Tarquini B

Evidence for bone mass and body fat distribution relationship in postmenopausal obese women

The measurement of bone mass, a reliable predictor of osteoporotic fractures, in obese subjects has yielded conflicting results and bone mass has been reported to be elevated, normal or decreased. These observations indicate that factors other than body weight may be involved in the less risk for osteoporosis in obese subjects. In order to clarify the role of body fat distribution on bone density we studied sixty postmenopausal overweight/obese women with Body Mass Index (BMI) over 25 kg/m(2). Thirty five age-matched, nonobese postmenopausal women, served as controls. Bone mineral density (BMD) was measured at the proximal and ultradistal non dominant forearm using a double energy X-ray absorption (DEXA) apparatus. The waist/hip circumferences ratio (WHR) was used, in obese group, as an anthropometric estimation of the abdominal (WHR>0.85) to lower-extremity (WHR>0.85) fat proportion. The results were analyzed by Student t-test, ANOVA, and multiple linear regression analysis. No difference was found in BMD between obese group and controls, but a highly significant (P<0.001) positive correlation has been documented between proximal and ultradistal radius bone mineral density and waist/hip ratio in the obese group. Instead not significant correlation was found with BMI. Regional fat topography may influence the bone mass independently of total adiposity and visceral fat was the primary parameter accounting for higher bone mineral density values. These finding suggest that women with android-like obesity are protected from osteoporosis.

Circadian mesor-hyperprolactinemia in fibrocystic mastopathy

Abstract Prolactin, assayed in serum obtained at six consecutive 4-hourly intervals from 22 women with fibrocystic mastopathy and 18 clinically healthy women (controls), undergoes a statistically significant circadian rhythm demonstrated by population-mean cosinor. In the group with fibrocystic mastopathy, as compared to the controls, the circadian amplitude is only slightly higher when summarized in original values and slightly lower in relative terms—as per cent of rhythm-adjusted mean or mesor. These differences are not statistically significant (P > 0.05). Nearly identical in the two groups is the rhythms timing, assessed by fitting a 24-hour cosine curve to the data to obtain an acrophase estimate. For the group with fibrocystic mastopathy and the controls, the point estimates of the acrophase are nearly the same at −18 ° and −26 ° from local midnight (01 12 and 01 44 , since 360 ° = 24 hours) with the 95 per cent confidence intervals extending from +4 ° (−356 °) to −38 ° and from −6 ° to −47 °, respectively. A mesor test establishes a mesor-hyperprolactinemia in patients with fibrocystic mastopathy who, as a group, represent a population differing from the clinically healthy control subjects (P

Influence of Non-Insulin-Dependent Diabetes Mellitus on Plasma Endothelin-1 Levels in Patients With Advanced Atherosclerosis

Endothelin-1 (ET-1) is an endothelium-derived vasoactive peptide with mitogen properties. Increased circulating ET-1 levels were found in patients with atherosclerosis as well as in patients with non-insulin-dependent diabetes mellitus (NIDDM) suggesting a role in the pathogenesis of these disorders. The aim of the present study was to ascertain the influence of the NIDDM on plasma ET-1 levels in patients with advanced atherosclerotic lesions. The circulating ET-1 levels were measured in 16 NIDDM patients (68.4 +/- 8.4 years) with macroangiopathy and in ten patients (65.3 +/- 11 years) with atherosclerosis without NIDDM. Twenty-two healthy subjects (43.1 +/- 18.3 years) served as controls. Circulating ET-1 levels were higher in NIDDM patients (6.8 +/- 2.8 pg/mL) than both controls (3.1 +/- 1 pg/mL; p < 0.001) and patients with vascular disease but without NIDDM (4.7 +/- 1.6 pg/mL; p < 0.04). No significant relationship was found between age and ET-1 concentrations, and no differences were noted between men and women in the control group. This study demonstrated that circulating ET-1 levels are increased in patients with atherosclerosis and that those with NIDDM showed the highest ET-1 levels. These observations strongly support a role for ET-1 in the pathogenesis of atherosclerosis and also suggest that this peptide may be involved in the development of atherosclerotic lesions in the NIDDM. We speculated that chronic exposure to hyperinsulinemia and hypertriglyceridemia in the diabetic patients could account for the increased ET-1 levels found in these patients.

Chronobiologic blood pressure assessment with a cardiovascular summary, the sphygmochron

Chronobiology deals with rhythmic patters that occur in all forms of life [1–5, 7–33, 35–38, 40–44, 47]. Virtually all organisms exhibit approximately daily (circadian) cycles. In human beings, prominent rhythms are found in blood pressure, circulatory pulse, body core and surface temperature and in chemical variables of blood, urine, and tissues. (Fig. 1). The medical section of this new science explores the relationships of rhythms to prediction, prevention, diagnosis, and treatment of diseases. Several decades of research worldwide have established that medical diagnoses can be subject to a much higher proportion of false positives (e. g., “office hypertension”) and false negatives (e. g., “odd-hour” hypertension) when only single samples are taken at arbitrary times of the day instead of taking rhythms into account. Radiation, chemotherapy, and other treatments have been shown to have markedly different efficacy and safety depending upon the pattern of administration within the day. Without modern engineering tools, chronobiology had to rely on manual measurement series that were cumbersome to collect and required methods of analysis that were not generally available. Modern bioengineering with microcomputers can bring the findings of chronobiology on circadian and other rhythms into the mainstream of medicine. Chronobiology can thus provide new dimensions to an individualized, positive assessment of health complementing the current negative approach relying solely on the absence of unusual values or overt disease.

Endothelin-1's Chronome Indicates Diabetic and Vascular Disease Chronorisk

Plasma endothelin-1 was measured around the clock in 72 subjects. Cosinor methods were used to assess circadian and other recurrent variation and trends, that is, the time structure (chronome) of this peptide. Multifactorial analyses of variance and linear regressions assessed chronome alterations associated with different risk factors: diabetes, obesity, high cholesterol, high blood pressure, vascular disease, smoking, and age. The rhythm-adjusted mean (MESOR) of endothelin-1 is elevated in diabetes and vascular disease. Diabetes is also associated with a larger circadian amplitude. A circadian variation in a subgroup of low-risk subjects is modulated by components with both lower and higher frequency.

Genetic and environmental influences on human cord blood leptin concentration.

Objective. To examine in a population sample of cord blood the time structure (chronome) of leptin, an adipocyte-derived hormone, and to assess any effect of a familial history of noninsulin-dependent diabetes mellitus and obesity, separately, on both the maternal and the paternal side. Subjects and Methods. Leptin concentration was determined in cord blood from 93 infants. Effects of gender, gestational age, birth weight, maternal weight, familial antecedents of obesity and noninsulin-dependent diabetes mellitus, and circadian and about-yearly stage were assessed by linear regression and ANOVA. Results. Cord blood leptin concentration is elevated in the presence of a family history of obesity on the paternal side, but not on the maternal side. Leptin concentrations are higher in spring and summer than in fall and are higher in infants born before noon. In keeping with earlier work, leptin concentration in cord blood correlates positively with birth weight and height and is higher in infants who are appropriate for or large for gestational age than in infants who are small for gestational age or born prematurely. Discussion. Changes along the scales of the day and the seasons point to synchronizing environmental as well as genetic influence. An association of cord blood leptin concentration with obesity on the paternal side may help clarify the role of leptin in parental contributions to human obesity and may prompt focus on cholesterol metabolism.

Endothelin-1 and Paget's Bone Disease: Is There a Link?

Abstract. The abundance of endothelial cells in bone marrow and the proximity of these cells to osteoclasts and osteoblasts suggest a role for endothelin-1 (ET-1) on bone metabolism. In vitro, the direct contact with bone endothelial cells induces osteoclastic progenitors to differentiate into mature elements. Recently it has been reported that ET-1 inhibits osteoclastic bone resorption and cell mobility through a specific receptor on osteoclasts; other authors demonstrated that ET-1 exerts a mitogenic activity on osteoblast-like cells (MC3T3) by stimulating tyrosin phosphorylation. We measured ET-1 circulating levels in patients with active Pagets bone disease, a condition with accelerated bone turnover. For the study we recruited 11 patients with Pagets bone disease (5F, 6M; mean age 68.2 ± 3.6) in the acute stage of the disease; 10 healthy subjects (7F, 3M; mean age 66.5 ± 3.9) were also enrolled as controls. Plasma ET-1 levels were measured with RIA kits provided by Nichols Institute. Patients showed significantly (P < 0.01) higher ET-1 circulating levels than controls (6.35 ± 1.9 versus 3.4 ± 1.2 pg/ml) with a positive correlation (r = 0.63; P= 0.038) with serum alkaline phosphatase (ALP), but not with urinary hydroxyproline. The higher levels of ET-1 in our patients suggest a physiopathological role for this peptide in the disease and, could perhaps represent a new useful marker of Pagets bone disease activity.

DAYTIME CIRCULATING MELATONIN LEVELS IN SMOKERS

Aims and background Melatonin secretion is required to be a potential inhibitor of the development and growth of tumors, and cigarette smoking is a well established risk factor for cancer at various sites. Methods Circulating melatonin levels of 20 smokers and 20 non smokers (controls), sampled at the same hour from awaking in order to obtain a comparable circadian synchronization, were compared. Results Our data showed higher melatonin circulating levels in smokers (17.44 ±1.8 pg/ml) than in nonsmokers (9.77 ± 1.4 pg/ml). Conclusions The causes, mechanism and meaning of this phenomenon are still unknown. The most actractive hypothesis considers higher melatonin levels in smokers as an attempt to counterbalance cellular growth stimulus, a natural “brake” mechanism to restrain the proliferation of normally differentiated tissues: smoke is a prominent risk factor for several different tumors.

Effects Lasting into Adolescence of Exposure to Betamimetics In Utero

SummaryThe range of the predictable within-day change in blood pressure, assessed as the circadian blood pressure amplitude, is greater in newborns who have been exposed in utero to betamimetics than in those not exposed. A larger circadian blood pressure amplitude is also found in infants and children with a positive versus those with a negative family history of high blood pressure. In adulthood, an excessive circadian blood pressure amplitude is associated with a 6-fold increase in risk of ischaemic stroke. To determine whether the large circadian blood pressure amplitude associated with intrauterine exposure to betamimetics in newborns persists later in life, the progeny of mothers who had had similar obstetric situations but had been treated either with spasmolytics (not including betamimetics) or with betamimetics to prevent premature labour was assessed. The blood pressure of 43 adolescents aged between 11 and 14 years was measured at 15-minute intervals for 2 days with an ambulatory monitor; an echocardiogram was also taken. A multiple regression analysis accounting for gender- and age-related changes revealed a dose-dependent effect of betamimetic exposure on the circadian blood pressure amplitude of the offspring. Exposed children also tended to have a larger left ventricular mass index. Thus, in utero exposure to betamimetic drugs may have cardiovascular effects lasting into adolescence.

Angiopathy affects circulating endothelin-1 levels in type 2 diabetic patients

To evaluate the role of endothelin-1 (ET-1), a vasoconstrictor and mitogenic peptide synthesized by endothelial cells, on the endothelial dysfunction in non-insulin-dependent diabetic (type 2) patients, we have measured the circulating ET-1 levels in 25 patients with and without clinically evident vascular complications and in a control group. Circulating ET-1 levels were significantly higher in diabetic patients with angiopathy than in diabetics without angiopathy and in controls (7.02±2.9 pg/ml vs 4.4±1.1 pg/ml and 3.08±0.7 pg/ml, respectively;P<0.001). No difference was demonstrated between diabetic patients without angiopathy and controls. These findings suggest that ET-1 may be a marker for arterial vascular disease only in patients with overt angiopathy. It is unclear whether it participates in the endothelial injury process or it is merely released from damaged endothelial cells.