Differential structural features in soleus and gastrocnemius of carnitine-treated cancer cachectic rats.

Muscle wasting is associated with chronic diseases and cancer. Elucidation of the biological mechanism involved in the process of muscle mass loss and cachexia may help identify therapeutic targets. We hypothesized that l-carnitine treatment may differentially revert muscle fiber atrophy and other structural alterations in slow- and fast-twitch limb muscles of rats bearing the Yoshida ascites hepatoma. In soleus and gastrocnemius of tumor-bearing rats (108 AH-130 Yoshida ascites hepatoma cells inoculated intraperitoneally) with and without treatment with l-carnitine (1 g/kg body weight for 7 days, intragastric), food intake, body and muscle weights, fiber typing and morphometry, morphological features, redox balance, autophagy and proteolytic, and signaling markers were explored. Levels of carnitine palmitoyl transferase were also measured in all the study muscles. l-Carnitine treatment ameliorated the atrophy of both slow- and fast-twitch fibers (gastrocnemius particularly), muscle structural alterations (both muscles), and attenuated oxidative stress, proteolytic and signaling markers (gastrocnemius). Despite that carnitine palmitoyl transferase-1 levels increased in both muscle types in a similar fashion, l-carnitine ameliorated muscle atrophy and proteolysis in a muscle-specific manner in cancer-induced cachexia. These data reveal the need to study muscles of different fiber type composition and function to better understand whereby l-carnitine exerts its beneficial effects on the myofibers in muscle wasting processes. These findings also have potential clinical implications, since combinations of various exercise and muscle training modalities with l-carnitine should be specifically targeted for the muscle groups to be trained.

Effects of a mini-trampoline rebounding exercise program on functional parameters, body composition and quality of life in overweight women.

BACKGROUND: Mini-trampoline rebounding exercise (MRE) is becoming a very popular form of fitness training. Despite awareness of this activity worldwide, a limited number of studies have systematically investigated the health effects correlated with MRE training. The aim of our study was to evaluate manifold health outcomes after 12 weeks of an MRE program in a group of overweight Italian women. METHODS: Eighteen overweight women (age 38.05±10.5 years, BMI: 27.6±2.1 kg/m2) were enrolled in this study. Functional profile, strength, body composition, quality of life and pain intensity were assessed at baseline and after 12 weeks of MRE. RESULTS: Significant improvements were observed in the measurements of anthropometric profile and body composition (circumferences, fat mass, lean and muscular mass). Both a significant decrease in systolic and diastolic blood pressure values (from 128/80.5 to 123/71 mmHg, P<0.05) and an improvement in lipid and glucose profiles were observed. At maximal exercise testing, an increase in work capacity (from 104 to 123 watts, P=0.003) and VO2max (from 15.4 to 16.9 mL/kg/min, P=0.04) was found. SF-36 showed positive changes in four of the eight items as well as in the Mental Component Summary. With regard to the Brief Pain Inventory-SF, a decrease in both pain severity and the pain interference score was detected. CONCLUSIONS: MRE appears feasible to ensure positive effects on overall health and can be proposed to populations that could greatly benefit from training programs, such as overweight women.

Antimicrobial sulfonamides clear latent Kaposi sarcoma herpesvirus infection and impair MDM2-p53 complex formation.

Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8, is the causative agent of Kaposi sarcoma; this malignant angiosarcoma is usually treated with conventional antitumor agents that can control disease evolution, but do not clear the latent KSHV episome that binds to cellular DNA. Some commercial antibacterial sulfonamides were tested for the ability to suppress latent KSHV. Quantitative PCR (qPCR) and cytofluorometry assays were used for detecting both viral DNA and the latency factor LANA (latency-associated nuclear antigen) in BC3 cells, respectively. The capacity of sulfonamides to impair MDM2-p53 complex formation was detected by an enzyme-linked immunosorbent assay method. The analysis of variance was performed according to one-way analysis of variance with Fisher as a post hoc test. Here we show that sulfonamide antibiotics are able to suppress the KSHV latent state in permanently infected BC3 lymphoma cells and interfere with the formation of the MDM2-p53 complex that KSHV seemingly needs to support latency and to trigger tumor cell transformation. These findings detected a new molecular target for the activity of sulfonamides and offer a new potential perspective for treating KSHV-induced lymphoproliferative diseases.

Validation of the CAchexia SCOre (CASCO). Staging Cancer Patients: The Use of miniCASCO as a Simplified Tool.

The CAchexia SCOre (CASCO) was described as a tool for the staging of cachectic cancer patients. The aim of this study is to show the metric properties of CASCO in order to classify cachectic cancer patients into three different groups, which are associated with a numerical scoring. The final aim was to clinically validate CASCO for its use in the classification of cachectic cancer patients in clinical practice. We carried out a case -control study that enrolled prospectively 186 cancer patients and 95 age-matched controls. The score includes five components: (1) body weight loss and composition, (2) inflammation/metabolic disturbances/immunosuppression, (3) physical performance, (4) anorexia, and (5) quality of life. The present study provides clinical validation for the use of the score. In order to show the metric properties of CASCO, three different groups of cachectic cancer patients were established according to the results obtained with the statistical approach used: mild cachexia (15 ≤ × ≤ 28), moderate cachexia (29 ≤ × ≤ 46), and severe cachexia (47 ≤ × ≤ 100). In addition, a simplified version of CASCO, MiniCASCO (MCASCO), was also presented and it contributes as a valid and easy-to-use tool for cachexia staging. Significant statistically correlations were found between CASCO and other validated indexes such as Eastern Cooperative Oncology Group (ECOG) and the subjective diagnosis of cachexia by specialized oncologists. A very significant estimated correlation between CASCO and MCASCO was found that suggests that MCASCO might constitute an easy and valid tool for the staging of the cachectic cancer patients. CASCO and MCASCO provide a new tool for the quantitative staging of cachectic cancer patients with a clear advantage over previous classifications.

[Cancer cachexia assessment: new tools for oncologists.] / La valutazione della cachessia neoplastica nella pratica clinica: nuovi strumenti per l'oncologo.

The cancer anorexia-cachexia syndrome (CACS) is considered a multifactorial syndrome that leads a general decline of the cancer patient conditions, prognosis and survival, and characterized by progressive loss of body mass and functional impairment, due to marked energy metabolism imbalance and immunological disorders. It is the cause of death in almost one out of five advanced cancer patients. CACS is also accompanied with loss of quality of life, reduced response and tolerance to anticancer therapies and affected outcome. This condition arises by acute-chronic inflammation, hypercatabolism and resulting in an increased energy expenditure, anorexia and negative caloric balance. Although the international scientific community has reached some important findings in last years regarding CACS, a precise definition agreement for CACS in order to a precise patients assessment is still lacking. In light of the advances in pathogenesis and evaluation of CACS, as well as those reached in the therapy, this review aims to draft a list of key points that could be useful for the oncologist to recognize the different signs and symptoms of this syndrome, in order to evaluate and stage the cancer patients in attempt to target an early multimodal pharmacological-nutritional treatment strategy to improve his outcome and his quality of life.

Cardiovascular effects, body composition, quality of life and pain after a Zumba fitness program in Italian overweight women.

BACKGROUND: The aim of this paper was to investigate the cardiovascular effects, body composition, quality of life and pain after a 12-week Zumba fitness program in a group of overweight women through an observational study, community physical activity program involving twenty-seven overweight women (38.9±9.7 years). METHODS: Cardiometabolic profile, body composition, quality of life and pain were assessed after a 12-week Zumba fitness program. RESULTS: Significant improvements in body weight and BMI (71.5 vs. 74.2 kg, 28.02 vs. 29.1 kg/m²), in circumferences (arm: 27.9 vs. 30.3, waist: 80.1 vs. 83.9, hip: 102 vs. 107.4 cm), in fat and muscular mass (25.2 vs. 26.9, 34.4 vs. 27.2 kg), in intracellular (19 vs. 17.5 kg), and in extracellular water (14.9 vs. 16.8 kg) were recorded. A decrease in blood pressure was observed (118.3/69.4 vs. 125/75.5 mmHg). Cardiovascular response to the maximal exercise test showed a decrease in heart rate and in systolic blood pressure with an increase of work (118.9 vs. 116.7 watt). SF-36 showed variations in physical functioning (99.4 vs. 92.8) and in the limitation on the emotional role (88.9 vs. 66.6). With regards the Brief Pain Inventory-SF, a decrease in pain severity and pain interference score was seen (0.5 vs. 1.6, 0.06 vs. 0.5). CONCLUSIONS: Results demonstrate that Zumba fitness can be an effective way to obtain beneficial health effects and that it can also be recommended for overweight women.

High-density lipoprotein contribute to G0-G1/S transition in Swiss NIH/3T3 fibroblasts.

High density lipoproteins (HDLs) play a crucial role in removing excess cholesterol from peripheral tissues. Although their concentration is lower during conditions of high cell growth rate (cancer and infections), their involvement during cell proliferation is not known. To this aim, we investigated the replicative cycles in synchronised Swiss 3T3 fibroblasts in different experimental conditions: i) contact-inhibited fibroblasts re-entering cell cycle after dilution; ii) scratch-wound assay; iii) serum-deprived cells induced to re-enter G1 by FCS, HDL or PDGF. Analyses were performed during each cell cycle up to quiescence. Cholesterol synthesis increased remarkably during the replicative cycles, decreasing only after cells reached confluence. In contrast, cholesteryl ester (CE) synthesis and content were high at 24 h after dilution and then decreased steeply in the successive cycles. Flow cytometry analysis of DiO-HDL, as well as radiolabeled HDL pulse, demonstrated a significant uptake of CE-HDL in 24 h. DiI-HDL uptake, lipid droplets (LDs) and SR-BI immunostaining and expression followed the same trend. Addition of HDL or PDGF partially restore the proliferation rate and significantly increase SR-BI and pAKT expression in serum-deprived cells. In conclusion, cell transition from G0 to G1/S requires CE-HDL uptake, leading to CE-HDL/SR-BI pathway activation and CEs increase into LDs.

Effects of a Nordic Walking program on motor and non-motor symptoms, functional performance and body composition in patients with Parkinson's disease.

BACKGROUND: Several studies have clearly shown that physical exercise can reduce the progression of motor symptoms in Parkinson's Disease (PD). However, little is known about the effects of a Nordic Walking (NW) program in PD patients. OBJECTIVE: To determine the effects of a NW program on motor and non-motor symptoms, functional performances and body composition in PD patients. METHODS: Twenty PD patients (16M, 4F, 67.3±7.8 years) were enrolled and randomly assigned to NW group (NWg, n = 10) and Control group (Cg, n = 10). The training consisted in 2 sessions per week for 12 weeks. Training effects were assessed by functional and instrumental tests and motor and non-motor symptoms were assessed by UPDRS-III, Hoehn and Yahr scale, PD Fatigue Scale, Beck Depression Inventory-II, Starkstein Apathy Scale, and Non-Motor Symptoms Scale. RESULTS: Significant changes in resting HR, in walked distance (p <  0.05), and in lower limbs muscles strength (p <  0.005) were observed in NWg. Both balance abilities and safety with mobility were increased (p <  0.005). Significant variations in some circumferences and body composition were registered. Finally, a significant improvement in motor and non-motor symptoms was detected: UPDRS-III, HY scale, PFS-16, BDI-II, SAS, NMSS. CONCLUSIONS: A tailored exercise program including NW proved to be an effective way to improve daily activities and both motor and non-motor symptoms in PD patients.

Effects of an adapted physical activity program on motor and non-motor functions and quality of life in patients with Parkinson's disease.

BACKGROUND: Several studies have clearly shown that strategies of health promotion, such as fitness and general exercise programs, may improve quality of life (QoL), motor and non-motor functions in Parkinson's disease (PD) patients. However, little is known about the effects of specific Adapted Physical Activity (APA) programs on PD patients. OBJECTIVE: To determine the effects of an APA program on motor and non-motor symptoms, functional performances and QoL in PD patients. METHODS: Nine consecutive PD patients (5 men, 4 women, 64.4 ± 6.8 years) able to ambulate independently (Hoehn and Yahr: from stage 1 to 3) and not demented, were enrolled. Patients performed an APA program, 3 sessions/week, for 9 weeks. Exercises focused on balance, walking, strength and functional activities. Functional effects were assessed by Six Minute Walking Test (6MWT), Five Time Sit to Stand Test (FTSST), Berg Balance Scale (BBS), Sit and Reach Test (SRT), and Timed Up and Go test (TUG). Motor impairment and disability were assessed using the Unified Parkinson's Disease Rating Scale - part III (UPDRS-III) and the Hoehn and Yahr Scale, respectively. Non-motor symptoms were evaluated by PD Fatigue Scale (PFS), Beck Depression Inventory II (BDI-II) and PD Quality of life scale, 8 items (PDQ-8). RESULTS: A significant decrease in resting HR (67.55 ± 10.85 vs 70.22 ± 12.34 bpm, p < 0.05) and a significant increase in walked distance (p < 0.0005) were observed. A significant impairment of the muscles strength was noted (FTSST, p < 0.05). BBS showed a significant increase in balance abilities (p < 0.0005) and safety with mobility (TUG, p < 0.005) was enhanced. Finally, a significant improvement in motor and non-motor symptoms was detected: UPDRS-III (p < 0.00005), PFS (p < 0.005), BDI-II (p < 0.05) and PDQ-8 (p < 0.05). CONCLUSIONS: A tailored exercise program in PD patients could be effective as an adjunct to conventional therapy on improving daily activities, motor and non-motor symptoms, with better QoL.

L-Carnitine: an adequate supplement for a multi-targeted anti-wasting therapy in cancer.

BACKGROUND & AIMS: Tumour growth is associated with weight loss resulting from both adipose and muscle wasting. METHODS: Administration of L-carnitine (1 g/kg body weight) to rats bearing the AH-130 Yoshida ascites hepatoma, a highly cachectic rat tumour. RESULTS: The treatment results in a significant improvement of food intake and in muscle weight (gastrocnemius, EDL and soleus). These beneficial effects are directly related to improved physical performance (total physical activity, mean movement velocity and total travelled distance). Administration of L-carnitine decreases proteasome activity and the expression of genes related with this activity, such as ubiquitin, C8 proteasome subunit and MuRF-1. Interestingly, L-carnitine treatment also decreases caspase-3 mRNA content therefore suggesting a modulation of apoptosis. Moreover, addition of 50 µM of L-carnitine to isolated EDL muscles results in a significant decrease in the proteolytic rate suggesting a direct effect. CONCLUSIONS: It can be concluded that L-carnitine supplementation may be a good approach for a multi-targeted therapy for the treatment of cancer-related cachexia.

Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib ± megestrol acetate for patients with cancer-related anorexia/cachexia syndrome.

BACKGROUND & AIMS: A phase III, randomized non-inferiority study was carried out to compare a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib ± megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total daily physical activity. Secondary endpoint was: increase of physical performance tested by grip strength and 6-min walk test. METHODS: Sixty eligible patients were randomly assigned to: arm 1, L-carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, L-carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months. Planned sample size was 60 patients. RESULTS: The results did not show a significant difference between tre atment arms in both primary and secondary endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) increased significantly in both arms as well as physical performance assessed by 6MWT. Toxicity was quite negligible and comparable between arms. CONCLUSIONS: The results of the present study showed a non-inferiority of arm 1 (two-drug combination) vs arm 2 (two-drug combination + megestrol acetate). Therefore, this simple, feasible, effective, safe, low cost with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS treatment.

The cachexia score (CASCO): a new tool for staging cachectic cancer patients.

BACKGROUND: According to a recent consensus, the cachectic syndrome is defined as: "… a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass. The prominent clinical feature of cachexia is weight loss in adults (corrected for fluid retention) or growth failure in children (excluding endocrine disorders). Anorexia, inflammation, insulin resistance, and increased muscle protein breakdown are frequently associated with cachexia." Although this definition is accompanied by diagnostic criteria, it does not consider the problem of staging. Stratification of patients is important when considering therapy. The very first stage of the wasting syndrome does not necessarily involve body weight loss-a state known as pre-cachexia. METHODS AND RESULTS: The aim of the present score was to overcome the problem of patient staging in cancer. This score considers five main different factors: body weight and lean body mass loss; anorexia; inflammatory, immunological, and metabolic disturbances; physical performance; and quality of life. The scoring scale goes from 0 to 100: mild cachexia (less than 25), moderate (more than 26 and less than 50), severe (more than 51 and less than 75), and terminal phase (more than 76 and up to 100). The score also takes into consideration the condition known as pre-cachexia. CONCLUSION: The present score will facilitate cachexia staging and will therefore allow for a more adequate therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13539-011-0027-5) contains supplementary material, which is available to authorized users.

Cancer cachexia: physical activity and muscle force in tumour-bearing rats.

Rats bearing the Yoshida AH-130 ascites hepatoma are subjected to substantial weight loss, which is accompanied by anorexia at the end of the tumour cycle. Total physical activity (measured using the IR Actimeter system and Actitrack software) was determined during 11 days in control and tumour-bearing animals, skeletal muscle strength being also by the grip-strength test. The results presented clearly show that the presence of the tumour induces an earlier decrease in physical performance, which affects both skeletal muscle force and physical activity (both locomotor movements and stereotyped movements and distance travelled, among others parameters).

Formoterol and cancer muscle wasting in rats: Effects on muscle force and total physical activity.

Cancer cachexia occurs in the majority of cancer patients before death, and it is responsible for the death of 22% of cancer patients. One of the most relevant characteristics of cachexia is that of asthenia, which reflects significant muscle wasting noted in cachectic cancer patients The aim of the present study was to assess whether the ß(2)-adrenergic agonist formoterol is associated with an improvement in physiological parameters such as grip force and total physical activity in cachetic rats. Administration of the ß(2)-agonist formoterol (0.3 mg/kg for 7 days) in rats bearing Yoshida AH-130 ascites hepatoma tumors, a model which induces a strong loss of both body and muscle weight, resulted in a significant reversal of the muscle wasting process, as reflected by individual muscle weights. The anti-wasting effects of the drug were also observed in terms of total physical activity and grip force, thus resulting in an improvement in physical performance in cachectic tumor-bearing rats.

Megestrol acetate: its impact on muscle protein metabolism supports its use in cancer cachexia.

BACKGROUND & AIMS: Cachexia is a multiorganic syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting and inflammation, being often associated with anorexia. The aim of the present investigation was to examine the effect of megestrol acetate (MA) in cachectic tumour-bearing animals analyzing changes in muscle proteolysis and in parameters related with quality of life. METHODS: The effects of MA (100mg/kg) were tested in cachectic tumour-bearing rats (Yoshida AH-130 ascites hepatoma). RESULTS: Administration of MA to tumour-bearing rats resulted in an important reversal of the muscle wasting process, as reflected by individual muscle weights. MA also decreased the rate of protein degradation in incubated isolated skeletal muscles. Real-time PCR analysis revealed that MA treatment resulted in a decrease in ubiquitin, E2 and atrogin-1 mRNA content in muscles, therefore suggesting that the main anti-proteolytic action of the drug may be based on an inhibition of the ATP-ubiquitin-dependent proteolytic system. The drug also improves appetite, weight loss, total physical activity and grip force. CONCLUSIONS: The results indicate that treatment with megestrol acetate increases appetite, weight loss, physical performance and muscle force in tumour-bearing rats suggesting that MA is a good candidate for muscle wasting treatment.

Improvement of physical activity as an alternative objective variable to measure treatment effects of anticachexia therapy in cancer patients.

PURPOSE OF REVIEW: The purpose of this review is to provide an update of physical activity improvement as an alternative objective variable to measure treatment effects of anticachexia therapy in cancer patients. The assessment of physical activity level as an outcome measure for cachexia studies is attractive as it offers a patient-centered outcome concerned with functional status and independence. RECENT FINDINGS: We present and review the most relevant recent clinical studies regarding the significance of physical activity in the context of the assessment of anticachexia treatment effects. Moreover, we have highlighted, on the basis of our recent phase III clinical trial on anticachexia treatment, the added value of correlating physical activity with the most common variables of cancer-related anorexia/cachexia syndrome. SUMMARY: We believe that presently, and even more so in the near future, the consistent application of objective, patient-centered endpoints in cachexia trials, such as physical activity monitoring, may provide an additional significant and useful tool for the evaluation of outcomes of medical interventions in cancer cachexia.

Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia.

PURPOSE: A phase III, randomized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia-lean body mass (LBM), resting energy expenditure (REE), and fatigue-and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines. PATIENTS AND METHODS: Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were randomly assigned to one of five treatment arms: arm 1, medroxyprogesterone (500 mg/day) or megestrol acetate (320 mg/day); arm 2, oral supplementation with eicosapentaenoic acid; arm 3, L-carnitine (4 g/day); arm 4, thalidomide (200 mg/day); and arm 5, a combination of the above. Treatment duration was 4 months. RESULTS: Analysis of variance showed a significant difference between treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern Cooperative Oncology Group performance status (ECOG PS) score decreased significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was comparable between arms. CONCLUSION: The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS, and ECOG PS score was the combination regimen that included all selected agents.

Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia.

Chronic inflammation is one of the main features of cancer cachexia. Experimental and clinical studies showed that cyclooxygenase-2 inhibitors, such as celecoxib, may be beneficial in counteracting major symptoms of this devastating syndrome. We carried out a prospective phase II clinical trial to test the safety and effectiveness of an intervention with the COX-2 inhibitor celecoxib (300 mg/day for 4 months) on key variables of cachexia (lean body mass, resting energy expenditure, serum levels of proinflammatory cytokines, and fatigue) in patients with advanced cancer at different sites. A sample of 24 patients was enrolled from January to December 2008 and all were deemed assessable. A significant increase of lean body mass and a significant decrease of TNF-alpha were observed. Moreover, an improvement of grip strength, quality of life, performance status, and Glasgow prognostic score was shown. There were no grade 3/4 toxicities. Patient compliance was very good; no patient had to reduce the celecoxib dosage nor interrupt treatment. Our results showed that the COX-2 selective inhibitor celecoxib is an effective single agent for the treatment of cancer cachexia. Although the treatment of cancer cachexia, a multifactorial syndrome, is more likely to yield success with a multitargeted approach; in the present study, we were able to show that a treatment, such as celecoxib, addressing a single target, albeit very important as chronic inflammation, could have positive effects. Therefore, phase III clinical trials are warranted to test the efficacy and safety of celecoxib.

Persistence, up to 18 months of follow-up, of epirubicin-induced myocardial dysfunction detected early by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers.

A phase II, open, nonrandomized trial was carried out in a group of epirubicin-treated cancer patients with the aim of detecting early preclinical changes that are predictive of the risk for heart failure. Thirty-one patients (male/female ratio, 8/23; mean age +/- standard deviation, 59 +/- 14 years) with tumors at different sites and scheduled to be treated with an epirubicin-based chemotherapy regimen, were enrolled. We prospectively evaluated the acute (1 week after) and late (3, 6, 12, and 18 months of follow-up) effects of epirubicin administration. A significant impairment in systolic left ventricular (LV) function was observed at a cumulative epirubicin dose of 200 mg/m(2). This was shown by a reduction in the strain rate (SR) peak in comparison with baseline and persisted throughout the treatment and follow-up, up to 18 months; strain (Sigma) remained unchanged. The Sm wave showed a progressive reduction that became significant only at the 18-month follow-up. On TDI the E(m)/A(m) ratio declined at the 200-mg/m(2) cumulative epirubicin dose versus baseline and persisted throughout the treatment and up to the 18-month follow-up. On conventional echocardiography the E/A ratio declined significantly only at the 300-mg/m(2) cumulative epirubicin dose. Interleukin (IL)-6, soluble IL-6 receptor, and reactive oxygen species (ROS) increased significantly at the 200-mg/m(2) dose, and IL-6 was persistently high at the 300- and 400-mg/m(2) doses, returning to within baseline values during follow-up. ROS, after the peak reached at the 200-mg/m(2) dose, returned to within baseline values. A significant inverse correlation between DeltaSR and the increase in both IL-6 and ROS was observed. A multiple regression analysis showed that both the IL-6 and ROS variables were independent and strongly predictive of DeltaSR. The clinical meaningfulness of our findings warrants further investigations on a larger number of patients for a longer period of follow-up.

Assessment of adiponectin and leptin as biomarkers of positive metabolic outcomes after lifestyle intervention in overweight and obese children.

BACKGROUND: A number of metabolic changes are caused by childhood obesity, including insulin resistance, diabetes, and dyslipidemia. To counteract them, lifestyle modification with changes in dietary habits and physical activity is the primary intervention. Anthropometric parameters may not identify all positive changes associated with lifestyle modifications, whereas circulating adipokines may represent an alternative as biomarkers. The aim of this study was to evaluate adiponectin and leptin levels as markers of positive metabolic outcomes in childhood obesity. METHODS: Changes in clinical, anthropometric, and metabolic parameters, including adiponectin and leptin, were assessed in 104 overweight and obese children before and after 1 yr of lifestyle intervention. Obesity and overweight were defined according to the Italian body mass index reference tables for age and sex. Fifty-four normal-weight children were evaluated as controls. Forty-eight of the children (47.5%) returned for follow-up at 1 yr. RESULTS: Compared with normal-weight children, overweight and obese subjects differed significantly at baseline for glycemia, insulinemia, homeostasis model assessment for insulin resistance, adiponectinemia (5.8 vs. 18.2 microg/ml in controls), low-density lipoprotein-cholesterol, and triglycerides. These parameters were all higher in the overweight/obese children. At follow-up, most parameters improved in overweight/obese children. The most significant changes were observed in adiponectin concentration, which increased by 245% (P < 0.0001), reaching the levels observed in normal-weight children. Leptin levels showed changes unrelated to positive metabolic outcomes, remaining high at 1 yr of follow-up in overweight/obese children. Regardless of changes in weight status, children with lifestyle intervention reported changes in homeostasis model assessment for insulin resistance and in adiponectin that were associated with loss of fat mass. CONCLUSIONS: After lifestyle intervention, adiponectin increased regardless of changes in weight, whereas no consistent changes was observed in serum leptin. Therefore, circulating adiponectin may represent a good biomarker to evaluate the efficacy of lifestyle intervention in overweight/obese children.