Helminthiasis may ameliorate inflammatory diseases, such as inflammatory bowel disease and asthma. Information about immunomodulators from Ascaris lumbricoides is scarce, but could be important considering the co-evolutionary relationships between helminths and humans. We evaluated the immunomodulatory effects of a recombinant cystatin from A. lumbricoides on an acute model of dextran sodium sulphate (DSS)-induced colitis in mice. From an A. lumbricoides cDNA library, we obtained a recombinant cystatin (rAl-CPI). Protease activity inhibition was demonstrated on cathepsin B and papain. Immunomodulatory effects were evaluated at two intraperitoneal doses (0.5 and 0.25 μg/G) on mice with DSS-induced colitis. Body weight, colon length, Disease Activity Index (DAI), histological inflammation score, myeloperoxidase (MPO) activity, gene expression of cytokines and cytokines levels in colon tissue were analysed. Treatment with rAl-CPI significantly reduced DAI, MPO activity and inflammation score without toxic effects. Also, IL-10 and TGF-B gene overexpression was observed in rAl-CPI-treated group compared to DSS-exposed control and healthy mice. Furthermore, a reduction in IL-6 and TNF-A expression was found, and this was confirmed by the levels of these cytokines in colonic tissue. In conclusion, rAl-CPI reduces inflammation in a mouse model of DSS-induced colitis, probably by increasing the expression of anti-inflammatory cytokines and reducing pro-inflammatory ones.

The aim of this epidemiological study was to determinate the effects on hematological and lipid profile in a young group of newcomers to altitude after being exposed chronically for 8 months to 3550 m (n = 50), age 17.8 +/- 0.7; and not overweight, BMI 22.9 +/- 0.5). Readings taken at altitude on day 1 and on month 8 were hematocrit (Hct, %), hemoglobin (Hb, g/dL), Sa(O(2)), total leukocyte and subset count (mm(3), %), and lipid profile (mg/dL). The same measurements were taken in a comparative group (CG) at sea level (SL). At altitude, elevations of Hct (44.6 +/- 0.4; 51.2 +/- 0.4) and Hb (15.5 +/- 0.1; 17.3 +/- 0.1) were seen (p < 0.001) and none with Hb >/= 21 g/dL. No correlation was observed between Hb and Sa(O(2)), r = 0.11, p > 0.05. Total leukocyte count showed no changes (6037 +/- 74; 6002 +/- 43), but a relative neutropenia (55.2 + -1.5; 50.6 + -1.3) and lymphocytosis (34.2 + 1; 42.4 + 1, p < 0.001) between periods were found and also when compared to SL. Also, an inverse relationship between Sa(O(2)) and total leukocytes on month 8 (r = 0.46; r(2) = 0.204), suggesting a probable representation of a hypoxia effect. Total cholesterol (153.8 +/- 4.5; 157.3 +/- 5.1; p, ns) showed no changes, but a mild decrease of LDL-cholesterol (88.4 +/- 3.3; 81.0 +/- 3.9; p < 0.05), and a rise in triglycerides (121.6 +/- 10.9; 178.8 +/- 11.7; p < 0.001) was found. Changes observed in leukocytes subset count and triglycerides could suggest a contributory role of hypoxic conditions, raising some future epidemiological concerns regarding immune system and fatty acid behaviour at altitude.

The aim of this study was to evaluate the effects of two periods of intermittent exposure to hypoxia (428 torr) in rats over 12 months. The conditions of CIH4x4 (4 days in hypoxia, 4 days in normoxia, n = 50) and CIH2x2 (2 days in hypoxia, 2 days in normoxia, n = 50) were selected for simulating in this animal model the chronic-intermittent exposure to high altitudes experienced by Andean miners. We assessed mortality, weight, hematological parameters, and time course of resting heart rate and systolic blood pressure. In general, mortality increased during the first month, with a tendency to stabilize during exposure; it was associated with lower weights and with higher hematocrit levels, making these possible predictor factors. Intermittence produced an increase in hematocrit and hemoglobin concentrations as previously seen in most hypoxic models, compared with normoxia (NX, n = 30), but attained lower levels compared with chronic hypoxia (CH, n = 28). CIH4x4 and CIH2x2 had similar sustained elevations of systolic blood pressure (171 +/- 3 and 174 +/- 2 mmHg, respectively) versus the basal level (163 +/- 3; 163 +/- 3 mmHg), whereas CH did not. Heart rate suffered an equally sustained decrease in all exposed groups (343 +/- 14 beats/min). Exposure to chronic-intermittent hypoxia led to a mild polycythemia and to a decrease in heart rate. The effects of hypoxia were already evident during the first month of exposure and attained a more pronounced expression and stabilization during the third month.

SUMMARYTo determine whether the antihypertensive effectiveness of lercanidipine was independent of the different cardiovascular risk levels. Patients with treated or untreated mild-to-moderate essential hypertension were included in a multicentre, prospective, non-comparative, open-label study. Patients received lercanidipine (10 mg/day, uptitrated to 20 mg/ day) during 6 months. A total of 3175 patients, age 63 AE 10 years, 51% women, were included. The cardiovascular risk was low in 237 patients, medium in 1396, high in 722, and very high in 820. At baseline, blood pressure (BP) was 159.5 AE 11.7/ 95.2 AE 7.4 mmHg. BP was progressively higher according to increase in cardiovascular risk. After 6 months of treatment, BP was 136.0 AE 9.7/79.7 AE 6.8 mmHg. The decrease in systolic BP and diastolic BP at each follow-up visit compared with baseline was statistically significant both in the intergroup and intragroup comparisons (p 0 0.001). Mean decreases of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were )18.5/ )13.8 mmHg in the low risk group, )23/)15.2 mmHg in the medium risk group, )24.4/)16.1 mmHg in the high risk group, and )27.4/)17.4 mmHg in the very high risk group. Most frequent side effects were oedema (5.1%), headache (3.3%), flushes (2.5%), and asthenia (1%). Only 1.7% of patients discontinued antihypertensive medication because of adverse events. Tolerability of lercanidipine was independent of the cardiovascular risk group. Lercanidipine was effective and well-tolerated in patients with mild-to-moderate hypertension in the daily practice. The effectiveness and safety of the drug were independent of the degree of cardiovascular risk.

The use of natural products by communities from the Colombian Caribbean region to treat health issues, together with biodiversity and geographical features, constitute a great scenery to develop new therapies based on ethnopharmacological heritage. Here, we investigated the anti-inflammatory potential of 10 commonly used plants in Colombian folk medicine, evaluating their effect on nitric oxide (NO) production by LPS-stimulated RAW 264.7 macrophages. The most active plant was evaluated in vivo using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema, along with its effect on the production of pro-inflammatory mediators in vitro. The extract of Physalis angulata L. calyces showed the highest activity. This extract was fractionated and its dichloromethane fraction (DF) was the most active in vitro, inhibiting the production of NO, prostaglandin E2 (PGE2), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and monocyte chemotactic protein (MCP)-1 (CCL2). In vivo, DF showed a significant inhibition of ear edema and myeloperoxidase (MPO) activity, with evident reduction of the leukocyte infiltration into tissue. Our results support the ethnopharmacological use of the selected plants in folk medicine. P. angulata dichloromethane fraction represents a promising source of pharmacological compounds with great potential therapeutic use to treat inflammatory illness.