ABSTRACT
A newly identified cytokine, osteoprotegerin (OPG) appears to be involved in the regulation of bone remodeling. In vitro studies suggest that OPG, a soluble member of the TNF receptor family of proteins, inhibits osteoclastogenesis by interrupting the intercellular signaling between osteoblastic stromal cells and osteoclast progenitors. As patients with chronic renal failure (CRF) often have renal osteodystrophy (ROD), we investigated the role of osteoprotegerin (OPG) in ROD, and investigated whether there was any relationship between serum OPG, intact parathyroid (PTH) (iPTH), vitamin D, and trabecular bone. Serum OPG combined with iPTH might be a useful tool in the noninvasive diagnosis of ROD, at least in cases in which the range of PTH values compromises reliable diagnosis. Thirty-six patients on maintenance hemodiafiltration (HDF) and a control group of 36 age and sex matched healthy subjects with no known metabolic bone disease were studied. The following assays were made on serum: iPTH, osteocalcin (BGP), bone alkaline phosphatase, 25(OH)-cholecalciferol, calcium, phosphate, OPG, IGF-1, estradiol, and free testosterone. Serum Ca++, P, B-ALP, BGP, IGF-1, iPTH, and OPG levels were significantly higher in HDF patients than in controls, while DXA measurements and quantitative ultrasound (QUS) parameters were significantly lower. On grouping patients according to their mean OPG levels, we observed significantly lower serum IGF-1, vitamin D3 concentrations, and lumbar spine and hip bone mineral density in the high OPG groups. No correlation was found between OPG and bone turnover markers, whereas a negative correlation was found between serum OPG and IGF-1 levels (r=-0.64, p=0.032). Serum iPTH concentrations were positively correlated with bone alkaline phosphatase (B-ALP) (r=0.69, p=0.038) and BGP (r=0.92, p<0.001). The findings made suggest that an increase in OPG levels may be a compensatory response to elevated bone loss. The low bone mineral density (BMD) levels found in the high OPG group might have been due to the significant decrease in serum IGF-1 and vitamin D3 observed. In conclusion, the findings made in the present study demonstrate that increased OPG in hemodiafiltration patients is only partly due to decreased renal clearance. As it may partly reflect a compensatory response to increased bone loss, this parameter might be helpful in the identification of patients with a marked reduction in trabecular BMD.
Subject(s)
Bone Density/physiology , Chronic Kidney Disease-Mineral and Bone Disorder/etiology , Glycoproteins/metabolism , Hemodiafiltration/adverse effects , Kidney Failure, Chronic/therapy , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Absorptiometry, Photon , Aged , Analysis of Variance , Biomarkers , Case-Control Studies , Chronic Kidney Disease-Mineral and Bone Disorder/physiopathology , Female , Glycoproteins/blood , Hemodiafiltration/methods , Humans , Kidney Failure, Chronic/diagnosis , Male , Middle Aged , Osteoprotegerin , Probability , Prognosis , Receptors, Cytoplasmic and Nuclear/blood , Receptors, Tumor Necrosis Factor/blood , Reference Values , Risk Assessment , Sensitivity and SpecificityABSTRACT
INTRODUCTION: The pathogenic mechanisms underlying the increase in peripheral resistance and the contraction of smooth muscular fibre cells in essential hypertension are not yet clearly understood. However, it is now known that immune system activation plays a role in the pathogenesis of some forms of arterial hypertension, and recent data show that the Ca2+ influx in some cells (i.e. red blood cells, leukocytes, platelets, smooth muscular fibre cells) is increased in subjects with essential hypertension, thus revealing a possible alteration in cellular membrane. The end-points of this study were therefore to ascertain whether red blood cells used as a cellular membrane model have a greater Ca2+ dependent K+ flow (Gardos effect) in hypertensive patients than in normotensive controls, to point out a different regulation of ionic channels, and whether IL-8 and the adhesion molecule ICAM-1 influence the membranous outflow. MATERIAL AND METHODS: The study was conducted on 87 Caucasian subjects. Of these, 50 (25 men, 25 women; mean age 43 +/- 3 years, mean body mass index (BMI) 27 +/- 0.5 and 22.3 +/- 0.3 kg/m(2), respectively) had mild-to-moderate hypertension (mean arterial blood pressure 120 +/- 8 mmHg ). The other 37 (18 men, 19 women; mean age 39 +/- 3 years; BMI 23.8 +/- 0.5 kg/m(2) and 22.8 +/- 0.5 kg/m(2), respectively were normotensive healthy volunteers (mean arterial blood pressure 89 +/- 2 mmHg). All the patients and subjects were untreated for at least 4 weeks before blood sampling. RESULTS: Ca2+-dependent K+ outflow was found to be greater in samples from patients with essential hypertension than in those from normotensive controls. lL-8 and ICAM-1 significantly enhanced the Ca2+-dependent K+ outflow in red blood cells from hypertensive subjects but had an inhibitory effect on cells from controls. In the experimental model, the presence of TMB-8, a membrane calcium antagonist, significantly reduced the Ca2+-dependent K+ efflux. CONCLUSION: Vasoconstriction in subjects with essential hypertension may therefore depend on a different regulation of ionic flow that probably supports an increased Ca2+ inflow in smooth muscle fibre cells. Under certain pathological conditions, some immune system components (i.e. interleukins, adhesion molecules) may directly enhance membrane permeability to Ca2+, thus inducing vasoconstriction in the smooth muscle cells.
Subject(s)
Calcium/physiology , Erythrocyte Membrane/physiology , Gallic Acid/analogs & derivatives , Hypertension/blood , Intercellular Adhesion Molecule-1/physiology , Interleukin-8/physiology , Potassium/blood , Adult , Calcium Channel Blockers/pharmacology , Female , Gallic Acid/pharmacology , Humans , Male , Potassium Channels/physiology , Vasoconstriction/physiologyABSTRACT
Colon diverticular disease is a very common pathology in western countries and represents a risk factor for septic-type complications, especially in peritoneal dialysis patients. We examined both diagnostic procedure and therapeutics options, either pharmacological or surgical. Ultrasonography, which is useful for the diagnosis of diverticulosis and diverticular disease, has been supported in the last few years by new imaging techniques, such as NMR and CT, that also find applications in the treatment of diverticulitis complications like peritoneal abscesses. Our emphasis is on the therapeutic perspective, either dietetic - based on the use of a fibre-rich diet and the infusion of liquids by intravenous injection - or surgical, such as the Hartmann procedure, single anastomosis with stomia conservation and laparoscopic and endoscopic treatment. These therapeutic approaches have reduced both morbidity and mortality rate and have emphasized how the reduction of surgical stress on the mesothelium promotes the recovery of the functional integrity and, consequently, faster resumption of peritoneal dialysis. In conclusion, diverticulosis alone is not a contraindication for peritoneal dialysis, but constitutes a risk factor for the continuation of this alternative treatment.
Subject(s)
Diverticulum/complications , Kidney Failure, Chronic/therapy , Peritoneal Dialysis , Peritonitis/etiology , Anastomosis, Surgical , Colonoscopy , Combined Modality Therapy , Contraindications , Diagnostic Imaging , Dietary Fiber/therapeutic use , Diverticulum/diagnosis , Diverticulum/diet therapy , Diverticulum/physiopathology , Diverticulum/surgery , Humans , Intestinal Perforation/etiology , Intestinal Perforation/prevention & control , Kidney Failure, Chronic/complications , Laparoscopy , Peritoneal Dialysis/adverse effects , Peritonitis/epidemiology , Prevalence , Retrospective Studies , Risk FactorsABSTRACT
Hemodialysis influences the transport of water through the erythrocytic membrane, and induces morphologic and functional modifications. Recently water channels, called aquaporins (AQP), have been identified on the membrane of red blood cells. The aim of the present study was, therefore, to evaluate any relationships between volumetric changes in erythrocytes (MCV), plasma osmolarity and membrane expression of AQP1 in 22 uremic patients during a hemodialysis session, and compare value with those in a control group of 22 healthy volunteers. Membranal AQP1 expression was evaluated using three methods: indirect immunofluorescence under confocal microscopy, immunoenzymatic method after membrane extraction, and immunoblotting. In uremic subjects, at baseline membrane AQP1 expression was significantly lower, whereas plasma osmolality was higher than in controls. At 1 and 2 h of replacement therapy, a progressive increase was observed in erythrocytic AQP1, values similar to those in controls being attained after 3.5 h. During the session osmolality values reduced progressively, becoming significantly lower than basal values. The mean erythrocytic corpuscular volume in patients with ESRD was significantly lower than in cntrols at baseline. This value increased during hemodialysis, attaining statistical significance with respect to the basal value at 3.5 h of dialysis. Close correlations were found between plasma osmolality and AQP1 values (r = -0.930; p < 0.05), and also between MCV and plasma osmolality trend (r = -0.909; p < 0.05). There was a linear correlation (r = 0.63, p < 0.05) between plasma AVP concentrations and plasma osmolality. The variations found in plasma osmolarity during hemodialysis, may induce AQP1 expression on the membrane of intact red blood cells.
Subject(s)
Aquaporins/blood , Erythrocytes/metabolism , Renal Dialysis , Uremia/blood , Adult , Aged , Aquaporin 1 , Blood Group Antigens , Blood Pressure , Erythrocyte Indices , Erythrocytes/cytology , Female , Hemoglobins/analysis , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Osmolar Concentration , Potassium/blood , Sodium/blood , Uremia/therapy , Vasopressins/bloodABSTRACT
AIMS AND BACKGROUND: This study was carried out to evaluate the IL-18 blood concentrations of operated colorectal cancer patients and their possible variation in response to combination chemotherapy with 5-fluorouracil (5-FU) and folinic acid. METHODS: IL-18 levels were assayed in sera of 18 healthy donors and 18 surgical colorectal cancer patients before and after adjuvant chemotherapy with 5-fluorouracil and folinic acid. An ELISA kit for human IL-18 was used for the assay. RESULTS: Colorectal cancer patients showed significantly higher baseline levels of IL-18 than healthy donors (p<0.005). Furthermore, serum IL-18 levels increased significantly with respect to baseline in patients receiving adjuvant chemotherapy (p<0.005). CONCLUSIONS: This study suggests that treatment with 5-fluorouracil and folinic acid may provoke an increase in IL-18 serum levels in colorectal cancer patients. This increase may help to explain the efficacy of adjuvant chemotherapy with 5-FU in colorectal cancer.
Subject(s)
Colorectal Neoplasms/metabolism , Fluorouracil/pharmacology , Interleukin-18/blood , Leucovorin/pharmacology , Adult , Aged , Aged, 80 and over , Antigens, Tumor-Associated, Carbohydrate/biosynthesis , Antimetabolites, Antineoplastic/pharmacology , CA-19-9 Antigen/blood , Carcinoembryonic Antigen/biosynthesis , Enzyme-Linked Immunosorbent Assay , Humans , Middle AgedABSTRACT
BACKGROUND: It is known that hyperhomocysteinemia is associated with an increased risk of vascular disease, yet little is known about the pathogenic mechanisms underlying the action of homocysteine (Hcy) itself. METHODS: We evaluated the effects of Hcy on cell proliferation, apoptosis, and necrosis in smooth muscle cells (SMCs) cultured for 24 h with different amounts of Hcy. The percentage of apoptotic and necrotic cells from the culture was evaluated using two different techniques: annexin V-FITC and propidium iodide (PI) fluorescence and apoptosis TUNEL assay. RESULTS: The addition of 10 microM/l of Hcy to the medium was followed by a significant increase in cell proliferation and death, through apoptosis and necrosis, respectively. Notwithstanding this apparent balance, a significant increase was found in the total number of cells present in Hcy-treated culture, thus demonstrating a positive dose-dependent correlation with Hcy concentrations in the culture medium. The addition of folic acid to the culture medium significantly reduced both Hcy concentrations in media and the effects of Hcy on the proliferation/apoptosis/necrosis balance of cells in culture. The percentages for apoptotic cells and for cells with a necrotic morphology continued to increase as Hcy concentrations increased, although the absolute values were lower in the culture treated than in that not treated with folic acid. CONCLUSIONS: In the presence of folic acid, at increasing concentrations of Hcy, the total number of cells in culture showed increases far less relevant with respect to the control. Also the percentage of apoptotic cells to that of cells with a necrotic morphology, although conserving the tendency to increase to growth of the concentrations of Hcy, have shown absolute values that were lower in the folic acid-treated cultures.
Subject(s)
Folic Acid/pharmacology , Homocysteine/pharmacology , Muscle, Smooth, Vascular/cytology , Apoptosis/drug effects , Cell Culture Techniques , Cell Division/drug effects , Cell Line , Dose-Response Relationship, Drug , Homocysteine/drug effects , Humans , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , NecrosisABSTRACT
BACKGROUND: In healthy primiparas the total body water content increases by about 8 liters within the last trimester, with a consequent reduction in plasma arginine-vasopressin (AVP) levels. The aim of the present study was to investigate the effect of normal pregnancy on urinary excretion of AQP2, a vasopressin sensitive water channel. METHODS: Forty-five healthy pregnant primiparas (specify mean age and range) with a physiological single-fetus pregnancy were studied during weeks 12, 24 and 36 of pregnancy and then for 3 to 5 days postpartum. The control group consisted of 14 age-matched women in the early follicular phase of the menstrual cycle (day 5 or 6). The behavior of plasma AVP, ANP, oxytocin, urinary 6-keto-PGF1alpha (a metabolite of prostacyclin) and urinary AQP-2 excretion were evaluated in all subjects. RESULTS: Plasma ANP and oxytocin, and urinary AQP-2 and 6kPGF1alpha excretion increased during all three trimesters, with the highest peaks at the 36(th) week. In the postpartum period, these values markedly decreased. No statistically significant changes were found in plasma AVP levels throughout the study period. CONCLUSIONS: Our findings suggest that a non-AVP factor present in pregnancy plays a role in the control of the excretion of AQP-2 water channels.
Subject(s)
Aquaporins/urine , Pregnancy/urine , 6-Ketoprostaglandin F1 alpha/urine , Adult , Aquaporin 2 , Aquaporin 6 , Aquaporins/blood , Arginine Vasopressin/blood , Atrial Natriuretic Factor/blood , Creatinine , Female , Humans , Osmolar Concentration , Oxytocin/blood , Postpartum Period , Pregnancy/blood , Pregnancy Trimesters , Sodium/blood , Sodium/urine , UrineABSTRACT
Interleukin-18 (IL-18), a cytokine that plays an important role in the T-cell-helper type 1 response, acts as an angiogenesis and tumor suppressor. Intercellular adhesion molecule-1 (ICAM-1) has a potential role in immunoregulation by mediating immune cell infiltration into the tissue. The aim of this study was to evaluate IL-18 and soluble (s) ICAM-1 serum levels in breast cancer (BCa) patients with liver (BCaM1 h) or bone (BCaM1 b) metastases compared to BCa patients without metastases (BCaM0) and healthy donors (HDs). Furthermore, since IL-18 enhances ICAM-1 expression, we investigated whether there was a direct correlation between sICAM-1 and IL-18 serum levels. Serum IL-18 and sICAM-1 levels were assayed by immunoenzymatic methods. The serum sICAM-1 levels in the three groups of cancer patients were significantly higher (p<0.05) than those of HDs. Serum IL-18 levels were significantly higher (p<0.05) in BCaM1h and BCaM1b patients compared to BCaM0 patients and HDs. sICAM-1 proved to be closely correlated with serum IL-18 levels in HDs, whereas a weaker correlation was found in BCaM1h, BCaM1b and BCaM0 patients. The defective correlation between sICAM-1 and IL-18 found in cancer patients may contribute to our understanding of the immunity upset occurring in cancer. Our data suggest that IL-18, irrespective of its biological activity, could represent a marker for metastatic breast cancer.
Subject(s)
Biomarkers, Tumor/blood , Breast Neoplasms/blood , Intercellular Adhesion Molecule-1/blood , Interleukin-18/blood , Aged , Aged, 80 and over , Bone Neoplasms/blood , Bone Neoplasms/secondary , Breast Neoplasms/pathology , Female , Humans , Liver Neoplasms/blood , Liver Neoplasms/secondary , Middle Aged , Neoplasm StagingABSTRACT
Lithium salt compounds are used to limit the degree and duration of neutropenia in patients receiving chemotherapy for cancer. Interleukin-15 (IL-15) is a cytokine which possesses promoting activities on hematopoiesis and is also involved in antitumor response, activating NK, CTL and LAK cells. In this study we analyzed IL-15 production by monocyte cultures treated with lithium chloride (LiCl). Monocytes were obtained from patients affected by non-metastatic and metastatic breast cancer. LiCl treatment induced IL-15 production by monocytes mainly from non-metastatic patients. Combined lipopolysaccharide/LiCl treatment of monocyte cultures up-regulated IL-15 release compared to those treated with LPS alone (p<0.0001). The modulation of LiCl-induced IL-15 could counteract the immunosuppression state of cancer patients, which should be taken into account when developing new immunotherapeutic strategies.
Subject(s)
Breast Neoplasms/blood , Interleukin-15/biosynthesis , Lithium Chloride/pharmacology , Monocytes/drug effects , Aged , Breast Neoplasms/pathology , Cells, Cultured , Female , Humans , Interleukin-15/blood , Interleukin-15/metabolism , Lipopolysaccharides/pharmacology , Middle Aged , Monocytes/metabolism , Neoplasm StagingABSTRACT
AIMS AND BACKGROUND: Since interleukin-8 (IL-8) has a suppressive effect on hematopoiesis, lithium induces leukocytosis and granulocytosis and mononuclear cells are defective in patients affected by neoplastic disease, we analyzed IL-8 production by monocytes obtained from patients with nonmetastatic breast cancer (BCaM0) and metastatic breast cancer (BCaM1) and the effect of lithium chloride (LiCl) on these cells. Lithium salt compounds are used to limit the degree and duration of neutropenia in patients receiving chemotherapy for cancer and acute leukemia. Lithium influences the hematopoietic system, which is known to be regulated by numerous cytokines including IL-8. METHODS: We selected three groups of subjects (15 per group): patients affected by BCaM0, BCaM1 and healthy donors (HD) matched for sex and age. IL-8 release was assessed in supernatants of lipopolysaccharide (LPS) and/or LiCl-treated monocyte cultures. RESULTS: Monocytes from BCaM1 released higher IL-8 levels than monocytes from BCaM0 (P <0.0001); the IL-8 levels of both groups were significantly higher (P <0.0001) than those of HD. In vitro LiCl treatment reduced IL-8 production by monocytes obtained from all subjects compared to the same cells when untreated or LPS treated. The suppressive effect of LiCl on IL-8 production by monocytes from breast cancer patients was particularly marked in monocytes from BCaM0 with respect to those from BCaM1. LPS treatment increased the IL-8 production more in BCaM1 monocytes than in BCaM0 monocytes. Moreover, combined LPS/LiCl treatment of monocytes significantly (p <0.0001) downregulated the release of IL-8 compared to treatment with LPS alone. CONCLUSIONS: Our data demonstrate that monocytes from BCaM0 release larger amounts of IL-8 than monocytes from BCaM0 and from HD. Lithium was able to downregulate IL-8 production by monocytes from different subgroups. Further studies are needed to clarify if the improvement of the hematopoietic system in vivo observed following lithium therapy could reside, at least in part, in the ability of lithium to downregulate this chemokine.
Subject(s)
Adjuvants, Immunologic/therapeutic use , Breast Neoplasms/drug therapy , Interleukin-8/biosynthesis , Lithium Chloride/therapeutic use , Monocytes/drug effects , Monocytes/metabolism , Breast Neoplasms/blood , Breast Neoplasms/pathology , Case-Control Studies , Down-Regulation/drug effects , Female , Humans , In Vitro Techniques , Leukopoiesis , Neoplasm StagingABSTRACT
Apoptosis, a form of programmed cell death, mediates the controlled deletion of so-called "unwanted" cells. This review deals with the key features of this cell death program, showing that apoptosis is regulated by factors extrinsic and intrinsic to the dying cell. The elucidation of the possible interactions between these factors may be of major interest in preventing the progression to cardiovascular remodeling in patients with hypertensive disease. New pathways of research are emerging for drugs, such as beta-blockers, ACE inhibitors, the calcium-antagonists, and the receptor antagonist of angiotensin II, all of which have beneficial effects on cardiovascular remodeling. This may be due to the direct effect of these drugs on the cell proliferation/apoptosis balance.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Apoptosis/physiology , Hypertension/drug therapy , Hypertension/physiopathology , Ventricular Remodeling/physiology , Adrenergic beta-Antagonists/therapeutic use , Calcium Channel Blockers/therapeutic use , HumansABSTRACT
We evaluated bcl-2 protein levels in whole blood, and intraerythrocytic products of lipoperoxidation, in 65 healthy pregnant primiparous women at the end of the first, second and third trimesters of pregnancy. During pregnancy we found a progressive increase in concentrations of bcl-2 and intraerythrocytic products of lipoperoxidation. Moreover, a positive correlation was found between bcl-2 concentrations and lipoperoxidation products, and between bcl-2 protein, E2 and progesterone. The results show that modifications occurring during pregnancy are accompanied by variations of bcl-2 protein.
Subject(s)
Pregnancy/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Female , Humans , Lipid Peroxides/metabolismABSTRACT
Interleukin-18 (IL-18) is a multifunctional cytokine which may play an important role in cancer. In previous studies it has been reported that mononuclear cells from breast cancer patients were defective in cytokine production. In this report we examined in vitro IL-18 release by monocytes (Mo) and differentiated monocytes (Mphi) for 6 or 12 days from healthy donors (HD) and nonmetastatic breast cancer (BCa) patients prior to chemo-, hormonal or radiotherapy. Our results show no production of this cytokine by Mo and Mphi for 6 days in all the experimental conditions. HD Mphi cultured for 12 days were responsive to lipopolysaccharides only after 24 h of treatment, while significantly (p<0.05) lower amounts of IL-18 were produced by BCa Mphi cultures in the same experimental conditions. Since BCa Mphi are defective in IL-18 production, and this cytokine elicits in vivo protective antitumor effects, we hypothesize a future possibility for the use of IL-18 in cancer therapy.
Subject(s)
Breast Neoplasms/pathology , Interleukin-18/biosynthesis , Monocytes/metabolism , Aged , Breast Neoplasms/metabolism , Cell Differentiation , Female , Humans , Middle AgedABSTRACT
We evaluated blood concentrations of bcl-2, a proto-oncogene that can inhibit apoptotic phenomena, in a group of patients with immunoglobulin A (IgA) nephropathy. Concentrations of bcl-2 were higher in patients with proteinuria than in those without proteinuria. A 6-month course of 5 mg/day lisinopril given to subjects with proteinuria significantly reduced blood bcl-2 concentrations and caused a reduction in proteinuria. Therefore increased blood bcl-2 concentrations may be considered an index of risk in subjects with IgA nephropathy, and the positive effects of angiotensin-converting enzyme inhibitors on proteinuria in patients with IgA nephropathy may be attributed, at least in part, to their effect on the mechanisms that regulate apoptosis. This is of fundamental importance in resolving glomerular hypercellularity in the course of glomerulonephritis.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Genes, bcl-2/drug effects , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, IGA/genetics , Lisinopril/pharmacology , Proteinuria/drug therapy , Proteinuria/genetics , Adult , Apoptosis , Female , Glomerulonephritis, IGA/blood , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/pathology , Humans , Male , Middle Aged , Proteinuria/blood , Proteinuria/etiology , Proteinuria/pathology , Proto-Oncogene Mas , Treatment OutcomeABSTRACT
OBJECTIVE: To evaluate the relationship between plasma leptin and the tumor necrosis factor-alpha (TNFalpha), TNF receptor p60 (TNF-R1) and TNF receptor p80 (TNF-R2) concentrations in obese subjects. DESIGN: Case-control study. SETTING: Outpatient's Service for Prevention and Treatment of Obesity at the University Hospital. MEASUREMENTS: Body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio (WHR), fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance (HOMA IR), plasma leptin, TNFalpha, TNF-R1 and TNF-R2 concentrations were evaluated in obese subjects (n = 42) and in age- and gender-matched, lean healthy controls (n = 16). RESULTS: In obese subjects, fasting plasma glucose and insulin, HOMA IR, plasma leptin, TNFalpha, TNF-R1 and TNF-R2 concentrations were significantly higher than in controls. Furthermore, females showed higher leptin, TNF-R1 and TNF-R2 plasma concentrations compared to males, in both control and obese subjects. In control subjects, plasma leptin concentrations showed a direct correlation with BMI (r=0.74, P<0.001), hip circumference (r=0.94, P<0.001), TNF-R1 (r=0.79, P<0.001) and TNF-R2 (r=0.64, P<0.01), and a negative correlation with WHR (r=-0.58, P<0.05). In obese subjects, we found a direct correlation between plasma leptin concentrations and BMI (r=0.67, P<0.001), hip circumference (r=0.66, P<0.001), fasting glucose (r=0.37, P<0.05), fasting insulin (r=0.31, P<0.05), HOMA IR (r=0.38, P<0.05), TNF-R1 (r=0.71, P<0.001) and TNR-R2 (r=0.66, P<0.001), while a negative correlation was found between circulating leptin and WHR (r=-0.44, P<0.01). In multivariate analysis, plasma leptin concentrations were significantly associated with BMI (P=0.015) and gender (P=0.047) in the control group, while in obese subjects, plasma leptin showed a significant association with BMI (P=0.019) and TNF-R1 (P=0.012). CONCLUSIONS: Our results are consistent with the hypothesis that the TNFalpha system could be involved in the regulation of plasma leptin concentrations in obese subjects.
Subject(s)
Obesity/blood , Proteins/metabolism , Tumor Necrosis Factor-alpha/metabolism , Adult , Antigens, CD/blood , Blood Glucose/analysis , Body Constitution , Body Mass Index , Case-Control Studies , Fasting , Female , Humans , Insulin/blood , Insulin Resistance , Leptin , Linear Models , Male , Receptors, Leptin , Receptors, Tumor Necrosis Factor/blood , Receptors, Tumor Necrosis Factor, Type I , Receptors, Tumor Necrosis Factor, Type IIABSTRACT
In 30 patients with essential hypertension and 30 healthy control subjects, we evaluated blood concentrations of B cell leukemia-2 (bcl-2), a protooncogene that can reduce apoptosis. Bcl-2 concentrations were higher in hypertensive than in normotensive subjects. The increase in pressure due to a cold pressor test caused a further increase in blood bcl-2 concentrations, in both hypertensive and normotensive subjects. Treatment of hypertensive patients with hypotensive drugs caused a reduction in bcl-2 concentrations, which was more marked after administration of lisinopril than of nifedipine. The results suggest that concentrations of bcl-2 are increased in patients with hypertension, which could be an important factor in cell proliferation underlying posthypertensive vascular remodeling. Moreover, lisinopril and nifedipine appear to be capable of reducing bcl-2 concentrations, with potentially beneficial effects on vascular modifications in patients with hypertension.
Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/blood , Lisinopril/therapeutic use , Nifedipine/therapeutic use , Proto-Oncogene Proteins c-bcl-2/blood , Vasodilator Agents/therapeutic use , Administration, Oral , Antihypertensive Agents/administration & dosage , Apoptosis/drug effects , Arteries/drug effects , Arteries/pathology , Biomarkers/blood , Blood Pressure/drug effects , Cell Division/drug effects , Cross-Over Studies , Double-Blind Method , Female , Follow-Up Studies , Humans , Hypertension/drug therapy , Hypertension/pathology , Lisinopril/administration & dosage , Lymphocyte Count/drug effects , Male , Middle Aged , Nifedipine/administration & dosage , Proto-Oncogene Proteins c-bcl-2/drug effects , Vasodilator Agents/administration & dosageABSTRACT
The beneficial effect of ACE inhibitors on cardiovascular remodelling from hypertension and ischemic disease may be due to the effect of these drugs on the proliferation/cell death balance. We therefore investigated the effect of the addition of captopril in vitro, on the onset of apoptosis in human vascular myocytes, by using a propidium iodide fluorescence analysis and a morphological analysis using the acridine orange technique. Captopril (0.23 mM) caused an increase in apoptotic phenomena that was more than 3. 5-fold than in controls both at the 24th (7.7 vs. 2%) and the 48th h (10.1 vs. 3.8%). The addition of propranolol strengthened the effect on apoptosis. The induction of apoptotic phenomena may be a mechanism by which ACE inhibitors affect cardiovascular remodelling and it might also explain the favorable effect these drugs have on diseases such as IgA nephropathy and diabetic nephropathy.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Apoptosis/drug effects , Captopril/pharmacology , Adrenergic beta-Antagonists/pharmacology , Cells, Cultured , Femoral Artery/cytology , Femoral Artery/drug effects , Flow Cytometry , Humans , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/drug effects , Propranolol/pharmacologyABSTRACT
OBJECTIVE: To study transforming growth factor-beta1 (TGF-beta1) plasma concentrations in elderly patients with nonthyroidal illnesses (NTI). DESIGN: Case-control study. METHODS: We measured plasma concentrations of tri-iodothyronine (T3), reverse T3 (rT3), thyroxine (T4), free T3 (fT3) and free T4 (fT4) estimates, TSH, and TGF-beta1 in 48 elderly NTI patients consecutively admitted in our Division of Internal Medicine and Metabolic Diseases, and in 11 healthy age- and sex-matched controls. RESULTS: The data on thyroid hormones enabled us to identify three groups: Group A, subjects (8 patients) with T3 and fT3 levels comparable to those in controls: Group B, subjects (30 patients) with T3 and fT3 levels lower than controls but rT3 levels comparable to those of controls; Group C, subjects (10 patients) with T3 and fT3 levels lower than those of controls and higher rT3 levels. The patients of Group C showed higher plasma levels of TGF-beta1 compared with controls. Moreover, we found a positive correlation between TGF-beta1 and rT3 (rs = 0.38, P < 0.01) in the whole group of NTI patients. CONCLUSIONS: Our data seem to confirm the hypothesis that TGF-beta1 could play a role in the pathogenesis of some modifications of thyroid function observed in patients with nonthyroidal illnesses.
Subject(s)
Thyroid Diseases/blood , Transforming Growth Factor beta/blood , Triiodothyronine/blood , Aged , Case-Control Studies , Female , Humans , Male , Osmolar Concentration , Reference Values , Triiodothyronine, Reverse/bloodABSTRACT
In patients with essential hypertension, elevated soluble E-selectin (sE-selectin) levels may indicate endothelial cell injury or activation. We therefore sought to ascertain whether arterial blood pressure increased by the cold pressor test can modify serum concentrations of sE-selectin and other soluble forms of adhesion molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), or the expression of any adhesion molecules in circulating monocytes and lymphocytes. Our findings show that levels of sE-selectin, sVCAM-1, and sICAM-1 are higher in patients with essential hypertension than in normotensive subjects (sICAM-1, 380 +/- 52 versus 262 +/- 96 ng/mL, P<.05; sVCAM-1, 720 +/- 52 versus 625 +/- 38 ng/mL, P<.05; and sE-selectin, 75 +/- 21 versus 61 +/- 22 ng/mL, P<.05). Furthermore, in normotensive and hypertensive patients, the cold pressor test caused an increase in serum concentrations of sICAM-1, sVCAM-1, and sE-selectin, but it did not cause changes in the expression of adhesion molecules in circulating monocytes and lymphocytes. High arterial blood pressure may therefore increase the production of serum adhesion molecules, probably through endothelial activation.
Subject(s)
Blood Pressure Determination/methods , Blood Pressure/physiology , Cold Temperature , E-Selectin/blood , Hypertension/blood , Intercellular Adhesion Molecule-1/blood , Vascular Cell Adhesion Molecule-1/blood , Female , Humans , Hypertension/physiopathology , Lymphocytes/metabolism , Male , Middle Aged , Monocytes/metabolism , Osmolar Concentration , Reference ValuesABSTRACT
The serum vascular adhesion molecule ICAM-1 that is involved in atherogenesis was determined in fertile, postmenopausal and at term pregnant women. The aim of the study was to ascertain if the antiatherogenic estrogens action may involve this adhesion molecule. The serum ICAM-1 concentrations resulted similar in the three groups studied: 331 +/- 35 ng/ml, 333 +/- 28 ng/ml and 302 +/- 53 ng/ml in fertile, postmenopausal and pregnant subjects respectively, despite the very different estrogen plasma levels. These data, the first on the ICAM-1 serum levels in women with different natural hormonal milieu, demonstrate that estrogens antiatherogenic action is not involving ICAM-1.