Home Blood Pressure Levels in Pregnant Women with Chronic Hypertension

Objective: To explore the difference between office and home blood pressure (BP) monitoring in normotensive and hypertensive pregnant women. Methods: We compared the mean of 1 week home BP with office BP, measured by aneroid devices, in 20 normotensive women (68 BP assessments) and 100 women with mild essential chronic hypertension without superimposed gestational hypertension (429 BP assessments). Different approaches were used including the Bland-Altman method to investigate the discrepancies between office and home BP. Results: Systolic office BP in normotensive women (p = 0.004) and diastolic office BP in hypertensive women (p = 0.001) were lower than home BP. The concordance between office and home BPs was better for diastolic BP than for systolic BP. Only a small number of hypertensive women presented home BP ≥135/85 mm Hg. Conclusions: In our study population, the concurrence between office and home BPs is good with the exception of systolic BP in normotensive women. Home blood pressure measurement criteria used in nonpregnant individuals are not adequate in pregnancy.     

Induction of Porcine Regulatory Cells by Mycophenolic Acid-Treated Dendritic Cells

Tolerance induction in murine allogeneic transplantation is relatively easy, often by induction of regulatory T cells (Treg). Unfortunately, the implementation of these models in clinical situations has not yielded reliable protocols of tolerance induction in humans. Our project sought to create a preclinical model of tolerance induction in large animals. Our current efforts seek to induce and characterize porcine Treg, obtaining dendritic cells (DC) able to preferentially stimulate them. DCs were differentiated from blood monocytes with porcine recombinant interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for 6 days. These DCs were then stimulated by human CD40 ligand-transfected L cells with or without mycophenolic acid (MPA) for 48 hours. We analyzed surface marker expression, cytokine synthesis, and ability to stimulate allogeneic peripheral blood mononuclear cells (PBMC). The porcine lymphocytes underwent 4 rounds of 1-week stimulation with allogeneic DC treated or not with MPA. At the end of this coculture we analyzed their capacity to suppress allogeneic PBMC proliferation induced by mature DC. Our results showed that porcine DCs pretreated with MPA display a low expression of B7 costimulatory molecules, produce low levels of IL-12, and induce weak proliferation of allogeneic lymphocytes. Moreover, after 4 rounds of stimulation with MPA-treated DCs, PBMCs were able to inhibit an alloreactive response. These preliminary results suggested induction of a regulatory T-cell population that we are currently seeking to characterize.     

The kinin B1 receptor antagonist SSR240612 reverses tactile and cold allodynia in an experimental rat model of insulin resistance

BACKGROUND AND PURPOSE: Diabetes causes sensory polyneuropathy with associated pain in the form of tactile allodynia and thermal hyperalgesia which are often intractable and resistant to current therapy. This study tested the beneficial effects of the non-peptide and orally active kinin B(1) receptor antagonist SSR240612 against tactile and cold allodynia in a rat model of insulin resistance. EXPERIMENTAL APPROACH: Rats were fed with 10% D-glucose for 12 weeks and effects of orally administered SSR240612 (0.3-30 mg kg(-1)) were determined on the development of tactile and cold allodynia. Possible interference of SSR240612 with vascular oxidative stress and pancreatic function was also addressed. KEY RESULTS: Glucose-fed rats exhibited tactile and cold allodynia, increases in systolic blood pressure and higher plasma levels of insulin and glucose, at 12 weeks. SSR240612 blocked tactile and cold allodynia at 3 h (ID(50)=5.5 and 7.1 mg kg(-1), respectively) in glucose-fed rats but had no effect in control rats. The antagonist (10 mg kg(-1)) had no effect on plasma glucose and insulin, insulin resistance (HOMA index) and aortic superoxide anion production in glucose-fed rats. CONCLUSIONS AND IMPLICATIONS: We provide the first evidence that the B(1) receptors are involved in allodynia in an experimental rat model of insulin resistance. Allodynia was alleviated by SSR240612 most likely through a direct inhibition of B(1) receptors affecting spinal cord and/or sensory nerve excitation. Thus, orally active non-peptide B(1) receptor antagonists should have clinical therapeutic potential in the treatment of sensory polyneuropathy.     

The endogenous cannabinoid system stimulates glucose uptake in human fat cells via phosphatidylinositol 3-kinase and calcium-dependent mechanisms

BACKGROUND: The endogenous cannabinoid system participates in the regulation of energy balance, and its dysregulation may be implicated in the pathogenesis of obesity. Adipose tissue endocannabinoids may produce metabolic and endocrine effects, but very few data are available in human adipose tissue and in primary human fat cells. EXPERIMENTAL DESIGN: We measured expression of type 1 and type 2 cannabinoid receptors (CNR), enzymes of cannabinoids synthesis and degradation in human omental, sc abdominal, and gluteal adipose tissue from lean and obese subjects. Furthermore, we assessed the effect of CNR1 stimulation on glucose uptake and intracellular transduction mechanisms in primary human adipocytes. Then we assessed the reciprocal regulation between CNR1 and peroxisome proliferator-activated receptor-gamma (PPARgamma). Finally, we tested whether leptin and adiponectin are regulated by CNR1 in human adipocytes. RESULTS: We found that most genes of the endocannabinoid system are down-regulated in gluteal fat and up-regulated in visceral and sc abdominal adipose tissue of obese patients. Treatment of adipocytes with rosiglitazone markedly down-regulated CNR1 expression, whereas Win 55,212 up-regulated PPARgamma. Win 55,212 increased (+50%) glucose uptake, the translocation of glucose transporter 4, and intracellular calcium in fat cells. All these effects were inhibited by SR141716 and wortmannin and by removing extracellular calcium. Win 55,212 and SR141716 had no effect on expression of adiponectin and leptin. CONCLUSIONS: These results indicate a role for the local endocannabinoids in the regulation of glucose metabolism in human adipocytes and suggest a role in channeling excess energy fuels to adipose tissue in obese humans.     

Identification of 23 novel MHC class I alleles in cynomolgus macaques of Philippine and Philippine/Mauritius origins

We report here novel Mafa-A, -AG and -B alleles identified in two groups of cynomolgus macaques.     

Presence of Duodenopancreatic Feedback in Minipigs and Possible Interference from the Bile

In two minipigs chronic pancreatic and duodenal fistulas, which allowed the diversion and the intestinal replacement of pancreatic secretion, were prepared. In a third minipig a chronic biliary fistula was also prepared so the bile secretion could be fed back into the intestine through a duodenal catheter. In these animals a chronic gastric fistula was made so gastric secretion could also be collected. Diversion-replacement of pure pancreatic juice and of bile were carried out in the fasting state. This study confirms the presence of a feedback regulatory mechanism in exocrine pancreatic secretion in the pig. Moreover, it suggests that bile can interfere with this phenomenon.     

Lipid and phospholipid profile after bowel resection for Crohn’s disease

BACKGROUND AND AIM: Chronic inflammation, impaired intestinal adsorption, and bowel resection may have an impact on lipid metabolism before and after intestinal surgery for Crohn's disease (CD). The aim of this prospective study was to define the impact of intestinal surgery for CD on plasma phospholipid fatty acid (FA) composition and of serum plasma lipoprotein concentrations and to investigate the role of CD recurrence on lipid parameters. MATERIALS AND METHODS: Twenty-four consecutive patients who had intestinal surgery for CD since December 2004 to March 2006 were enrolled in this prospective study. The total amount of calorie intake and the quality of the aliments, systemic inflammatory activity, and plasma lipoproteins and phospholipid fatty acid composition were determined at operation and at follow-up. Statistical analysis was performed with pair-matched tests. RESULTS: The median follow-up was 6 (4-20) months. During the follow-up, no significant modification of body mass index was observed. An increase of high-density lipoprotein (HDL) cholesterol (p = 0.02) without other modifications in the plasma phospholipid FA composition were evidenced after surgery. The comparison between colectomy and ileo-colonic or ileal resection groups did not show any significant difference in the lipoprotein concentration and phospholipid FA profile. The length of resected bowel did not show any significant correlation with any relevant difference in lipid, phospholipid profile, or in inflammatory parameters. Patients who experienced a recurrence of CD reported significantly higher levels of total (p < 0.01), HDL (p = 0.01), and low-density lipoprotein cholesterol (p = 0.01) were observed in patients in remission than in those with recurrent active disease. CONCLUSIONS: Patients who are submitted to intestinal resection for CD improve their inflammatory status as well as their lipid metabolism, and CD recurrence, but not the extent of bowel resection, is the main predictor of alteration of serum lipid concentration.