laboratory tests showed cholestasis in 94% and positive anti ANCA, SMA, ANA and AMA antibodies in 28, 18, 15 and 9% of cases, respectively. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiography were diagnostic in 43 and 58% of patients, respectively. There was an association with ulcerative colitis in 12% of cases. Liver biopsies showed grade I PSC in 76% and grade II-III in 6% of patients. It also showed a concomitant chronic hepatitis and primary biliary cirrhosis in 12 and 6% of cases, respectively. Treatment consisted on ursodeoxycholic acid (UDCA) in 45%, UDCA plus 5-aminosalicylic acid derivatives in 12% and UDCA plus immunosuppresors in 12% of patients. Two patients had to be transplanted. CONCLUSIONS: PSC is an uncommon cause of chronic liver disease. It is suspected in cholestatic patients and confirmed with a liver biopsy. It can be associated with other autoimmune hepatic and extrahepatic diseases.

Adolescent↗

PubMed2004

Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease.

Human nonalcoholic fatty liver disease (NAFLD) associated with obesity is characterized by depletion of hepatic n-3 long-chain polyunsaturated fatty acids (LCPUFA), with lower LCPUFA product/precursor ratios and higher 18:1n-9 trans levels in adipose tissue, both in patients with steatosis and in those with steatohepatitis. These changes point to modification of gene expression, with decreased fatty acid oxidation and triacylglycerol export and enhanced lipid synthesis, thereby leading to fat accumulation in the liver. Changes in oxidative stress-related parameters indicate a moderate enhancement in the pro-oxidant status of the liver in steatosis, which is further exacerbated in steatohepatitis. It is proposed that oxidative stress plays a dual role in NAFLD by contributing to steatosis due to higher peroxidation of LCPUFA, in addition to defective fatty acid desaturation and diet imbalance, and by promoting progression of steatosis to steatohepatitis, features that might involve changes in the activity of transcriptional mediators.

Animals↗

PubMed2004

Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients.

Oxidative stress is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In the present study, hepatic and plasma oxidative stress-related parameters were measured and correlated with clinical and histological findings in 31 NAFLD patients showing increased body mass index. Liver protein carbonyl content was enhanced by 403% in patients with steatosis (n=15) compared with control values (n=12), whereas glutathione content, superoxide dismutase (SOD) activity and the ferric reducing ability of plasma (FRAP) were decreased by 57%, 48% and 21% (P<0.05) respectively. No changes in microsomal p-nitrophenol hydroxylation and the total content of cytochrome P450 (CYP) or CYP2E1 were observed. Patients with steatohepatitis (n=16) exhibited protein carbonyl content comparable with that of controls, whereas glutathione content, SOD and catalase activities were decreased by 27%, 64% and 48% (P<0.05). In addition, FRAP values in patients with steatohepatitis were reduced by 33% and 15% (P<0.05) when compared with controls and patients with steatosis respectively, whereas p-nitrophenol hydroxylation (52%) and CYP2E1 content (142%) were significantly increased (P<0.05) compared with controls. It is concluded that oxidative stress is developed in the liver of NAFLD patients with steatosis and is exacerbated further in patients with steatohepatitis, which is associated with CYP2E1 induction. Substantial protein oxidation is followed by proteolysis of the modified proteins, which may explain the co-existence of a diminished antioxidant capacity and protein oxidation in the liver of patients with steatohepatitis.

Adolescent↗

PubMed2004

Increase in long-chain polyunsaturated fatty acid n - 6/n - 3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease.

Hepatic steatosis is a major feature associated with NAFLD (non-alcoholic fatty liver disease). The aims of the present study were to assess the levels of PUFA (polyunsaturated fatty acids) in liver total lipids, triacylglycerols (triglycerides) and phospholipids of NAFLD patients in relation to those in adipose tissue and hepatic indexes related to oxidative stress as factors contributing to hepatic steatosis. Eleven control subjects and 19 patients with NAFLD were studied. Analysis of liver and abdominal adipose tissue fatty acids was carried out by GLC. The liver content of protein carbonyl groups and malondialdehyde were taken as indexes related to oxidative stress. NAFLD patients had a depletion in LCPUFA (long-chain PUFA) of the n -6 and n -3 series in liver triacylglycerols, with decreased 20:4, n -6/18:2, n -6 and (20:5, n -3+22:6, n -3)/18:3, n -3 ratios, whereas liver phospholipids contained higher n -6 and lower n -3 LCPUFA. These findings were accompanied by an enhancement of (i) n -6/ n -3 ratio in liver and adipose tissue, (ii) 18:1, n -9 trans levels in adipose tissue, and (iii) hepatic lipid peroxidation and protein oxidation indexes. It is concluded that a marked enhancement in LCPUFA n -6/ n -3 ratio occurs in the liver of NAFLD patients, a condition that may favour lipid synthesis over oxidation and secretion, thereby leading to steatosis. Depletion of hepatic LCPUFA may result from both defective desaturation of PUFA, due to inadequate intake of precursors, such as 18:3, n -3, and higher intake of the 18:1, n -9 trans isomer leading to desaturase inhibition, and from an increased peroxidation of LCPUFA due to oxidative stress.

Adipose Tissue↗

PubMed2004

[Albumin dialysis MARS (Molecular Adsorbent Recirculating System) as a bridge for liver transplantation in acute liver failure. Report of three cases].

The most successful therapy for acute liver failure is liver transplantation. However, due to the low number of donors, organ support therapies need to be used as a bridge to liver transplantation. Molecular Adsorbents Recirculating System (MARS) is a dialysis treatment that uses a recirculating dialysate containing albumin. This allows the removal of both hydrosoluble and albumin-related substances. This system improves hepatic encephalopathy, renal dysfunction and some clinical parameters in acute liver failure, but there is no clear decrease in mortality. We report three women aged 23, 21 and 61 years, that were subjected to liver transplantation, in whom this therapy was successfully used.

Acute Kidney Injury↗

PubMed2003

[Familial transmission of hepatitis C virus infection in Chilean subjects].

BACKGROUND: Intravenous drug use, sexual promiscuity and a longer cohabitation period are considered risk factors for familial transmission of hepatitis C virus. The relative importance of this type of transmission is a subject of controversy. AIM: To study familial clustering of hepatitis C virus infection and its risk factors. MATERIAL AND METHODS: HCV positive patients (91 with chronic hepatitis, 88 with cirrhosis, nine with hepatic carcinoma and 29 hemophiliacs) were the index cases. HCV antibodies were measured by ELISA and the type of relationship with the index case was investigated in 317 family members. RESULTS: Positive anti HVC antibodies were detected in 12 of 243 family members of patients with chronic liver disease and in none of the family members of patients with hemophilia. Of these, five were couples of an index case with a long cohabitation period. Ten members had an index case with a severe liver disease (three with Child C cirrhosis and seven with liver carcinoma). CONCLUSIONS: Family transmission of HCV infection is uncommon in Chile. The association of severe liver disease and family transmission could be due to a higher viral load as responsible for transmission during the early periods of a long lasting disease.

Adolescent↗

PubMed2003

[Drug induced liver disease: clinical and pathological patterns in 33 cases].

BACKGROUND: Drug induced liver disease (DILD) is common and of difficult diagnosis. AIM: To report the clinical, laboratory and pathological findings in 33 patients with DILD. PATIENTS AND METHODS: We revised 1,164 liver biopsies and 57 were selected as suspicious of DILD. In these, the scale proposed by Maria et al was applied to assess the possibility of hepatotoxicity reactions and 33 were selected. RESULTS: The 33 cases had a mean age of 48 +/- 18 years and 14 were male. Forty eight medications were involved, with an average of 1.4 drugs per patient. The main drugs were antimicrobials, antineoplastics-immunosuppressives and non-steroidal antiinflammatory drugs. The clinical presentations in order of frequency were cholestasis, hepatitis, asymptomatic, fulminant hepatitis and cirrhosis. The laboratory alterations observed in cases with hepatitis were 20 fold transaminase and bilirubin elevation. In cholestasis, moderate elevations of alkaline phosphatases and gamma glytamyl transferase were observed. Pathology showed hepatocellular damage, cholestasis and mixed damage, but also submassive necrosis and cirrhosis in one case. CONCLUSIONS: The present study confirms that DILD is frequently unpredictable and that it can cause a wide variety of clinical and pathological presentations, that can even evolve to chronicity.

Adult↗

PubMed2002

[Intrarenal arterial doppler ultrasonography in cirrhotic patients with ascites, with and without hepatorenal syndrome].

BACKGROUND: The pathophysiological hallmark of the hepatorenal syndrome (HRS) is renal vasoconstriction. Doppler ultrasonography can be used to assess the vascular resistance in small renal intraparenchymal vessels through analysis of the Doppler waveform by a parameter termed Resistive Index (RI). We postulated that the RI could be important for the diagnosis and prognosis of HRS. AIMS: To assess the RI in cirrhotic patients with ascites, with and without HRS. PATIENTS AND METHODS: We studied 48 cirrhotics with ascites, of whom 12 were with and 36 without HRS and other 23 were normal subjects. We measured the intrarenal arterial RI (Resistive index = Peak systolic velocity - Minimum diastolic velocity/Peak systolic velocity) with color Doppler ultrasonography after visualization of interlobular or arcuate arteries. It was considered abnormal when higher than 0.70. RESULTS: The RI values, mean and SD) were: normal subjects: 0.58 +/- 0.05, cirrhotics with ascites: 0.65 +/- 0.05 and cirrhotics with ascites and HRS: 0.78 +/- 0.11. Patients with HRS had significantly higher values than those without HRS (p < 0.001). The Relative Risk of developing the HRS in patients with a RI > or = 0.70 were 3.32 (CI 95% = 1.79-6.2) CONCLUSIONS: The RI was useful in patients with cirrhosis and ascites for the prognosis of HRS and could suggest diagnosis of HRS with values of 0.78 or higher, if other clinical conditions that produce renal vasoconstriction are excluded.

Aged↗

PubMed2002

[Fulminant hepatic failure].

Fulminant hepatic failure (FHF) is an acute and eventually fatal illness, caused by a severe hepatocyte damage with massive necrosis. Its hallmarks are hepatic encephalopathy and a prolonged prothrombin time (< 40%). FHF is currently defined as hyperacute (encephalopathy appearing within 7 days of the onset of jaundice), acute (encephalopathy appearing between 8 and 28 days) or subacute (encephalopathy appearing between 5 and 12 weeks). FHF can be caused by viruses, drugs, toxins, and miscellaneous conditions such as Wilson's disease, Budd-Chiari syndrome, ischemia and others. However, a single most common etiology is still not defined. Factors that are valuable in assessing the likelihood of spontaneous recovery are age, etiology, degree of encephalopathy, prothrombin time and serum bilirubin. The management is based in the early treatment of infections, hemodynamic abnormalities, cerebral edema, and other associated conditions. Liver transplant has emerged as the most important advance in the therapy of FHF, with a survival rate that ranges between 60 and 80%. The use of hepatic support systems, extracorporeal liver support and auxiliary liver transplantation are innovative therapies.

Humans↗

PubMed2002

[Obesity: risk factor for steatohepatitis and hepatic fibrosis].

BACKGROUND: Nonalcoholic fatty liver (NAFL) has been recognized as a cause of chronic liver disease. Its main risk factor is obesity. AIM: To describe the clinical and liver pathological findings in a group of patients who underwent surgery as obesity treatment. PATIENTS AND METHODS: Sixty eight patients with severe or morbid obesity were subjected to surgery as obesity treatment. Each patient was evaluated with a complete clinical and laboratory medical assessment. A wedge of liver was excised during surgery. Liver biopsies were analyzed without knowledge of clinical and laboratory findings. The presence of steatosis, inflammation (portal or lobular), fibrosis and cirrhosis were recorded in the pathological analysis. Age and body mass index (BMI) were correlated with pathological data. Significance was set at a p value of less than 0.05. RESULTS: Ninety one percent of patients had steatosis, 45% inflammation and 47% fibrosis. One patient had cirrhosis (1.4%). There was a statistically significant association between BMI and moderate or severe steatosis (p < 0.03). There was also an association between BMI and portal (p = 0.017) and lobular inflammation (p = 0.034). A BMI over 40 kg/m2 (morbid obesity) was significantly associated with the presence of fibrosis (p = 0.032). Moreover, the presence of moderate or severe steatosis was a risk factor for the development of hepatic fibrosis (p = 0.026). CONCLUSIONS: Obesity is a major and independent risk factor for steatohepatitis and fibrosis. The degree of steatosis in the liver biopsy, is a risk factor for the development of fibrosis.

Adolescent↗

PubMed2002

[Gastric neuroendocrine tumors: clinical, endoscopic presentation and alternatives of treatment].

BACKGROUND: Gastric neuroendocrine tumors correspond to less than 1% of all gastric tumors. These tumors can be of three types. Seventy five percent are type I and are associated to chronic atrophic gastritis type A (CAG-A). Half of them are associated with pernicious anemia. Type II tumors are associated with Zollinger Ellison syndrome and type I multiple endocrine neoplasia. Type III are sporadic tumors. AIM: To report the clinical, endoscopical features and response to the treatment of gastric neuroendocrine tumors. PATIENTS AND METHODS: A retrospective study of eleven patients (seven male, aged 38 to 72 years old) with a pathological diagnosis of gastric neuroendocrine tumor. Their clinical presentation, associated diseases, treatment and follow up were reviewed. RESULTS: Epigastric pain was present in eight patients, weight loss in three, epigastric pain and weight loss in one and post prandial abdominal pain in two. At endoscopy, multiple polyps in the fundus were observed in six, verrucose gastritis in one, polyps in the antrum in one, two subcardial polyps in 1, a fundus ulcer in one and a Bormann III type lesion in one. Chronic atrophic gastritis was diagnosed in seven patients and pernicious anemia in five. Serum gastrin levels were determined in 4 patients and were high in all. Four subjects were treated with endoscopic polipectomy only. A partial or total gastrectomy was done in seven patients. No complications or mortality occurred during the follow up. CONCLUSIONS: Abdominal pain is a common presentation of patients with gastric neuroendocrine neoplasia. Polyps predominantly in the fundus are the most common endoscopic finding. Surgical treatment or endoscopical polypectomy, depending of the extension of the disease, yield satisfactory results.

Adult↗

PubMed2002

[Laparoscopic and classic cholecystectomy in patients with liver cirrhosis].

BACKGROUND: The prevalence of gallstones is increased in patients with cirrhosis. However the presence of cirrhosis has been generally considered a relative contraindication to cholecystectomy. AIM: To investigate the complications and the outcomes of laparoscopic and open cholecystectomy in patients with cirrhosis. PATIENTS AND METHODS: Sixty seven patients with gallstones with well-documented cirrhosis undergoing cholecystectomy (laparoscopic cholecystectomy (LC) in 35 and open cholecystectomy (OC) in 32), were studied. The mean age was 57.7 + 10.3 years for LC and 58.9 + 11.6 years for OC. In the LC group, 26 were classified as Child-Pugh class A, 8 as Child's B class and 1 as Child's class C. In the OC group, 12 were classified as Child's class A, 15 as Child's B and 5 as Child's C. RESULTS: Complications occurred in 4 of 35 (12.3%) LC patients (1 patients was Child A and 3 were B). In the OC group 14 of 32 patients had complications (4 Child A, 7 B and 3 C, 43.7% p < 0.05 as compared with LC group). Three patients in the OC group died (9.4%). Mean hospital stay was 2.8 + 1.9 and 13 + 12 days in LC and OC patients, respectively (p < 0.05). CONCLUSIONS: LC has a lower rate of complications than OC and is a reasonable option for Child's class A and B patients with cirrhosis and gallstones.

Adult↗