A critical review of the neurovascular nature of migraine and the main mechanisms of action of prophylactic antimigraine medications.

INTRODUCTION: Migraine involves neurovascular, functional, and anatomical alterations. Migraineurs experience an intense unilateral and pulsatile headache frequently accompanied with vomiting, nausea, photophobia, etc. Although there is no ideal preventive medication, frequency in migraine days may be partially decreased by some prophylactics, including antihypertensives, antidepressants, antiepileptics, and CGRPergic inhibitors. However, the mechanisms of action involved in antimigraine prophylaxis remain elusive. AREAS COVERED: This review recaps some of the main neurovascular phenomena related to migraine and currently available preventive medications. Moreover, it discusses the major mechanisms of action of the recommended prophylactic medications. EXPERT OPINION: In the last three years, migraine prophylaxis has evolved from nonspecific to specific antimigraine treatments. Overall, nonspecific treatments  mainly involve neural actions, whereas specific pharmacotherapy (represented by CGRP receptor antagonists and CGRPergic monoclonal antibodies) is predominantly mediated by neurovascular mechanisms that may include, among others: (i) reduction in the cortical spreading depression (CSD)-associated events; (ii) inhibition of pain sensitization; (iii) blockade of neurogenic inflammation; and/or (iv) increase in cranial vascular tone. Accordingly, the novel antimigraine prophylaxis promises to be more effective, devoid of significant adverse effects (unlike nonspecific treatments), and more beneficial for the quality of life of migraineurs.

The utility of the 13C-methacetin breath test in predicting the long-term survival of patients with decompensated cirrhosis.

AIM: The 13C-methacetin breath test (13C-MeBT) is a noninvasive tool that allows evaluation of the functional activity of the liver and the prediction of liver cirrhosis. Nevertheless, there is no information on its potential utility to predict long-term survival in patients with liver disease. METHODS: Patients with cirrhosis were selected. All patients underwent a complete clinical assessment, standard biochemical tests, and 13C-MeBT at the beginning of the study. Death was recorded during the three years of follow-up. Survival curves were calculated by the Kaplan-Meier method, and Cox proportional risk models were used to identify predictive factors. The ability to classify the overall risk was assessed by the C statistic. RESULTS: One hundred and twenty-three patients were included. A significant inverse correlation was found between delta over baseline at the 15 min point (DOB15) after ingestion of 13C-methacetin and the Child-Pugh score (r = -0.411, p < 0.001). In multivariate analysis, DOB15 ≤ 4.5‰ was associated with mortality, [HR = 2.58 95% CI (1.17-5.69)]. In conclusion, our results confirm the utility of 13C-MeBT as a simple, noninvasive tool to quantitatively assess the liver's functional reserve and as a potential predictor of long-term survival in patients with decompensated cirrhosis.

[Level of expression of gene CTSL and its correlation with natural killer T-Cells in mexican pediatric patients with recent-onset type 1 diabetes]. / Asociación de células NKT con la expresión del gen CTSL en población pediátrica mexicana con diabetes tipo 1 de reciente diagnóstico.

OBJECTIVE: To compare the level of expression of the gene CTSL and its correlation with NKT cells in patients with recent-onset type 1 diabetes (T1D), their siblings, and healthy controls. METHODS: Analytical cross-sectional design. Patients with T1D < 3 months evolution, their siblings, and healthy controls were included. Percentages and absolute numbers of NKT cells were measured with expression of the CTSL gene. RESULTS: 124 subjects: with T1D (n = 48), siblings (n = 44) and controls (n = 32) were included. HbA1c was greater and C-peptide lower in T1D than the other groups and sibling age was higher (p < 0.001). There were no differences in NKT cells between T1D (0.176 ± 0.202) and controls (0.118 ± 0.133), but the percentage was higher in siblings (0.246 ± 0.188; p = 0.002). Lower level of expression of the CTSL gene associated with both absolute number (r: 0.4607; 95% CI: -0.08425 to -0.7935; p = 0.043) and percentage of NKT cells (r: 0.4540; 95% CI: -0.0927 to -0.7903; p = 0.045) in the T1D group. CONCLUSIONS: Patients with T1D have lower percentage and absolute number of NKT cells compared to their siblings. NKT cells absolute numbers are correlated with the expression of CTSL in T1D patients.

Autologous subcutaneous adipose tissue transplants improve adipose tissue metabolism and reduce insulin resistance and fatty liver in diet-induced obesity rats.

Long-term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90 days. The study was performed using two different diet-induced obesity (DIO) rat models: one using a high-fat diet (HFD) and the other using a high-carbohydrate diet (HCHD). Autologous SAT transplant reduced hypertrophic adipocytes, improved insulin sensitivity, reduced hepatic lipid content, and fasting serum-free fatty acids (FFAs) concentrations in the two DIO models. In addition, the reductions in FFAs and glycerol were accompanied by a greater reduction in lipolysis, assessed via the phosphorylation status of HSL, in the transplanted adipose tissue localized in the omentum compared with that localized in the retroperitoneal compartment. Therefore, the improvement in hepatic lipid content after autologous SAT transplant may be partially attributed to a reduction in lipolysis in the transplanted adipose tissue in the omentum due to the direct drainage of FFAs into the liver. The HCHD resulted in elevated fasting and postprandial serum insulin levels, which were dramatically reduced by the autologous SAT transplant. In conclusion, the specific intraabdominal localization of the autologous SAT transplant improved the carbohydrate and lipid metabolism of adipose tissue in obese rats and selectively corrected the metabolic parameters that are dependent on the type of diet used to generate the DIO model.

HLA Risk Haplotype: Insulin Deficiency in Pediatric Type 1 Diabetes.

BACKGROUND: Certain HLA class II haplotypes have long been related with the risk of developing type 1 diabetes. The presence of the HLA haplotype DRB1*04/DQA1*03/DQB1*03:02, together with specific ß-cell autoantibodies, contributes to the development and/or severity of insulin deficiency in type 1 diabetes. OBJECTIVE: To evaluate the association of HLA risk haplotype HLA-DRB1/-DQA1/-DQB1 with ß-cell function and antibody markers in recent-onset type 1 diabetes patients, their siblings, and controls. METHODS: We studied recently diagnosed type 1 diabetes pediatric patients, their siblings, and healthy controls, analyzing autoantibodies (anti-glutamic acid decarboxylase, anti-IA-2, and anti-insulin), HLA risk and protector haplotypes, and ß-cell function (plasma proinsulin, insulin and C-peptide). X2, ANOVA or Kruskal-Wallis and multiple logistic regression were used to analyze data. RESULTS: We included 46 patients, 72 siblings, and 160 controls. Prevalence of anti-tyrosine phosphatase-related islet antigen 2 and anti-glutamic acid decarboxylase antibodies was higher in patients than siblings and controls. We found risk haplotype DRB1*04/DQA1*03/DQB1*03:02 in 95.7% of patients vs. 51.87% of controls; DRB1*03:01/DQA1*05/DQB1*02 in 47.8% of patients vs. 8.12% of controls; and DRB1*14/DQA1*05/DQB1*03:01 in 2.2% of patients vs. 20.0% of controls. With DRB1*04/DQA1*03/DQB1*03:02, the prevalence of antibodies was significantly higher in patients, although not within any single group. In regression model based on insulin secretion, only anti-tyrosine phosphatase-related islet antigen 2 antibodies and age were associated with the risk haplotype. CONCLUSIONS: The DRB1*04/DQA1*03/DQB1*03:02 haplotype increased the risk for lower insulin, proinsulin, and C-peptide concentrations, suggesting an association with the severity of insulin deficiency in type 1 diabetes patients. This haplotype, added to antibody positivity, is a predictor of deficient insulin secretion in a Mexican pediatric population.

[Intestinal obstruction secondary to postoperative adhesion formation in abdominal surgery. Review]. / Obstrucción intestinal secundaria a formación de adherencias postoperatorias en cirugía abdominal. Revisión de la literatura.

The development of intestinal obstruction after upper and lower abdominal surgery is part of the daily life of each every surgeon. Despite this, there are very few good quality studies that allow enable assessment of the frequency of intestinal obstruction to be assessed, even although postoperative adhesions are the cause of considerable direct and indirect morbidity and its prevention can be considered a public health problem. And yet, in Mexico, at this time, there is no validated recommendation validated on the prevention of adhesions, or more particularly, in connection with the use of a variety of anti-adhesion commercial products which have been marketed for at least a decade. Intraperitoneal adhesions develop between surfaces without peritoneum of the abdominal organs, mesentery, and abdominal wall. The most common site of adhesions is between the greater omentum and anterior abdominal wall previous. Despite the frequency of adhesions and their direct and indirect consequences, just there is only one published a recommendation (from gynaecological literature), regarding peritoneal adhesion prevention. As regards of colorectal surgery, performed more than 250,000 colorectal resections are performed annually in the United States, and from 24% to 35% of them will develop a complication. The clinical and economic financial burden of these complications is enormous, and surgeries colorectal surgery been specifically highlighted as a potential point prevention point of surgical morbidity.

Combined high-fat diet and sustained high sucrose consumption promotes NAFLD in a murine model.

BACKGROUND: The study of NAFLD in humans has several limitations. Using murine models helps to understand disease pathogenesis. AIM: Evaluate the impact of 4 different diets in the production of NAFLD with emphasis on a combined high-fat plus sustained high sucrose consumption. MATERIAL AND METHODS: Eight week-old male Wistar rats were divided in four groups and fed for 90 days with the following diets: 1) Control chow diet (C); 2) High-fat cholesterol diet (HFC) + 5% sucrose in drinking water. 3) High-fat cornstarch diet (HFCO) + 5% sucrose in drinking water. 4) Chow diet + 20% sucrose in drinking water (HSD). Metabolic changes, leptin levels, liver histology, hepatic and plasma lipid composition, fasting plasma glucose and insulin and liver gene expression of FAS, SREBP-1 and PPAR-α were evaluated. RESULTS: The HFC diet had the highest grade of steatosis (grade 2 of 3) and HSD showed also steatosis (grade 1). Liver weight TG and colesterol concentrations in liver were greater in the HFC diet. There were no increased levels of iron in the liver. Rats in HFC gained significantly more weight (P < 0.001). All experimental groups showed fasting hyperglycemia. HFC had the highest glucose level (158.5 ± 7 mg/dL) (P < 0.005). The HSD and the HFCO diets developed also hyperglycemia. HSD had significantly higher fasting hyperinsulinemia. Serum leptin was higher in the HFC diet (p = 0.001). In conclusion, the HFC diet with combination of high fat and high sucrose is more effective in producing NAFLD compared with a high sucrose diet only.

Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced external carotid vasodilatation in anaesthetised dogs.

BACKGROUND: During migraine, capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception. Moreover, 5-HT is involved in the pathophysiology of migraine and depression. Interestingly, some limited lines of evidence suggest that fluoxetine may be effective in migraine prophylaxis, but the underlying mechanisms are uncertain. Hence, this study investigated the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine before and after acute and chronic oral treatment with fluoxetine. METHODS: Forty-eight vagosympathectomised male mongrel dogs were prepared to measure blood pressure, heart rate and external carotid blood flow. The thyroid artery was cannulated for infusions of agonists. In 16 of these dogs, a spinal cannula was inserted (C1-C3) for infusions of 5-HT. RESULTS: The external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine remained unaffected after intracarotid or i.v. fluoxetine. In contrast, the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine, were inhibited after chronic oral treatment with fluoxetine (300 µg/kg; for 90 days) or intrathecal 5-HT. CONCLUSIONS: Chronic oral fluoxetine inhibited capsaicin-induced external carotid vasodilatation, and this inhibition could partly explain its potential prophylactic antimigraine action.

Clinical benefits of femoroplasty: a nonsurgical alternative for the management of femoral metastases.

BACKGROUND: Bone metastases occur frequently in advanced cancer. The spine, pelvis, ribs, skull and femur are the most affected sites. It is reported that up to 83% of the patients develop pain at some point of the disease. The patient can also develop fractures and disability, particularly in the femur.. OBJECTIVES: To evaluate the effectiveness of percutaneous femoroplasty in patients with metastatic osseous disease located in the proximal femur (trochanter, neck, and femoral head). STUDY DESIGN: A retrospective clinical review, comparing pain status "before vs after" intervention. SETTING: National Cancer Institute in Mexico. METHODS: We included patients over 18 years old, with mild to severe pain due to metastasis in the proximal femur (trochanter, neck, or head), or with a high risk of fracture according to Mirels scale (> 8 points) or severe osteoporosis according to the World Health Organization (a Karnofsky score more than 50%). Exclusion criteria were femoral fracture. We recorded the following variables age, sex, type of neoplasm, concomitant therapy, We used the Karnofsky functionality scale, the VAS pain intensity assessment, the "Mayo Clinic" scale to measure improved functionality, and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative (EORTC QLQ-C15-PAL) (Spanish version) questionnaires. Follow-up was performed at 7 days, one month after femoroplasty, and during the individual outpatient that lasted one year on average. RESULTS: Eighty subjects were enrolled. Seventy-three percent were women. The most frequent tumors were breast (46.3%), followed by multiple myeloma (18.7%). All patients had a decrease in the intensity of pain, analgesic consumption, and improved quality of life, at 7 and 30 days after the intervention. There were no complications with serious consequences. Two participants experienced polymethylmetacrylate (PMMA) leakage, without clinical or functional impact. In 4 patients, the needle was occluded during the filling process and we had to place another biopsy needle through the same entry site to finish the injection process. LIMITATIONS: The sample was a single group of patients evaluated before and after the femoroplasty. We did not include a control group. CONCLUSION: The results of the current report suggest that femoroplasty, a percutaneous cement placement analogous to a vertebroplasty, might be a therapeutic option for patients with metastatic bone disease of the proximal femur, providing the patient an analgesic reduction and a better quality of life.

Hepatic manifestations of metabolic syndrome.

The prevalence of metabolic syndrome is growing around the world at an alarming rate. Obesity involves a plethora of molecules that predispose individuals to an inflammatory state and various metabolic complications. Dysregulation of nutrient metabolism is a key step during the progression of chronic liver disease that induces an inflammatory state, cellular damage, and impaired hepatic insulin signaling, which leads to insulin resistance. Insulin resistance arises from multiple defects in the liver, adipose tissues, and muscle signaling, which leads to a failure to suppress hepatic gluconeogenesis and glycogenolysis, thereby enhancing fat accumulation in the hepatocytes via increased lipolysis and increased hepatic synthesis of triglycerides. This metabolic condition also increases the frequency of other comorbidities such as liver and biliary diseases. Nonalcoholic fatty liver disease is the hepatic expression of metabolic syndrome, which comprises a spectrum of clinical and histological events ranging from simple and benign fatty liver to steatohepatitis, which is characterized by the abnormal activation of pathways leading to an aggressive inflammatory condition. This pathological state may progress to more severe damage known as cirrhosis, which endangers the anatomy and function of liver tissue. In addition, a small group of patients with end-stage liver disease may develop hepatocellular carcinoma and finally death. By contrast, cholesterol gallstone disease is a common metabolic disease, and is considered to be the main biliary indicator of metabolic syndrome. This review provides a detailed summary of the hepatic manifestations associated with metabolic syndrome. Copyright © 2013 John Wiley & Sons, Ltd.

The R230C variant of the ATP binding cassette protein A1 (ABCA1) gene is associated with a decreased response to glyburide therapy in patients with type 2 diabetes mellitus.

OBJECTIVE: To test the hypothesis that persons with the R230C allele of ABCA1 show a decreased glycemic response to glyburide. This polymorphism is exclusively found in Ameri-indian populations and is associated with type 2 diabetes. RESEARCH DESIGN AND METHODS: This is a single blind controlled study including participants with type 2 diabetes (fasting glucose levels 126-250 mg/dl and HbA1c 7%-10%) managed with metformin and a lifestyle program. Each person with the risk allele (R230C) was matched by age, gender and BMI to three others with the wild type variant (R230R). Following a four week stabilization period, only participants with a greater than 70% adherence to metformin and a stable body weight were prescribed glyburide therapy for a further 16 weeks. The main outcome variable was the glyburide dose required to achieve treatment goals. RESULTS: No significant difference was observed in the glucose lowering effect of glyburide between subjects with the R230C and R230R alleles. However, the dose of sulfonylurea was significantly higher in the R230C participants compared with the R230R subjects (3.3±2.1 vs 6.3±5 mg/day, p<0.001). A higher percentage of R230C participants required at least 5mg of glyburide per day to achieve treatment goals. The glyburide dose was determined by the presence of the risk allele, among other factors. CONCLUSIONS: Patients with type 2 diabetes who have the R230C allele of ABCA1 needed a higher dose of glyburide in order to achieve the same glucose lowering effect as that in persons with the wild type variant.

Femoroplasty: a new option for femur metastasis.

Bone metastases are very frequent in patients with cancer and usually are located in the patient's long bones and spine. Various approaches to pain relief and stability to the affected bone have been used. The aim of the study is to report our experience with a new minimally invasive percutaneous technique in patients with bone metastases located in the head, neck, and proximal femur. The technique is performed under fluoroscopic guidance through the application of polymethylmethacrylate bone cement. Our descriptive, retrospective, longitudinal case series included 15 patients who underwent femoroplasty. All patients reported pain reduction and improved mobility, with no complications observed. The femoroplasty procedure caused pain relief by stabilizing the bone through the consolidation of the microfractures because of bone metastases.

Management of chronic upper abdominal pain in cancer: transdiscal blockade of the splanchnic nerves.

BACKGROUND: The use of celiac plexus block to relieve the intractable pain caused by upper abdominal malignancies is well established. However, its effects are inconsistent for many reasons, mainly because of structural anatomic distortion as a consequence for the malignancy. The splanchnic nerve blockade (SNB) seems to be a useful alternative to the celiac plexus block in upper abdominal pain relief. MATERIALS AND METHODS: The pain of 109 patients with unresectable upper abdominal or lower esophageal neoplasms was managed by posterior transdiscal SNBs guided by computed tomography at the Instituto Nacional de Cancerología in Mexico City from January 2004 to June 2007. The study evaluated SNB efficacy with regard to pain relief, its adverse effects/complications, and patient satisfaction. RESULTS: Splanchnic nerve blockade efficacy with regard to pain relief was exhibited by a marked decrease in the visual analog score and in opioid consumption, with preprocedural mean values dropping from 6.1 ± 2.4 and 102.4 mg/d of morphine to 2.7 ± 2.4 and 53.3 mg/d at the first postprocedural visit, respectively. These results persisted during the 1-year follow-up period or until death. Minor adverse effects (moderate diarrhea and mild hypotension) were frequent (n = 64 and n = 47, respectively), and severe complications occurred in 1 patient with a transient paraparesis (n = 1). No procedure-related mortality was observed. CONCLUSIONS: Splanchnic nerve blockade via a transdiscal approach is a technique that provides analgesia and the alleviation of the secondary undesirable effects of analgesic drugs resulting from the decrease of morphine consumption in patients with upper abdominal malignancies. In experienced teams, the reliability of its analgesic effect is high, with a low rate of severe complications.

New insights into the pathophysiology of nonalcoholic fatty liver disease.

The consequences of pathologic adipose tissue accumulation have been described for almost all organs. Nonalcoholic fatty liver disease (NAFLD) is considered the most relevant hepatic manifestation of obesity. There is great interest in the study of NAFLD, and new insights into its pathogenic process have been described. Currently, in addition to insulin resistance, which was considered the hallmark of this disease, endocrine, immunologic, and central nervous system factors are attracting interest as explanatory variables. In this review, new factors associated with the main theories on the pathophysiology of NAFLD are analyzed.

Comparative bioavailability of two oral formulations of omeprazole.

Omeprazole is a very widely used proton-pump inhibitor. Currently, there are several branches available in Mexico, however, limited information about their bioavailabilities is available. The purpose of this study was to compare the bioavailability of two of them, Losec and Omelcid. Twenty-eight healthy volunteers were enrolled in this study that was carried out following the recommendations of the Declaration of Helsinki. Subjects read the protocol that was approved by the institutional research and ethics committees and gave written consent for participation. After an overnight fast, volunteers received an oral dose of 20 mg omeprazole (formulation A or B) and blood samples were obtained at selected times during 8 hours. Plasma was obtained by centrifugation and stored frozen until analyzed by a validated HPLC method. Pharmacokinetic parameters were obtained by non-compartmental analysis and values (+/- s.e.m.) obtained were as follows: Cmax 354.28 +/- 51.57 and 308.95 +/- 44.42 ng/ml, t(max) 2.26 +/- 0.22 and 2.63 +/- 0.24 h and AUC(8h) 701.01 +/- 109.34 and 774.13 +/- 132.84 ngh/ml for formulations A and B respectively. Log transformed Cmax and AUC(8h) were compared by analysis of variance and 90% confidence limits of the parameters ratios (B/A) were 72.73-106.34% and 90.32-124.96%, for Cmax and AUC(8h) respectively. As confidence intervals did not exceed the 70-142.9% limits for Cmax and 80-125% for AUC(8h), it is concluded that the formulations tested are bioequivalent.

Effect of vanadium on insulin sensitivity in patients with impaired glucose tolerance.

BACKGROUND/AIM: Impaired glucose tolerance (IGT) is considered a risk factor for developing type 2 diabetes mellitus (T2DM) and is associated with insulin resistance. Vanadium seems to block protein tyrosine phosphatase with the consequent increment in insulin sensitivity (INS) in T2DM patients, but this effect has not been studied in IGT patients. The aim of this study was to evaluate the effect of vanadium on INS in IGT patients. METHODS: A randomized, double-blind, placebo-controlled clinical trial was carried out in 14 overweight/obese patients with IGT. Intervention consisted of vanadyl sulfate (VS, 50 mg p.o. twice daily) or placebo for 4 weeks. Before and after the intervention, a metabolic profile was performed and INS was assessed using the euglycemic-hyperinsulinemic clamp technique. Mann-Whitney U and Wilcoxon rank tests were used for statistical analyses. RESULTS: There were no significant differences in basal characteristics between groups. VS did not affect INS [2.7+/-0.8 vs. 2.9+/-0.9 mg/(kg/min), p=0.735] but increased triglyceride levels (1.35+/-0.61 vs. 1.70+/-0.46 mmol/l, p=0.018). CONCLUSIONS: VS administration in IGT patients increased triglyceride concentrations without changes in INS.

Synergistic antiallodynic interaction between gabapentin or carbamazepine and either benfotiamine or cyanocobalamin in neuropathic rats.

Anticonvulsants, including gabapentin and carbamazepine, have shown activity against several types of neuropathic pain; however, they have limiting side effects that may minimize their use. In this study the possible synergistic interaction between anticonvulsants and benfotiamine or cyanocobalamin on spinal nerve ligation-induced tactile allodynia was assessed. Oral administration of gabapentin (15-300 mg/kg), carbamazepine (10-300 mg/kg), benfotiamine (30-600 mg/kg) or cyanocobalamin (0.3-6.0 mg/kg) significantly reduced tactile allodynia in rats. Maximal antiallodynic effects were reached with gabapentin 300 mg/kg (approximately 70%), carbamazepine 300 mg/kg (approximately 66%), benfotiamine 600 mg/kg (approximately 51%) and cyanocobalamin 6 mg/kg (approximately 59%). At the highest tested doses, gabapentin, but not carbamazepine, benfotiamine or cyanocobalamin, significantly reduced motor coordination. Coadministration of gabapentin or carbamazepine with benfotiamine or cyanocobalamin in a fixed ratio markedly reduced spinal nerve ligation-induced tactile allodynia, showing a synergistic interaction between anticonvulsants and B vitamins. Data indicate that combinations of anticonvulsants with benfotiamine or cyanocobalamin are able to reduce tactile allodynia without affecting motor coordination in rats, and suggest the possible clinical use of these combinations in the treatment of neuropathic pain in humans.

[Levels of soluble adhesion molecules among normal and hypertensive type 2 diabetic patients]. / Niveles de moléculas de adhesión solubles en pacientes diabéticos tipo 2 normotensos e hipertensos.

BACKGROUND: Hypertension and type-2 diabetes affect endothelial function, which in turn increases the expression of soluble adhesion molecules and lead to the development of vascular damage. The aim of this study was to assess soluble adhesion molecule levels among normotensive and hypertensive diabetic patients. MATERIAL AND METHODS: Serum levels of soluble VCAM1, ICAM1 and e-selectin were measured in 80 type-2 diabetic patients, (40 normotensive and 40 hypertensive), and in 40 normotensive non-diabetic subjects by ELISA (RyDSystems Minneapolis). Statistical analysis was performed with ANOVA. RESULTS: Among diabetic patients, levels of all three soluble adhesion molecules were significantly increased when compared with non-diabetic patients (p < 0.001 for all three molecules), In diabetic hypertensive patients, higher levels of ICAM1 were detected in comparison to normotensive diabetic patients (316 vs. 295 ng/ml p < 0.01), VCAM1 and e-selectin levels were not different between diabetic patients with and without hypertension. CONCLUSIONS: Diabetes is associated with increased levels of soluble adhesion molecules, suggesting a role of these molecules may play in endothelial damage. ICAM1 is further increased when hypertension and diabetes are present. The latter may explain why diabetic-hypertensive patients displayed more complications than normotensive patients.

Hepatic expression of ghrelin and adiponectin and their receptors in patients with nonalcoholic fatty liver disease.

BACKGROUND & AIM: Adiponectin and ghrelin are hormones that participate in hepatic lipid metabolism, and their expression in liver tissue could have important implications for nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the hepatic expression of ghrelin, adiponectin, AdipoR, and IL-6 in patients with NAFLD and normal liver. METHODS: We studied patients with clinical-pathological diagnosis of NAFLD or a normal liver. Patients were classified according to their diagnosis into three groups: normal liver, nonalcoholic hepatic steatosis, and nonalcoholic steatohepatitis (NASH). Adiponectin, AdipoR1, AdipoR2, IL-6, and ghrelin mRNA levels were assessed in biopsies by reverse transcriptase-polymerase chain reaction. RESULTS: Of the 21 patients, three had a normal liver biopsy, 14 had nonalcoholic steatosis, and four had NASH. Patients with NAFLD exhibited significantly higher HOMA-IR and triglyceride concentration (both P<0.05). There was a nonsignificant trend towards higher ghrelin expression in patients with NASH > nonalcoholic steatosis > normal liver. Patients with NASH had significantly higher mRNA adiponectin levels and lower IL-6 levels than did those with a normal liver (P<0.05). AdipoR expression did not differ significantly between groups. CONCLUSION: Adiponectin overexpression was observed in patients with NASH. The role of hepatic ghrelin in NAFLD requires further research.

Kidney damage after renal ablation is worsened in endothelial nitric oxide synthase -/- mice and improved by combined administration of L-arginine and antioxidants.

AIM: Reduction in nitric oxide (NO) levels during kidney failure has been related to the reaction of NO with superoxide anions to yield peroxynitrite which possesses the biological activity responsible for renal damage. However, stimulation of the NO pathway ameliorates the progression of kidney failure. Thus, it is unclear whether NO prevents or acts as the compound responsible for the cytotoxicity observed during kidney failure. METHODS: We evaluated the development of kidney failure in animals that were wild type and deficient in endothelial NO synthase (eNOS -/-) and tested the effects of an antioxidant treatment and NO precursors on the generation of superoxide anion and kidney failure parameters. RESULTS: In wild-type mice, five-sixths nephrectomy increased proteinuria from 3.0 +/- 0.35 to 14.5 +/- 0.76 mg protein/24 h (P < 0.05), blood pressure from 83.1 +/- 1.8 to 126.6 +/- 1.7 mmHg (P < 0.05), and superoxide production from 1.4 +/- 0.6% to 74.3 +/- 0.8% (P < 0.05). The effects of five-sixths nephrectomy on the eNOS -/- mice were greater compared with wild-type mice. Proteinuria increased from 6.7 +/- 0.5 to 22.7 +/- 2.0 mg protein/24 h (P < 0.05), blood pressure increased from 93.3 +/- 0.9 to 151.2 +/- 3.4 mmHg (P < 0.05), and superoxide production increased from 12.9 +/- 0.5% to 99.8 +/- 1.3% (P < 0.05). The nitrotyrosine levels were lower in eNOS -/- mice as compared to wild-type mice. A combination of L-arginine and antioxidant treatment ameliorated renal damage. The effect was improved in wild-type animals. CONCLUSION: Our data support the relevance of NO as an antagonist to superoxide in renal tissues and suggest that the loss of this mechanism promotes the progression of kidney failure.