Relationship between plasma aldosterone levels and arterial stiffness parameters in hypertensive patients with subclinical vascular damage.

Purpose: Aldosterone plays important role in cardiovascular damage. Aim was to evaluate arterial subclinical damage through arterial stiffness parameters in patients with Essential Hypertension (EH) and Primary Aldosteronism (PA). Methods: From 2018 to 2019 we consecutively enrolled 82 subjects (37 males and 45 women), distinguished in two groups: 60 EH [systolic blood pressure (SBP) 143.4 ± 16.7 mmHg, diastolic blood pressure (DBP) 89.5 ± 12.1 mmHg] and 22 PA (SBP 149 ± 19.5 mmHg, DBP 92.7 ± 12.4 mmHg) [5 with aldosterone-secreting adrenal adenoma(APA), 17 with idiopathic aldosteronism(IHA)]; 40 matched normotensive subjects (NS) were enrolled (SBP 109.7 ± 6.2 mmHg, DBP 71.3 ± 9.7 mmHg). We used non-invasive applanation tonometer to acquire pressure waveform. Results: PA patients showed higher µ-Albuminuria (UAE) (65.7 ± 11.0mg/24 h) than EH and NS (21.5 ± 7.0 mg/24 h and 21.5 ± 7.0 mg/24 h, respectively); APA group showed increased levels of arterial stiffness index (11.7 ± 4.8 m/s; p < 0.02) compared to EH subjects (8.3 ± 3 m/s) and NS subjects (7.2 ± 1.7 m/s) as well as higher carotid intima-media thickness (c-IMT); APA patients showed significant reduction of subendocardial viability ratio (SEVR) and travel time of the reflected waves (TI) respect EH and NS. PA groups showed high percentage of augmented "worsening age" (60%), compared to EH (38%) and NS (37%). PAC was positively correlated with Arterial Stiffness Index. Performing multiple linear regression analysis (evaluating anthropometric and biochemical parameters), we found UAE as predictor of Augmentation Index, Arterial Stiffness Index and Travel Time of reflected waves in the enrolled population. Conclusion: PA patients showed higher cardiovascular subclinical damage respect to EH; UAE excretion had significant correlation with aldosterone, resulting best marker of subclinical vascular remodeling.

Prevention of neural tube defects and maternal gestational diabetes through the inositol supplementation: preliminary results.

OBJECTIVE: Our study aims to demonstrate that the use in the preconceptional period until the 24th week of pregnancy of inositol and folic acid, first of all, preserves the product of conception from neural tube defects (NTDs) and then, thanks to inositol supplementation, it possibly counteracts and prevents the onset of maternal gestational diabetes (GDM). PATIENTS AND METHODS: We have collected data derived from pregnant women arrived at our laboratory, from January 2014 to January 2016, with no family history of type 2 diabetes and hypertension. The first group (n = 68 women) was treated from the preconceptional period until the 24th week of pregnancy with 1.75 g/day myo-inositol, 250 mg/day D-chiro-inositol, 12.5 mg/day Zinc pidolate, 100 mg/day methylsulfonylmethane, 120 mg/day Vitamin C and 400 mcg/day (6S)-5-methyltetrahydrofolic acid. The control group (n = 72) was only treated with 400 mcg/day folic acid. The main outcome measure was the prevalence of maternal GDM. Secondary outcome measures were the prevalence of NTDs and fetal macrosomia. RESULTS: A significant difference was found regarding body mass index (BMI), fasting oral glucose tolerance test (OGTT), after 1-h-glucose OGTT, 2-h-glucose OGTT, glycated hemoglobin (HbA1c) and serum folate, between the two groups. Five infants, in the control group, weighted greater than 4 kg. Moreover, we found a positive correlation between HbA1c and OGTT at the 24th week of pregnancy. CONCLUSIONS: This study shows the efficacy of preconceptional supplementation of inositol to reduce the risk of the onset of GDM and to confirm the importance of folic acid supplementation to avoid NTDs development. Moreover, the positive correlation between HbA1c and OGTT may be useful to consider the use of HbA1c as a single tool for GDM prevention and diagnosis in selected woman in pregnancy.

Role of TNF-alpha polymorphism in patients with nickel allergy: a marker of susceptibility to contact polysensitization.

OBJECTIVE: Nickel allergy is the most frequent contact allergy in the industrialized country. In allergic contact dermatitis after the presentation of haptenated peptides by resident or newly recruited skin cells, activated CD8+ T cells release IFN-γ and TNF-α, these cytokines are potent activator of keratinocytes. The role of specific cytokines in nickel allergy is not yet fully elucidated. The adenine nucleotide at position -308 in the promoter region of the TNFA gene is associated with an increased production of TNF-α, that is a potent activator of keratinocytes. PATIENTS AND METHODS: To evaluate the expression of TNF-α polymorphism in patients with allergic contact dermatitis and in healthy people, 41 patients with allergic contact dermatitis to nickel and 40 healthy controls were enrolled. A total of 81 subjects (41 cases and 40 controls) underwent genotyping for the 308 genetic polymorphism in the TNFA gene. RESULTS: The distribution of TNF genotypes TNF-α 308 G/A polymorphism in cases didn't differ significantly in the controls group. The genotype GA was present in the 75% of the patients with polysensitization. In one patient was observed the rare genotype A/A. CONCLUSIONS: The carriage of the TNFA-308 A/A and GA genotype may act as a marker of enhanced susceptibility to contact polysensitization, indicating that TNF-α is a key regulator of the initiation of delayed-type hypersensitivity reactions, the polymorphism seems to be not enough for the development of nickel monosensitization.

Association between -308 G/A TNF-α polymorphism and appendicular skeletal muscle mass index as a marker of sarcopenia in normal weight obese syndrome.

BACKGROUND AND AIM: Normal weight obese (NWO) syndrome is characterized by normal body mass index (BMI), but high amount of fat mass and reduced lean mass. We evaluated allelic frequency of the G/A -308 TNF-α polymorphism and prevalence of sarcopenia in NWO. METHODS: We enrolled 120 Italian healthy women, distinguished into 3 groups: normal weight (NW); NWO, and preobese-obese (PreOB/OB) and evaluated anthropometric parameters, body composition by dual X-ray absorptiometry, blood tests, and genotyping of G/A -308 TNF-α polymorphism. RESULTS: We found a positive association between sarcopenic obesity and -308 TNF-α polymorphism. All obese women were sarcopenic and were no carrier of mutation (G/G). Among all G/G, NWO showed significant differences in lean mass and total body lean mass (TBLean) with respect to NW and PreOB/OB (P < 0.001). Regarding appendicular skeletal muscle mass index values, 4.21% of NW were sarcopenic (50% G/G and 50% G/A); the same percentage was observed in NWO subjects (100% G/G). Moreover, 2.10% of PreOB/OB were sarcopenic and all were G/G. CONCLUSION: Our study suggests that TNF-α polymorphism contributes to sarcopenic obesity susceptibility, in association with body composition. This is the first study that shows the importance of TNF-α polymorphism to determine TBLean variation in NWO syndrome.

Body composition phenotype: Italian Mediterranean Diet and C677T MTHFR gene polymorphism interaction.

OBJECTIVES: Strategies to improve weight maintenance are focused on considering the genetic makeup and its interaction with dietary intake, with the aim to identify vulnerable individuals that will benefit from a variety of more personalized dietary recommendations. The aim of the study was to examine the impact of the C677T MTHFR gene Polymorphism on body composition changes induced by a balanced hypocaloric Italian Mediterannean diet (IMD). SUBJECTS AND METHODS: Participation in the study included a complete screening of anthropometry and body composition by Dual-energy X-ray absorptiometry (DXA), and a genotyping for the C677T MTHFR polymorphism. 70 Italian Caucasian obese were enrolled and 56 of them completed the screening at baseline and 12 weeks after the nutritional intervention. RESULTS: T(+) carriers had a higher content of Total Body Fat (TBFat), and Lean (TBLean), reflecting on higher weight and BMI, than T(-) carriers. After IMD, the 28.6% and 71.4% of total subjects decreased weight and TBFat (Kg), respectively. The relative changes were: delta % = -9.09±3.85 for weight; delta % = -15.79±8.51 for TBFat; delta % = -3.80±5.60 for TBLean. The 5.3% of subjects who reached the end point of intervention, and the 8.9% who reduced TBFat (%) below the cut-off of preobesity, were T(-) carriers. A loss of TBLean (Kg) was observed in the 5.1% and 23.5% of T(-) and T(+) carriers. CONCLUSIONS: MTHFR genetic variations analysis would be an innovative tool for the nutritional assessment, in order to predict the therapeutic response of obese subjects, in terms of fat and lean mass loss.

Effects of dark chocolate in a population of normal weight obese women: a pilot study.

BACKGROUND: Normal weight obese (NWO) syndrome is defined as an excessive body fat associated with a normal body mass index and characterized by a higher risk for cardiovascular morbidity and mortality. Recent studies have demonstrated that dark chocolate (DC) has beneficial effects in the prevention of cardiovascular diseases (CVD) due to its anti-inflammatory and antioxidant properties. AIM: The aim of the present study was to investigate the effects of DC consumption on lipid profile, inflammatory markers, biochemical parameters, and blood pressure, in NWO women. MATERIALS AND METHODS: 15 women affected by NWO syndrome, aged 20-40 years, were included in the study. After a DC-free washout period, subjects received DC (100 g/die) containing 70% cocoa for 7-days. Body composition by Dual energy-X-ray absorptiometry (DXA) was performed at baseline. Blood pressure, anthropometric measurements, biochemical parameters and plasma levels of some cytokines were measured before and after DC consumption. RESULTS: After DC consumption, we observed a significant increase in the HDL cholesterol level (Delta% = +10.41±13,53; p ≤ 0.05), a significant decrease of total cholesterol/HDL cholesterol ratio (Delta %= -11.45±7.03; p ≤ 0.05), LDL/HDL cholesterol ratio (Delta % = -11.70±8.91; p ≤ 0.05), and interleukin-1 receptor antagonist (IL-1Ra) (Delta % = -32.99±3.84; p ≤ 0.05). In addition, a reduction in abdomen circumference was observed. We also found a positive correlation between changes in atherogenic indices, and IL-1Ra, abdomen reduction. CONCLUSIONS: Our findings suggest that regular consumption of DC could be useful in maintaining a good atherogenic profile, due to the favourable effects on HDL cholesterol, lipoprotein ratios and inflammation markers.

Rapid and easy assessment of insulin resistance contributes to early detection of polycystic ovary syndrome.

AIMS: Polycystic ovary syndrome (PCOS) is frequently observed in women of reproductive age, and is associated with disturbances in both reproductive and metabolic function. Insulin resistance (IR) is key to the pathophysiology of PCOS, and early detection may improve outcomes in this patient group. Rapid and straightforward laboratory tests may contribute towards early detection. METHODS: A retrospective chart review of 185 women presenting for the first time to a gynecology clinic was carried out. Of this group, 77 met the inclusion criteria. The sample was divided according to insulin sensitivity (IS) given by the Matsuda Index, and the two groups were compared using correlation analysis. Furthermore, the sensitivity and specificity of the Matsuda, homeostasis model assessment of IR (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) indexes were compared. RESULTS: Although bodu mass index (BMI) was higher in the insulin resistant group than the insulin sensitive group, the mean age of the IR group was actually lower. HOMA-IR and QUICKI correlated well with the Matsuda index in both groups. The HOMA-IR test showed the highest sensitivity and specificity in the detection of IR when compared to the Matsuda Index, and no added benefit was derived from using a combination of both QUICKI and HOMA- 1R. CONCLUSIONS: In a group of 77 women diagnosed with PCOS, 49 (63.6%) had IR according to the Matsuda index. The HOMA-IR index, which is based on fasting serum insulin and glucose, correlated closely with the Matsuda index, indicating it may be a reliable substitute in the detection and subsequent early intervention required to improve outcomes in PCOS.

Chronic treatment with sulfhydryl angiotensin-converting enzyme inhibitors reduce susceptibility of plasma LDL to in vitro oxidation, formation of oxidation-specific epitopes in the arterial wall, and atherogenesis in apolipoprotein E knockout mice.

The effects of chronic treatment with the new sulfhydryl angiotensin-converting enzyme (ACE)-inhibitor, zofenopril, in comparison with the classical sulfhydryl ACE-inhibitor captopril or enalapril or placebo on the development of atherosclerosis were determined in apolipoprotein-E knockout (apoE(-/-)) mice. Groups of 2-month-old male mice received either placebo (N=10), 0.05 mg/kg/day of zofenopril (N=10), 1 mg/kg/day of zofenopril (N=10), 5 mg/kg/day of captopril (N=10) or 0.5 mg/kg/day of enalapril (N=8). After 29 weeks of treatment, computer-assisted imaging analysis revealed that zofenopril reduced the aortic cumulative lesion area by 78% at 0.05 mg/kg/day and by 89% at 1 mg/ml/day of zofenopril compared to that of the placebo (P<0.0001). Captopril reduced by 52% aortic lesions compared to placebo (P<0.01 vs. placebo; P<0.05 vs. zofenopril at both doses). Enalapril did not reduce aortic lesions. Furthermore, 0.05 mg/kg/day of zofenopril reduced susceptibility of plasma LDL to in vitro oxidation compared to captopril, enalapril or placebo, as shown by significant reduction of malondialdehyde content (P<0.001 vs. placebo or enalapril; P<0.05 vs. captopril), as well as by the prolongation of lag-time (P<0.01 vs. placebo or enalapril P<0.05 vs. captopril). More importantly, mice treated with 1 mg/ml/day of zofenopril had a significant decrease in the intimal immunohistochemical presence of oxidation-specific epitopes on oxLDL (NA59 monoclonal antibody, P<0.01), macrophages derived foam cells (F4/80 monoclonal antibody, P<0.05) and native LDL (NP monoclonal antibody, P<0.01) compared to placebo, captopril or enalapril. Thus, chronic treatment with the new sulfhydryl ACE-inhibitor zofenopril has antiatherosclerotic and antioxidant effects in the arterial wall of hypercholesterolemic apoE(-/-) mice. This protection was significantly higher than that reached with captopril and at lower doses of the drug. Treatment with 0.5 mg/kg/day of enalapril did not provide any protective effect.

Pulmonary disposition of lomefloxacin in patients with acute exacerbation of chronic obstructive pulmonary disease. A multiple-dose study.

In this study we have measured the concentrations of lomefloxacin at steady state in serum and in the intrapulmonary region at specified intervals for 24 h following administration of the last dose of drug in patients suffering from acute exacerbation of chronic obstructive pulmonary disease (COPD). Twenty subjects were enrolled. They received lomefloxacin 400 mg orally once-daily for 5 consecutive days. All patients were divided into five groups, with 4 subjects in each group, according to sampling times (2, 4, 8, 12, and 24 h after the last dose). At bronchoscopy, bronchial biopsies and bronchoalveolar lavage (BAL) were performed. At 12 h after the last dose, serum concentration of lomefloxacin was >1.0 microg/mL and at 24 h it was still detectable, but, at all times, the concentrations in bronchial secretion, bronchial mucosa, and epithelial lining fluid (ELF) were greater than the concentrations in serum [bronchial secretions (pg/mL) = 2.5+/-1.2; 2.2+/-1.0: 2.0+/-1.1; 1.8+/-1.1; 0.6+/-0.3. bronchial mucosa (microg/g) = 5.9+/-2.1; 6.2+/-1.8; 2.6+/-2.2; 1.9+/-1.5; 1.0+/-0.9. ELF (microg/mL) = 6.9+/-2.8; 5.9+/-2.6; 3.1+/-1.9; 2.2+/-1.0; 0.8+/-1.3. serum (microg/mL) = 3.2+/-1.4; 2.8+/-0.9: 2.1+/-1.5; 1.2+/-1.1; 0.4+/-0.81. We must stress that we observed a large inter-individual variability in concentrations. Our data show that lomefloxacin once-daily induces high and sustained concentrations in the various potential sites of pulmonary infection and clearly indicate that the pharmacokinetic behavior of this fluoroquinolone permits once-daily administration in patients with acute exacerbations of COPD.

Safety and effectiveness of lomefloxacin in patients with acute exacerbation of chronic bronchitis (AECB) chronically treated with oral theophyllines.

Lomefloxacin is a difluorinated quinolone with excellent activity against a wide range of pathogens including those responsible for acute exacerbations of chronic bronchitis (AECB). This open, cross-sectional, multicenter study has evaluated the efficacy and safety of a once-daily dosage of 400 mg lomefloxacin in patients with AECB chronically treated with theophylline. 137 patients (96 males, 41 females; mean age 66.1+/-11.2 yrs) were enrolled and 133 completed the study. 81% suffered from moderate AECB, 16% severe AECB. The clinical success rate was very high (95%), as well as the microbiological (93%). Side effects were scarce and were significant only in 3 patients, with 2 dropouts. All patients were using theophylline derivatives twice daily and continued without any variation in dosage during the lomefloxacin treatment. Theophylline plasma levels determined in 103 patients at baseline, during and at the end of the lomefloxacin treatment did not significantly change. We conclude that orally administered lomefloxacin at standard recommended dosage is well tolerated and effective in elderly patients with AECB. No dose adjustment is required even when it is co-administered with methylxanthines.

Synthesis of taurine analogues from alkenes: preparation of 2-aminocycloalkanesulfonic acids.

(+/-)trans 2-Aminocyclohexanesulfonic acid and (+/-)trans 2-aminocyclopentanesulfonic acid were prepared from cyclohexene and cyclopentene respectively by sulfur monochloride addition, followed by oxidation to 2-chlorosulfonic acid and substitution of chlorine.

Extensor carpi radialis recovery predicted by qualitative SEP and clinical examination in quadriplegia.

This prospective study examined the efficacy of the qualitative somatosensory evoked potential (SEP) and the initial clinical neurologic evaluation to predict motor power recovery of the extensor carpi radialis muscle (ECR). Twenty three C5-6 Frankel A-D spinal cord injured (SCI) subjects had SEPs of the median nerve (MN) and superficial radial nerve (SRN) performed within 72 hours to one week post injury. The MN and SRN cortical SEPs were qualitatively graded as either present or absent. Fifteen subjects whose initial ECR muscle strength was less than or equal to 3/5 and eight subjects whose muscle strength was greater than 3/5 were followed up to 12 to 18 months post injury for improvement in ECR muscle strength. The subject's ECR strength was evaluated by manual muscle testing (MMT) at 72 hours, weekly for three weeks, monthly for three months, and then at six, 12, and 18 months. The pin sensation at the C-5 dermatome was also tested at the above intervals and graded as either present or absent. A one tail Fisher Exact test compared the presence or absence of the MN and SRN SEPs to the recovery of the ECR to 3/5. The same one tail test also compared the presence or absence of the 72 hour C-5 pin sensation and the 72 hour MMT to the ECR recovery. Among the 15 subjects with an initial MMT of less than or equal to 3/5, ten subjects had successful ECR recovery (greater than 3/5); 5 did not. The C-5 pin sensation correctly predicted ECR recovery in all subjects studied (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Immunosuppressive activity of 13-cis-retinoic acid and prevention of experimental autoimmune encephalomyelitis in rats.

Some activities of retinoids on cellular and humoral immunity have been described, but the available data are conflicting or obtained at concentrations that are toxic in vivo. In this study, we demonstrate that 13-cis-retinoic acid (13-cRA), a retinoid well tolerated in human therapy, can suppress T cell-mediated immunity in rats. Treatment with pharmacological concentrations of 13-cRA prevented active as well as passive transfer experimental autoimmune encephalomyelitis (EAE) and suppressed lymphocyte responsiveness to T cell mitogens, suggesting that the drug activity included suppression of an effector T cell response. In addition, mitogen- and antigen-induced lymphocyte proliferation was inhibited in vitro in the presence of concentrations of 13-cRA equivalent to or less than those achieved in vivo, further suggesting that the prevention of EAE was due to a suppressive activity on T cell-mediated immunity. The immunosuppressive activity of 13-cRA included suppression of interleukin 2, whose production was inhibited in splenocytes. These data indicate that, in an in vivo mammalian system, 13-cRA exerts a suppressive activity on T cell-mediated immunity intensive enough to suppress an ongoing immune response, and that this effect can be achieved at nontoxic concentrations that may also be attained in human therapy.

Suppression of experimental allergic encephalomyelitis by retinoic acid.

Administration of retinoic acid (RA) prevented the development of experimental allergic encephalomyelitis (EAE) in Lewis rats. RA suspended in corn oil was given for 3 days before the expected onset of the disease to rats immunized with myelin and to controls. The drug suppressed the neurological symptoms as well as the perivascular infiltrates observed in vehicle-treated animals. The results indicate that under these experimental conditions, RA has immunosuppressive activity by interfering with the efferent phase of the immune response.

The control of experimental allergic encephalomyelitis with retinoic acid. Further studies.

Two form of retinoic acid (RA) prevented the development of experimental allergic encephalomyelitis (EAE) in Lewis rats. RA suspended in corn oil was given before the expected onset of the disease to rats immunized with myelin and to controls. The drug suppressed the neurological symptoms as well as the perivascular infiltrates observed in vehicle treated animals. The results indicate that, under these experimental conditions, RA has immunosuppressive activity by interfering with the efferent phase of the immune response.

2,2'-dihydroxy-3,3'-di-t-butyl-5,5'-dimethoxydiphenyl, a new metabolite of 2-t-butyl-4-methoxyphenol in the rat.

A method has been developed for the determination of 2-t-butyl-4-methoxyphenol (BHA) and its metabolite di-BHA in rat plasma and tissues using gas chromatography-mass spectrometry with selected ion detection. Deuterium labeled BHA-d3 and di-BHA-d6 were synthesized and added to the tissue specimens as internal standards before methylene chloride extraction. The extracted compounds were derivatized with trifluoroacetic anhydride and analyzed by selected ion monitoring. Rat plasma and intestine concentrations of BHA and di-BHA at different times (0.15-24 hr) following the oral administration of a single dose of BHA (2 g X kg-1 body weight) were determined. Both BHA and di-BHA were present in all the analyzed samples, their concentration peaking within 1 hr after treatment. While in the intestine BHA levels were about 10 times higher than those of di-BHA, in the plasma they were between 100 and 15 times higher. These findings indicate that rat intestine is capable of transforming in vivo BHA into di-BHA and suggest that this organ is the major site where this transformation occurs.

Oxidation of 2-t-butyl-4-methoxyphenol (BHA) by horseradish and mammalian peroxidase systems.

Di-BHA, 2,2'-dihydroxy-3,3'-di-t-butyl-5,5'-dimethoxy-diphenyl, was isolated as the product of the reaction of either commercial horseradish peroxidase or partially purified rat intestine peroxidase (Donor-H(2)O(2) oxidoreductase, EC 1.11.1.7.) and hydrogen peroxide with 2-t-butyl-4-methoxyphenol (BHA). BHA, Di-BHA and other cyclic compounds possessing a hydroxyl group in the ring were found to be competitive inhibitors with respect to guaiacol, and non-competitive inhibitors with respect to hydrogen peroxide in a system containing guaiacol, hydrogen peroxide and peroxidase. A free radical intermediate generated during peroxidatic oxidation of BHA was detected and identified by means of EPR spectroscopy. It was estimated that during one hour incubation the peroxidase activity present in the rat ileum mucosa is able to oxidise 12mumoles BHA at a saturating concentration. It is suggested that peroxidative oxidation at the intestinal wall may represent a contribution to the inactivation of some phenol derivatives potentially toxic to mammals.