Screening of hypercortisolism among patients with hypertension: an Italian nationwide survey.

PURPOSE: Screening of Cushing Syndrome (CS) and Mild Autonomous Cortisol Secretion (MACS) in hypertensive patients is crucial for proper treatment. The aim of the study was to investigate screening and management of hypercortisolism among patients with hypertension in Italy. METHODS: A 10 item-questionnaire was delivered to referral centres of European and Italian Society of Hypertension (ESH and SIIA) in a nationwide survey. Data were analyzed according to type of centre (excellence vs non-excellence), geographical area, and medical specialty. RESULTS: Within 14 Italian regions, 82 centres (30% excellence, 78.790 patients during the last year, average 600 patients/year) participated to the survey. Internal medicine (44%) and cardiology (31%) were the most prevalent medical specialty. CS and MACS were diagnosed in 313 and 490 patients during the previous 5 years. The highest number of diagnoses was reported by internal medicine and excellence centres. Screening for hypercortisolism was reported by 77% in the presence of specific features of CS, 61% in resistant hypertension, and 38% in patients with adrenal mass. Among screening tests, the 24 h urinary free cortisol was the most used (66%), followed by morning cortisol and ACTH (54%), 1 mg-dexamethasone suppression test (49%), adrenal CT or MRI scans (12%), and late night salivary cortisol (11%). Awareness of referral centres with expertise in management of CS was reported by 67% of the participants, which reduced to 44% among non-excellence centres. CONCLUSIONS: Current screening of hypercortisolism among hypertensive patients is unsatisfactory. Strategies tailored to different medical specialties and type of centres should be conceived.

Nutritional assessment and medical dietary therapy for management of obesity in patients with non-dialysis chronic kidney disease: a practical guide for endocrinologist, nutritionists and nephrologists. A consensus statement from the Italian society of endocrinology (SIE), working group of the club nutrition-hormones and metabolism; the Italian society of nutraceuticals (SINut), club ketodiets and nutraceuticals "KetoNut-SINut"; and the Italian society of nephrology (SIN).

PURPOSE: Chronic kidney disease (CKD) is a serious health concern with an estimated prevalence of about 13.4% worldwide. It is cause and consequence of various comorbidities, including cardiovascular diseases. In parallel, common pathological conditions closely related to ageing and unhealthy dietary habits increase the risk of CKD development and progression, including type 2 diabetes and obesity. Among these, obesity is either independent risk factor for new onset kidney disease or accelerates the rate of decline of kidney function by multiple mechanisms. Therefore, the role of diets aimed at attaining weight loss in patients with obesity is clearly essential to prevent CKD as to slow disease progression. Various dietary approaches have been licensed for the medical dietary therapy in CKD, including low-protein diet and Mediterranean diet. Interestingly, emerging evidence also support the use of low-carbohydrate/ketogenic diet (LCD/KD) in these patients. More specifically, LCD/KDs may efficiently promote weight loss, improve metabolic parameters, and reduce inflammation and oxidative stress, resulting in a dietary strategy that act globally in managing collateral conditions that are directly and indirectly related to the kidney function. CONCLUSION: This consensus statement from the Italian Society of Endocrinology (SIE), working group of the Club Nutrition - Hormones and Metabolism; the Italian Society of Nutraceuticals (SINut), Club Ketodiets and Nutraceuticals "KetoNut-SINut"; and the Italian Society of Nephrology (SIN) is intended to be a guide for Endocrinologist, Nutritionists and Nephrologist who deal with the management of patients with obesity with non-dialysis CKD providing a practical guidance on assessing nutritional status and prescribing the optimal diet in order to best manage obesity to prevent CKD and its progression to dialysis.

Impact of simultaneous management of hypertension and hypercholesterolemia with ACE inhibitors and statins on cardiovascular outcomes in the Brisighella Heart Study: A 8-year follow-up.

BACKGROUND AND AIMS: To evaluate the long-term effect of simultaneous treatment of hypertension and hypercholesterolemia with angiotensin-converting enzyme (ACE) inhibitors and statins on the incidence of major cardiovascular events (MACE) and other clinical outcomes. METHODS AND RESULTS: We considered data from a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. We excluded normotensive subjects and individuals with a low calculated 10-year CVD risk, hypertensive patients treated with antihypertensive drugs different from ACE inhibitors and patients who changed antihypertensive medications during follow-up. The remaining participants were divided into four groups depending on whether they were treated with (I) perindopril ± amlodipine without statin treatment (N. 132), (II) perindopril ± amlodipine and atorvastatin (N. 132), (III) an ACE inhibitor other than perindopril ± a calcium-channel blocker without statin therapy (N. 133), (IV) an ACE inhibitor other than perindopril ± a calcium-channel blocker and statin therapy (N. 145). The long-term (8 years) effects of the different combined treatment were compared among the pre-defined groups. Over the follow-up period of 8 years, the proportion of subjects who developed MACE, type 2 diabetes mellitus and hyperuricemia, and the proportion of subjects needing for the intensification of antihypertensive treatment to improve blood pressure control were statistically different among the predefined groups (P < 0.05). CONCLUSION: Combined treatment with ACE inhibitors and statins (especially atorvastatin) in hypertensive patients seems to significantly reduce the risk of developing CVD in comparison with treatment with ACE inhibitors alone.

Renin-angiotensin system at the crossroad of hypertension and hypercholesterolemia.

AIM: The aim of this study is to discuss the reliable scientific evidence of an interactive link between hypertension and hypercholesterolemia considering the metabolic pathways and the pathogenetic mechanisms connecting the two risk factors. DATA SYNTHESIS: Hypertension and hypercholesterolemia are highly prevalent in the general population and their coexistence in the same subjects additively increases the risk of cardiovascular disease. Probably, hypercholesterolemia is also a risk factor for the development of hypertension. On the other side, it is also possible that lipid-lowering treatment could improve blood pressure control. Although the mechanisms of interaction between these two risk factors have not been completely elucidated thus far, there is rapidly growing evidence that the involvement of the renin-angiotensin system (RAS) can be considered as the common link between hypertension and hypercholesterolemia. In particular, hypercholesterolemia seems to promote the upregulation of type 1 angiotensin II (AT1) receptor genes because of an increase in the stability of mRNA followed by structural overexpression of vascular AT1 receptors for angiotensin II. The treatment of both risk factors greatly improves individual risk profile, especially when statins and RAS blockers are used together. CONCLUSIONS: Hypertension and hypercholesterolemia are highly coprevalent and strongly related from a pathophysiological point of view. The RAS could be the main mediator of this link.

Novel role of the nutraceutical bioactive compound berberine in lectin-like OxLDL receptor 1-mediated endothelial dysfunction in comparison to lovastatin.

BACKGROUND AND AIMS: Oxidized LDL (oxLDL) or pro-inflammatory stimuli lead to increased oxidative stress linked to endothelial dysfunction and atherosclerosis. The oxLDL receptor-1 (LOX1) is elevated within atheromas and cholesterol-lowering statins inhibit LOX1 expression. Berberine (BBR), an alkaloid extracted from plants of gender Berberis, has lipid-lowering and anti-inflammatory activity. However, its role in regulating LOX1-mediated signaling is still unknown. The aim of this study was to investigate the effect of BBR on oxLDL- and TNFα-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs) and to compare it with that of lovastatin (LOVA). METHODS AND RESULTS: Cytotoxicity was determined by lactate dehydrogenase assay. Antioxidant capacity was measured with chemiluminescent and fluorescent method and intracellular ROS levels through a fluorescent dye. Gene and protein expression levels were assayed by qRT-PCR and western blot, respectively. HUVECs exposure to oxLDL (30 µg/ml) or TNFα (10 ng/ml) for 24 h led to a significant increase in LOX1 expression, effect abrogated by BBR (5 µM) and LOVA (5 µM). BBR but not LOVA treatment abolished the TNFα-induced cytotoxicity and restored the activation of Akt signaling. In spite of a low direct antioxidant capacity, both compounds reduced intracellular ROS levels generated by treatment of TNFα but only BBR inhibited NOX2 expression, MAPK/Erk1/2 signaling and subsequent NF-κB target genes VCAM and ICAM expression, induced by TNFα. CONCLUSIONS: These findings demonstrated for the first time that BBR could prevent the oxLDL and TNFα - induced LOX1 expression and oxidative stress, key events that lead to NOX, MAPK/Erk1/2 and NF-κB activation linked to endothelial dysfunction. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Berberine (PubChem CID: 2353); Lovastatin (PubChem CID: 53232).

Efficacy and tolerability of a combined lipid-lowering nutraceutical on cholesterolemia, hs-CRP level and endothelial function in moderately hypercholesterolemic subjects.

Our aim was to test, by a double-blind, placebo-controlled randomized clinical trial, whether a short-term treatment with a combined lipid-lowering nutraceutical could improve endothelial function in a cohort of moderately hypercholesterolemic subjects. Thus, 80 healthy, moderately hypercholesterolemic subjects were consecutively enrolled and, after 4 weeks of stabilization diet, they were randomized to either the tested lipid-lowering nutraceutical or placebo for 8 weeks. At the beginning and end of treatment a complete lipid pattern, safety parameters, hs-CRP and endothelial function were measured. When compared to placebo, during nutraceutical treatment patients experienced a more favorable percentage change in total cholesterol (TC vs baseline: -17.9%; TC vs placebo: -5.6%), LDL-cholesterol (LDL-C vs baseline: -23.3%; LDL-C vs placebo: -2.8%), hs-CRP (hs-CRP vs baseline: -2.4%; hs-CRP vs placebo: -1.5%), and endothelial function (pulse volume displacement vs baseline: +17%; pulse volume displacement vs placebo treatment: -3.3%). No significant difference was observed in respect to effects on triglycerides, HDL-cholesterol and safety parameters. On the basis of our data, the tested lipid-lowering nutraceutical seems to significantly improve endothelial function in moderately hypercholesterolemic subjects. These results have to be confirmed on larger patient samples and over longer periods.

Nutraceutical approaches to homocysteine lowering in hypertensive subjects at low cardiovascular risk: a multicenter, randomized clinical trial.

Although the role of homocysteine (HCys) in secondary cardiovascular prevention has been scaled down, hyper-homocysteinemia remains a risk factor for cerebrovascular events. The aim of this study was to investigate the efficacy of nutraceuticals in lowering HCys serum levels versus a conventional vitamin supplementation in hypertensive subjects at low cardiovascular risk. One-hundred and four patients (mean age 62.8±14.5 years, 63.5% males), 52 for each treatment group, were enrolled. The study recruited patients with stage 1 essential hypertension and hyper-homocysteinemia (HCys ≥15 µmol/L), without a history of cardiovascular and cerebrovascular disease. They were sequentially randomized to receive a combined nutraceutical containing 400 µg folate-6-5-methyltetrahydrofolate, 3 mg vitamin B6, 5 µg vitamin B12, 2.4 mg vitamin B2, 12.5 mg zinc and 250 mg betaine (Normocis400®) once daily for two months, or supplementation with highly dosed folic acid (5 mg/day) (control group). Differences in serum HCys values were compared by ANOVA for repeated measures. A significant HCys reduction in comparison to baseline was found in both groups at the end of the study treatment, from 21.5±8.7 to 10.0±1.7 µmol/L for Normocis400® subjects (p less than 0.0001), and from 22.6±6.2 to 14.3±2.8 µmol/L for controls (p less than 0.0001). HCys reduction was significantly higher among patients treated with Normocis400® (p less than 0.035). The ideal HCys level (i.e. less than 10 µmol/L) was reached in 55.8% of cases in theNormocis400® group, and it was significantly higher than in controls. No side effects were observed in either treatment group. Randomized clinical trials are ongoing to test the effect of folate, B6, and B12 supplementation in primary prevention of cardiovascular and cerebrovascular events. In the meantime, especially when the ideal HCys level is far from being reached, Normocis400® appears to be safe, well tolerated and effective in reducing HCys levels.

A comparison between sitagliptin or glibenclamide in addition to metformin + pioglitazone on glycaemic control and ß-cell function: the triple oral therapy.

AIMS: To evaluate which triple oral therapy between metformin + pioglitazone + sitagliptin and metformin + pioglitazone + glibenclamide can be more useful in improving glycaemic control and should be preferred in clinical practice. METHODS: During the 2-year run-in period, patients were instructed to take metformin monotherapy for the first year, then a combination of metformin and pioglitazone for the second year, then patients were randomized to add glibenclamide or sitagliptin to the dual combination of metformin and pioglitazone for another year. RESULTS: Body weight reached with sitagliptin at 36 months was lower than that reached with glibenclamide. Fasting plasma insulin and homeostasis model assessment of insulin resistance were significantly increased by triple therapy with glibenclamide and decreased by that with sitagliptin. While sitagliptin did not change homeostasis model assessment of ß-cell function, this value was significantly increased by glibenclamide. Fasting plasma proinsulin was not influenced by triple oral therapy including glibenclamide, while it was decreased by the therapy including sitagliptin compared to glibenclamide. Triple oral therapy with sitagliptin better improved ß-cell function measures compared with the glibenclamide therapy. CONCLUSIONS: Sitagliptin should be preferred to glibenclamide as an addition to the metformin + pioglitazone combination for its better protection of ß-cell secretion and its neutral effect on body weight.

Effects of an olmesartan/amlodipine fixed dose on blood pressure control, some adipocytokines and interleukins levels compared with olmesartan or amlodipine monotherapies.

WHAT IS KNOWN AND OBJECTIVE: To evaluate the effects of an olmesartan/amlodipine single pill combination compared with olmesartan or amlodipine monotherapies on blood pressure control, lipid profile, insulin sensitivity and some adipocytokines levels. METHODS: Two hundred and seventy-six patients were enroled in the study and were randomly assigned to take olmesartan 20 mg, amlodipine 10 mg, or a single pill containing an olmesartan/amlodipine combination 20 mg/5 mg for 12 months. We evaluated at the baseline, and after 6 and 12 months: body weight, body mass index, systolic and diastolic blood pressure (SBP and DBP), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, adiponectin (ADN), resistin (r), interleukin-1ß (IL-1ß) and interleukin-5 (IL-5). At the baseline, and after 6 and 12 months, patients underwent an euglycemic, hyperinsulinemic clamp to assess insulin sensitivity (M value). RESULTS AND DISCUSSION: There was a similar decrease in SBP and DBP after 6 and 12 months in all groups, even if olmesartan/amlodipine combination gave a major decrease in SBP and DPB compared with amlodipine and olmesartan monotherapies. Olmesartan/amlodipine combination decreased FPG after 12 months compared with amlodipine monotherapy. Olmesartan/amlodipine combination decreased FPI and HOMA index and increased M value both compared with baseline and compared with olmesartan and amlodipine monotherapies. Both olmesartan and olmesartan/amlodipine increased ADN and reduced r, without significant differences between the two groups. Regarding interleukins, no differences emerged in group to group comparison. WHAT IS NEW AND CONCLUSION: Olmesartan/amlodipine combination resulted more effective than olmesartan and amlodipine monotherapies in reducing blood pressure, and in increasing insulin sensitivity parameters, but not resulted more effective in improving adipocytokines and interleukins levels analysed, compared with amlodipine or olmesartan monotherapy in hypertensive patients in this double-blind, randomized clinical trial.

Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes.

WHAT IS KNOWN AND OBJECTIVE: The behavioural approach is usually slow and not always sufficient to achieve optimal targets in weight and metabolic control in obese diabetic patients, and a pharmacological treatment is often necessary. The aim of this study was to compare the effects of orlistat and placebo on body weight, glycaemic and lipid profile and insulin resistance in patients with type 2 diabetes. METHODS: Two hundred and fifty-four obese, diabetic patients were enrolled in this study and randomized to take orlistat 360mg or placebo for 1year. We evaluated at baseline and after 3, 6, 9 and 12months body weight, waist circumference (WC), body mass index (BMI), glycated haemoglobin (HbA(1c) ), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), lipid profile, retinol-binding protein-4 (RBP-4), resistin, visfatin and high-sensitivity C-reactive protein (Hs-CRP). RESULTS AND DISCUSSION: We observed a significant reduction in body weight, WC, BMI, lipid profile, RBP-4 and visfatin in the orlistat group but not in control group. Faster improvements in HbA(1c) , PPG, FPI, HOMA-IR, resistin and Hs-CRP were recorded with orlistat than with placebo. A similar decrease in FPG was seen in the two groups. Significant predictors of change in insulin resistance (HOMA-IR) were RBP-4 and resistin concentration in the orlistat group (r=-0·53, P<0·05, and r=-0·59, P<0·01, respectively). WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first study investigating the effect of orlistat on insulin resistance and markers of inflammation. Orlistat improved lipid profile and led to faster glycaemic control and insulin resistance parameters than the control, without any serious adverse event. Orlistat also improved RBP-4 and visfatin, effects not observed with placebo.

Predictors of the short-term effect of isoleucine-proline-proline/valine-proline-proline lactotripeptides from casein on office and ambulatory blood pressure in subjects with pharmacologically untreated high-normal blood pressure or first-degree hypertension.

Our aim was to evaluate the predictors of Isoleucine-Proline-Proline/Valine-Proline-Proline (IPP-VPP) lactotripeptides (LTPs) antihypertensive effect in the context of a short-term large double-blind randomized clinical trial involving 164 pharmacologically untreated subjects in primary prevention for cardiovascular disease. When compared with the baseline, office systolic blood pressure (SBP) (-3.42 mm Hg, P < .001) and diastolic blood pressure (DBP) (-2.35 mm Hg, P < .001) significantly decreased, in the LTP-treated patients only. No significant change in predictors during the study of ambulatory blood pressure measurement (ABPM) parameters was observed. A short-term supplementation with LTPs significantly improves the office SBP and DBP, especially in male subjects. The main predictor of LTP antihypertensive effect was the baseline BP.

Combined action of SAMe, Folate, and Vitamin B12 in the treatment of mood disorders: a review.

Mood disorders affect more than 500 million people around the world. In the last decade, their prevalence has increased, and many people suffer from nervousness, anxiety, and stress at least once in their lives. The incidence of mood disorders and anxiety increases during perimenopause or under stressful conditions. The social restrictions introduced during the COVID-19 pandemic have significantly increased the normal burden of psychological and psychic disorders. In moderate to severe cases, pharmacological treatment is currently recommended, while in mild disorders, especially in the initial phase, psychological therapy is preferable. It is known that several nutrients are crucial for brain function. Among them, folate (vitamin B9), cyanocobalamin (vitamin B12), and S-adenosyl-L-methionine (SAMe) have been shown to influence various neurobiological processes. Overall, the available evidence suggests that dietary supplementation with folic acid, vitamin B12, and SAMe can be beneficial for people with mild mood disorders.

Pioglitazone compared to glibenclamide on lipid profile and inflammation markers in type 2 diabetic patients during an oral fat load.

The aim of the study was to evaluate the effect of pioglitazone and glibenclamide on lipid profile and inflammatory parameters during an oral fat load (OFL). A total of 201 type 2 diabetic patients on treatment with metformin were enrolled in the study; pioglitazone was titrated till 45 mg/day and glibenclamide till 15 mg/day, in association with metformin, respectively. The patients underwent an OFL at baseline and after 12 months. The OFL was given between 08.00 and 09.00 h after a 12-h fast. Blood samples were drawn before and 3, 6, 9, and 12 h after the OFL. We evaluated glycemic-metabolic parameters [glycated hemoglobin (HbA (1c)), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment (Homa) index], total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tgs), interleukin-6 (IL-6), high sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α), and adiponectin (ADN). Pioglitazone was better than glibenclamide in decreasing HbA (1c), FPG, FPI, lipid profile, and in improving inflammatory parameters such as Hs-CRP, and ADN. Comparing the OFL performed at baseline, and the OFL performed at the end of the study, pioglitazone, but not glibenclamide, improved all post-OFL peaks for all parameters. Comparing the 12 months OFL in the group treated with pioglitazone and in the group treated with glibenclamide, the values recorded with pioglitazone were significantly better than the ones obtained with glibenclamide. We can conclude that pioglitazone was better than glibenclamide in mitigating the variations of lipid components and inflammation parameters in type 2 diabetic patients.

Sex hormones and adipokines in healthy pre-menopausal, post-menopausal and elderly women, and in age-matched men: data from the Brisighella Heart study.

BACKGROUND: Sex hormones and adipokines seem to differently interact in both genders at different ages. AIM: To comparatively evaluate the serum level of adipokines and sex hormones in healthy non-pharmacologically treated premenopausal women, post-menopausal women, and elderly women, and in age-matched men. SUBJECTS: From the historical cohort of the Brisighella Heart Study we selected 199 adult healthy subjects (males: 89; females: 110), aged 62.5±12.4 yr. Men and women included in the age-class subgroups were matched for body mass index (BMI), waist circumference, blood pressure, heart rate, fasting plasma glucose, plasma lipids. RESULTS: Leptin did not differ among various age classes in men, while pre-menopausal women displayed significantly lower serum leptin than post-menopausal women (-6.7 ± 2.2 pg/ml, p=0.036). Post-menopausal women had significantly greater serum leptin when compared with age-matched men (+13.1 ± 2.0 pg/ml, p<0.001); the same was observed for elderly women when compared with elderly men (+11.2 ± 2.3 pg/ml, p<0.001). At any age, women had significantly lower serum testosterone/estrone ratio than age-matched men (p<0.01). Serum DHEAS was inversely proportional to age in both genders. The main predictors of adiponectin level are age in men (p=0.027) and BMI in women (p=0.003). The main predictors of leptin level are BMI and the testosterone/estrone ratio in both sexes (p<0.05). The testosterone/estrone ratio is also the main predictor of ghrelin levels in women (p=0.006). CONCLUSION: Sex hormones and adipokines show specific interactions in the two genders and in different age-classes in a representative sample of adult healthy subjects.

Variation of inflammatory parameters after sibutramine treatment compared to placebo in type 2 diabetic patients.

WHAT IS KNOWN AND OBJECTIVE: The efficacy of sibutramine has been demonstrated in randomized trials in obese/overweight patients including those with type 2 diabetes mellitus (T2DM). Our objective was to evaluate the effects of 1-year treatment with sibutramine compared to placebo on body weight, glycaemic control, lipid profile, and inflammatory parameters in type 2 diabetic patients. METHODS: Two hundred and forty-six patients with uncontrolled T2DM [glycated haemoglobin (HbA(1c) ) > 8·0%] in therapy with different oral hypoglycaemic agents or insulin were randomized to take 10 mg of sibutramine or placebo for 12 months. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c) , fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), leptin, tumour necrosis factor-α (TNF-α), adiponectin (ADN), vaspin, high sensitivity C-reactive protein (Hs-CRP). RESULTS AND DISCUSSION: We observed a decrease of body weight after 9 and 12 months in the group treated with sibutramine, but not in the control group. Regarding glycaemic and lipid profile, although there are differences seen over time within each of the groups, we did not obtain any significant differences between the two groups. Both placebo and sibutramine gave a similar improvement of HOMA-IR, leptin, TNF-α, ADN, and Hs-CRP. No vaspin variations were observed in either group. WHAT IS NEW AND CONCLUSION: Sibutramine resulted in a decrease in body weight at 9 months and at 12 months that was not observed with placebo. Although there were differences seen over time within each of the groups, there were no significant differences between groups for any other parameter that we measured.

Investigation of the relaxing effect of a camphor nanoemulsion on rat isolated trachea.

Asthma is a chronic inflammatory disease that targeting lower airways, being characterized by bronchial smooth muscle hyper responsiveness and mucus hypersecretion. Asthma is considered the most common respiratory disease in the world, affecting approximately 235 million individuals. The main therapy sometimes fails to establish clinical improvement in patients, which leads to a constant search for new alternatives. Camphor is a transparent solid monoterpene with a strong aroma, which due to its high lipophilicity is insoluble in water. Nanostructured carrier systems have shown promise as a delivery system for lipophilic compounds such as monoterpenes. Therefore, the objective of this work was to evaluate the relaxant effect of nanoemulsified camphor (NEC), as well as the mechanism of action of that monoterpene, in isolated rat trachea. The results obtained demonstrated that NEC promote relaxation of the isolated rat trachea when smooth muscle contraction was induced by both carbachol (CCh) and KCl, presenting a pCE50 of 2.25 ± 0.27 and 3.30 ± 0.07, respectively. In the presence of dexamethasone (DEXA), tetraethylammonium (TEA), glibenclamide (GLIB), 1H-[1,2,4]-oxadiazole-[4,3,-a]-quinoxaline-1-one (ODQ) and ruthenium red (RR) there was a significant difference in at least one of the evaluated pharmacological parameters, such as concentration-response curves shape, Emax or pCE50. As conclusion, NEC may be involved with ß-adrenergic receptors, channels for K+ sensitive to ATP (KATP) or Channels for K+ opened by Ca2+ (KCa), increase in prostanoids and with receptor channel with transient potential (TRPv). In conclusion, ß-adrenergic receptors, prostanoids, nitric oxide (NO), ATP-sensitive K+ channels (KATP), Ca2+-opened K+ channels (KCa), and transient receptor potential cation channel subfamily V (TRPV) are involved in the relaxing effect of NEC. In addition, the mechanism of action of NEC may be involved with the signal transduction pathway Nitric Oxide/soluble guanylyl cyclase/cGMP/cGMP-activated protein kinase. NEC, therefore, demonstrates spasmolytic activity when presenting tracheal relaxation compared to CCh and KCl contracturants.

Oral glucose tolerance test effects on endothelial inflammation markers in healthy subjects and diabetic patients.

The aim of this study was to evaluate the effect of an oral glucose tolerance test (OGTT) on the level of endothelial dysfunction and vascular inflammation markers in healthy subjects (H) and diabetic overweight patients (D). We enrolled 256 healthy subjects and 274 type 2 diabetic patients. We evaluated blood glucose (BG), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-alpha (TNF-alpha) at baseline and after OGTT. We observed that BG, sICAM-1, IL-6, hs-CRP, sVCAM-1, sE-selectin, and TNF-alpha values were higher in D group than in H group. In a large sample of adult healthy subjects and type 2 diabetics we observed that both answer to an OGTT with a significant increase in biomarkers of systemic low-grade inflammation and endothelial dysfunction such as hsCRP, IL-6, TNF-alpha, sICAM-1, sVCAM-1, and sE-selectin. Type 2 diabetics experienced, however, a more significant increase in TNF-alpha, and sE-selectin.

Prospective evaluation of the effect of statins on blood pressure control in hypertensive patients in clinical practice.

BACKGROUND AND AIM: Some clinical evidence supports a statin antihypertensive effect. Our aim is to evaluate the statin effect on blood pressure control in hypertensive patients in the setting of clinical practice, and the role of some predetermined individual patient characteristics (age, gender, baseline BP levels, pre-treatment LDL-C levels) on the supposed statin BP lowering effect. METHODS AND RESULTS: Two hundred and fifty-four hypertensive patients with hypercholesterolemia were enrolled in the Ambulatory service of the Hypertension Research Unit of Bologna University Hospital. After 2-4 weeks of a run-in period patients were allocated to statin treatment and followed-up for 24 weeks. The blood pressure response to statins was compared in several subgroups of patients according to age, gender, baseline BP and pre-treatment cholesterolemia. In the overall study population, the use of statins was associated with a significant reduction in systolic (-7.6+/-4 mmHg, p<0.05) and diastolic blood pressures (-5.2+/-3 mmHg, p<0.05) in comparison to baseline. The blood pressure decrease was more pronounced in patients younger than 65 years (p<0.05), with higher baseline systolic blood pressure (p<0.005), and in those with higher cholesterolemia before statins (p<0.05). CONCLUSIONS: Our study suggests a BP-lowering effect of statins, consistent with some other literature. Some parameters like age, baseline systolic blood pressure and cholesterolemia influence the antihypertensive effect of statins. The lack of consideration for these confounding factors may be one of the reasons for the conflicting results about the BP lowering effects of statins.