Effects of a 3-month weight-bearing and resistance exercise training on circulating osteogenic cells and bone formation markers in postmenopausal women with low bone mass.

Osteoporosis is a health issue in postmenopausal women. Physical activity is recommended in these subjects, since it has positive effects on bone mass. Cellular mechanisms underlying this effect are still unclear. Osteogenic cells, released after physical exertion, could be a key factor in exercise-induced bone formation. INTRODUCTION: The aim of our research was to explore if a weight-bearing and resistance exercise program could positively affect circulating osteogenic cells (OCs), markers of bone formation and quality of life (QoL) in osteopenic postmenopausal women. METHODS: We recruited 33 postmenopausal women with a T-score at lumbar spine or femoral neck between - 1 and - 2.5 SD. Anthropometric and fitness parameters, bone-remodeling markers, OCs, and QoL were evaluated at the time of enrolment, after 1-month run-in period, and after 3 months of weight-bearing and resistance exercise. RESULTS: After 3 months of training, the pro-collagen type 1 N-terminal peptide (P1NP) and the number of OCs were significantly increased, with no significant increase of the type 1 collagen cross-linked C-telopeptide (sCTX). We also observed a significant increase in body height, one-repetition maximum (1RM) on the pull-down lat machine and leg press, and mean VO2max. The increase of immature circulating OCs was significantly correlated with the improvement of 1RM both of the upper and lower limbs. Moreover, QoL was significantly improved with regard to pain, physical function, mental function, and general QoL. The improvement in QoL, namely in the overall score and in the pain score, was significantly correlated with the increase in height. CONCLUSIONS: The exercise program we trialed is able to increase the markers of bone formation and the commitment of immature OCs with no significant increase in the markers of bone resorption. Our results confirm that combined weight-bearing and resistance physical activity is an effective tool to improve QoL of postmenopausal women with low bone mass. TRIAL REGISTRATION: NCT03195517.

Postprandial endothelial impairment and reduced glutathione levels in postmenopausal women.

BACKGROUND/AIM: Postmenopausal age is characterized by a higher risk for coronary heart disease (CHD) and postprandial lipemia is strictly related with the evidence of CHD. The aim of the study was to clarify the vascular effects of postprandial state in postmenopausal women. METHODS: Ten postmenopausal women (mean age 57 +/- 8 years) without vascular risk factors and history of cardiovascular disease underwent an oral fat load test. Endothelial function, expressed as brachial flow-mediated vasodilation (FMV), lipid parameters and reduced glutathione (GSH) were evaluated at baseline and 2, 4 and 6 h after the load. RESULTS: FMV showed a significant decrease at the 2nd hour (2.3 +/- 2.6%, vs. baseline 7.7 +/- 2.8%, p < 0.05) and overlapping to the basal value after 4 h. Triglycerides increased postprandially at the 2nd and 4th hour (1.6 +/- 0.6 micromol/l, 1.8 +/- 0.5 micromol/l vs. baseline 0.9 +/- 0.4 micromol/l, p < 0.05), decreasing thereafter. GSH decreased at the 2nd hour of the postprandial phase (5.1 +/- 1.9 micromol/l vs. baseline 8.4 +/- 1.9 micromol/l, p < 0.05), normalizing successively. At the univariate analysis a negative correlation was found between FMV and triglyceride changes (r = -0.37, p < 0.05) and a positive one between FMV and GSH modifications (r = 0.40, p < 0.05). CONCLUSION: These data demonstrated that postprandial lipemia transiently impairs endothelial reactivity by an oxidative burden, partly dependent to triglyceride increase.

Neutrophil-derived adhesion molecules in human digital ischaemia and reperfusion.

In order to see whether leucocyte-derived adhesion molecules are involved in ischaemia and reperfusion, the total and differential leucocyte counts and expression of the LFA complex i.e. CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1) and CD11c/CD18 (p 150,95) were monitored before and after standard cold and heat tests in 8 females with Raynaud's Disease and 8 matched controls. All patients suffered from vasoconstriction during the cold test which, compared with controls, was associated with fewer granulocytes expressing significantly more CD11b/CD18 (Mac-1) integrin and a significant degree of neutropenia persisting during reperfusion. Leucocyte-endothelial adhesive interactions may therefore occur during ischaemia and reperfusion.

Leucocyte activity in chronic venous insufficiency.

Before and after venous stasis and upon recovery blood samples were drawn from the saphenous vein in 10 patients with varicose veins (Group 1), in 10 with venous hypertension (Group 2) and in 10 healthy controls. The total leucocyte count, the leucocyte filterability rate (LFR), superoxide dismutase blood concentrations (SOD) and the production of superoxide anions from granulocytes were determined. After stasis, the total leucocyte count increased significantly (p < 0.01) in both groups of patients and the LFR was significantly (p < 0.01) impaired. SOD blood concentrations fell significantly (p < 0.01) and oxygen free radical production dropped significantly (p < 0.01) in both groups. Upon recovery, all parameters returned to normal in Group 1 but significant differences remained in Group 2. No significant modification was observed at any stage of the study in the control group. These results suggest that impairments in leucocyte rheology and granulocyte production of oxygen free radicals cause capillary plugging and possibly damage to microcirculatory vessel walls in venous disease.

Treating peripheral arterial occlusive disease: pentoxifylline vs exercise.

The effects of three months therapy with Pentoxifylline (800 mg three times daily) and physical training were compared in two age- and sex-matched groups of Stage II PAOD patients. Before therapy and after 12 and 13 weeks each patient underwent a standard treadmill test. The maximum walking time, TcPO2 half recovery time to basal values after the induced ischaemia, granulocyte production of free radicals (by the superoxide dismutase-inhibitable reduction of ferricytochrome) and surface expression of the CD11/CD18 complex of adhesion molecules (by using specific monoclonal antibodies) were determined. Pentoxifylline inhibited free radical production and reduced the percentage of granulocytes expressing adhesion receptors while exercise had no significant effect on these parameters. These changes, which reflect improved microcirculatory functioning, were associated with a greater walking capacity and shorter half recovery time (+14% vs exercise group, p < 0.01; -39% vs exercise group, p < 0.01 respectively).

Lipoprotein (a) in peripheral arterial occlusive disease.

Recent studies have shown high levels of lipoprotein (a),--Lp(a)-, an atherogenic and thrombogenic lipoprotein, are considered a risk factor for coronary heart disease. This study evaluated Lp(a) levels, as well as other lipid factors, in a group of 45 patients affected by stage II peripheral arterial occlusive disease (PAOD). An age-, sex- and Body Mass Index-matched group of healthy controls was also recruited. Exclusion criteria were diseases or drugs which could alter Lp(a) levels. Alterations in lipid profiles, which are often associated with PAOD, were observed in the patients. Lp(a) levels did not differ significantly in the two groups (median 16.4 mg/dl, range 10-104, in PAOD and 9.9 mg/dl, range 7.4-66.7, in controls and means 21.7 +/- 17.5 mg/dl and 21.2 +/- 16.8 mg/dl respectively) but in 51% of the controls Lp(a) levels were < 10 mg/dl compared with 20% of the PAOD patients (p < 0.05).

Human leucocyte-endothelial interactions in peripheral arterial occlusive disease.

This ex vivo study determined the expression of leucocyte adhesion receptors for endothelial adhesion molecules in 10 patients with peripheral arterial occlusive disease (PAOD) and in 10 healthy controls before and after treadmill exercise. Granulocytes from venous blood samples were separated on a Ficoll-Hypaque gradient and the phenotypical expression of CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1) and CD11c/CD18 (p150,95) was observed by double indirect immunofluorescence using specific monoclonal antibodies. The total and differential white blood cell counts were monitored before and after exercise. In the PAOD patients a significant reduction in the number of granulocytes expressing CD11b/CD18 (Mac-1) and CD11c/CD18 (p150,95) associated with a significant neutropenia was observed after exercise, suggesting that leucocyte-endothelial interactions occur during ischaemia.

In vitro bone marrow cell culture and cytogenetic analysis in a case of myelodysplasia.

A case of refractory anemia with sideroblastosis and a number of bone-marrow blasts slightly over the limit which separates the I/II and III FAB-subtypes of myelodysplastic syndromes is described. The leukemic-like type of in vitro growth and the multiple karyotypic changes observed in the bone-marrow cells at presentation were both indicators of the malignant nature of the disorder and underlined the importance of these studies in assessing diagnosis and prognosis in patients with preleukemic disorders. The role that the chromosome aberrations, del(11)(q14) and del(18)(q21), both found in 100% of the bone-marrow metaphases examined, may play in the pathogenesis of the disease is also discussed.

[Rheologic effects of salmon calcitonin on post-menopausal osteoporosis. Results of a preliminary study]. / Effetti reologici della calcitonina di salmone nell'osteoporosi post-menopausale. Risultati di uno studio preliminare.

The aim of this random blind vs placebo study was to assess the effect of salmon calcitonin (sCT) (100 UI/day intermuscular for 4 weeks) on the haemorheological pattern of 20 women, all non-smokers, aged between 50 and 65 years of age and affected by post-menopausal osteoporosis. Hematocrit, whole blood viscosity at high and low shear rates, plasma viscosity, red blood cell aggregation, dynamic deformation and viscosity were monitored. Our results show sCT ex vivo seems to act upon mechanisms regulating the plastic properties of the red blood cell membrane.

Use of pentoxifylline as an inhibitor of free radical generation in peripheral vascular disease. Results of a double-blind placebo-controlled study.

The effects of an infusion of pentoxifylline 1 g as an inhibitor of free radical generation have been determined in a double-blind placebo-controlled study. Leucocyte-derived free radical generation (by the superoxide dismutase-inhibitable reduction of ferricytochrome), the release of reactive oxygen metabolites (as plasma oxidant activity), unfractionated leucocyte and erythrocyte filterability rates (using a constant-flow positive-pressure system), plasma viscosity, and plasma fibrinogen concentration have been measured in two matched groups of 10 patients with Stage II peripheral vascular disease, before and after treatment. Transcutaneous oxygen pressure (PtcO2) during treadmill exercise to stress leg circulation was also measured. Leucocyte-derived free radicals were generated during peripheral ischaemia. Pentoxifylline inhibited their generation, blocked the release of reactive oxygen metabolites, and reduced impairment of the filterability rate of unfractionated leucocytes. The improvements were accompanied by significant shortening of the half-time of recovery of transcutaneous oxygen pressure, indicating that ischaemic damage had been contained.

Sympathetic vascular function in patients with central dysautonomia.

This study used digital photoplethysmography (d-FPG) to investigate alterations in skin blood flow after exposure to cold as well as the post-prandial blood pressure pattern to assess how the sympathetic branch of autonomic nervous system (ANS) functioned in 31 patients with cerebral dysautonomia and in 27 healthy controls. d-FPG was carried out on all ten fingers in basal conditions and after exposure to ice-cold water (4-5 degrees C). Amplitude, crest time and inclination time were used to calculate the alterations induced by the cold pressor test. After a standard lunch blood pressure was monitored every 20 minutes using a fully automatic non-invasive sphygmanometer. Unlike the controls the amplitude of the photoplethysmographic wave increased in all patients except 2; crest time and inclination time decreased in all except 3; post-prandial diastolic and systolic blood pressure levels fell markedly in all but 3. Blood vessel smooth muscle tone is disturbed in patients with ANS failure because dysautonomia may permit the action of vasodilating substances to predominate. The post-prandial blood pressure pattern and the d-FPG used in conjunction with a cold pressor test are useful tools in the non-invasive investigation of ANS function.

Effects of ticlopidine on the neurologic outcome and the hemorheologic pattern in the postacute phase of ischemic stroke: a pilot study.

This double-blind pilot study observed the effects of a twenty-one day oral ticlopidine treatment (250 mg/twice daily) on the neurologic outcome and the hemorheologic pattern of 15 patients and 15 placebo-treated controls. Patients and controls (age range sixty-six to eighty-six years) were included in the study within twelve hours of the onset of ischemic stroke, confirmed clinically and by computerized tomography. Scores on Hachinski's Scale and the following hemorheologic parameters were monitored weekly for twenty-one days: fibrinogen levels, the whole blood, unfractionated white and red blood cell filterability rates (through 5-micron-pore-diameter filters using a constant-flow positive-pressure system), and the leukocyte count and activation (by microscopic observation). The results showed treatment with ticlopidine improved the neurologic outcome (Hachinski's Score +36%, p less than 0.03) slightly but significantly (p less than 0.001) increased the average values of the whole blood (+19%) and red cell (+17%) filterability rates and decreased fibrinogen levels (-17%).

Reactive oxygen metabolites in peripheral arterial occlusive disease.

Plasma oxidant activity (marker of reactive oxygen metabolites) and the unfractionated leucocyte filterability rate (determined through 5 micron pore diameter Nuclepore filters, using a positive pressure system) were monitored in 15 stage II peripheral vascular disease (PVD) patients before and after ischaemia was induced by treadmill exercise (12 degrees slope/2 km/hour). Plasma oxidant activity increased (+ 115%) significantly (p less than 0.001) at the maximum walking time, correlating (r = 0.79) with a significant (p less than 0.001) impairment (+23%) in the unfractionated leucocyte filterability rate. At the transcutaneous oxygen pressure (tcPO2) half recovery time the plasma oxidant activity approached basal values but the unfractionated leucocyte filterability rate remained significantly (p less than 0.001) impaired (+16%). It returned to basal values at the full tcPO2 recovery time. These results show reactive oxygen metabolites are released during ischaemia of the lower limbs and are correlated with a significant impairment in the flow properties of leucocytes.