Concomitant carotid plaque development and brachial artery diameter enlargement: a retrospective, recall-based study in postmenopausal women.

BACKGROUND AND AIM: To verify if the carotid plaque development is concomitant to brachial artery diameter enlargement, in healthy postmenopausal women. METHODS AND RESULTS: This is a retrospective, recall study. We enrolled 40 postmenopausal women, selected from a database for the period 2000-2008, not affected by subclinical carotid atherosclerosis and without risk factors for cardiovascular disease. At the recall visit, carotid and brachial duplex scan was again obtained. The incidence of plaque was 30% after a mean follow-up period of 60 months. There were no differences in baseline characteristics between subjects developing carotid atherosclerosis and subjects who did not, except for the brachial diameter change, follow-up and heart rate. The logistic-regression analysis confirmed that only brachial diameter change resulted to be correlated with the development of carotid atherosclerosis. CONCLUSION: Brachial artery diameter increase is concomitant to carotid plaque development. Vascular enlargement could not be a focal change but a systemic process associated with atherosclerotic plaque development. Brachial diameter could be a tool with a predictive significance.

Brachial artery diameter measurement: a tool to simplify non-invasive vascular assessment.

AIM: The mechanisms of vascular remodeling have attracted great interest since it is a phenomenon related to cardiovascular diseases. We would like to examine studies that contributed to clarify the remodeling mechanisms, to explore the different faces of atherosclerosis process. DATA SYNTHESIS: A number of invasive and non-invasive vascular assessment methods were developed, to detect the early sign of atherosclerosis. It became clear that the invasive tests were not applicable to large-scale studies. Consequently, a non-invasive test was developed. Studies showed that the endothelial function evaluation is a predictor of future cardiac events in individuals at cardiovascular risk and in those with established disease. However, analyzing several works, an interesting concept emerged, i.e., the inverse relation between endothelium-dependent dilation and vessel size, since large vessel tend not to dilate significantly. This notion emphasized the role of basal diameter on vascular response. In particular, as brachial artery diameter is the measure on which FMD is based, it could add more information in clinical evaluation, simplifying the assessment. Several studies showed that morphological change of brachial artery is a better indicator of the extent of coronary disease rather than FMD. Other studies showed that brachial diameter has predictive significance in the stratification of cardiovascular risk. CONCLUSION: Brachial diameter is a useful and simple tool. It should be incorporated into the overall assessment of cardiovascular risk but further studies are warranted to determine the final place of brachial diameter assessment in routine clinical setting.

Large brachial artery diameter and diabetes in post-menopausal women.

BACKGROUND AND AIM: Vascular remodelling is one of the possible compensatory mechanisms in response to artery wall injury. It was demonstrated that post-menopausal women with carotid atherosclerosis had a larger brachial artery diameter (BAD) than women without carotid plaques. Therefore, it is possible to hypothesise that artery enlargement could be a marker of early atherosclerosis. To investigate the eventual association between carotid and brachial artery diameter and disease affecting the vascular wall, we performed a case-control study in post-menopausal women with or without type II diabetes mellitus. METHODS AND RESULTS: We enrolled 28 cases (with diabetes) and 56 controls (without diabetes) matched for age and carotid atherosclerosis presence and severity. On the t-test, women with diabetes showed significantly larger brachial and common carotid artery diameters and, as expected, higher plasma glucose level and homeostasis model assessment (HOMA) than women without diabetes. On the univariate analysis, only plasma glucose level results correlated to BAD in the whole sample. Multivariate analysis confirmed that diabetes was a good predictor of brachial and carotid artery diameter, while age, systolic blood pressure and triglycerides were correlated only to the carotid diameter. CONCLUSIONS: Our data confirm that vascular remodelling is a systemic process occurring in conditions related to atherosclerosis, such as type II diabetes. Indeed, artery diameter could be a marker of early response of vessel wall to injury.

Hyperhomocysteinemia recurrence in levodopa-treated Parkinson's disease patients.

BACKGROUND: Patients with Parkinson's disease (PD) and chronically treated with L-DOPA exhibit, in a percentage of 10-30%, supra-physiological levels of plasma total homocysteinemia (tHcy). In this study, we have investigated, in a group of hyper-homocysteinemic PD patients, the time of hyper-tHcy recurrence after discontinuation of 1-month folate supplementation given to normalize plasma tHcy levels. METHODS: Plasma tHcy, cobalamin and folate were assayed before and after 1-month folate supplementation (5 mg/day), and after 2 and 4 months after folate discontinuation in 29 PD patients (16M/13F, mean age 69.4 +/- 6.9 years) stabilized on a mean L-DOPA dose of 509.4 +/- 312.1 mg/day. RESULTS: After folate supplementation, plasma tHcy levels fell within the normal range in all patients. At the 2-month control after folate discontinuation, plasma tHcy remained within physiological values in 25 out of 29 patients. Conversely, 4 months after folate discontinuation, all patients exhibited hyper-tHcy. CONCLUSIONS: One-month intake of 5 mg/day folate normalizes plasma tHcy levels in all hyper-homocysteinemic PD patients. Following folate discontinuation, hyper-tHcy recurs in all patients within 4 months. Knowledge of this time interval is useful to optimize pulses of folate therapy in hyper-homocysteinemic patients with PD.

Implications of metal exposure and liver function in Parkinsonian patients resident in the vicinities of ferroalloy plants.

Valcamonica is an Italian valley where ferro-manganese industries have been active for a century and where an increased prevalence of parkinsonism was observed. A group of 93 patients (65 from Valcamonica, 28 from the reference area of Brescia city) and 76 controls (52 from Valcamonica, 24 from Brescia) were screened for serum Cu, Zn, Fe, Mn in blood (MnB) and urine (MnU), transferrin, peroxides, alanine (ALT) and aspartate (AST) transaminases and direct bilirubin. Test results were compared among groups according to the residential area and related to the disease severity. Valcamonica patients had a serum-increase of Cu, as well as of AST/ALT ratio, and a serum-decrease of Zn and Fe compared with other subgroups of cases and controls. Cases and controls from Valcamonica had higher MnB and MnU levels compared to cases and controls from Brescia. After controlling for the duration of illness, the Unified Parkinson's Disease Rating Scale III domain correlated with serum Cu and AST/ALT ratio. Our results suggest the possibility that, in this area, a lifetime exposure to neurotoxicants and to Mn in particular, when accompanied to a subclinical liver dysfunction, may pose an increased risk for neurodegenerative disorders via metal metabolism (Cu, Zn, Fe) abnormalities.

Effect of MTHFR polymorphisms on hyperhomocysteinemia in levodopa-treated Parkinsonian patients.

High plasma homocysteine levels have been observed in Parkinson's disease (PD) patients treated with levodopa. In this study, we investigated the effects of C677T and A1298C MTHFR polymorphisms, in association with L-DOPA daily dose and vitamin status, on hyperhomocysteinemia development in PD patients. Plasma homocysteine and folate/vitamin B12 levels were assayed in 49 L-DOPA-treated PD patients, and compared with those of 86 healthy subjects. Genotyping for MTHFR polymorphisms was carried out by DG-DGGE. Homocysteine levels were significantly higher in patients than in controls (16.3 +/- 5.7 vs. 11.7 +/- 2.7 micromol/l, P < 0.01). No significant differences were found between patients and controls with regard to folate/vitamin B12 levels, and MTHFR allele distribution. The TT+AA genotype was significantly more frequent in PD patients than in controls (32.5% vs. 17.4%, P < 0.05), but not associated with an increased risk for PD (OR = 2.3, CI = 1.0-5.2). Further, patients carrier of this genotype exhibited a mild hyperhomocysteinemia (22.1 +/- 4.9 micromol/l), while a protective effect was observed in patients having the CC+AA genotype (11.2 +/- 1.6 micromol/l; OR = 0.19, CI = 0.06-0.59). Interestingly, homocysteine levels were also moderately increased in patients with CT heterozygous genotype, in the context of either AA or AC (14.5 +/- 3.6 micromol/l), in comparison to subjects with the CC + AA genotype. Finally, we did not find any significant association of combined C677T and A1298C MTHFR polymorphisms with an increased risk for hyperhomocysteinemia in PD patients. A better understanding of the role of homocysteine and MTHFR genotypes in PD is needed to reveal novel approaches for disease management.

Role of endogenous androgens on carotid atherosclerosis in non-obese postmenopausal women.

BACKGROUND: Recent randomized trials on hormone replacement therapy in postmenopausal women raised many doubts about their role in cardiovascular disease prevention. Therefore the role of other sex hormones needed to be investigated. In particular androgens seem to have a protective role on atherosclerosis. The present study was performed to assess the role of endogenous sex hormones on carotid atherosclerosis in postmenopausal women. METHODS AND RESULTS: We consecutively enrolled 101 postmenopausal women aged 45-75 (mean age 57.4) years referred to our University hospital menopausal health-screening clinic. The subjects underwent a medical history, a physical examination and biochemical analysis. Extracranial carotid arteries were assessed by ultrasound. Fifty percent of our sample had carotid plaques. On the multivariate logistic regression analysis age, glycaemia (positively) and testosterone (negatively) (P=0.02) were significantly correlated to carotid atherosclerosis. In non-obese subjects we found that participants in the third tertile had a significantly lower prevalence of carotid atherosclerosis (P=0.02) compared to those in the first tertile of testosterone. CONCLUSIONS: These results suggest a possible protective role of endogenous androgens at least on carotid atherosclerosis. Of course these preliminary results should be supported by prospective studies. Also the different role of these hormones on obese and non-obese subjects needs to be clarified.

[Metals and oxidative stress in Parkinson's disease from industrial areas with exposition to environmental toxins or metal pollution]. / Dismetabolismo dei metalli e stress ossidativo in pazienti con in Parkinson's disease di un'area industriale esposta ad inquinamento da metalli.

BACKGROUND: Parkinson's disease (PD) is characterized by a progressive degeneration of the nigrostriatal dopaminergic pathway resulting in movement disorders. PD is a complex disease, in which and environmental factors, as exposure to toxins or metals coul be involved. OBJECTIVE: To assess if serum metals (Cu, Fe, Zn), biological variables of their metabolism, total peroxides and antioxidants were abnormal in PD, in relation to environmental exposure. METHODS: We compared levels of serum copper, iron, zinc, ceruloplasmin and transferrin, peroxides, antioxidants (TRAP) in 65 PD patients coming from an Industrial zone highly exposed to metal pollution (Valcamonica) with measures from 28 PD patients from no metal pollution areas of the province of Brescia and 52 healthy controls coming from Valcamonica and 24 from the province of Brescia. RESULTS: PD patients had higher serum concentration of zinc than controls. Only in PD patients coming from Valcamonica levels of Cu were higher than in subjects coming from the province of Brescia. Moreover, In patients with PD levels of sieric Cu significantly correlated with score of the Unified Parkinson's Disease Rating Scale (UDPRS). CONCLUSIONS: Zinc seems to be higher in PD independently from the exposition to metal pollution. Perturbation of copper metabolism in PD seems to be related to exposition to environmental toxins or metal pollution and coul be involved in the progression of the disease itself.

Screening for C677T and A1298C MTHFR polymorphisms in patients with epilepsy and risk of hyperhomocysteinemia.

Hyperhomocysteinemia can result from decreased methylenetetrahydrofolate reductase (MTHFR) enzyme activity, owing to genetic polymorphisms andor inadequate folate intake. This study was aimed at investigating the prevalence of C677T and A1298C MTHFR polymorphisms, and their impact on hyperhomocysteinemia in 95 epileptic patients and 98 controls. Double gradient-denaturing gradient gel electrophoresis screening revealed that the frequency of T677 polymorphic allele was similar between cases and controls (46.3% vs 42.3%), whereas that of C1298 allele was significantly higher in patients (30.5% vs 19.4%, p < 0.05). Significant differences between the two groups were also found for the frequencies of genotypes AA1298 (46.3% in cases vs 67.3% in controls, p < 0.01) and AC1298 (46.3% in cases vs 26.6% in controls, p < 0.01). Other genotype frequencies did not show any statistically significant differences. Haplotype frequencies significantly differed between the two groups. The CT677/AC1298 diplotype was significantly more frequent in epileptic patients than in controls (32.6% vs 18.4%, p < 0.05). Patients treated with enzyme-inducing antiepileptic drugs, having this diplotype and concomitant low folate concentration (i.e., < 3.4 nmol/L), exhibited plasma homocysteine levels significantly higher than normal values (27.1 +/- 2.44 micromol/L, p < 0.001). This increase, however, was lower than that observed in folate-deficient patients with diplotype TT677/AA1298 (41.3 +/- 3.41 micromol/L, p < 0.001). Indeed, these two diplotypes could be regarded as risk factors for hyperhomocysteinemia. Conversely, we found that the CC677/AA1298 diplotype was significantly more frequent in controls (p < 0.01), suggesting a protective role. Our study suggests that both C677T and A1298C MTHFR polymorphisms should be examined when assessing genetic risk factors of hyperhomocysteinemia in epilepsy.

Cross-reactive antigenic domains of the flagellin protein of Borrelia burgdorferi.

The p41 flagellin of Borrelia burgdorferi is the most common antigen recognized by serum of patients with Lyme borreliosis. This antigen shares amino acid homology, particularly in the amino and carboxy termini, with periflagellar antigens found in other microorganisms including Treponema pallidum. We cloned and expressed the p41 open reading frame in Escherichia coli and expressed it both as TrpE fusion and full-length unfused proteins. Also, we generated deletion constructs of various portions of the gene. Sera from patients with late Lyme borreliosis and secondary syphilis were used to identify the recombinant proteins by immunoblot analysis. Sera from 26 patients with Lyme borreliosis, 20 with secondary syphilis and 10 controls were used to identify cross-reactive domains of the B. burgdorferi flagellin. The variable region (amino acids 131-234) of the protein was recognized by 59% (15/26) of patients with late Lyme borreliosis compared to 30% (6/20) of patients with secondary syphilis and no (0/10) control patients. It appears that cross-reactive epitopes between B. burgdorferi and T. pallidum extend to the variable region of the flagellin.

Characterization of Alzheimer amyloid precursor protein transcripts in platelets and megakarocytes.

Immunoblot analyses indicate that the platelet is a reservoir of several Alzheimer amyloid precursor protein (APP) isoforms, including C-terminal reactive species which could potentially serve as the precursor of the amyloid beta protein (AB*) in Alzheimer's disease (AD). Since platelets are known to sequester several plasma proteins from the blood, we employed the polymerase chain reaction (PCR) to amplify reverse transcribed mRNA and detect the 3 major APP transcripts (APP695,751,770) in platelets and the Dami megakaryocyte cell line. PCR amplification of glycoprotein IIb and HLA-DR mRNA was used to demonstrate that APP transcripts were derived from cells of megakaryocytic lineage, and the results were compared with those obtained from peripheral blood mononuclear cells, human umbilical vein endothelial cells, B lymphocyte and astrocytoma cell lines. The identity of PCR products was confirmed by hybridization with APP specific oligonucleotide probes, and sequencing of amplified segments.

Opiate receptors in the rabbit iris.

Evidence pointing to the presence of opiate receptors in the rabbit iris was obtained in an in vivo study of the effects on the pupil of the intraocular injection of morphine (10--100 micrograms) and D-Ala2-met-enkephalinamide (D-Ala-E) (5--50 micrograms). Both opiates induced a significant dose-dependent decrease in pupillary size and an appreciable fluctuation of pupillary size. I.v. administration of naloxone (0.5 mg/kg) before or after injection of opiates prevented the miotic effect and the fluctuation of pupil size. The parallelism of the dose-response curves of opiates in the presence and absence of naloxone indicated competitive reversible antagonism.

[Correlation of waist-to-hip circumference ratio and cardiovascular risk factors in a population of Southern Italy]. / Rapporto circonferenza addome/circonferenza bacino e fattori di rischio cardiovascolare in una popolazione del sud Italia.

AIM: To evaluate the relationship between body mass index (BMI), body fat distribution and some coronary heart disease risk factors like hyperlipidemia, hypertension and cigarette smoking. STUDY DESIGN: Cross-sectional. PLACE: Tiriolo, a little town close to Catanzaro, of prevalent rural economy. PARTICIPANTS: Volunteers, both males and females, aged more than 30 years and living in Tiriolo. MEASUREMENTS: Body weight and height with subjects in ordinary street clothes and without shoes. Systolic (SBP) and diastolic blood pressure (DBP) by a zero-random sphygmomanometer. Total (TC) and HDL cholesterol (HDL-C) using fingerstick capillary sample technology by a Cholestech analyzer. Waist circumference (W), measured midway between the lower rib margin and the iliac crest, and hip circumference (H) measured at the widest point over the greater trocanthers. Smoking habit by questionnaire. RESULTS: Females had higher values of SBP, DBP, BMI and HDL-C and lower of TC/HDL-C ratio and W/H ratio. Age was similar in both sexes. Females had lower prevalence of hyperlipidemia and cigarette smoking and higher prevalence of hypertension. BMI was strongly associated to blood pressure levels whereas W/H ratio was correlated to TC/HDL-C ratio. CONCLUSION: BMI and W/H ratio give complementary information, useful to assess the cardiovascular risk profile. The simplicity and quickness of these measurements should lead to their large utilization both in epidemiological prevention studies and everyday clinical practice.

[An atypical case of Marcus Gunn's syndrome]. / Un cas atypique de syndrome de Marcus Gunn.

The authors examine a clinical case of the Marcus Gunn phenomenon, characterized by the lid retraction when the patient closes her mouth. The peculiarity of this clinical case would consist in a partial synkinesis involving the masseter and temporal muscles.

Artery remodeling and abdominal adiposity in nonobese postmenopausal women.

BACKGROUND/OBJECTIVES: We aimed to assess, in nonobese postmenopausal women, whether markers of central adiposity, especially waist-to-hip ratio (WHR), would be associated with vascular remodeling. SUBJECT/METHODS: We enrolled 263 postmenopausal nonobese women without metabolic syndrome or diabetes. The strongest anthropometric measure related to brachial artery diameter (BAD) was WHR. Therefore, we divided the population in tertiles according to WHR values. Women in third tertiles were older, with higher body mass index, had worse lipid profile and a higher BAD than women in the first and second tertiles. RESULTS: An analysis of covariance confirmed that BAD was increased with increasing tertiles after correction for confounding variables. CONCLUSION: BAD, a surrogate measure of cardiovascular disease, was correlated to WHR in nonobese population; therefore, nonobese women with high WHR should be carefully considered because of a possible worse cardiovascular risk profile.

Relation between serum uric acid and carotid intima-media thickness in healthy postmenopausal women.

OBJECTIVE: Serum uric acid (SUA) is associated with cardiovascular disease (CVD). However it is still disputed whether the relationship is mediated by other risk factors such as obesity, dyslipidaemia, hypertension and insulin resistance. We explored the association of the uric acid level with carotid intima-media thickness (IMT), a well known marker of CVD, in postmenopausal healthy women. METHODS: We consecutively enrolled postmenopausal women undergoing a screening for health evaluation. After an accurate clinical examination, and a biochemical evaluation, the enrolled subjects underwent B mode ultrasonography to assess common carotid intima media thickness. RESULTS: Among 234 women aged 45-70 years, the uric acid level is associated with carotid IMT independently of other prognostic factors (p=0.03). In particular, women in the highest tertiles of uric acid level have a greater IMT than women in the lowest tertile (p=0.007). CONCLUSIONS: Independently of other cardiovascular risk factors, SUA levels are associated with carotid IMT even in subjects without the metabolic syndrome. This confirms and expands the role of uric acid in the determinism of CVD. Prospective trials would be useful to evaluate interventions aimed at lowering the uric acid level.

Carteolol: preliminary study on ocular pressure-reducing action.

The authors studied the pressure-reducing action of a new beta-blocking agent (carteolol) in a group of subjects affected with open angle glaucoma. The drug was efficacious in all cases treated and did not show any noteworthy side effects.