WorldWideScience

Sample records for cachexia

  1. Cancer cachexia

    OpenAIRE

    Raghu Dhanapal; T R Saraswathi; N Govind Rajkumar

    2011-01-01

    Cancer cachexia is a wasting syndrome characterized by weight loss, anorexia, asthenia and anemia. The pathogenicity of this syndrome is multifactorial, due to a complex interaction of tumor and host factors. The signs and symptoms of cachexia are considered as the prognostic parameters in cancer patients. This review gives an emphasis on the various mechanisms involved in cachexia and an insight into head and neck cancer cachexia.

  2. Cachexia: a nutritional syndrome?

    OpenAIRE

    Anker, Stefan D.; Morley, John E.

    2015-01-01

    Cachexia leads to nutritional deficits including anorexia and loss of fat and muscle mass. In persons with precachexia or early cachexia, for example, old persons with weight loss and chronic obstructive pulmonary disease, there is strong evidence that nutritional support improves outcomes. Limited evidence suggests that this may be true for heart failure and chronic kidney disease. The evidence for nutritional support in refractory cachexia is, not surprisingly, less dramatic. It would appea...

  3. Pathophysiology of cancer cachexia

    OpenAIRE

    Younes Riad N.; Noguchi Yoshikazu

    2000-01-01

    Cancer cachexia is a frequent complication observed in patients with malignant tumors. Although several decades have passed since the first focus on the metabolic dysfunction's associated with cancer, few effective therapeutic interventions have been successfully introduced into the medical armamentarium. The present study thoroughly reviews the basic pathophysiology of cancer cachexia and the treatment options already investigated in that field. Experimental and clinical studies were evaluat...

  4. Animal models of cardiac cachexia.

    Science.gov (United States)

    Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

    2016-09-15

    Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. PMID:27317993

  5. Beneficial bacteria inhibit cachexia.

    Science.gov (United States)

    Varian, Bernard J; Goureshetti, Sravya; Poutahidis, Theofilos; Lakritz, Jessica R; Levkovich, Tatiana; Kwok, Caitlin; Teliousis, Konstantinos; Ibrahim, Yassin M; Mirabal, Sheyla; Erdman, Susan E

    2016-03-15

    Muscle wasting, known as cachexia, is a debilitating condition associated with chronic inflammation such as during cancer. Beneficial microbes have been shown to optimize systemic inflammatory tone during good health; however, interactions between microbes and host immunity in the context of cachexia are incompletely understood. Here we use mouse models to test roles for bacteria in muscle wasting syndromes. We find that feeding of a human commensal microbe, Lactobacillus reuteri, to mice is sufficient to lower systemic indices of inflammation and inhibit cachexia. Further, the microbial muscle-building phenomenon extends to normal aging as wild type animals exhibited increased growth hormone levels and up-regulation of transcription factor Forkhead Box N1 [FoxN1] associated with thymus gland retention and longevity. Interestingly, mice with a defective FoxN1 gene (athymic nude) fail to inhibit sarcopenia after L. reuteri therapy, indicating a FoxN1-mediated mechanism. In conclusion, symbiotic bacteria may serve to stimulate FoxN1 and thymic functions that regulate inflammation, offering possible alternatives for cachexia prevention and novel insights into roles for microbiota in mammalian ontogeny and phylogeny. PMID:26933816

  6. Pathophysiology of cancer cachexia

    Directory of Open Access Journals (Sweden)

    Riad N. Younes

    2000-10-01

    Full Text Available Cancer cachexia is a frequent complication observed in patients with malignant tumors. Although several decades have passed since the first focus on the metabolic dysfunction's associated with cancer, few effective therapeutic interventions have been successfully introduced into the medical armamentarium. The present study thoroughly reviews the basic pathophysiology of cancer cachexia and the treatment options already investigated in that field. Experimental and clinical studies were evaluated individually in order to clarify the intricate alterations observed in tumor-bearing patients. The difficulties in introducing sound and effective nutritional support or metabolic manipulation to reverse cancer cachexia are outlined in this review.A caquexia é uma complicação freqüentemente observada em pacientes portadores de tumores malignos. Apesar de várias décadas transcorrerem desde a descrição inicial das disfunções metabólicas associadas ao câncer, poucas medidas terapêuticas foram induzidas com sucesso na prática médica. O presente estudo apresenta uma revisão detalhada da fisiopatologia básica da caquexia em câncer, e as opções terapêuticas desenvolvidas nesta área. Estudos experimentais, assim como clínicos, são avaliados individualmente para esclarecer as alterações complexas observadas em pacientes portadores de tumores. As dificuldades encontradas para introduzir manipulações metabólicas e terapias de suporte nutricional eficientes são discutidas nesta revisão.

  7. Cachexia Syndrome, anorexia patient

    International Nuclear Information System (INIS)

    Introduction: Two thirds of patients (ptes) cancer present slimming recognized a negative prognostic factor. Anorexia cachexia syndrome (SCA) results from the interaction of multiple factors and causes death of 22% of these patients. Nutritional support produces a moderate recovery weight without affecting the underlying metabolic disorders. Objectives: Conduct a review of current knowledge of the underlying pathophysiology and management the cachexia-anorexia syndrome in cancer patients. Designing indications possible policy interventions in the management of these patients. Method: Performed an a literature review on SCA. Conclusions: We identify patients at risk for early implementation of non-pharmacological measures preventive. The control side effects to treatment oncospecific with particular attention to the need for antiemetics, laxatives / antidiarrheal control dental and proper pain management is fundamental. Keep track enteral is a priority. In those with swallowing disorders or dysphagia, nasogastric feeding tube should be considered early. Indications for gastrostomy / jejunostomy and total parenteral nutrition (TPN) are very limited. The NPT is a complementary treatment maneuver a temporary and reversible complication, in order to prevent deterioration

  8. Cancer cachexia, mechanism and treatment

    Institute of Scientific and Technical Information of China (English)

    Tomoyoshi Aoyagi; Krista P Terracina; Ali Raza; Hisahiro Matsubara; Kazuaki Takabe

    2015-01-01

    It is estimated that half of all patients with cancereventually develop a syndrome of cachexia, with anorexiaand a progressive loss of adipose tissue and skeletalmuscle mass. Cancer cachexia is characterized by systemicinflammation, negative protein and energy balance, andan involuntary loss of lean body mass. It is an insidioussyndrome that not only has a dramatic impact on patientquality of life, but also is associated with poor responsesto chemotherapy and decreased survival. Cachexia isstill largely an underestimated and untreated condition,despite the fact that multiple mechanisms are reported tobe involved in its development, with a number of cytokinespostulated to play a role in the etiology of the persistentcatabolic state. Existing therapies for cachexia, includingorexigenic appetite stimulants, focus on palliation ofsymptoms and reduction of the distress of patients andfamilies rather than prolongation of life. Recent therapiesfor the cachectic syndrome involve a multidisciplinaryapproach. Combination therapy with diet modificationand/or exercise has been added to novel pharmaceuticalagents, such as Megestrol acetate, medroxyprogesterone,ghrelin, omega-3-fatty acid among others. These agentsare reported to have improved survival rates as well asquality of life. In this review, we will discuss the emergingunderstanding of the mechanisms of cancer cachexia,the current treatment options including multidisciplinarycombination therapies, as well an update on new andongoing clinical trials.

  9. Treatment of cachexia in oncology

    Directory of Open Access Journals (Sweden)

    E M Tazi

    2010-01-01

    Full Text Available Background: Cachexia is a complex metabolic syndrome associated with many chronic or end-stage diseases, especially cancer, and is characterized by loss of muscle with or without loss of fat mass. The management of cachexia is a complex challenge that should address the different causes underlying this clinical event with an integrated or multimodal treatment approach targeting the different factors involved in its pathophysiology. Aims and Objectives : The purpose of this article was to review the current medical treatment of cancer-related cachexia, in particular focusing on combination therapy and ongoing research. Results : Among the treatments proposed in the literature for cancer-related cachexia, some proved to be ineffective, namely, cyproheptadine, hydrazine, metoclopramide, and pentoxifylline. Among effective treatments, progestagens are currently considered the best available treatment option for cancer-related cachexia, and they are the only drugs approved in Europe. Drugs with a strong rationale that have failed or have not shown univocal results in clinical trials so far include eicosapentaenoic acid, cannabinoids, bortezomib, and anti-TNF-alpha MoAb. Several emerging drugs have shown promising results but are still under clinical investigation (thalidomide, selective cox-2 inhibitors, ghrelin mimetics, insulin, oxandrolone, and olanzapine. Conclusions : To date, despite several years of coordinated efforts in basic and clinical research, practice guidelines for the prevention and treatment of cancer-related muscle wasting are lacking, mainly because of the multifactorial pathogenesis of the syndrome. From all the data presented, one can speculate that one single therapy may not be completely successful in the treatment of cachexia. From this point of view, treatments involving different combinations are more likely to be successful.

  10. Cancer Cachexia: Classification, Pathophysiology and Treatment

    OpenAIRE

    Solheim, Tora Skeidsvoll

    2014-01-01

    Cachexia is a very common condition in patients with cancer and it has detrimental effects on both mortality and morbidity. Cachexia is characterized by progressive unintentional loss of muscle mass, with or without loss of fat mass.When the work on this thesis started there was neither any efficient treatment available against cachexia nor a consensus on how to define or classify the condition. The overall aim of this thesis was to contribute to the improvement of classification and treatmen...

  11. Cancer Cachexia, Recent Advances, and Future Directions

    Science.gov (United States)

    Penet, Marie-France; Bhujwalla, Zaver M.

    2016-01-01

    Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass with or without loss of fat mass. The syndrome cannot be fully reversed by conventional nutritional support, and despite an increased number of studies related to cancer cachexia, the underlying mechanisms are still poorly defined and therapeutic options are limited. This review focuses on recent studies investigating mechanisms and pathways in cancer cachexia. The role of molecular and functional imaging in identifying cachexia at an earlier stage, in identifying potential metabolic targets and pathways, and in assessing treatment efficacy is also reviewed. PMID:25815852

  12. Cardiac cachexia: hic et nunc

    Science.gov (United States)

    Loncar, Goran; Springer, Jochen; Anker, Markus; Doehner, Wolfram

    2016-01-01

    Abstract Cardiac cachexia (CC) is the clinical entity at the end of the chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely, the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. A better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia, and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF. PMID:27386168

  13. Cardiac cachexia: hic et nunc.

    Science.gov (United States)

    Loncar, Goran; Springer, Jochen; Anker, Markus; Doehner, Wolfram; Lainscak, Mitja

    2016-06-01

    Cardiac cachexia (CC) is the clinical entity at the end of the chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely, the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. A better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia, and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF. PMID:27386168

  14. Liver and muscle protein metabolism in cachexia

    NARCIS (Netherlands)

    Peters, J.A.C.

    2009-01-01

    Up to 50% of cancer patients suffer from progressive weight loss (cachexia). Cachexia is induced by proinflammatory mediators (cytokines), induced by the tumor’s presence. These cytokines induce so-called acute phase protein synthesis by the liver, followed by skeletal muscle protein breakdown. Skel

  15. Cancer Cachexia: Muscle Physiology and Exercise Training

    Directory of Open Access Journals (Sweden)

    Matthew L. Goodwin

    2012-11-01

    Full Text Available Cachexia in cancer patients is a condition marked by severe tissue wasting and a myriad of quality of life and health consequences. Cachexia is also directly linked to the issues of morbidity and survivability in cancer patients. Therapeutic means of mitigating cachexia and its effects are thus critical in cancer patient treatment. We present a discussion on the use of physical exercise activities in the context of such treatment as a means to disruption the tissue wasting effects (i.e., muscle tissue losses via anorexigenic pro-inflammatory cytokines of cachexia. In addition we propose a theoretical model (Exercise Anti-Cachectic Hypothetical—“EACH” model as to how exercise training may promote a disruption in the cycle of events leading to advancing cachexia and in turn promote an enhanced functionality and thus improved quality of life in cancer patients.

  16. Malnutrition and Cachexia in Heart Failure.

    Science.gov (United States)

    Rahman, Adam; Jafry, Syed; Jeejeebhoy, Khursheed; Nagpal, A Dave; Pisani, Barbara; Agarwala, Ravi

    2016-05-01

    Heart failure is a growing public health concern. Advanced heart failure is frequently associated with severe muscle wasting, termed cardiac cachexia This process is driven by systemic inflammation and tumor necrosis factor in a manner common to other forms of disease-related wasting seen with cancer or human immunodeficiency virus. A variable degree of malnutrition is often superimposed from poor nutrient intake. Cardiac cachexia significantly decreases quality of life and survival in patients with heart failure. This review outlines the evaluation of nutrition status in heart failure, explores the pathophysiology of cardiac cachexia, and discusses therapeutic interventions targeting wasting in these patients. PMID:25634161

  17. Liver and muscle protein metabolism in cachexia

    OpenAIRE

    Peters, J.A.C.

    2009-01-01

    Up to 50% of cancer patients suffer from progressive weight loss (cachexia). Cachexia is induced by proinflammatory mediators (cytokines), induced by the tumor’s presence. These cytokines induce so-called acute phase protein synthesis by the liver, followed by skeletal muscle protein breakdown. Skeletal muscle protein breakdown seems to serve for providing amino acids (AA) for acute phase protein synthesis in the liver. The net effect of cytokines is a negative protein balance in the skeletal...

  18. Nonmuscle Tissues Contribution to Cancer Cachexia

    OpenAIRE

    Argilés, Josep M.; Britta Stemmler; López-Soriano, Francisco J.; Silvia Busquets

    2015-01-01

    Cachexia is a syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting, and inflammation, being often associated with anorexia. In spite of the fact that muscle tissue represents more than 40% of body weight and seems to be the main tissue involved in the wasting that occurs during cachexia, recent developments suggest that tissues/organs such as adipose (both brown and white), brain, liver, gut, and heart are directly involved in the cachectic pro...

  19. Nutritional Interventions for Cancer-induced Cachexia

    OpenAIRE

    Gullett, Norleena P.; Mazurak, Vera; Hebbar, Gautam; Ziegler, Thomas R

    2011-01-01

    Cancer-induced cachexia remains a significant cause of morbidity and mortality in cancer treatment. Cancer research and development continues at an aggressive pace and yet a degree of cancer-induced cachexia is experienced by up to 80% of advanced stage cancer patients. Unfortunately, there are no established treatment regimens for this condition. Weight loss and fatigue consistently appear in patient oncologic histories and progress notes. However, few oncologists fully understand the pathol...

  20. Nutrition in cachexia: from bench to bedside.

    Science.gov (United States)

    Konishi, Masaaki; Ishida, Junichi; von Haehling, Stephan; Anker, Stefan D; Springer, Jochen

    2016-05-01

    As malnutrition is often present in cachexia, nutritional intervention has been one of the widely accepted strategies. A literature review of cachexia models with dietary interventions in the present issue of this journal pointed out that the majority of nutrient intervention studies were of n-3 fatty acid, mainly eicosapentaenoic acid and docosahexaenoic acid. Effect on protein catabolism and anti-inflammation are most pronounced benefits of n-3 fatty acid. The effectiveness of n-3 fatty acid may depend on control diet or even be attributed to the polyunsaturated fatty acid deficiency inadvertently produced in control group. However, there is not enough clinical evidence to support a benefit of n-3 fatty acid substitution in patients with cachexia. The second important result from this review is that the majority of studies did not provide information about dietary design or did not standardize design, content, source, and overall composition. To guide dietary design for researchers in preclinical studies, a model has been proposed in this review, which may be useful to predict the efficacy of new dietary intervention in cachexia science. From a clinical point of view, the limited effectiveness of nutritional support in cachexia may partly be explained by the multifactorial nature of this condition. Cachexia differs from malnutrition inasmuch as malnutrition can be reversed by adequate nutrition and/or by overcoming problems of absorption or utilization of nutrients, but cachexia cannot be successfully treated by nutrition alone. Multidisciplinary approach including the assessment and intervention in feeding, appetite, swallowing, exercise, psychosocial, and psychological issue may be needed to improve nutrition in patients with cachexia. PMID:27030816

  1. Protein breakdown in cancer cachexia.

    Science.gov (United States)

    Sandri, Marco

    2016-06-01

    Skeletal muscle is a highly adaptive tissue, capable of altering muscle fiber size, functional capacity and metabolism in response to physiological stimuli. However, pathological conditions such as cancer growth compromise the mechanisms that regulate muscle homeostasis, resulting in loss of muscle mass, functional impairment and compromised metabolism. This tumor-induced condition is characterized by enhanced muscle protein breakdown and amino acids release that sustain liver gluconeogenesis and tissue protein synthesis. Proteolysis is controlled by the two most important cellular degradation systems, the ubiquitin proteasome and autophagy lysosome. These systems are carefully regulated by different signalling pathways that determine protein and organelle turnover. In this review we will describe the involvement of the ubiquitin proteasome and autophagy lysosome systems in cancer cachexia and the principal signalling pathways that regulate tumor-induced protein breakdown in muscle. PMID:26564688

  2. Adipokines and ghrelin in gastric cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    Mustafa Kerem; Zafer Ferahkose; Utku Tonguc Yilmaz; Hatice Pasaoglu; Ebru Ofluoglu; Abdulkadir Bedirli; Bulent Salman; Tevfik Tolga Sahin; Murat Akin

    2008-01-01

    AIM: To investigate the roles of the adipocytokines, ghrelin and leptin in gastric cancer cachexia.METHODS: Resistin, ghrelin, leptin, adiponectin, insulin and insulin-like growth factor (IGF-I), were measured in 30 healthy subjects, and 60 gastric cancer patients of which 30 suffered from cancer- induced cachexia and 30 served as a control group. The relationships between hormones, body mass index (BMI) loss ratio, age, gender, and Glasgow Prognostic Score (GPS) were investigated.RESULTS: Cachexia patients had higher tumor stage and GPS when compared with non-cachexia patients (P<0.05). Ghrelin, resistin, leptin, adiponectin and IGF-I, showed a significant correlation with BMI loss ratio and GPS (P < 0.05). A strong correlation was seen between GPS and BMI loss (R = -0.570, P < 0.0001). Multivariate analysis indicated that BMI loss was significantly independent as a predictor of ghrelin, resistin, leptin and IGF-I (P<0.05). Existence of an important significant relationship between resistin and insulin resistance was also noted.CONCLUSION: These results showed that serum ghrelin, leptin, adiponectin, and IGF-I play important roles in cachexia-related gastric cancers. No relationship was found between resistin and cancer cachexia. Also, because of the correlation between these parameters and GPS, these parameters might be used as a predictor factor.

  3. Omics/systems biology and cancer cachexia.

    Science.gov (United States)

    Gallagher, Iain J; Jacobi, Carsten; Tardif, Nicolas; Rooyackers, Olav; Fearon, Kenneth

    2016-06-01

    Cancer cachexia is a complex syndrome generated by interaction between the host and tumour cells with a background of treatment effects and toxicity. The complexity of the physiological pathways likely involved in cancer cachexia necessitates a holistic view of the relevant biology. Emergent properties are characteristic of complex systems with the result that the end result is more than the sum of its parts. Recognition of the importance of emergent properties in biology led to the concept of systems biology wherein a holistic approach is taken to the biology at hand. Systems biology approaches will therefore play an important role in work to uncover key mechanisms with therapeutic potential in cancer cachexia. The 'omics' technologies provide a global view of biological systems. Genomics, transcriptomics, proteomics, lipidomics and metabolomics approaches all have application in the study of cancer cachexia to generate systems level models of the behaviour of this syndrome. The current work reviews recent applications of these technologies to muscle atrophy in general and cancer cachexia in particular with a view to progress towards integration of these approaches to better understand the pathology and potential treatment pathways in cancer cachexia. PMID:26783720

  4. The wasting continuum in heart failure: from sarcopenia to cachexia.

    Science.gov (United States)

    von Haehling, Stephan

    2015-11-01

    Sarcopenia (muscle wasting) and cachexia share some pathophysiological aspects. Sarcopenia affects approximately 20 %, cachexia exercise training, appetite stimulants, essential amino acids, growth hormone, testosterone, electrical muscle stimulation, ghrelin and its analogues, ghrelin receptor agonists and myostatin antibodies. PMID:26264581

  5. Cancer cachexia-anorexia syndrome and skeletal muscle wasting

    OpenAIRE

    Jurdana, Mihaela

    2013-01-01

    Cachexia-anorexia syndrome is a common and important indicator of cancer. It occurs in 30% to 80% of cancer patients. Cachexia means "bad condition" and may be present in the early stages of tumor growth, before any signs of malignancy. Cancer cachexia is a syndrome of progressive body wasting, characterized by loss of adipose tissue and skeletal muscle mass. In most cancer patients, cachexia is characteriyed by anorexia, which implies a failure of food intake, regulated through a complex sys...

  6. Estimation of Cachexia among Cancer Patients Based on Four Definitions

    OpenAIRE

    Fox, Kathleen M; Brooks, John M.; Gandra, Shravanthi. R.; Richard Markus; Chiun-Fang Chiou

    2009-01-01

    Objectives. Estimate and compare the proportion of cancer patients with cachexia using different definitions from available clinical data. Methods. Electronic medical records were examined to estimate the proportion of cancer patients with cachexia using 4 definitions: (1) ICD-9 diagnostic code of 799.4 (cachexia), (2) ICD-9 diagnosis of cachexia, anorexia, abnormal weight loss, or feeding difficulties, (3) prescription for megestrol acetate, oxandrolone, somatropin, or dronabinol, and (4) ≥ ...

  7. STAT3 in the systemic inflammation of cancer cachexia.

    Science.gov (United States)

    Zimmers, Teresa A; Fishel, Melissa L; Bonetto, Andrea

    2016-06-01

    Weight loss is diagnostic of cachexia, a debilitating syndrome contributing mightily to morbidity and mortality in cancer. Most research has probed mechanisms leading to muscle atrophy and adipose wasting in cachexia; however cachexia is a truly systemic phenomenon. Presence of the tumor elicits an inflammatory response and profound metabolic derangements involving not only muscle and fat, but also the hypothalamus, liver, heart, blood, spleen and likely other organs. This global response is orchestrated in part through circulating cytokines that rise in conditions of cachexia. Exogenous Interleukin-6 (IL6) and related cytokines can induce most cachexia symptomatology, including muscle and fat wasting, the acute phase response and anemia, while IL-6 inhibition reduces muscle loss in cancer. Although mechanistic studies are ongoing, certain of these cachexia phenotypes have been causally linked to the cytokine-activated transcription factor, STAT3, including skeletal muscle wasting, cardiac dysfunction and hypothalamic inflammation. Correlative studies implicate STAT3 in fat wasting and the acute phase response in cancer cachexia. Parallel data in non-cancer models and disease states suggest both pathological and protective functions for STAT3 in other organs during cachexia. STAT3 also contributes to cancer cachexia through enhancing tumorigenesis, metastasis and immune suppression, particularly in tumors associated with high prevalence of cachexia. This review examines the evidence linking STAT3 to multi-organ manifestations of cachexia and the potential and perils for targeting STAT3 to reduce cachexia and prolong survival in cancer patients. PMID:26860754

  8. Biomarkers for cardiac cachexia: reality or utopia.

    Science.gov (United States)

    Martins, Telma; Vitorino, Rui; Amado, Francisco; Duarte, José Alberto; Ferreira, Rita

    2014-09-25

    Cardiac cachexia is a serious complication of chronic heart failure, characterized by significant weight loss and body wasting. Chronic heart failure-related muscle wasting results from a chronic imbalance in the activation of anabolic or catabolic pathways, caused by a series of immunological, metabolic, and neurohormonal processes. In spite of the high morbidity and mortality associated to this condition, there is no universally accepted definition or specific biomarkers for cardiac cachexia, which makes its diagnosis and treatment difficult. Several hormonal, inflammatory and oxidative stress molecules have been proposed as serological markers of prognosis in cardiac cachexia but with doubtful success. As individual biomarkers may have limited sensitivity and specificity, multimarker strategies involving mediators of the biological processes modulated by cardiac cachexia will strongly contribute for the diagnosis and management of the disease, as well as for the establishment of new therapeutic targets. An integrated analysis of the biomarkers proposed so far for cardiac cachexia is made in the present review, highlighting the biological processes to which they are related. PMID:24978823

  9. Cachexia in patients with oesophageal cancer.

    Science.gov (United States)

    Anandavadivelan, Poorna; Lagergren, Pernilla

    2016-03-01

    Oesophageal cancer is a debilitating disease with a poor prognosis, and weight loss owing to malnutrition prevails in the majority of patients. Cachexia, a multifactorial syndrome characterized by the loss of fat and skeletal muscle mass and systemic inflammation arising from complex host-tumour interactions is a major contributor to malnutrition, which is a determinant of tolerance to treatment and survival. In patients with oesophageal cancer, cachexia is further compounded by eating difficulties owing to the stage and location of the tumour, and the effects of neoadjuvant therapy. Treatment with curative intent involves exceptionally extensive and invasive surgery, and the subsequent anatomical changes often lead to eating difficulties and severe postoperative malnutrition. Thus, screening for cachexia by means of percentage weight loss and BMI during the cancer trajectory and survivorship periods is imperative. Additionally, markers of inflammation (such as C-reactive protein), dysphagia and appetite loss should be assessed at diagnosis. Routine assessments of body composition are also necessary in patients with oesophageal cancer to enable assessment of skeletal muscle loss, which might be masked by sarcopenic obesity in these patients. A need exists for clinical trials examining the effectiveness of therapeutic and physical-activity-based interventions in mitigating muscle loss and counteracting cachexia in these patients. PMID:26573424

  10. Understanding cachexia as a cancer metabolism syndrome.

    Science.gov (United States)

    Porporato, P E

    2016-01-01

    Metabolic reprogramming occurs in tumors to foster cancer cell proliferation, survival and metastasis, but as well at a systemic level affecting the whole organism, eventually leading to cancer cachexia. Indeed, as cancer cells rely on external sources of nitrogen and carbon skeleton to grow, systemic metabolic deregulation promoting tissue wasting and metabolites mobilization ultimately supports tumor growth. Cachectic patients experience a wide range of symptoms affecting several organ functions such as muscle, liver, brain, immune system and heart, collectively decreasing patients' quality of life and worsening their prognosis. Moreover, cachexia is estimated to be the direct cause of at least 20% of cancer deaths. The main aspect of cachexia syndrome is the unstoppable skeletal muscle and fat storage wasting, even with an adequate caloric intake, resulting in nutrient mobilization - both directly as lipid and amino acids and indirectly as glucose derived from the exploitation of liver gluconeogenesis - that reaches the tumor through the bloodstream. From a metabolic standpoint, cachectic host develops a wide range of dysfunctions, from increased insulin and IGF-1 resistance to induction of mitochondrial uncoupling proteins and fat tissue browning resulting in an increased energy expenditure and heat generation, even at rest. For a long time, cachexia has been merely considered an epiphenomenon of end-stage tumors. However, in specific tumor types, such as pancreatic cancers, it is now clear that patients present markers of tissue wasting at a stage in which tumor is not yet clinically detectable, and that host amino acid supply is required for tumor growth. Indeed, tumor cells actively promote tissue wasting by secreting specific factors such as parathyroid hormone-related protein and micro RNAs. Understanding the molecular and metabolic mediators of cachexia will not only advance therapeutic approaches against cancer, but also improve patients' quality of life

  11. Serum interleukin-15 levels in cancer patients with cachexia

    OpenAIRE

    Martínez Hernández, Pedro Luis; Hernanz Macías, Ángel; Gómez-Candela, Carmen; Grande Aragón, Cristina; Feliu Batlle, Jaime; Castro-Carpeño, Javier; MARTÍNEZ MUÑOZ, ISABEL; Zurita Rosa, Laura; Villarino Sanz, Marta; Prados, Concepción; García-Girón, Joaquín Sánchez

    2012-01-01

    Interleukin-15 (IL-15) has important anabolic effects on muscle protein metabolism through a decrease in the ATP-ubiquitin-dependent proteolytic pathway. The role of IL-15 in human cancer cachexia is unknown. The aim of this study was to assess the relationship between interleukin-15 (IL-15) in cancer patients with cachexia at diagnosis of malignancy and 8 weeks later. An observational study of 21 cancer patients (with and without cachexia) and 8 healthy subjects was conducted. Body compositi...

  12. Optimal management of cancer anorexia–cachexia syndrome

    OpenAIRE

    Josep M Argilés; Mireia Olivan; Sílvia Busquets; et al

    2010-01-01

    Josep M Argilés, Mireia Olivan, Sílvia Busquets, Francisco Javier López-SorianoDepartament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, SpainAbstract: According to a recent consensus, cachexia is 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. Cachexia occurs in the majority of c...

  13. Pancreatic cancer cachexia: a review of mechanisms and therapeutics

    OpenAIRE

    Carlyn Rose Tan; Laith eJamil; Patrick eYaffee; Richard eTuli; Nick eNissen; Simon eLo; Stephen J Pandol; Andrew Eugene Hendifar

    2014-01-01

    Over the last decade, we have gained new insight into the pathophysiology of cachexia associated with pancreatic cancer. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiolog...

  14. Leptin in Anorexia and Cachexia Syndrome

    Directory of Open Access Journals (Sweden)

    Diana R. Engineer

    2012-01-01

    Full Text Available Leptin is a product of the obese (OB gene secreted by adipocytes in proportion to fat mass. It decreases food intake and increases energy expenditure by affecting the balance between orexigenic and anorexigenic hypothalamic pathways. Low leptin levels are responsible for the compensatory increase in appetite and body weight and decreased energy expenditure (EE following caloric deprivation. The anorexia-cachexia syndrome is a complication of many chronic conditions including cancer, chronic obstructive pulmonary disease, congestive heart failure, chronic kidney disease, and aging, where the decrease in body weight and food intake is not followed by a compensatory increase in appetite or decreased EE. Crosstalk between leptin and inflammatory signaling known to be activated in these conditions may be responsible for this paradox. This manuscript will review the evidence and potential mechanisms mediating changes in the leptin pathway in the setting of anorexia and cachexia associated with chronic diseases.

  15. Leptin in Anorexia and Cachexia Syndrome

    OpenAIRE

    Engineer, Diana R; Garcia, Jose M.

    2012-01-01

    Leptin is a product of the obese (OB) gene secreted by adipocytes in proportion to fat mass. It decreases food intake and increases energy expenditure by affecting the balance between orexigenic and anorexigenic hypothalamic pathways. Low leptin levels are responsible for the compensatory increase in appetite and body weight and decreased energy expenditure (EE) following caloric deprivation. The anorexia-cachexia syndrome is a complication of many chronic conditions including cancer, chronic...

  16. Cancer Cachexia:Mechanisms and Clinical Implications

    OpenAIRE

    Donohoe, Claire L.; Ryan, Aoife M.; John V. Reynolds

    2011-01-01

    PUBLISHED Cachexia is amultifactorial process of skeletal muscle and adipose tissue atrophy resulting in progressive weight loss. It is associated with poor quality of life, poor physical function, and poor prognosis in cancer patients. It involves multiple pathways: procachectic and proinflammatory signals from tumour cells, systemic inflammation in the host, and widespread metabolic changes (increased resting energy expenditure and alterations in metabolism of protein, fat, and ...

  17. The pathogenesis and treatment of cardiac atrophy in cancer cachexia.

    Science.gov (United States)

    Murphy, Kate T

    2016-02-15

    Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. In addition to a loss of skeletal muscle mass and function, many patients with cancer cachexia also experience cardiac atrophy, remodeling, and dysfunction, which in the field of cancer cachexia is described as cardiac cachexia. The cardiac alterations may be due to underlying heart disease, the cancer itself, or problems initiated by the cancer treatment and, unfortunately, remains largely underappreciated by clinicians and basic scientists. Despite recent major advances in the treatment of cancer, little progress has been made in the treatment of cardiac cachexia in cancer, and much of this is due to lack of information regarding the mechanisms. This review focuses on the cardiac atrophy associated with cancer cachexia, describing some of the known mechanisms and discussing the current and future therapeutic strategies to treat this condition. Above all else, improved awareness of the condition and an increased focus on identification of mechanisms and therapeutic targets will facilitate the eventual development of an effective treatment for cardiac atrophy in cancer cachexia. PMID:26718971

  18. [The cachexia-anorexia syndrome among oncological patients].

    Science.gov (United States)

    Sosa-Sánchez, Ricardo; Sánchez-Lara, Karla; Motola-Kuba, Daniel; Green-Renner, Dan

    2008-01-01

    Approximately two thirds of cancer patients at advanced stages of the disease suffer from anorexia, which leads to significant weight loss and progressive cachexia, an important factor that contributes to death. It has been observed that cancer cachexia differs from simple starvation, although the exact mechanisms associated with cancer cachexia are not well known. Several theories regarding its pathogenesis point to a complex mixture of tumor, host and treatment variables. Unfortunately, the wasting syndrome also constitutes for the patient, a progression of the cancer process, significantly affecting quality of life and social interactions. Treatable causes should be identified and treated. Knowledge of the mechanisms underlying the effects of caquexia on the patient may play a role in identifying treatment measures targetted to muscle wasting and to maintain body strength. In this article we review the main features and mechanisms of the anorexia-cachexia syndrome in patients with cancer. PMID:19043964

  19. Emerging markers of cachexia predict survival in cancer patients

    OpenAIRE

    MONDELLO, PATRIZIA; Lacquaniti, Antonio; Mondello, Stefania; Bolignano, Davide; Pitini, Vincenzo; Aloisi, Carmela; Buemi, Michele

    2014-01-01

    Background Cachexia may occur in 40% of cancer patients, representing the major cause of death in more than 20% of them. The aim of this study was to investigate the role of leptin, ghrelin and obestatin as diagnostic and predictive markers of cachexia in oncologic patients. Their impact on patient survival was also evaluated. Methods 140 adults with different cancer diagnoses were recruited. Thirty healthy volunteers served as control. Serum ghrelin, obestatin and leptin were tested at basel...

  20. Rikkunshito, a ghrelin potentiator, ameliorates anorexia-cachexia syndrome

    Directory of Open Access Journals (Sweden)

    Naoki eFujitsuka

    2014-12-01

    Full Text Available Anorexia-cachexia syndrome develops during the advanced stages of various chronic diseases in which patients exhibit a decreased food intake, weight loss, and muscle tissue wasting. For these patients, this syndrome is a critical problem leading to an increased rate of morbidity and mortality. The present pharmacological therapies for treating anorexia-cachexia have limited effectiveness. The Japanese herbal medicine rikkunshito is often prescribed for the treatment of anorexia and upper gastrointestinal disorders. Thus, rikkunshito is expected to be beneficial for the treatment of patients with anorexia-cachexia syndrome. In this review, we summarize the effects of rikkunshito and its mechanisms of action on anorexia-cachexia.Persistent loss of appetite leads to a progressive depletion of body energy stores, which is frequently associated with cachexia. Consequently, regulating appetite and energy homeostasis is critically important for treating cachexia. Ghrelin is mainly secreted from the stomach, and it plays an important role in initiating feeding, controlling gastrointestinal motility, and regulating energy expenditure. Recent clinical and basic science studies have demonstrated that the critical mechanism of rikkunshito underlies endogenous ghrelin activity. Interestingly, several components of rikkunshito target multiple gastric and central sites, and regulate the secretion, receptor sensitization, and degradation of ghrelin. Rikkunshito is effective for the treatment of anorexia, body weight loss, muscle wasting, and anxiety-related behavior. Furthermore, treatment with rikkunshito was observed to prolong survival in an animal model of cachexia. The use of a potentiator of ghrelin signaling, such as rikkunshito, may represent a novel approach for the treatment of anorexia-cachexia syndrome.

  1. Rikkunshito, a ghrelin potentiator, ameliorates anorexia–cachexia syndrome

    OpenAIRE

    Fujitsuka, Naoki; Uezono, Yasuhito

    2014-01-01

    Anorexia–cachexia syndrome develops during the advanced stages of various chronic diseases in which patients exhibit a decreased food intake, weight loss, and muscle tissue wasting. For these patients, this syndrome is a critical problem leading to an increased rate of morbidity and mortality. The present pharmacological therapies for treating anorexia–cachexia have limited effectiveness. The Japanese herbal medicine rikkunshito is often prescribed for the treatment of anorexia and upper gast...

  2. Therapeutic exercise in cancer cachexia: exploring approaches and outcomes

    OpenAIRE

    Maddocks, Matthew

    2010-01-01

    Cachexia is common in patients with incurable cancer, particularly of the lung and upper-gastrointestinal tract, and impacts adversely on treatment options, morbidity, quality of life and survival. Current management of cancer cachexia is inadequate and progress is required. This thesis explores the use of exercise as a proactive supportive therapy with a focus on maintaining physical function. The first piece of work was a systematic review of the use of therapeutic exercise in patients ...

  3. Systemic zinc redistribution and dyshomeostasis in cancer cachexia

    OpenAIRE

    Siren, Pontus M. A.; Siren, Matti J.

    2010-01-01

    Cachexia affects up to two thirds of all cancer patients and is a significant cause of morbidity and mortality. It is a complex metabolic syndrome associated with the underlying illness and characterized by loss of skeletal muscle tissue with or without loss of fat mass. Cachexia’s other prominent clinical symptoms include anorexia, systemic inflammation, pediatric growth failure, and hypogonadism. The relationship between the symptoms of cancer cachexia and the underlying illness is unclear,...

  4. Spontaneous Physical Activity Downregulates Pax7 in Cancer Cachexia

    OpenAIRE

    Dario Coletti; Paola Aulino; Eva Pigna; Fabio Barteri; Viviana Moresi; Daniela Annibali; Sergio Adamo; Emanuele Berardi

    2015-01-01

    Emerging evidence suggests that the muscle microenvironment plays a prominent role in cancer cachexia. We recently showed that NF-kB-induced Pax7 overexpression impairs the myogenic potential of muscle precursors in cachectic mice, suggesting that lowering Pax7 expression may be beneficial in cancer cachexia. We evaluated the muscle regenerative potential after acute injury in C26 colon carcinoma tumor-bearing mice and healthy controls. Our analyses confirmed that the delayed muscle regenerat...

  5. Research on cachexia, sarcopenia and skeletal muscle in cardiology

    OpenAIRE

    Coats, Andrew J S

    2012-01-01

    Background The awareness of cardiac cachexia, i.e. involuntary weight loss in patients with underlying cardiovascular disease, has increased over the last two decades. Methods and results This mini-review looks at recent research in the cardiovascular literature that is relevant to the areas of interest of the Journal of Cachexia, Sarcopenia and Muscle. It identifies significant research in the last 3 years on the obesity paradox, the causes and effects of skeletal muscle wasting, animal mode...

  6. Caquexia cardíaca Cardiac cachexia

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    Alberto Miján

    2006-05-01

    .Chronic heart failure (CHF, especially affecting the right heart, frequently leads to malnutrition. If the latter is severe and is combined to other factors, it may lead to cardiac cachexia. This one is associated to increased mortality and lower survival of patients suffering from it. The causes of cardiac cachexia are diverse, generally associated to maintenance of a negative energy balance, with increasing evidence of its multifactorial origin. Neurohumoral, inflammatory, immunological, and metabolic factors, among others, are superimposed in the patient with CHF, leading to involvement and deterioration of several organs and systems, since this condition affects both lean (or active cellular mass and adipose and bone tissue - osteoporosis. Among all, the most pronounced deterioration may be seen at skeletal muscle tissue, at both structural and functional levels, the heart not being spared. As for treatment, it should be based on available scientific evidence. Assessment of nutritional status of any patient with CHF is a must, with the requirement of nutritional intervention in case of malnutrition. In this situation, especially if accompanied by cardiac cachexia, it is required to modify energy intake and oral diet quality, and to consider the indication of specific complementary or alternative artificial nutrition. Besides, the causal relationship of the beneficial role of moderate physical exertion is increasing, as well as modulation of metabolic and inflammatory impairments observed in cardiac cachexia with several drugs, leading to a favorable functional and structural response in CHF patients.

  7. Systemic zinc redistribution and dyshomeostasis in cancer cachexia.

    Science.gov (United States)

    Siren, Pontus M A; Siren, Matti J

    2010-09-01

    Cachexia affects up to two thirds of all cancer patients and is a significant cause of morbidity and mortality. It is a complex metabolic syndrome associated with the underlying illness and characterized by loss of skeletal muscle tissue with or without loss of fat mass. Cachexia's other prominent clinical symptoms include anorexia, systemic inflammation, pediatric growth failure, and hypogonadism. The relationship between the symptoms of cancer cachexia and the underlying illness is unclear, and there is an urgent need for a better understanding of the pathophysiology of this syndrome. Normal Zn metabolism is often disrupted in cancer patients, but the possible effects of systemic Zn dyshomeostasis in cachexia have not been investigated. We propose that the acute phase response can mediate Zn redistribution and accumulation in skeletal muscle tissue and contribute to the activation of the ubiquitin-proteasome pathway that regulates protein catabolism. This chronic redistribution deprives Zn from other tissues and organs and compromises critical physiological functions in the body. The cardinal symptoms of Zn deficiency are anorexia, systemic inflammation, growth failure in children, and hypogonadism. These symptoms also prominently characterize cancer cachexia suggesting that the role of systemic Zn dyshomeostasis in cachexia should be investigated. PMID:21475700

  8. Liver macrophages contribute to pancreatic cancer-related cachexia.

    Science.gov (United States)

    Martignoni, Marc E; Dimitriu, Corneliu; Bachmann, Jeaninne; Krakowski-Rosen, Holger; Ketterer, Knut; Kinscherf, Ralf; Friess, Helmut

    2009-02-01

    Cachexia is a devastating process especially in pancreatic cancer patients and contributes to their poor survival. We attempted to clarify the pathological and molecular changes that occur in the liver during the development of cachexia. Using immunohistochemistry we investigated the infiltration of inflammatory mononuclear cells in liver biopsies of pancreatic cancer patients with or without cachexia, and the potential relevance of the cells for the nutritional and inflammatory status. Additionally, these findings were compared with the patients' clinical parameters. We found a significantly higher amount of CD68 immunoreactive macrophages in liver cross sections of patients with pancreatic cancer and cachexia. The number of CD68-positive macrophages was significantly inversely correlated with the nutritional status. Additionally, in these CD68-positive areas a significant increase in IL-6 and IL-1 immunoreactive cells was localized. Moreover, we found significantly increased areas of CD68-positive macrophages in liver biopsies of patients with a more dedifferentiated (aggressive) grading of the tumor. In conclusion, these results suggest that a crucial interaction between the tumor, PBMCs, and the liver may play a central role in the development and regulation of cachexia. Furthermore, pancreatic cancer may be able to alter systemic organ function even without obvious metastatic disease. PMID:19148509

  9. Optimal management of cancer anorexia–cachexia syndrome

    Directory of Open Access Journals (Sweden)

    Josep M Argilés

    2010-01-01

    Full Text Available Josep M Argilés, Mireia Olivan, Sílvia Busquets, Francisco Javier López-SorianoDepartament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, SpainAbstract: According to a recent consensus, cachexia is 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. Cachexia occurs in the majority of cancer patients before death and it is responsible for the deaths of 22% of cancer patients. Although bodyweight is the most important endpoint of any cachexia treatment, body composition, physical performance and quality of life should be monitored. From the results presented here, one can speculate that a single therapy may not be completely successful in the treatment of cachexia. From this point of view, treatments involving different combinations are more likely to be successful. The objectives of any therapeutic combination are two-fold: an anticatabolic aim directed towards both fat and muscle catabolism and an anabolic objective leading to the synthesis of macromolecules such as contractile proteins.Keywords: wasting, cancer, anorexia, nutraceuticals, drugs

  10. Sarcopenia, cachexia and congestive heart failure in the elderly.

    Science.gov (United States)

    Zamboni, Mauro; Rossi, Andrea P; Corzato, Francesca; Bambace, Clara; Mazzali, Gloria; Fantin, Francesco

    2013-03-01

    Skeletal muscle abnormalities and loss are frequently present in patients with mild or moderate cardiac heart failure (CHF) and may contribute to fatigue and dyspnea. These muscle abnormalities may be associated with age related body composition changes, such as sarcopenia. Muscle damage has also been observed in subjects with cardiac cahexia, a serious CHF complication, associated with poor prognosis independently of functional disease severity, age, and measures of exercise capacity and cardiac function. Loss of muscle mass is a feature of cachexia, whereas most sarcopenic subjects are not cachectic. Individuals with no weight loss, no anorexia, and no measurable systemic inflammatory response may be sarcopenic. Patients with severe CHF show multiple marked histological abnormalities of skeletal muscle, such as muscle fiber atrophy. These abnormalities are different in sarcopenia and cachexia. The majority of mechanisms involved in sarcopenia play a role even in the determination of cachexia and they are amplified in cachexia where they may induce both muscle damage as well as other abnormalities, such as fat and weight loss, through activation of lypolisis or anorexia. To distinguish cachexia and sarcopenia in CHF patients, even if not easy, should be clinically relevant, because no specific treatment is available for cachectic patients whereas treatment options are possible for sarcopenia. PMID:23369138

  11. Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia.

    Science.gov (United States)

    Tsoli, Maria; Swarbrick, Michael M; Robertson, Graham R

    2016-06-01

    Although muscle wasting is the obvious manifestation of cancer cachexia that impacts on patient quality of life, the loss of lipid reserves and metabolic imbalance in adipose tissue also contribute to the devastating impact of cachexia. Depletion of fat depots in cancer patients is more pronounced than loss of muscle and often precedes, or even occurs in the absence of, reduced lean body mass. Rapid mobilisation of triglycerides stored within adipocytes to supply the body with fatty acids in periods of high-energy demand is normally mediated through a well-defined process of lipolysis involving the lipases ATGL, HSL and MGL. Studies into how these lipases contribute to fat loss in cancer cachexia have revealed the prominent role for ATGL in initiating lipolysis during adipose tissue atrophy, together with links between tumour-derived factors and the signalling pathways that control lipid flux within fat cells. The recent findings of increased thermogenesis in brown fat during cancer cachexia indicate that metabolically active adipose tissue contributes to the imbalance in energy homeostasis involved in catabolic wasting. Such energetically futile use of fatty acids liberated from adipose tissue to generate heat represents a maladaptive response in conjunction with anorexia experienced by cancer patients. As IL-6 release by tumours provokes lipolysis and activates the thermogenic programme in brown fat, this review explores the overlap in dysregulated metabolic processes due to inflammatory mediators in cancer cachexia and other disease states characterised by elevated cytokines such as obesity and diabetes. PMID:26529279

  12. Heterogeneous response of adipose tissue to cancer cachexia

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    P.S. Bertevello

    2001-09-01

    Full Text Available Cancer cachexia causes disruption of lipid metabolism. Since it has been well established that the various adipose tissue depots demonstrate different responses to stimuli, we assessed the effect of cachexia on some biochemical and morphological parameters of adipocytes obtained from the mesenteric (MES, retroperitoneal (RPAT, and epididymal (EAT adipose tissues of rats bearing Walker 256 carcinosarcoma, compared with controls. Relative weight and total fat content of tissues did not differ between tumor-bearing rats and controls, but fatty acid composition was modified by cachexia. Adipocyte dimensions were increased in MES and RPAT from tumor-bearing rats, but not in EAT, in relation to control. Ultrastructural alterations were observed in the adipocytes of tumor-bearing rat RPAT (membrane projections and EAT (nuclear bodies.

  13. Cardiac cachexia and muscle wasting: definition, physiopathology, and clinical consequences

    Directory of Open Access Journals (Sweden)

    Okoshi MP

    2014-11-01

    Full Text Available Marina P Okoshi,1 Fernando G Romeiro,1 Paula F Martinez,1,2 Silvio A Oliveira Jr,1,2 Bertha F Polegato,1 Katashi Okoshi11Internal Medicine Department, Botucatu Medical School, Sao Paulo State University, UNESP, Sao Paulo, Brazil; 2School of Physiotherapy, Federal University of Mato Grosso do Sul, Campo Grande, BrazilAbstract: Cachexia and muscle wasting are frequently observed in heart failure patients. Cachexia is a predictor of reduced survival, independent of important parameters such as age, heart failure functional class, and functional capacity. Muscle and fat wasting can also predict adverse outcome during cardiac failure. Only more recently were these conditions defined in International Consensus. Considering that heart failure is an inflammatory disease, cardiac cachexia has been diagnosed by finding a body weight loss >5%, in the absence of other diseases and independent of other criteria. Muscle wasting has been defined as lean appendicular mass corrected for height squared of 2 standard deviations or more below the mean for healthy individuals between 20 years and 30 years old from the same ethnic group. The etiology of heart failure-associated cachexia and muscle wasting is multifactorial, and the underlying physiopathological mechanisms are not completely understood. The most important factors are reduced food intake, gastrointestinal alterations, immunological activation, neurohormonal abnormalities, and an imbalance between anabolic and catabolic processes. Cachexia and muscle wasting have clinical consequences in several organs and systems including the gastrointestinal and erythropoietic systems, and the heart, previously affected by the primary disease. We hope that a better understanding of the mechanisms involved in their physiopathology will allow the development of pharmacological and nonpharmacological therapies to effectively prevent and treat heart failure-induced cachexia and muscle wasting before significant body

  14. Spontaneous Physical Activity Downregulates Pax7 in Cancer Cachexia

    Directory of Open Access Journals (Sweden)

    Dario Coletti

    2016-01-01

    Full Text Available Emerging evidence suggests that the muscle microenvironment plays a prominent role in cancer cachexia. We recently showed that NF-kB-induced Pax7 overexpression impairs the myogenic potential of muscle precursors in cachectic mice, suggesting that lowering Pax7 expression may be beneficial in cancer cachexia. We evaluated the muscle regenerative potential after acute injury in C26 colon carcinoma tumor-bearing mice and healthy controls. Our analyses confirmed that the delayed muscle regeneration observed in muscles form tumor-bearing mice was associated with a persistent local inflammation and Pax7 overexpression. Physical activity is known to exert positive effects on cachectic muscles. However, the mechanism by which a moderate voluntary exercise ameliorates muscle wasting is not fully elucidated. To verify if physical activity affects Pax7 expression, we hosted control and C26-bearing mice in wheel-equipped cages and we found that voluntary wheel running downregulated Pax7 expression in muscles from tumor-bearing mice. As expected, downregulation of Pax7 expression was associated with a rescue of muscle mass and fiber size. Our findings shed light on the molecular basis of the beneficial effect exerted by a moderate physical exercise on muscle stem cells in cancer cachexia. Furthermore, we propose voluntary exercise as a physiological tool to counteract the overexpression of Pax7 observed in cancer cachexia.

  15. Spontaneous Physical Activity Downregulates Pax7 in Cancer Cachexia.

    Science.gov (United States)

    Coletti, Dario; Aulino, Paola; Pigna, Eva; Barteri, Fabio; Moresi, Viviana; Annibali, Daniela; Adamo, Sergio; Berardi, Emanuele

    2016-01-01

    Emerging evidence suggests that the muscle microenvironment plays a prominent role in cancer cachexia. We recently showed that NF-kB-induced Pax7 overexpression impairs the myogenic potential of muscle precursors in cachectic mice, suggesting that lowering Pax7 expression may be beneficial in cancer cachexia. We evaluated the muscle regenerative potential after acute injury in C26 colon carcinoma tumor-bearing mice and healthy controls. Our analyses confirmed that the delayed muscle regeneration observed in muscles form tumor-bearing mice was associated with a persistent local inflammation and Pax7 overexpression. Physical activity is known to exert positive effects on cachectic muscles. However, the mechanism by which a moderate voluntary exercise ameliorates muscle wasting is not fully elucidated. To verify if physical activity affects Pax7 expression, we hosted control and C26-bearing mice in wheel-equipped cages and we found that voluntary wheel running downregulated Pax7 expression in muscles from tumor-bearing mice. As expected, downregulation of Pax7 expression was associated with a rescue of muscle mass and fiber size. Our findings shed light on the molecular basis of the beneficial effect exerted by a moderate physical exercise on muscle stem cells in cancer cachexia. Furthermore, we propose voluntary exercise as a physiological tool to counteract the overexpression of Pax7 observed in cancer cachexia. PMID:27034684

  16. Cachexia as a major underestimated and unmet medical need: facts and numbers

    OpenAIRE

    von Haehling, Stephan; Anker, Stefan D.

    2010-01-01

    Cachexia is a serious, however underestimated and underrecognised medical consequence of malignant cancer, chronic heart failure (CHF), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), cystic fibrosis, rheumatoid arthritis, Alzheimer's disease, infectious diseases, and many other chronic illnesses. The prevalence of cachexia is high, ranging from 5% to 15% in CHF or COPD to 60% to 80% in advanced cancer. By population prevalence, the most frequent cachexia subtypes ...

  17. The effect of exercise on IL-6-induced cachexia in the Apc Min /+ mouse

    OpenAIRE

    Puppa, Melissa J.; White, James P.; Kandy T Velázquez; Baltgalvis, Kristen A.; Sato, Shuichi; Baynes, John W.; Carson, James A.

    2011-01-01

    Background Cachexia involves unintentional body weight loss including diminished muscle and adipose tissue mass and is associated with an underlying disease. Systemic overexpression of IL-6 accelerates cachexia in the ApcMin/+ mouse, but does not induce wasting in control C57BL/6 mice. With many chronic diseases, chronic inflammation and metabolic dysfunction can be improved with moderate exercise. A direct effect of regular moderate exercise on the prevention of IL-6-induced cachexia in the ...

  18. Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma

    OpenAIRE

    Mu, Xiaodong; Agarwal, Rashmi; March, Daniel; Rothenberg, Adam; Voigt, Clifford; Tebbets, Jessica; Huard, Johnny; Weiss, Kurt

    2016-01-01

    Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notc...

  19. A role of active brown adipose tissue in cancer cachexia?

    Directory of Open Access Journals (Sweden)

    Emiel Beijer

    2012-06-01

    Full Text Available Until a few years ago, adult humans were not thought to have brown adipose tissue (BAT. Now, this is a rapidly evolving field of research with perspectives in metabolic syndromes such as obesity and new therapies targeting its bio-energetic pathways. White, brown and socalled brite adipose fat seem to be able to trans-differentiate into each other, emphasizing the dynamic nature of fat tissue for metabolism. Human and animal data in cancer cachexia to date provide some evidence for BAT activation, but its quantitative impact on energy expenditure and weight loss is controversial. Prospective clinical studies can address the potential role of BAT in cancer cachexia using 18F-fluorodeoxyglucose positron emission tomography-computed tomography scanning, with careful consideration of co-factors such as diet, exposure to the cold, physical activity and body mass index, that all seem to act on BAT recruitment and activity.

  20. Update on Melanocortin Interventions for Cachexia: Progress Toward Clinical Application

    OpenAIRE

    DeBoer, Mark Daniel

    2009-01-01

    Cachexia is a devastating syndrome of body wasting that is associated with multiple common chronic diseases including cancer, chronic kidney disease, and chronic heart failure. These underlying diseases are associated with increased levels of inflammatory cytokines and result in anorexia, increased resting energy expenditure and loss of fat and lean body mass. Prior experiments have implicated the central melanocortin system in the hypothalamus with the propagation of these symptoms of cachex...

  1. The role of triglyceride lipases in cancer associated cachexia

    OpenAIRE

    Das, Suman K.; Hoefler, Gerald

    2013-01-01

    Cancer associated cachexia (CAC) is a complex multiorgan syndrome frequently associated with various forms of cancer. Affected patients suffer from a dramatic loss of skeletal muscle and adipose tissue. Most cases are accompanied by anorexia, and nutritional supplements are not sufficient to stop or reverse its course. CAC impairs many forms of therapeutic interventions and accounts for 15–20% of all deaths of cancer patients. Recently, several studies have recognized the importance of lipid ...

  2. Pathophysiology of anorexia in the cancer cachexia syndrome

    OpenAIRE

    Ezeoke, Chukwuemeka Charles; Morley, John E.

    2015-01-01

    Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increas...

  3. Herbal medicines for cancer cachexia: protocol for a systematic review

    OpenAIRE

    Park, Bongki; Jun, Ji Hee; Jung, Jeeyoun; You, Sooseong; Lee, Myeong Soo

    2014-01-01

    Introduction To assess the efficacy of herbal medicines as a treatment of cancer cachexia. Methods and analysis We will search the following 13 electronic databases from their inception. MEDLINE (PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Allied and Complementary Medicine Database (AMED), China National Knowledge Infrastructure (CNKI), Wanfang, Journal Integration Platform (VIP) and six Korean Medical Databases (KoreaMed, the Korean Traditional knowledge Po...

  4. Sarcopenia, Cachexia and Aging: Diagnosis, Mechanisms and Therapeutic Options

    OpenAIRE

    Ali, Sumbul; Garcia, Jose M.

    2014-01-01

    By the year 2050, individuals over the age of 65 will comprise 20% of the US population. Loss of muscle mass and strength is common in this age group and it is associated with increased dependence, frailty and mortality. Sarcopenia defined as the loss of muscle mass and function associated with aging, and cachexia defined as weight loss due to an underlying illness, are muscle wasting disorders of particular relevance in the aging population but they go largely unrecognized. In this review we...

  5. The effectiveness of nutritional interventions in malnutrition and cachexia.

    Science.gov (United States)

    Baldwin, Christine

    2015-11-01

    Cancer is a common diagnosis and leading cause of death worldwide. Amounts of weight loss vary but it is associated with considerable morbidity, poorer quality of life and reduced survival. Nutritional intervention has the potential to maximise response to treatment and improve functioning and quality of life. The aim of this paper was to review the evidence for oral nutritional interventions in the management of weight loss in patients with cancer. Comparison of studies of nutritional support interventions in people with cancer is complicated by variations in understanding of what constitutes a compromised nutritional status. There are similarities and differences between definitions of both malnutrition and cachexia and studies of oral nutritional interventions have failed to use standard criteria at study inclusion contributing to heterogeneity amongst studies. Meta-analysis of randomised controlled trials has suggested limited evidence of benefit to nutritional and clinical outcomes but some improvements to aspects of quality of life. The presence of cachexia in patients with cancer might explain the limited efficacy of simple oral nutritional interventions, which lack a component designed to address metabolic abnormalities associated with cachexia. Novel strategies combining nutritional support with therapeutic agents designed to down-regulate the metabolic aberrations have failed to demonstrate consistent benefits and the results of multimodal treatments combining several interventions are awaited. There is a need for intervention studies recruiting patients early in the disease course, which underlines the need for definitions which predict poor outcome and hence allow early recognition of vulnerable patients. PMID:26087760

  6. Pay attention to cardiac remodeling in cancer cachexia.

    Science.gov (United States)

    Zheng, Yawen; Chen, Han; Li, Xiaoqing; Sun, Yuping

    2016-07-01

    Cancer cachexia is a complex and multifaceted disease state characterized by fatigue, weakness, and loss of skeletal muscle and adipose tissue. Recently, the profound negative effects of cancer cachexia on cardiac tissue draw much attention, which is likely to contribute to mortality in tumor-bearing animals. The mechanism of cardiac remodeling is not so clear and involved with a series of molecular alterations. In cancer cachexia model, progressive loss of left ventricular mass and decrease in myocardial function is observed and cardiac autonomic functions are altered. Levels of several emerging cardiovascular neurohormones are found elevating in patients with cancer, but it is still controversial whether the changes could reflect the heart injury accurately. The remedy for cardiac remodeling has been explored. It is showed that exercise can modulate signaling pathways activated by wasting cytokines and impact on the resulting outcomes on heart adaptation. Some drugs, such as bisoprolol, spironolactone, perindopril, tandospirone, and simvastatin, can mitigate adverse effects of the tumor on the heart and prolong survival. PMID:27108265

  7. Malnutrition, cachexia and nutritional intervention: when much becomes too much

    Directory of Open Access Journals (Sweden)

    Serena Rianda

    2013-06-01

    Full Text Available Disease-associated malnutrition, also defined as cachexia, is a complex syndrome characterised by the progressive deterioration of nutritional status resulting from the combined effects of reduced appetite and food intake, and profound changes in host metabolism. Cachexia has been repeatedly demonstrated to represent a negative prognostic factor for patients suffering from acute and chronic diseases, including cancer. In oncology patients, early diagnosis of cachexia and timely nutritional intervention have been demonstrated not only to prevent further deterioration of nutritional status, but also to increase quality of life and survival when integrated in a multiprofessional and multidisciplinary approach. However, nutritional therapy is associated to the possible development of complications, which may be fatal. Therefore, nutritional therapy in severely malnourished patients should be cautiously prescribed by experts in the field, who should develop a monitoring program to early detect complications and to maximise the clinical efficacy.Here we describe a cancer patient affected by refeeding syndrome, who was fortunately early diagnosed and properly treated.

  8. Drugs in development for treatment of patients with cancer-related anorexia and cachexia syndrome

    Directory of Open Access Journals (Sweden)

    Mantovani G

    2013-08-01

    Full Text Available Giovanni Mantovani, Clelia Madeddu, Antonio Macciò Department of Medical Oncology, University of Cagliari, Cagliari, Italy Abstract: Cancer-related anorexia and cachexia syndrome (CACS is a complex multifactorial condition, with loss of lean body mass, chronic inflammation, severe metabolic derangements, reduced food intake, reduced physical activity, and poor quality of life as key symptoms. Cachexia recognizes different phases or stages, moving from precachexia through overt cachexia to advanced or refractory cachexia. The purpose of this review is to describe currently effective approaches for the treatment of cachexia, moving forward to drugs and treatments already shown to be effective but needing further clinical trials to confirm their efficacy. We then introduce novel promising investigational drugs and approaches which, based on a strong rationale from the most recent data on the molecular targets/pathways driving the pathophysiology of cachexia, need to be tested either in currently ongoing or appropriate future clinical trials to confirm their clinical potential. Although different drugs and treatments have been tested, we can speculate that a single therapy may not be completely successful. Indeed, considering the complex clinical picture and the multifactorial pathogenesis of CACS, we believe that its clinical management requires a multidisciplinary and multitargeted approach. In our opinion, appropriate treatment for cachexia should target the following conditions: inflammatory status, oxidative stress, nutritional disorders, muscle catabolism, immunosuppression, quality of life, and above all, fatigue. A comprehensive list of the most interesting and effective multitargeted treatments is reported and discussed, with the aim of suggesting the most promising with regard to clinical outcome. A critical issue is that of testing therapies at the earliest stages of cachexia, possibly at the precachexia stage, with the aim of preventing

  9. Pharmacokinetics of Cannabis in Cancer Cachexia-Anorexia Syndrome.

    Science.gov (United States)

    Reuter, Stephanie E; Martin, Jennifer H

    2016-07-01

    Anorexia can affect up to 90 % of people with advanced cancer. It is a complex symptom associated with changes in taste, lack of hunger at mealtimes and lack of food enjoyment. Associated weight loss is part of the physical decline that occurs as cancer worsens. Weight loss can also occur from cachexia, the increased metabolism of energy due to raised inflammatory cytokines, liver metastases and other factors seen in several advanced cancers. Independent of anorexia, although frequently associated (where it is referred to as the cachexia-anorexia syndrome), it accounts for a significant amount of morbidity and deaths in people with cancer. In particular, quality of life for the patient and the family is significantly affected with this syndrome as it causes anxiety and distress. Therefore, it is important that research into therapies is undertaken, particularly focusing on an understanding of the pharmacokinetic properties of compounds in this cachexic population. Cannabinoids are one such group of therapies that have received a large amount of media focus recently. However, there appears to be a lack on rigorous pharmacokinetic data of these complex and varied compounds in the cachexic population. Similarly, there is a lack of pharmacokinetic data in any population group for the non- tetrahydrocannabinol (THC) and cannabidiol (CBD) cannabinoids (often due to the lack of analytical standards for quantification). This review will thus examine the pharmacokinetics of major cannabinoids i.e. THC and CBD in a cancer population. Overall, based on the current literature, evidence for the use of cannabinoids for the treatment of cancer-related cachexia-anorexia syndrome remains equivocal. A high-quality, rigorous, phase I/II study to elicit pharmacokinetic dose-concentration and concentration-response data, with a clinically acceptable mode of delivery to reduce intrapatient variability and enable more consistent bioavailability is needed in this population. PMID

  10. Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

    International Nuclear Information System (INIS)

    Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

  11. Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, B.M. [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States); Frye, G.S.; Ahn, B.; Ferreira, L.F. [1864 Stadium Road, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32610 (United States); Judge, A.R., E-mail: arjudge@phhp.ufl.edu [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States)

    2013-06-07

    Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

  12. A role of active brown adipose tissue in cancer cachexia?

    OpenAIRE

    Emiel Beijer; Janna Schoenmakers; Guy Vijgen; Fons Kessels; Anne-Marie Dingemans; Patrick Schrauwen; Miel Wouters; Wouter van Marken Lichtenbelt; Jaap Teule; Boudewijn Brans

    2012-01-01

    Until a few years ago, adult humans were not thought to have brown adipose tissue (BAT). Now, this is a rapidly evolving field of research with perspectives in metabolic syndromes such as obesity and new therapies targeting its bio-energetic pathways. White, brown and socalled brite adipose fat seem to be able to trans-differentiate into each other, emphasizing the dynamic nature of fat tissue for metabolism. Human and animal data in cancer cachexia to date provide some evidence for BAT activ...

  13. Identification of possible genetic polymorphisms involved in cancer cachexia: a systematic review

    Indian Academy of Sciences (India)

    Benjamin H. L. Tan; James A. Ross; Stein Kaasa; Frank Skorpen; Kenneth C. H. Fearon; European Palliative Care Research Collaborative

    2011-04-01

    Cancer cachexia is a polygenic and complex syndrome. Genetic variations in regulation of the inflammatory response, muscle and fat metabolic pathways, and pathways in appetite regulation are likely to contribute to the susceptibility or resistance to developing cancer cachexia. A systematic search of Medline and EmBase databases, covering 1986–2008 was performed for potential candidate genes/genetic polymorphisms relating to cancer cachexia. Related genes were then identified using pathway functional analysis software. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Genes with variants which had functional or clinical associations with cachexia and replicated in at least one study were entered into pathway analysis software to reveal possible network associations between genes. A total of 184 polymorphisms with functional or clinical relevance to cancer cachexia were identified in 92 candidate genes. Of these, 42 polymorphisms (in 33 genes) were replicated in more than one study with 13 polymorphisms found to influence two or more hallmarks of cachexia (i.e. inflammation, loss of fat mass and/or lean mass and reduced survival). Thirty-three genes were found to be significantly interconnected in two major networks with four genes (ADIPOQ, IL6, NFKB1 and TLR4) interlinking both networks. Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides an initial framework to select genes/polymorphisms for further study in cancer cachexia, and to develop their potential as susceptibility biomarkers of developing cachexia.

  14. Review article: anorexia and cachexia in gastrointestinal cancer.

    Science.gov (United States)

    Ockenga, J; Valentini, L

    2005-10-01

    In patients with gastrointestinal malignancies, i.e. cancers of the stomach, colon, liver, biliary tract or pancreas, progressive undernutrition can be regularly observed during the course of illness. Undernutrition significantly affects the patients' quality of life, morbidity and survival. Pathogenetically, two different causes are relevant in the development of undernutrition in patients with gastrointestinal cancer. One cause is reduced nutritional intake. This condition is referred to as anorexia and can be worsened by the side effects of cancer therapy. The other cause is the release of endogenous transmitters and/or other products of the tumour leading to the cachexia syndrome, which is characterized by loss of body weight, negative nitrogen balance and fatigue. Cancer anorexia and cancer cachexia may have synergistic negative effects in affecting the patients' status. In this review, current nutritional support strategies with respect to different clinically relevant situations are described. An algorithm of the treatment strategies, including dietetic counselling, oral supplements, enteral and parenteral nutritional support is given. One focus is the approach of nutrition-focused patient care, which shows promising results. In addition, the possibilities of pharmacological intervention are discussed. PMID:16181298

  15. Autophagic degradation contributes to muscle wasting in cancer cachexia.

    Science.gov (United States)

    Penna, Fabio; Costamagna, Domiziana; Pin, Fabrizio; Camperi, Andrea; Fanzani, Alessandro; Chiarpotto, Elena M; Cavallini, Gabriella; Bonelli, Gabriella; Baccino, Francesco M; Costelli, Paola

    2013-04-01

    Muscle protein wasting in cancer cachexia is a critical problem. The underlying mechanisms are still unclear, although the ubiquitin-proteasome system has been involved in the degradation of bulk myofibrillar proteins. The present work has been aimed to investigate whether autophagic degradation also plays a role in the onset of muscle depletion in cancer-bearing animals and in glucocorticoid-induced atrophy and sarcopenia of aging. The results show that autophagy is induced in muscle in three different models of cancer cachexia and in glucocorticoid-treated mice. In contrast, autophagic degradation in the muscle of sarcopenic animals is impaired but can be reactivated by calorie restriction. These results further demonstrate that different mechanisms are involved in pathologic muscle wasting and that autophagy, either excessive or defective, contributes to the complicated network that leads to muscle atrophy. In this regard, particularly intriguing is the observation that in cancer hosts and tumor necrosis factor α-treated C2C12 myotubes, insulin can only partially blunt autophagy induction. This finding suggests that autophagy is triggered through mechanisms that cannot be circumvented by using classic upstream modulators, prompting us to identify more effective approaches to target this proteolytic system. PMID:23395093

  16. Cachexia in chronic obstructive pulmonary disease: new insights and therapeutic perspective.

    Science.gov (United States)

    Sanders, Karin J C; Kneppers, Anita E M; van de Bool, Coby; Langen, Ramon C J; Schols, Annemie M W J

    2016-03-01

    Cachexia and muscle wasting are well recognized as common and partly reversible features of chronic obstructive pulmonary disease (COPD), adversely affecting disease progression and prognosis. This argues for integration of weight and muscle maintenance in patient care. In this review, recent insights are presented in the diagnosis of muscle wasting in COPD, the pathophysiology of muscle wasting, and putative mechanisms involved in a disturbed energy balance as cachexia driver. We discuss the therapeutic implications of these new insights for optimizing and personalizing management of COPD-induced cachexia. PMID:27066314

  17. An Epidemiological Survey of Cachexia in Advanced Cancer Patients and Analysis on Its Diagnostic and Treatment Status.

    Science.gov (United States)

    Sun, Lei; Quan, Xiao-Qing; Yu, Shiying

    2015-01-01

    Recently, an international consensus diagnostic criterion for cancer cachexia was proposed. The aim of the study is to assess the prevalence of cachexia in patients with advanced cancer and to assess the current status of the diagnosis and management of cancer cachexia. A total of 390 patients with advanced cancer were included. There were 140 patients with cachexia and the prevalence was 35.9%. The prevalence was highest in pancreatic cancer (88.9%), followed by gastric cancer (76.5%) and esophageal cancer (52.9%). Sixty-three patients with cancer cachexia have CT scans available for muscle mass evaluation and 98.4% were sarcopenic. Cachectic patients have a significantly lower overall quality of life and a higher symptom burden. According to oncology physicians, only 33 patients were considered to have cancer cachexia. The false negative rate amounted to 76.4%. The positive rate was related to the body mass index and Eastern Cooperative Oncology Group performance status of the patients. There were few types of pharmacological approaches for cancer cachexia and more than half of cachectic patients did not receive any anticachexia treatment. These results indicate that the prevalence of cachexia in advanced cancer patients was high. However, cancer cachexia was rarely recognized and clinical management for cancer cachexia was very inadequate. PMID:26317149

  18. Knowledge and practice among dietitians in four Western European countries regarding malnutrition, starvation, cachexia and sarcopenia

    NARCIS (Netherlands)

    Beek, Lies ter; Vanhauwaert, Erika; Slinde, Frode; Orrevall, Ylva; Henriksen, Christine; Johansson, Madelene; Vereecken, Carine; Rothenberg, Elisabet; Jager-Wittenaar, Harriët

    2015-01-01

    Adequate distinction between malnutrition, starvation, cachexia and sarcopenia is important in clinical care. Despite the overlap in physical characteristics, differences in etiology have therapeutical and prognostic implications. We aimed to determine whether dietitians in selected European countri

  19. Prevalence of cachexia in chronic heart failure and characteristics of body composition and metabolic status

    DEFF Research Database (Denmark)

    Christensen, Heidi Marie; Kistorp, Caroline Michaela Nervil; Schou, Morten;

    2012-01-01

    characterize a CHF population with and without cachexia with respect to body composition and related biomarkers. From 2008 to 2011, we screened 238 optimally treated, non-diabetic CHF patients for cardiac cachexia, defined as unintentional non-oedematous weight loss of >5 % over ≥6 months. CHF patients (LVEF...... 45 % (n = 19). The groups were matched for age, sex, and kidney function. Body composition was assessed by dual energy X-ray absorptiometry. The prevalence of cachexia was 10.5 %. Abdominal fat ± SD (%) was reduced in cachectic CHF: 27.4 ± 10.0 versus 37.5 ± 10.6 % (CHF, no cachexia) and 40...

  20. Refractory cachexia is associated with increased plasma concentrations of fentanyl in cancer patients

    Directory of Open Access Journals (Sweden)

    Suno M

    2015-05-01

    Full Text Available Manabu Suno,1,* Yuriko Endo,1,* Hiroyuki Nishie,2 Makoto Kajizono,3 Toshiaki Sendo,3 Junji Matsuoka4 1Department of Oncology Pharmaceutical Care and Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 3Department of Pharmacy, Okayama University Hospital, 4Faculty of Health Sciences, Okayama University Medical School, Okayama, Japan *These authors contributed equally to this work Background: An appropriate plasma concentration of fentanyl is the key to achieving good pain control in cancer patients. Cachexia, a multifactorial syndrome, is known to affect drug-metabolizing enzymes. However, the fentanyl concentrations in the blood of patients with cachexia have not been analyzed. The aim of this study was to evaluate the influence of cancer cachexia on dose-adjusted plasma fentanyl concentrations in cancer patients.Methods: Blood was collected from 21 Japanese cancer patients treated with a 24-hour transdermal fentanyl patch during the steady state of fentanyl plasma concentration. Plasma fentanyl concentrations were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS, and the levels were adjusted with the dose of fentanyl. Laboratory data were collected, and the cachexia stage was determined, based on study by Fearon et al. Multiple regression analysis was performed to identify the factors that affected fentanyl plasma concentrations.Results: Eight patients were classified as precachexia, nine as cachexia, and four as refractory cachexia, and the median dose-adjusted fentanyl concentrations (ng/mL per mg/kg/day were 27.5, 34.4, and 44.5, respectively. The dose-adjusted fentanyl concentration in patients with refractory cachexia was higher than that in patients with precachexia (Kruskal–Wallis test and post hoc Mann–Whitney U-test, P<0.01. The factors that

  1. Molecular biomarker discovery and physiological assessment of skeletal muscle in cancer cachexia

    OpenAIRE

    Stephens, Nathan Andrew

    2014-01-01

    Cachexia affects up to two thirds of all cancer patients with progressive disease. It is a syndrome characterised by weight-loss, anorexia, fatigue, asthenia, peripheral oedema, and is responsible for around 20% of cancer deaths. Cachectic patients suffer loss of both muscle mass and adipose tissue (with comparative sparing of visceral protein) and the lean tissue loss appears resistant to nutritional support. Progress in the treatment of cancer cachexia has been hampered due t...

  2. Muscle Paralysis and Myosin Loss in a Patient with Cancer Cachexia

    OpenAIRE

    Banduseela, V; Ochala, J.; Lamberg, K; Kalimo, H.; Larsson, L

    2007-01-01

    Cancer cachexia has a significant negative effect on quality of life, survival and the response to treatment. Recent in vitro and experimental animal studies have shown that myosin may be the primary target of the muscle wasting associated with cancer cachexia. In this study, we have extended these analyses to detailed studies of regulation of myofibrillar protein synthesis at the gene level, myofibrillar protein expression and regulation of muscle contraction at the muscle cell level in a 63...

  3. Drugs in development for treatment of patients with cancer-related anorexia and cachexia syndrome

    OpenAIRE

    Mantovani G.; Madeddu C; Maccio A

    2013-01-01

    This paper has been retracted. Giovanni Mantovani, Clelia Madeddu, Antonio MacciòDepartment of Medical Oncology, University of Cagliari, Cagliari, ItalyAbstract: Cancer-related anorexia and cachexia syndrome (CACS) is a complex multifactorial condition, with loss of lean body mass, chronic inflammation, severe metabolic derangements, reduced food intake, reduced physical activity, and poor quality of life as key symptoms. Cachexia recognizes different phases or st...

  4. Potentiation of ghrelin signaling attenuates cancer anorexia–cachexia and prolongs survival

    OpenAIRE

    Fujitsuka, N.; Asakawa, A; Uezono, Y; K. Minami; Yamaguchi, T.; Niijima, A.; Yada, T.; Maejima, Y; Sedbazar, U; Sakai, T; Hattori, T.; Kase, Y; Inui, A

    2011-01-01

    Cancer anorexia–cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut–brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia–cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropi...

  5. Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia

    OpenAIRE

    Ihnatko, Robert; Post, Claes; Blomqvist, Anders

    2013-01-01

    Background: Anorexia-cachexia is a common and severe cancer-related complication but the underlying mechanisms are largely unknown. Here, using a mouse model for tumour-induced anorexia-cachexia, we screened for proteins that are differentially expressed in the hypothalamus, the brain’s metabolic control centre. Methods: The hypothalamus of tumour-bearing mice with implanted methylcholanthrene-induced sarcoma (MCG 101) displaying anorexia and their sham-implanted pair-fed or free-fed litterma...

  6. EICOSAPENTAENOIC ACID AS ADJUVANT FOR CACHEXIA IN CANCER’S PATIENTS

    OpenAIRE

    Soeseno Hadi; Cynthia Kurniawan; Jansen Budiono

    2015-01-01

    Cachexia is a frequent problem in cancer patients associated with mortality and morbidity since it causes death, reduced therapy effectiveness, as well as decreased quality of life. Cachexia emerges from interactions of several factors, namely metabolic effect of cancer cells, factors released by cancer cells, cytokines release from host cell in response to tumors, and side effects of therapies. Combination of these factors contributes to anorexia, decreased body fat and muscle, and weight lo...

  7. Combined approach to counteract experimental cancer cachexia: eicosapentaenoic acid and training exercise

    OpenAIRE

    Penna, Fabio; Busquets, Silvia; Pin, Fabrizio; Toledo, Miriam; Francesco M Baccino; López-Soriano, Francisco J.; Costelli, Paola; Argilés, Josep M.

    2011-01-01

    Background Cancer cachexia is a syndrome characterized by loss of skeletal muscle protein, depletion of lipid stores, anorexia, weakness, and perturbations of the hormonal homeostasis. Despite several therapeutic approaches described in the past, effective interventions countering cancer cachexia are still lacking. Methods The present work was aimed to verify the ability of eicosapentaenoic acid (EPA) to prevent the muscle depletion in Lewis lung carcinoma-bearing mice and to test the ability...

  8. Erythropoietin administration partially prevents adipose tissue loss in experimental cancer cachexia models

    OpenAIRE

    Penna, Fabio; Busquets, Silvia; Toledo, Miriam; Pin, Fabrizio; Massa, David; López-Soriano, Francisco J.; Costelli, Paola; Argilés, Josep M.

    2013-01-01

    Cancer-associated cachexia is characterized, among other symptoms, by a dramatic loss of both muscle and fat. In addition, the cachectic syndrome is often associated with anemia. The object of the present investigation was to assess the effects of erythropoietin (EPO) treatment on experimental cancer cachexia models. The results clearly show that, in addition to the improvement of the hematocrit, EPO treatment promoted a partial preservation of adipose tissue while exerting negligible effects...

  9. A Pegylated Leptin Antagonist Ameliorates CKD-Associated Cachexia in Mice

    OpenAIRE

    Cheung, Wai W.; Ding, Wei; Gunta, Sujana S.; Gu, Yong; Tabakman, Rinat; Klapper, Leah N.; Gertler, Arieh; Mak, Robert H.

    2013-01-01

    Elevated serum leptin levels correlate with inflammation and predict changes in lean body mass in patients with CKD, and activation of the melanocortin system by leptin signaling mediates the pathophysiology of CKD-associated cachexia. We tested whether treatment with a pegylated leptin receptor antagonist (PLA) attenuates cachexia in mice with CKD. CKD and Sham mice received vehicle or PLA (2 or 7 mg/kg per day). At these doses, PLA did not influence serum leptin levels in mice. Treatment wi...

  10. P-selectin genotype is associated with the development of cancer cachexia

    OpenAIRE

    Tan, Benjamin H.L.; Fladvad, Torill; Braun, Theodore P.; Vigano, Antonio; Strasser, Florian; Deans, D A Christopher; Skipworth, Richard J. E.; Solheim, Tora S; Damaraju, Sambasivarao; Ross, James A.; Kaasa, Stein; Marks, Daniel L.; Baracos, Vickie E; Skorpen, Frank; Fearon, Kenneth C H

    2012-01-01

    The variable predisposition to cachexia may, in part, be due to the interaction of host genotype. We analyzed 129 single nucleotide polymorphisms (SNPs) in 80 genes for association with cachexia based on degree of weight loss (>5, >10, >15%) as well as weight loss in the presence of systemic inflammation (C-reactive protein, >10 mg/l). 775 cancer patients were studied with a validation association study performed on an independently recruited cohort (n = 101) of cancer patients. The C allele ...

  11. [The Nutritional Care Experience of a Post-Operative Periampullary Cancer Patient With Cachexia].

    Science.gov (United States)

    Liou, Yan-Ting; Chiang, Pin-Yi; Shun, Shiow-Ching

    2016-04-01

    Cachexia is one of the most widely overlooked of the syndromes that are experienced by cancer patients. This syndrome is especially prevalent among patients with gastroenterology tract cancer. Although the National Comprehensive Cancer Network (NCCN) issued palliative-care practice guidelines for cachexia in 2015, guidelines have yet to be issued for the clinical setting. The authors reviewed the literature and applied their clinical experience to create an approach for identifying the degree of cachexia in a post-operative patient with periampullary cancer. This approach assesses the nutritional status, physical status, laboratory results, and gastrointestinal system functions of the patient using the Cachexia Assessment Scale (CAS) and NCCN Practice Guidelines for Cachexia. The patient improved under nursing care with an increase in nutritional intake and physical activity facilitating their process of post-surgical physical recovery. The authors hope that this experience using the combined CAS-NCCN Practice Guidelines will help clinical caregivers better understand how to apply the relevant guidelines in clinical settings. The developed approach may help nurses assess the comprehensive nutrition status of patients and related factors in order to provide interventions that will decrease the progression of cachexia effectively and promote quality of life. PMID:27026565

  12. Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting: potential therapeutic targets for cardiac cachexia

    OpenAIRE

    Yoshida, Tadashi; Tabony, A. Michael; Galvez, Sarah; Mitch, William E.; Higashi, Yusuke; Sukhanov, Sergiy; Delafontaine, Patrice

    2013-01-01

    Cachexia is a serious complication of many chronic diseases, such as congestive heart failure (CHF) and chronic kidney disease (CKD). Many factors are involved in the development of cachexia, and there is increasing evidence that angiotensin II (Ang II), the main effector molecule of the renin-angiotensin system (RAS), plays an important role in this process. Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme (ACE) inhibitor tr...

  13. The regulation of skeletal muscle protein turnover during the progression of cancer cachexia in the Apc(Min/+ mouse.

    Directory of Open Access Journals (Sweden)

    James P White

    Full Text Available Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The Apc(Min/+ mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the Apc(Min/+ mouse is not known. Cachexia progression was studied in Apc(Min/+ mice that were either weight stable (WS or had initial (≤5%, intermediate (6-19%, or extreme (≥20% body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172, AMPK activity, and raptor phosphorylation (Ser 792 were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process.

  14. Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia

    International Nuclear Information System (INIS)

    At present pathogenic mechanisms of cancer cachexia are poorly understood. Previous evidence in animal models implicates the melanocortin-4 receptor gene (MC4R) in the development of cancer cachexia. In humans, MC4R mutations that lead to an impaired receptor function are associated with obesity; in contrast, the most frequent polymorphism (Val103Ile, rs2229616; heterozygote frequency approximately 2%) was shown to be negatively associated with obesity. We tested if cancer patients that are homo-/heterozygous for the Val103Ile polymorphism are more likely to develop cachexia and/or a loss of appetite than non-carriers of the 103Ile-allele. BMI (body mass index in kg/m2) of 509 patients (295 males) with malignant neoplasms was determined; additionally patients were asked about premorbid/pretherapeutical changes of appetite and weight loss. Cachexia was defined as a weight loss of at least 5% prior to initiation of therapy; to fulfil this criterion this weight loss had to occur independently of other plausible reasons; in single cases weight loss was the initial reason for seeing a physician. The average age in years (± SD) was 59.0 ± 14.5 (males: 58.8 ± 14.0, females 59.2 ± 14.0). Blood samples were taken for genotyping of the Val103Ile by PCR- RFLP. Most of the patients suffered from lymphoma, leukaemia and gastrointestinal tumours. 107 of the patients (21%) fulfilled our criteria for cancer cachexia. We did not detect association between the Val103Ile polymorphism and cancer cachexia. However, if we exploratively excluded the patients with early leucaemic stages, we detected a trend towards the opposite effect (p < 0.05); heterozygotes for the 103Ile-allele developed cancer cachexia less frequently in comparison to the rest of the study group. Changes of appetite were not associated with the 103Ile-allele carrier status (p > 0.39). Heterozygotes for the 103Ile-allele are not more prone to develop cancer cachexia than patients without this allele; possibly, Ile

  15. Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia

    International Nuclear Information System (INIS)

    Cachexia, progressive loss of fat and muscle mass despite adequate nutrition, is a devastating complication of cancer associated with poor quality of life and increased mortality. Myostatin is a potent tonic muscle growth inhibitor. We tested how myostatin inhibition might influence cancer cachexia using genetic and pharmacological approaches. First, hypermuscular myostatin null mice were injected with Lewis lung carcinoma or B16F10 melanoma cells. Myostatin null mice were more sensitive to tumor-induced cachexia, losing more absolute mass and proportionately more muscle mass than wild-type mice. Because myostatin null mice lack expression from development, however, we also sought to manipulate myostatin acutely. The histone deacetylase inhibitor Trichostatin A has been shown to increase muscle mass in normal and dystrophic mice by inducing the myostatin inhibitor, follistatin. Although Trichostatin A administration induced muscle growth in normal mice, it failed to preserve muscle in colon-26 cancer cachexia. Finally we sought to inhibit myostatin and related ligands by administration of the Activin receptor extracellular domain/Fc fusion protein, ACVR2B-Fc. Systemic administration of ACVR2B-Fc potently inhibited muscle wasting and protected adipose stores in both colon-26 and Lewis lung carcinoma cachexia, without affecting tumor growth. Enhanced cachexia in myostatin knockouts indicates that host-derived myostatin is not the sole mediator of muscle wasting in cancer. More importantly, skeletal muscle preservation with ACVR2B-Fc establishes that targeting myostatin-family ligands using ACVR2B-Fc or related molecules is an important and potent therapeutic avenue in cancer cachexia.

  16. Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia

    Energy Technology Data Exchange (ETDEWEB)

    Benny Klimek, Margaret E.; Aydogdu, Tufan [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Link, Majik J.; Pons, Marianne [Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Koniaris, Leonidas G. [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology and Experimental Therapeutics Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL (United States); Zimmers, Teresa A., E-mail: tzimmers@med.miami.edu [Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology Program, Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL (United States); Molecular Oncology and Experimental Therapeutics Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL (United States)

    2010-01-15

    Cachexia, progressive loss of fat and muscle mass despite adequate nutrition, is a devastating complication of cancer associated with poor quality of life and increased mortality. Myostatin is a potent tonic muscle growth inhibitor. We tested how myostatin inhibition might influence cancer cachexia using genetic and pharmacological approaches. First, hypermuscular myostatin null mice were injected with Lewis lung carcinoma or B16F10 melanoma cells. Myostatin null mice were more sensitive to tumor-induced cachexia, losing more absolute mass and proportionately more muscle mass than wild-type mice. Because myostatin null mice lack expression from development, however, we also sought to manipulate myostatin acutely. The histone deacetylase inhibitor Trichostatin A has been shown to increase muscle mass in normal and dystrophic mice by inducing the myostatin inhibitor, follistatin. Although Trichostatin A administration induced muscle growth in normal mice, it failed to preserve muscle in colon-26 cancer cachexia. Finally we sought to inhibit myostatin and related ligands by administration of the Activin receptor extracellular domain/Fc fusion protein, ACVR2B-Fc. Systemic administration of ACVR2B-Fc potently inhibited muscle wasting and protected adipose stores in both colon-26 and Lewis lung carcinoma cachexia, without affecting tumor growth. Enhanced cachexia in myostatin knockouts indicates that host-derived myostatin is not the sole mediator of muscle wasting in cancer. More importantly, skeletal muscle preservation with ACVR2B-Fc establishes that targeting myostatin-family ligands using ACVR2B-Fc or related molecules is an important and potent therapeutic avenue in cancer cachexia.

  17. Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies

    Indian Academy of Sciences (India)

    N. Johns; B. H. Tan; M. Macmillan; T. S. Solheim; J. A. Ross; V. E. Baracos; S. Damaraju; K. C. H. Fearon

    2014-12-01

    Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986–2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and

  18. Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R in cancer cachexia

    Directory of Open Access Journals (Sweden)

    Scherag André

    2008-03-01

    Full Text Available Abstract Background At present pathogenic mechanisms of cancer cachexia are poorly understood. Previous evidence in animal models implicates the melanocortin-4 receptor gene (MC4R in the development of cancer cachexia. In humans, MC4R mutations that lead to an impaired receptor function are associated with obesity; in contrast, the most frequent polymorphism (Val103Ile, rs2229616; heterozygote frequency approximately 2% was shown to be negatively associated with obesity. We tested if cancer patients that are homo-/heterozygous for the Val103Ile polymorphism are more likely to develop cachexia and/or a loss of appetite than non-carriers of the 103Ile-allele. Methods BMI (body mass index in kg/m2 of 509 patients (295 males with malignant neoplasms was determined; additionally patients were asked about premorbid/pretherapeutical changes of appetite and weight loss. Cachexia was defined as a weight loss of at least 5% prior to initiation of therapy; to fulfil this criterion this weight loss had to occur independently of other plausible reasons; in single cases weight loss was the initial reason for seeing a physician. The average age in years (± SD was 59.0 ± 14.5 (males: 58.8 ± 14.0, females 59.2 ± 14.0. Blood samples were taken for genotyping of the Val103Ile by PCR- RFLP. Results Most of the patients suffered from lymphoma, leukaemia and gastrointestinal tumours. 107 of the patients (21% fulfilled our criteria for cancer cachexia. We did not detect association between the Val103Ile polymorphism and cancer cachexia. However, if we exploratively excluded the patients with early leucaemic stages, we detected a trend towards the opposite effect (p 0.39. Conclusion Heterozygotes for the 103Ile-allele are not more prone to develop cancer cachexia than patients without this allele; possibly, Ile103 carriers might be more resistant to cancer cachexia in patients with solid tumors. Further studies of the melanocortinergic system in cachexia of

  19. Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia

    Science.gov (United States)

    Schäfer, Michaela; Oeing, Christian U.; Rohm, Maria; Baysal-Temel, Ezgi; Lehmann, Lorenz H.; Bauer, Ralf; Volz, H. Christian; Boutros, Michael; Sohn, Daniela; Sticht, Carsten; Gretz, Norbert; Eichelbaum, Katrin; Werner, Tessa; Hirt, Marc N.; Eschenhagen, Thomas; Müller-Decker, Karin; Strobel, Oliver; Hackert, Thilo; Krijgsveld, Jeroen; Katus, Hugo A.; Berriel Diaz, Mauricio; Backs, Johannes; Herzig, Stephan

    2015-01-01

    Objectives Cancer cachexia affects the majority of tumor patients and significantly contributes to high mortality rates in these subjects. Despite its clinical importance, the identity of tumor-borne signals and their impact on specific peripheral organ systems, particularly the heart, remain mostly unknown. Methods and results By combining differential colon cancer cell secretome profiling with large-scale cardiomyocyte phenotyping, we identified a signature panel of seven “cachexokines”, including Bridging integrator 1, Syntaxin 7, Multiple inositol-polyphosphate phosphatase 1, Glucosidase alpha acid, Chemokine ligand 2, Adamts like 4, and Ataxin-10, which were both sufficient and necessary to trigger cardiac atrophy and aberrant fatty acid metabolism in cardiomyocytes. As a prototypical example, engineered secretion of Ataxin-10 from non-cachexia-inducing cells was sufficient to induce cachexia phenotypes in cardiomyocytes, correlating with elevated Ataxin-10 serum levels in murine and human cancer cachexia models. Conclusions As Ataxin-10 serum levels were also found to be elevated in human cachectic cancer patients, the identification of Ataxin-10 as part of a cachexokine cocktail now provides a rational approach towards personalized predictive, diagnostic and therapeutic measures in cancer cachexia. PMID:26909315

  20. Rikkunshito Ameliorates Cancer Cachexia Partly through Elevation of Glucarate in Plasma

    Directory of Open Access Journals (Sweden)

    Katsuya Ohbuchi

    2015-01-01

    Full Text Available Cancer cachexia, which is characterized by decreased food intake, weight loss and systemic inflammation, increases patient’s morbidity and mortality. We previously showed that rikkunshito (RKT, a Japanese traditional herbal medicine (Kampo, ameliorated the symptoms of cancer cachexia through ghrelin signaling-dependent and independent pathways. To investigate other mechanisms of RKT action in cancer cachexia, we performed metabolome analysis of plasma in a rat model bearing the Yoshida AH-130 hepatoma. A total of 110 metabolites were detected in plasma and RKT treatment significantly altered levels of 23 of those metabolites in cachexia model rats. Among them, glucarate, which is known to have anticarcinogenic activity through detoxification of carcinogens via inhibition of β-glucuronidase, was increased in plasma following administration of RKT. In our AH-130 ascites-induced cachexia rat model, administration of glucarate delayed onset of weight loss, improved muscle atrophy, and reduced ascites content. Additionally, glucarate reduced levels of plasma interferon-γ (IFN-γ in tumor-bearing rats and was also found to suppress LPS-induced IFN-γ expression in splenocytes in vitro. These results suggest that glucarate has anti-inflammatory activity via a direct effect on immune host cells and suggest that RKT may also ameliorate inflammation partly through the elevation of glucarate in plasma.

  1. A non-human primate model of radiation-induced cachexia

    Science.gov (United States)

    Cui, Wanchang; Bennett, Alexander W.; Zhang, Pei; Barrow, Kory R.; Kearney, Sean R.; Hankey, Kim G.; Taylor-Howell, Cheryl; Gibbs, Allison M.; Smith, Cassandra P.; MacVittie, Thomas J.

    2016-01-01

    Cachexia, or muscle wasting, is a serious health threat to victims of radiological accidents or patients receiving radiotherapy. Here, we propose a non-human primate (NHP) radiation-induced cachexia model based on clinical and molecular pathology findings. NHP exposed to potentially lethal partial-body irradiation developed symptoms of cachexia such as body weight loss in a time- and dose-dependent manner. Severe body weight loss as high as 20–25% was observed which was refractory to nutritional intervention. Radiographic imaging indicated that cachectic NHP lost as much as 50% of skeletal muscle. Histological analysis of muscle tissues showed abnormalities such as presence of central nuclei, inflammation, fatty replacement of skeletal muscle, and muscle fiber degeneration. Biochemical parameters such as hemoglobin and albumin levels decreased after radiation exposure. Levels of FBXO32 (Atrogin-1), ActRIIB and myostatin were significantly changed in the irradiated cachectic NHP compared to the non-irradiated NHP. Our data suggest NHP that have been exposed to high dose radiation manifest cachexia-like symptoms in a time- and dose-dependent manner. This model provides a unique opportunity to study the mechanism of radiation-induced cachexia and will aid in efficacy studies of mitigators of this disease. PMID:27029502

  2. Resistance Exercise Reduces Skeletal Muscle Cachexia and Improves Muscle Function in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Salaheddin Sharif

    2011-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic, systemic, autoimmune, inflammatory disease associated with cachexia (reduced muscle and increased fat. Although strength-training exercise has been used in persons with RA, it is not clear if it is effective for reducing cachexia. A 46-year-old woman was studied to determine: (i if resistance exercise could reverse cachexia by improving muscle mass, fiber cross-sectional area, and muscle function; and (2 if elevated apoptotic signaling was involved in cachexia with RA and could be reduced by resistance training. A needle biopsy was obtained from the vastus lateralis muscle of the RA subject before and after 16 weeks of resistance training. Knee extensor strength increased by 13.6% and fatigue decreased by 2.8% Muscle mass increased by 2.1%. Average muscle fiber cross-sectional area increased by 49.7%, and muscle nuclei increased slightly after strength training from 0.08 to 0.12 nuclei/μm2. In addition, there was a slight decrease (1.6% in the number of apoptotic muscle nuclei after resistance training. This case study suggests that resistance training may be a good tool for increasing the number of nuclei per fiber area, decreasing apoptotic nuclei, and inducing fiber hypertrophy in persons with RA, thereby slowing or reversing rheumatoid cachexia.

  3. Pathophysiology of anorexia in the cancer cachexia syndrome.

    Science.gov (United States)

    Ezeoke, Chukwuemeka Charles; Morley, John E

    2015-12-01

    Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients. PMID:26675762

  4. Rheumatoid cachexia revisited: a metabolic co-morbidity in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kayo eMasuko

    2014-11-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease in which pro-inflammatory cytokines, including tumor necrosis factor (TNF-alpha, play a crucial role. The chronic inflammation, combined with reduced physical activity, leads to muscle wasting whereas fat mass would be maintained; the resulting abnormal metabolic state is described as rheumatoid cachexia. Since the loss of muscle volume would be compensated by the increased fat mass, body mass index (BMI is reported not to reflect the nutritional status in RA patients. The implication of rheumatoid cachexia for cardiovascular risk and clinical prognosis is not clearly understood, however, adequate control of disease activity in combination with appropriate physical exercise could be the most important strategy to control rheumatoid cachexia and related metabolic problems.

  5. Intervention of Mirtazapine on gemcitabine-induced mild cachexia in nude mice with pancreatic carcinoma xenografts

    Institute of Scientific and Technical Information of China (English)

    Shu-Man Jiang; Jian-Hua Wu; Lin Jia

    2012-01-01

    AIM:To investigate the effect of Mirtazapine on tumor growth,food intake,body weight,and nutritional status in gemcitabine-induced mild cachexia.METHODS:Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into Mirtazapine and control groups.Either Mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation.A model of mild cachexia was then established in both groups by intraperitoneal injection of Gemcitabine (50 mg/kg) 10 d,13 d,and 16 d after tumor implantation.Tumor size,food intake,body weight,and nutritional status were measured during the experiment.All mice were sacrificed at day 28.RESULTS:(1) After 7 d of gemcitabine administration,body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the Mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period,food intake and body weight were slightly greater for the Mirtazapine group compared with controls (although these differences were not statistically significant).After 21 d,mice in the Mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g,P =0.004).After 25 d,mice in the Mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g,P =0.014).CONCLUSION:Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice.Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice.It was believed to provide a potential therapeutic perspective for further studies on cachexia.

  6. Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer

    International Nuclear Information System (INIS)

    IL-1beta has been implicated in inflammatory episode. In view of the inflammatory nature of cancer cachexia, we determined the predictive value of IL-1B-31 T/C, -511 C/T, +3954 C/T and IL-1RN VNTR gene polymorphisms on the occurrence of cachexia associated with locally advanced gastric cancer. The study included 214 patients and 230 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using restriction fragment length polymorphism analysis of polymerase chain reaction products. The overall frequencies of IL-1B-31 T, -511 T, +3954 T and IL-1RN VNTR alleles in patients with locally advanced gastric cancer were all comparable with those in controls. No significant differences were found in the distribution of IL-1B-31 T, -511 T and IL-1RN VNTR between patients with cachexia and without. Patients with cachexia showed a significantly higher prevalence of IL-1B+3954 T allele than those without (P = 0.018). In a logistic regression analysis adjusted for actual weight, carcinoma location and stage, the IL-1B+3954 CT genotype was associated with an odds ratio of 2.512 (95% CI, 1.180 – 5.347) for cachexia. The IL-1B+3954 T allele is a major risk for cachexia from locally gastric cancer. Genetic factors studied are not likely to play an important role in the determination of susceptibility to locally advanced gastric cancer

  7. Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Yu Baojun

    2007-03-01

    Full Text Available Abstract Background IL-1beta has been implicated in inflammatory episode. In view of the inflammatory nature of cancer cachexia, we determined the predictive value of IL-1B-31 T/C, -511 C/T, +3954 C/T and IL-1RN VNTR gene polymorphisms on the occurrence of cachexia associated with locally advanced gastric cancer. Methods The study included 214 patients and 230 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using restriction fragment length polymorphism analysis of polymerase chain reaction products. Results The overall frequencies of IL-1B-31 T, -511 T, +3954 T and IL-1RN VNTR alleles in patients with locally advanced gastric cancer were all comparable with those in controls. No significant differences were found in the distribution of IL-1B-31 T, -511 T and IL-1RN VNTR between patients with cachexia and without. Patients with cachexia showed a significantly higher prevalence of IL-1B+3954 T allele than those without (P = 0.018. In a logistic regression analysis adjusted for actual weight, carcinoma location and stage, the IL-1B+3954 CT genotype was associated with an odds ratio of 2.512 (95% CI, 1.180 – 5.347 for cachexia. Conclusion The IL-1B+3954 T allele is a major risk for cachexia from locally gastric cancer. Genetic factors studied are not likely to play an important role in the determination of susceptibility to locally advanced gastric cancer.

  8. Unlocking the wasting enigma: Highlights from the 8th Cachexia Conference.

    Science.gov (United States)

    Ebner, Nicole; von Haehling, Stephan

    2016-03-01

    This article highlights pre-clinical and clinical studies into the field of wasting disorders that were presented at the 8th Cachexia Conference held in Paris, France December 2015. This year some interesting results of clinical trials and different new therapeutic targets were shown. This article presents the biological and clinical significance of different markers and new drugs for the treatment of skeletal muscle wasting. Effective treatments of cachexia and wasting disorders are urgently needed in order to improve the patients' quality of life and their survival. PMID:27128291

  9. Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer

    OpenAIRE

    Yu Baojun; Tang Xingming; Zhou Yanbing; Zheng Hongmei; Zhang Dianliang; Li Jieshou

    2007-01-01

    Abstract Background IL-1beta has been implicated in inflammatory episode. In view of the inflammatory nature of cancer cachexia, we determined the predictive value of IL-1B-31 T/C, -511 C/T, +3954 C/T and IL-1RN VNTR gene polymorphisms on the occurrence of cachexia associated with locally advanced gastric cancer. Methods The study included 214 patients and 230 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in pat...

  10. [Contribution of nutritional support to fight cancer cachexia].

    Science.gov (United States)

    Planas, M; Puiggrós, C; Redecillas, S

    2006-05-01

    To increase dietary intake and to fight anorexia several measures to treat symptoms and administer the most adequate diet according to composition, texture and flavour are proposed. However, in the anorexia-caquexia present in cancer patients not always these measures are effective. Now a day it seems more reasonable to approach this problem with different strategies directed to modulate the pathologic alterations associated. The analysis of specific nutritional support as part as the treatment of these patients from a systematic review conclude that no high methodological quality studies to analyze the impact of oral supplementation on a specific group of patients, neither the study of functional effects are done. However, an increase in the total energy intake, not maintained over the time, was observed. The effects on weight and corporal composition are variable, with small differences between groups with o without supplementation and confuse due to, mainly, the heterogeneity of the patients included in the different studies analyzed. The analysis of the effects of nutritional supplements administered by enteral feeding shown an increase in the energy intake with an increase in body weight or a lack of decrease it, and with some functional and clinical beneficial effects. Despite the results and conclusions obtained, a strong recommendation to conduct clinical trials in specific group of cancer patients with different antineoplasic treatment seems necessary. N-3 fatty acids, especially eicosapentaenoic acid may have anticachectic properties. Although further trials are necessary the limited results available suggests that nutritional supplements enriched with EPA may reverse cachexia in cancer patients. PMID:16768028

  11. Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma.

    Science.gov (United States)

    Mu, Xiaodong; Agarwal, Rashmi; March, Daniel; Rothenberg, Adam; Voigt, Clifford; Tebbets, Jessica; Huard, Johnny; Weiss, Kurt

    2016-01-01

    Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy. In vitro coculture of osteosarcoma cells with muscle-derived stem cells (MDSCs) isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia. PMID:27378829

  12. Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia

    Directory of Open Access Journals (Sweden)

    Michaela Schäfer

    2016-02-01

    Conclusions: As Ataxin-10 serum levels were also found to be elevated in human cachectic cancer patients, the identification of Ataxin-10 as part of a cachexokine cocktail now provides a rational approach towards personalized predictive, diagnostic and therapeutic measures in cancer cachexia.

  13. Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia.

    Science.gov (United States)

    Bindels, Laure B; Neyrinck, Audrey M; Claus, Sandrine P; Le Roy, Caroline I; Grangette, Corinne; Pot, Bruno; Martinez, Inés; Walter, Jens; Cani, Patrice D; Delzenne, Nathalie M

    2016-06-01

    Cancer cachexia is a multifactorial syndrome that includes muscle wasting and inflammation. As gut microbes influence host immunity and metabolism, we investigated the role of the gut microbiota in the therapeutic management of cancer and associated cachexia. A community-wide analysis of the caecal microbiome in two mouse models of cancer cachexia (acute leukaemia or subcutaneous transplantation of colon cancer cells) identified common microbial signatures, including decreased Lactobacillus spp. and increased Enterobacteriaceae and Parabacteroides goldsteinii/ASF 519. Building on this information, we administered a synbiotic containing inulin-type fructans and live Lactobacillus reuteri 100-23 to leukaemic mice. This treatment restored the Lactobacillus population and reduced the Enterobacteriaceae levels. It also reduced hepatic cancer cell proliferation, muscle wasting and morbidity, and prolonged survival. Administration of the synbiotic was associated with restoration of the expression of antimicrobial proteins controlling intestinal barrier function and gut immunity markers, but did not impact the portal metabolomics imprinting of energy demand. In summary, this study provided evidence that the development of cancer outside the gut can impact intestinal homeostasis and the gut microbial ecosystem and that a synbiotic intervention, by targeting some alterations of the gut microbiota, confers benefits to the host, prolonging survival and reducing cancer proliferation and cachexia. PMID:26613342

  14. The central role of hypothalamic inflammation in the acute illness response and cachexia.

    Science.gov (United States)

    Burfeind, Kevin G; Michaelis, Katherine A; Marks, Daniel L

    2016-06-01

    When challenged with a variety of inflammatory threats, multiple systems across the body undergo physiological responses to promote defense and survival. The constellation of fever, anorexia, and fatigue is known as the acute illness response, and represents an adaptive behavioral and physiological reaction to stimuli such as infection. On the other end of the spectrum, cachexia is a deadly and clinically challenging syndrome involving anorexia, fatigue, and muscle wasting. Both of these processes are governed by inflammatory mediators including cytokines, chemokines, and immune cells. Though the effects of cachexia can be partially explained by direct effects of disease processes on wasting tissues, a growing body of evidence shows the central nervous system (CNS) also plays an essential mechanistic role in cachexia. In the context of inflammatory stress, the hypothalamus integrates signals from peripheral systems, which it translates into neuroendocrine perturbations, altered neuronal signaling, and global metabolic derangements. Therefore, we will discuss how hypothalamic inflammation is an essential driver of both the acute illness response and cachexia, and why this organ is uniquely equipped to generate and maintain chronic inflammation. First, we will focus on the role of the hypothalamus in acute responses to dietary and infectious stimuli. Next, we will discuss the role of cytokines in driving homeostatic disequilibrium, resulting in muscle wasting, anorexia, and weight loss. Finally, we will address mechanisms and mediators of chronic hypothalamic inflammation, including endothelial cells, chemokines, and peripheral leukocytes. PMID:26541482

  15. Recombinant human erythropoietin attenuates weight loss in a murine cancer cachexia model.

    NARCIS (Netherlands)

    Halteren, H.K. van; Bongaerts, G.P.A.; Verhagen, C.A.H.H.V.M.; Kamm, Y.J.L.; Willems, J.L.; Grutters, G.J.; Koopman, J.P.; Wagener, D.J.T.

    2004-01-01

    BACKGROUND: Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact

  16. Pancreatic cancerrelated cachexia: influence on metabolism and correlation to weight loss and pulmonary function

    International Nuclear Information System (INIS)

    Dramatic weight loss is an often underestimated symptom in pancreatic cancer patients. Cachexia- defined as an unintended loss of stable weight exceeding 10% – is present in up to 80% of patients with cancer of the upper gastrointestinal tract, and has a significant influence on survival. The aim of the study was to show the multiple systemic effects of cachexia in pancreatic cancer patients, in terms of resection rate, effects on pulmonary function, amount of fat and muscle tissue, as well as changes in laboratory parameters. In patients with pancreatic cancer, clinical appearance was documented, including the amount of weight loss. Laboratory parameters and lung-function tests were evaluated, and the thickness of muscle and fat tissue was measured with computed tomography scans. Statistical analysis, including multivariate analysis, was performed using SPSS software. Survival curves were calculated using Kaplan-Meier analysis and the log-rank test. To test for significant differences between the examined groups we used Student's t-test and the Mann-Whitney U test. Significance was defined as p < 0.05. Of 198 patients with a ductal adenocarcinoma of the pancreas, 70% were suffering from weight loss when they presented for operation, and in 40% weight loss exceeded 10% of the stable weight. In patients with cachexia, metastases were diagnosed significantly more often (47% vs. 24%, P < 0.001), leading to a significantly reduced resection rate in these patients. Patients with cachexia had significantly reduced fat tissue amounts. Hence, dramatic weight loss in a patient with pancreatic cancer may be a hint of a more progressed or more aggressive tumour. Pancreatic cancer patients with cachexia had a higher rate of more progressed tumour stages and a worse nutritional status. Furthermore, patients with cachexia had an impaired lung function and a reduction in fat tissue. Patients with pancreatic cancer and cachexia had significantly reduced survival. If weight

  17. Proteomic analysis of media from lung cancer cells reveals role of 14-3-3 proteins in cachexia

    OpenAIRE

    Julie B. McLean; Moylan, Jennifer S.; Horrell, Erin M. W.; Andrade, Francisco H.

    2015-01-01

    Aims: At the time of diagnosis, 60% of lung cancer patients present with cachexia, a severe wasting syndrome that increases morbidity and mortality. Tumors secrete multiple factors that contribute to cachectic muscle wasting, and not all of these factors have been identified. We used Orbitrap electrospray ionization mass spectrometry to identify novel cachexia-inducing candidates in media conditioned with Lewis lung carcinoma cells (LCM). Results: One-hundred and 58 proteins were confirmed in...

  18. Cleavage of caspases-1, -3, -6, -8 and -9 substrates by proteases in skeletal muscles from mice undergoing cancer cachexia

    OpenAIRE

    Belizário, J E; Lorite, M. J.; Tisdale, M J

    2001-01-01

    A prominent feature of several type of cancer is cachexia. This syndrome causes a marked loss of lean body mass and muscle wasting, and appears to be mediated by cytokines and tumour products. There are several proteases and proteolytic pathways that could be responsible for the protein breakdown. In the present study, we investigated whether caspases are involved in the proteolytic process of skeletal muscle catabolism observed in a murine model of cancer cachexia (MAC16), in comparison with...

  19. Effect of Sipjeondaebo-Tang on Cancer-Induced Anorexia and Cachexia in CT-26 Tumor-Bearing Mice

    OpenAIRE

    Youn Kyung Choi; Ki Yong Jung; Sang-Mi Woo; Yee Jin Yun; Chan-Yong Jun; Jong Hyeong Park; Yong Cheol Shin; Sung-Gook Cho; Seong-Gyu Ko

    2014-01-01

    Cancer-associated anorexia and cachexia are a multifactorial condition described by a loss of body weight and muscle with anorexia, asthenia, and anemia. Moreover, they correlate with a high mortality rate, poor response to chemotherapy, poor performance status, and poor quality of life. Cancer cachexia is regulated by proinflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor- α (TNF- α ). In addition, glucagon like peptide-1...

  20. A systematic review and thematic synthesis of quality of life in the informal carers of cancer patients with cachexia

    OpenAIRE

    Darlington, Anne-Sophie; Hopkinson, J.B.; Fitzsimmons, D.; Johnson, C.D.

    2015-01-01

    Background: informal carers of cancer patients with cachexia face additional challenges to those encountered by informal carers in general because of the central role food and eating play in everyday life. Patient weight loss and anorexia, core features of cancer cachexia, are frequent causes of distress in caregivers. Identification of quality of life (QOL) issues can inform the development of interventions for both caregivers and patients, and facilitate communication with healthcare profes...

  1. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia

    OpenAIRE

    Stephanie H Greco; Lena Tomkötter; Anne-Kristin Vahle; Rae Rokosh; Antonina Avanzi; Syed Kashif Mahmood; Michael Deutsch; Sara Alothman; Dalia Alqunaibit; Atsuo Ochi; Constantinos Zambirinis; Tasnima Mohaimin; Mauricio Rendon; Elliot Levie; Mridul Pansari

    2015-01-01

    Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this s...

  2. Anorexia/cachexia of chronic diseases: a role for the TGF-β family cytokine MIC-1/GDF15

    OpenAIRE

    Tsai, Vicky W. W.; Husaini, Yasmin; Manandhar, Rakesh; Lee-Ng, K. K. Michelle; Zhang, Hong Ping; Harriott, Kate; Jiang, Lele; Lin, Shu; Sainsbury, Amanda; Brown, David A.; Samuel N. Breit

    2012-01-01

    Anorexia/cachexia is a common and currently mostly untreatable complication of advanced cancer. It is also a feature of a number of chronic diseases and can also occur as part of the normal ageing process. Over recent years, two different, but sometimes overlapping, processes have been identified to mediate anorexia/cachexia: those that act primarily on muscle reducing its mass and function, and processes that decrease nutrition leading to loss of both fat and muscle. In the case of at least ...

  3. Diet-induced Obesity and Insulin Resistance Spur Tumor Growth and Cancer Cachexia in Rats Bearing the Yoshida Sarcoma

    OpenAIRE

    Honors, Mary Ann; Kinzig, Kimberly P.

    2014-01-01

    Obesity and insulin resistance are associated with increased risk of cancer and cancer mortality. However, it is currently unknown whether they contribute to the development of cancer cachexia, a syndrome that contributes significantly to morbidity and mortality in individuals with cancer. The present experiment addresses the question of whether pre-existing obesity and insulin resistance alter tumor growth and cancer cachexia symptoms in Yoshida sarcoma bearing male rats. Obesity and insulin...

  4. The Challenge of Appropriate Identification and Treatment of Starvation, Sarcopenia, and Cachexia: A Survey of Australian Dietitians

    OpenAIRE

    Alison Yaxley; Miller, Michelle D.

    2011-01-01

    Malnutrition is an umbrella term that includes starvation, sarcopenia, and cachexia; however, differentiating between these terms is infrequent in clinical practice. Given that the effectiveness of treatment depends on the aetiology of unintentional weight loss, it is important that clinicians are aware of the defining characteristics. The aim of this study was to determine whether Australian dietitians understand and use the terms starvation, sarcopenia, and cachexia and provide targeted tre...

  5. The Challenge of Appropriate Identification and Treatment of Starvation, Sarcopenia, and Cachexia: A Survey of Australian Dietitians

    Directory of Open Access Journals (Sweden)

    Alison Yaxley

    2011-01-01

    Full Text Available Malnutrition is an umbrella term that includes starvation, sarcopenia, and cachexia; however, differentiating between these terms is infrequent in clinical practice. Given that the effectiveness of treatment depends on the aetiology of unintentional weight loss, it is important that clinicians are aware of the defining characteristics. The aim of this study was to determine whether Australian dietitians understand and use the terms starvation, sarcopenia, and cachexia and provide targeted treatment strategies accordingly. Members of the Dietitians Association of Australia were surveyed to gain information on practices and attitudes to diagnosis and treatment of adult malnutrition. In addition, three case studies were provided to examine understanding of starvation, sarcopenia, and cachexia. 221 dietitians accessed the survey. 81 respondents (43% indicated the use of at least one alternate term (starvation, sarcopenia, and/or cachexia. Muscle wasting was the most commonly used diagnostic criterion. High-energy high-protein diet was the most common therapy prescribed. Correct diagnoses for case studies were recorded by 6% of respondents for starvation, 46% for sarcopenia, and 21% for cachexia. There is a need for increased awareness of the existence of starvation, sarcopenia, and cachexia amongst Australian dietitians and research into appropriate methods of identification and treatment for each condition.

  6. Theophylline is able to partially revert cachexia in tumour-bearing rats

    Directory of Open Access Journals (Sweden)

    Olivan Mireia

    2012-08-01

    Full Text Available Abstract Background and aims The aim of the present investigation was to examine the anti-wasting effects of theophylline (a methylxantine present in tea leaves on a rat model of cancer cachexia. Methods The in vitro effects of the nutraceuticals on proteolysis were examined on muscle cell cultures submitted to hyperthermia. Individual muscle weights, muscle gene expression, body composition and cardiac function were measured in rats bearing the Yoshida AH-130 ascites hepatoma, following theophylline treatment. Results Theophylline treatment inhibited proteolysis in C2C12 cell line and resulted in an anti-proteolytic effect on muscle tissue (soleus and heart, which was associated with a decrease in circulating TNF-alpha levels and with a decreased proteolytic systems gene expression. Treatment with the nutraceutical also resulted in an improvement in body composition and cardiac function. Conclusion Theophylline - alone or in combination with drugs - may be a candidate molecule for the treatment of cancer cachexia.

  7. Cachexia in chronic kidney disease: a link to defective central nervous system control of appetite

    OpenAIRE

    Mitch, William E.

    2005-01-01

    Anorexia is one of several abnormalities characterizing chronic kidney disease (CKD) that cause cachexia, the loss of muscle and adipose stores. It has been attributed to mechanisms ranging from accumulation of toxic “middle molecules” to psychological problems. In this issue of the JCI, Cheung and coworkers used elegant techniques to demonstrate that CKD-associated anorexia is caused by defective hypothalamic regulation of appetite. They attributed the defect to an alteration in the hypothal...

  8. A Key Role for Leukemia Inhibitory Factor in C26 Cancer Cachexia.

    Science.gov (United States)

    Seto, Danielle N; Kandarian, Susan C; Jackman, Robert W

    2015-08-01

    Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling, and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-κB, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. LIF was elevated in C26 conditioned medium (CM), but IL-6, OSM, TNFα, and myostatin were not. A LIF-blocking antibody abolished C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and myotube atrophy but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3Cβ-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together, these data support an important role of LIF-JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia. PMID:26092726

  9. Is Cancer Cachexia Attributed to Impairments in Basal or Postprandial Muscle Protein Metabolism?

    Science.gov (United States)

    Horstman, Astrid M H; Olde Damink, Steven W; Schols, Annemie M W J; van Loon, Luc J C

    2016-01-01

    Cachexia is a significant clinical problem associated with very poor quality of life, reduced treatment tolerance and outcomes, and a high mortality rate. Mechanistically, any sizeable loss of skeletal muscle mass must be underpinned by a structural imbalance between muscle protein synthesis and breakdown rates. Recent data indicate that the loss of muscle mass with aging is, at least partly, attributed to a blunted muscle protein synthetic response to protein feeding. Whether such anabolic resistance is also evident in conditions where cachexia is present remains to be addressed. Only few data are available on muscle protein synthesis and breakdown rates in vivo in cachectic cancer patients. When calculating the theoretical changes in basal or postprandial fractional muscle protein synthesis and breakdown rates that would be required to lose 5% of body weight within a six-month period, we can define the changes that would need to occur to explain the muscle mass loss observed in cachectic patients. If changes in both post-absorptive and postprandial muscle protein synthesis and breakdown rates contribute to the loss of muscle mass, it would take alterations as small as 1%-2% to induce a more than 5% decline in body weight. Therefore, when trying to define impairments in basal and/or postprandial muscle protein synthesis or breakdown rates using contemporary stable isotope methodology in cancer cachexia, we need to select large homogenous groups of cancer patients (>40 patients) to allow us to measure physiological and clinically relevant differences in muscle protein synthesis and/or breakdown rates. Insight into impairments in basal or postprandial muscle protein synthesis and breakdown rates in cancer cachexia is needed to design more targeted nutritional, pharmaceutical and/or physical activity interventions to preserve skeletal muscle mass and, as such, to reduce the risk of complications, improve quality of life, and lower mortality rates during the various

  10. Treatment of cancer cachexia in the very advanced or terminal phase: a systematic review

    OpenAIRE

    Giuseppe Arvia; Stefano Giordani; Ismaeil Ghaderi; Sharon Nahas; Stefano Diana; Raffaella Indelli; Beatrice Traverso; Giorgio Lelli

    2013-01-01

    The therapeutic approach to refractory cancer cachexia represents an unmet need and an important research priority in the field of palliative care. Unfortunately, clinical studies in this area are scarce, both regarding nutritional and pharmacological approach. We performed a systematic literature search through Pubmed. The search algorithm considered: the clinical context, the related pathology, the therapeutic approach. The abstracts obtained were entered in a spreadsheet and analyzed in fu...

  11. Management of Anorexia-Cachexia in Late Stage Lung Cancer Patients

    OpenAIRE

    Del Ferraro, Catherine; Grant, Marcia; Koczywas, Marianna; Dorr-Uyemura, Laura A.

    2012-01-01

    Nutritional deficiencies are experienced by most adults with advanced lung cancer during the course of their disease and treatment. Well-nourished individuals tolerate cancer treatment with less morbidity, mortality, and increased response to treatment as compared to those who are malnourished. Novel anti-cancer therapies cause many deficits that impact nutritional and functional status during the treatment process. Nutritional deficits include weight loss, malnutrition, and anorexia-cachexia...

  12. Evidence for partial pharmaceutical reversal of the cancer anorexia–cachexia syndrome: the case of anamorelin

    OpenAIRE

    Anker, Stefan D.; Coats, Andrew J S; Morley, John E.

    2015-01-01

    A major component of the cancer anorexia-cachexia syndrome is a decline in food intake. Up until now none of the drugs that improve appetite also improve skeletal muscle. Recent studies have suggested that the oral ghrelin-analog, anamorelin, increased food intake and muscle mass. Unfortunately, it does not increase muscle power. Its regulatory future is uncertain, although it has important clinical effects.

  13. Drugs in development for treatment of patients with cancer-related anorexia and cachexia syndrome [Retraction

    OpenAIRE

    Mantovani G.; Madeddu C; Macciò A

    2013-01-01

     The Editor-in-Chief, Dr Pilch, of Drug Design, Development and Therapy has been alerted to unacceptable levels of duplication between a previously published paper: Macciò A, Madeddu C, Mantovani G. Current pharmacotherapy options for cancer anorexia and cachexia. Expert Opin. Pharmacotherapy 2012 13(17) 2453–2472 and one published subsequently in Drug Design, Development and Therapy: Mantovani G, Madeddu C, Macciò A. Drugs in development for treatment...

  14. Sarcopenia and cachexia: the adaptations of negative regulators of skeletal muscle mass

    OpenAIRE

    Sakuma, Kunihiro; Yamaguchi, Akihiko

    2012-01-01

    Recent advances in our understanding of the biology of muscle, and how anabolic and catabolic stimuli interact to control muscle mass and function, have led to new interest in the pharmacological treatment of muscle wasting. Loss of muscle occurs as a consequence of several chronic diseases (cachexia) as well as normal aging (sarcopenia). Although many negative regulators [Atrogin-1, muscle ring finger-1, nuclear factor-kappaB (NF-κB), myostatin, etc.] have been proposed to enhance protein de...

  15. Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia

    OpenAIRE

    Hall, Derek T; Ma, Jennifer F; Di Marco, Sergio; Gallouzi, Imed-Eddine

    2011-01-01

    Muscle atrophy—also known as muscle wasting—is a debilitating syndrome that slowly develops with age (sarcopenia) or rapidly appears at the late stages of deadly diseases such as cancer, AIDS, and sepsis (cachexia). Despite the prevalence and the drastic detrimental effects of these two syndromes, there are currently no widely used, effective treatment options for those suffering from muscle wasting. In an attempt to identify potential therapeutic targets, the molecular mechanisms of sarcopen...

  16. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training

    OpenAIRE

    Bowen, T Scott; Schuler, Gerhard; Adams, Volker

    2015-01-01

    Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Transmission of external stimuli to intracellular effector proteins via signalling pathways is a highly regulated and controlled process that determines muscle mass by balancing protein synthesis and protein degradation. An impaired balance between protein synthesis and breakdown leads to the development of specific myopathies. Sarcopenia and cachexia represent two distinct muscle wasting dis...

  17. Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer.

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    Stefanie Aust

    Full Text Available Tumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC. Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs ascertained by pre-operative computed tomography (CT. Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients.We evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient's outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis.Muscle attenuation (MA-a well established BCM parameter-is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028. Low MA-reflecting a state of cachexia-is also associated with residual tumor after cytoreductive surgery (p = 0.046 and with an unfavorable performance status (p = 0.015. Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively.MA-ascertained by routine pre-operative CT-is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA.

  18. Improvement of cancer cachexia with chemothermotherapy in a patient with advanced pancreatic cancer

    International Nuclear Information System (INIS)

    The ultimate goal of cancer treatment is to achieve a complete eradication of the cancer. However, patients with terminal cancer are also treated to obtain an improvement in their quality of life (QOL). In this report, we describe the dramatic response of an end-stage pancreatic cancer patient with cachexia to a combination of hyperthermia (HT) and chemotherapy (CH). The patient was treated with a combination of intermittent 5-fluorouracil (5-FU)/cisplatin (CDDP) therapy and HT. Three months later, the local recurrent cancer had disappeared, the liver metastases were reduced by 80%, the lung metastatic lesion was markedly reduced, tumor markers had returned to normal, and the cachexia had been almost reversed. Performance status (PS) improved from 4 to 1, QOL improved, and the patient survived until his 258th hospital day. In this patient, the combination of CH and HT was useful not only for improvement of cachexia, but also for tumor reduction. A possible mechanism leading to this effect is discussed. (author)

  19. A pegylated leptin antagonist ameliorates CKD-associated cachexia in mice.

    Science.gov (United States)

    Cheung, Wai W; Ding, Wei; Gunta, Sujana S; Gu, Yong; Tabakman, Rinat; Klapper, Leah N; Gertler, Arieh; Mak, Robert H

    2014-01-01

    Elevated serum leptin levels correlate with inflammation and predict changes in lean body mass in patients with CKD, and activation of the melanocortin system by leptin signaling mediates the pathophysiology of CKD-associated cachexia. We tested whether treatment with a pegylated leptin receptor antagonist (PLA) attenuates cachexia in mice with CKD. CKD and Sham mice received vehicle or PLA (2 or 7 mg/kg per day). At these doses, PLA did not influence serum leptin levels in mice. Treatment with 7 mg/kg per day PLA stimulated appetite and weight gain, improved lean mass and muscle function, reduced energy expenditure, and normalized the levels of hepatic TNF-α and IL-6 mRNA in mice with CKD. Furthermore, treatment with 7 mg/kg per day PLA attenuated the CKD-associated increase in the transcriptional and protein abundance of uncoupling proteins that mediates thermogenesis, and it normalized the molecular signatures of processes associated with muscle wasting in CKD, including proteolysis, myogenesis and muscle regeneration, and expression of proinflammatory muscle cytokines, such as IL-1α, -1β, and -6 and TNF-α. Our results suggest that leptin antagonism may represent a viable therapeutic strategy for cachexia in CKD. PMID:24115476

  20. IL-6 regulation on skeletal muscle mitochondrial remodeling during cancer cachexia in the ApcMin/+ mouse

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    White James P

    2012-07-01

    Full Text Available Abstract Background Muscle protein turnover regulation during cancer cachexia is being rapidly defined, and skeletal muscle mitochondria function appears coupled to processes regulating muscle wasting. Skeletal muscle oxidative capacity and the expression of proteins regulating mitochondrial biogenesis and dynamics are disrupted in severely cachectic ApcMin/+ mice. It has not been determined if these changes occur at the onset of cachexia and are necessary for the progression of muscle wasting. Exercise and anti-cytokine therapies have proven effective in preventing cachexia development in tumor bearing mice, while their effect on mitochondrial content, biogenesis and dynamics is not well understood. The purposes of this study were to 1 determine IL-6 regulation on mitochondrial remodeling/dysfunction during the progression of cancer cachexia and 2 to determine if exercise training can attenuate mitochondrial dysfunction and the induction of proteolytic pathways during IL-6 induced cancer cachexia. Methods ApcMin/+ mice were examined during the progression of cachexia, after systemic interleukin (IL-6r antibody treatment, or after IL-6 over-expression with or without exercise. Direct effects of IL-6 on mitochondrial remodeling were examined in cultured C2C12 myoblasts. Results Mitochondrial content was not reduced during the initial development of cachexia, while muscle PGC-1α and fusion (Mfn1, Mfn2 protein expression was repressed. With progressive weight loss mitochondrial content decreased, PGC-1α and fusion proteins were further suppressed, and fission protein (FIS1 was induced. IL-6 receptor antibody administration after the onset of cachexia improved mitochondrial content, PGC-1α, Mfn1/Mfn2 and FIS1 protein expression. IL-6 over-expression in pre-cachectic mice accelerated body weight loss and muscle wasting, without reducing mitochondrial content, while PGC-1α and Mfn1/Mfn2 protein expression was suppressed and FIS1 protein expression

  1. Expression of CCAAT/Enhancer Binding Protein Beta in Muscle Satellite Cells Inhibits Myogenesis in Cancer Cachexia.

    Directory of Open Access Journals (Sweden)

    François Marchildon

    Full Text Available Cancer cachexia is a paraneoplastic syndrome that causes profound weight loss and muscle mass atrophy and is estimated to be the cause of up to 30% of cancer deaths. Though the exact cause is unknown, patients with cancer cachexia have increased muscle protein catabolism. In healthy muscle, injury activates skeletal muscle stem cells, called satellite cells, to differentiate and promote regeneration. Here, we provide evidence that this mechanism is inhibited in cancer cachexia due to persistent expression of CCAAT/Enhancer Binding Protein beta (C/EBPβ in muscle myoblasts. C/EBPβ is a bzip transcription factor that is expressed in muscle satellite cells and is normally downregulated upon differentiation. However, in myoblasts exposed to a cachectic milieu, C/EBPβ expression remains elevated, despite activation to differentiate, resulting in the inhibition of myogenin expression and myogenesis. In vivo, cancer cachexia results in increased number of Pax7+ cells that also express C/EBPβ and the inhibition of normal repair mechanisms. Loss of C/EBPβ expression in primary myoblasts rescues differentiation under cachectic conditions without restoring myotube size, indicating that C/EBPβ is an important inhibitor of myogenesis in cancer cachexia.

  2. Brief versions of the FACIT-fatigue and FAACT subscales for patients with non-small cell lung cancer cachexia

    OpenAIRE

    Salsman, John M.; Beaumont, Jennifer L.; WORTMAN, KATY; Yan, Ying; Friend, John; Cella, David

    2014-01-01

    Purpose Cancer anorexia-cachexia syndrome (CACS) is common in advanced cancer patients and associated with weight loss, fatigue, impaired quality of life (QoL), and poor prognosis. The goal of this project was to identify the most responsive items from two QoL measures in the ROMANA 2 (NCT01387282) phase III global study evaluating anamorelin HCl in the treatment of non-small cell lung cancer (NSCLC) cachexia: the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Func...

  3. Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness.

    Science.gov (United States)

    Chacon-Cabrera, Alba; Fermoselle, Clara; Urtreger, Alejandro J; Mateu-Jimenez, Mercè; Diament, Miriam J; de Kier Joffé, Elisa D Bal; Sandri, Marco; Barreiro, Esther

    2014-11-01

    Cachexia is a relevant comorbid condition of chronic diseases including cancer. Inflammation, oxidative stress, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPK) are involved in the pathophysiology of cancer cachexia. Currently available treatment is limited and data demonstrating effectiveness in in vivo models are lacking. Our objectives were to explore in respiratory and limb muscles of lung cancer (LC) cachectic mice whether proteasome, NF-κB, and MAPK inhibitors improve muscle mass and function loss through several molecular mechanisms. Body and muscle weights, limb muscle force, protein degradation and the ubiquitin-proteasome system, signaling pathways, oxidative stress and inflammation, autophagy, contractile and functional proteins, myostatin and myogenin, and muscle structure were evaluated in the diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing cachectic mice (BALB/c), with and without concomitant treatment with NF-κB (sulfasalazine), MAPK (U0126), and proteasome (bortezomib) inhibitors. Compared to control animals, in both respiratory and limb muscles of LC cachectic mice: muscle proteolysis, ubiquitinated proteins, autophagy, myostatin, protein oxidation, FoxO-1, NF-κB and MAPK signaling pathways, and muscle abnormalities were increased, while myosin, creatine kinase, myogenin, and slow- and fast-twitch muscle fiber size were decreased. Pharmacological inhibition of NF-κB and MAPK, but not the proteasome system, induced in cancer cachectic animals, a substantial restoration of muscle mass and force through a decrease in muscle protein oxidation and catabolism, myostatin, and autophagy, together with a greater content of myogenin, and contractile and functional proteins. Attenuation of MAPK and NF-κB signaling pathway effects on muscles is beneficial in cancer-induced cachexia. PMID:24615622

  4. Vagus nerve schwannoma presenting with dysphagia and prolonged cachexia: a case report

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    Ali Ghafouri

    2010-03-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Intraabdominal schwannomas are rare tumors mostly occur in patients with neurofibromatosis. Tumors arisen from vagus nerve are rarer especially in sporadic cases.  "n"nCase: A 34-year-old man admitted in surgery ward Milad Hospital, in Tehran, Iran with long-lasting vomiting, dysphagia, and cachexia for four years. Multiple previous paraclinical assessments were normal, he had been treated as anorexia nervosa for three years without improvement. Our evaluations showed a mass in diaphragmatic hiatus. Explorative laparotomy revealed a mass parallel to distal esophagus, which was resected completely. Immunohistochemical examinations revealed a benign schwannoma. After surgery, the patient's symptoms recovered and he returned to normal life. "n"nConclusions: Vagus nerve schwannoma can present with dysphagia and cachexia with normal endoscopic evaluations. It is important to rule out physical causes in patients with cachexia who are treated with psychiatric diagnoses.

  5. Caquexia associada à insuficiência cardíaca Heart failure-induced cachexia

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    Marina Politi Okoshi

    2013-05-01

    Full Text Available Pacientes com insuficiência cardíaca frequentemente desenvolvem estado de caquexia, que constitui fator independente de redução da sobrevida. Caquexia pode ser diagnosticada quando ocorre perda de peso corporal maior que 6% do peso habitual, na ausência de outras doenças. Embora sua fisiopatologia não esteja completamente esclarecida, vários fatores parecem estar envolvidos, como diminuição da ingestão alimentar, anormalidades do trato gastrointestinal, ativação imunológica e neuro-hormonal e alteração da relação entre processos anabólicos e catabólicos. Como não há terapia específica para a caquexia associada à insuficiência cardíaca, o tratamento baseia-se no suporte nutricional, bloqueio neuro-hormonal, controle do edema e anemia e exercícios físicos. Fármacos com propriedades imunomodulatórias e anabólicas encontram-se em investigação clínica e experimental.Heart failure patients often develop cachexia, which is an independent factor for survival reduction. Cachexia can be diagnosed when there is loss of more than 6% of the body weight, in the absence of other diseases. Even though its pathophysiology has not yet been completely clarified, various factors seem to be involved, such as reduction in food consumption, gastrointestinal tract abnormalities, immunologic and neuro-hormonal activarion and changes in the relationship between anabolic and catabolic processes. Since there is not specific therapy for heart failure-induced cachexia, management is based on nutritional support, neuro-hormonal blockade, control of edema and anemia and exercise. Drugs with anabolic and immunomodulating properties are being evaluated and clinical and non-clinical trials.

  6. Clinical classification of cancer cachexia: phenotypic correlates in human skeletal muscle.

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    Neil Johns

    Full Text Available BACKGROUND: Cachexia affects the majority of patients with advanced cancer and is associated with a reduction in treatment tolerance, response to therapy, and duration of survival. One impediment towards the effective treatment of cachexia is a validated classification system. METHODS: 41 patients with resectable upper gastrointestinal (GI or pancreatic cancer underwent characterisation for cachexia based on weight-loss (WL and/or low muscularity (LM. Four diagnostic criteria were used >5%WL, >10%WL, LM, and LM+>2%WL. All patients underwent biopsy of the rectus muscle. Analysis included immunohistochemistry for fibre size and type, protein and nucleic acid concentration, Western blots for markers of autophagy, SMAD signalling, and inflammation. FINDINGS: Compared with non-cachectic cancer patients, patients with LM or LM+>2%WL, mean muscle fibre diameter was reduced by about 25% (p = 0.02 and p = 0.001 respectively. No significant difference in fibre diameter was observed if patients had WL alone. Regardless of classification, there was no difference in fibre number or proportion of fibre type across all myosin heavy chain isoforms. Mean muscle protein content was reduced and the ratio of RNA/DNA decreased in patients with either >5%WL or LM+>2%WL. Compared with non-cachectic patients, SMAD3 protein levels were increased in patients with >5%WL (p = 0.022 and with >10%WL, beclin (p = 0.05 and ATG5 (p = 0.01 protein levels were increased. There were no differences in phospho-NFkB or phospho-STAT3 levels across any of the groups. CONCLUSION: Muscle fibre size, biochemical composition and pathway phenotype can vary according to whether the diagnostic criteria for cachexia are based on weight loss alone, a measure of low muscularity alone or a combination of the two. For intervention trials where the primary end-point is a change in muscle mass or function, use of combined diagnostic criteria may allow identification of a more

  7. Real-imaging cDNA-AFLP transcript profiling of pancreatic cancer patients: Egr-1 as a potential key regulator of muscle cachexia

    International Nuclear Information System (INIS)

    Cancer cachexia is a progressive wasting syndrome and the most prevalent characteristic of cancer in patients with advanced pancreatic adenocarcinoma. We hypothesize that genes expressed in wasted skeletal muscle of pancreatic cancer patients may determine the initiation and severity of cachexia syndrome. We studied gene expression in skeletal muscle biopsies from pancreatic cancer patients with and without cachexia utilizing Real-Imaging cDNA-AFLP-based transcript profiling for genome-wide expression analysis. Our approach yielded 183 cachexia-associated genes. Ontology analysis revealed characteristic changes for a number of genes involved in muscle contraction, actin cytoskeleton rearrangement, protein degradation, tissue hypoxia, immediate early response and acute-phase response. We demonstrate that Real-Imaging cDNA-AFLP analysis is a robust method for high-throughput gene expression studies of cancer cachexia syndrome in patients with pancreatic cancer. According to quantitative RT-PCR validation, the expression levels of genes encoding the acute-phase proteins α-antitrypsin and fibrinogen α and the immediate early response genes Egr-1 and IER-5 were significantly elevated in the skeletal muscle of wasted patients. By immunohistochemical and Western immunoblotting analysis it was shown, that Egr-1 expression is significantly increased in patients with cachexia and cancer. This provides new evidence that chronic activation of systemic inflammatory response might be a common and unifying factor of muscle cachexia

  8. Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia

    Science.gov (United States)

    Chinnasamy, Dhanalakshmi; Yu, Zhiya; Morgan, Richard A.; Lee, Chyi-Chia Richard; Restifo, Nicholas P.

    2013-01-01

    Fibroblast activation protein (FAP) is a candidate universal target antigen because it has been reported to be selectively expressed in nearly all solid tumors by a subset of immunosuppressive tumor stromal fibroblasts. We verified that 18/18 human tumors of various histologies contained pronounced stromal elements staining strongly for FAP, and hypothesized that targeting tumor stroma with FAP-reactive T cells would inhibit tumor growth in cancer-bearing hosts. T cells genetically engineered with FAP-reactive chimeric antigen receptors (CARs) specifically degranulated and produced effector cytokines upon stimulation with FAP or FAP-expressing cell lines. However, adoptive transfer of FAP-reactive T cells into mice bearing a variety of subcutaneous tumors mediated limited antitumor effects and induced significant cachexia and lethal bone toxicities in two mouse strains. We found that FAP was robustly expressed on PDGFR-α+, Sca-1+ multipotent bone marrow stromal cells (BMSCs) in mice, as well as on well-characterized, clinical-grade multipotent human BMSCs. Accordingly, both mouse and human multipotent BMSCs were recognized by FAP-reactive T cells. The lethal bone toxicity and cachexia observed after cell-based immunotherapy targeting FAP cautions against its use as a universal target. Moreover, the expression of FAP by multipotent BMSCs may point toward the cellular origins of tumor stromal fibroblasts. PMID:23712432

  9. Treatment of cancer cachexia in the very advanced or terminal phase: a systematic review

    Directory of Open Access Journals (Sweden)

    Giuseppe Arvia

    2013-12-01

    Full Text Available The therapeutic approach to refractory cancer cachexia represents an unmet need and an important research priority in the field of palliative care. Unfortunately, clinical studies in this area are scarce, both regarding nutritional and pharmacological approach. We performed a systematic literature search through Pubmed. The search algorithm considered: the clinical context, the related pathology, the therapeutic approach. The abstracts obtained were entered in a spreadsheet and analyzed in full text. The results were then analyzed according to the PRISMA method. Overall, 258 records were screened: 244 were excluded (not in English, n=44; no abstract, n=12; literature reviews, n=108; not relevant for not advanced phase or phase II studies, n=80. The remaining 14 papers were read in full text: 10 were excluded (4 phase II studies, 4 including patients with a performance status score of ≥70%, 2 including patients concomitantly treated by palliative chemotherapy. The remaining 4 studies of qualitative synthesis included: a study on megestrol acetate; a comparison between supportive treatment with/without melatonin; a placebo-controlled study on intravenous adenosine 5’-triphosphate; a comparison of indomethacin plus erythropoietin with/without nutritional support. The reported data do not allow us to draw any conclusion concerning the efficacy of pharmacological or nutritional treatment for cancer cachexia in very advanced or terminal phase and specific studies are, therefore, awaited.

  10. Orally available selective melanocortin-4 receptor antagonists stimulate food intake and reduce cancer-induced cachexia in mice.

    Directory of Open Access Journals (Sweden)

    Philipp Weyermann

    Full Text Available BACKGROUND: Cachexia is among the most debilitating and life-threatening aspects of cancer. It represents a metabolic syndrome affecting essential functional circuits involved in the regulation of homeostasis, and includes anorexia, fat and muscle tissue wasting. The anorexigenic peptide alpha-MSH is believed to be crucially involved in the normal and pathologic regulation of food intake. It was speculated that blockade of its central physiological target, the melanocortin (MC-4 receptor, might provide a promising anti-cachexia treatment strategy. This idea is supported by the fact that in animal studies, agouti-related protein (AgRP, the endogenous inverse agonist at the MC-4 receptor, was found to affect two hallmark features of cachexia, i.e. to increase food intake and to reduce energy expenditure. METHODOLOGY/PRINCIPAL FINDINGS: SNT207707 and SNT209858 are two recently discovered, non peptidic, chemically unrelated, orally active MC-4 receptor antagonists penetrating the blood brain barrier. Both compounds were found to distinctly increase food intake in healthy mice. Moreover, in mice subcutaneously implanted with C26 adenocarcinoma cells, repeated oral administration (starting the day after tumor implantation of each of the two compounds almost completely prevented tumor induced weight loss, and diminished loss of lean body mass and fat mass. CONCLUSIONS/SIGNIFICANCE: In contrast to the previously reported peptidic and small molecule MC-4 antagonists, the compounds described here work by the oral administration route. Orally active compounds might offer a considerable advantage for the treatment of cachexia patients.

  11. Effects of denervation, immobilization and cachexia on fibre size in the anterior tibial muscle of the rat.

    Science.gov (United States)

    Lindboe, C F; Presthus, J

    1985-01-01

    The effects of denervation, immobilization and cachexia on the size of the various histochemical fibre types were studied in the anterior tibial muscle of male Wistar rats aged 60-100 days. Denervation was induced by unilateral sectioning of the sciatic nerve, immobilization by a plaster cast on one hindlimb and cachexia by restriction of food intake. In the anterior tibial muscle of the normal rat, three fibre types can be identified by myofibrillar ATPase stain after alkaline preincubation. These fibres were called dark (D-fibres), intermediate (I-fibres) and light fibres (L-fibres), respectively. The I-fibres correspond to the fast-twitch type 2 fibres and the L-fibres to the slow-twitch type 1 fibres. The D-fibres have intermediate characteristics, but they probably belong to the type 2 group. The three fibre types reacted differently to denervation, immobilization and cachexia. Denervation caused progressive atrophy of the D- and I-fibres and almost no change of the L-fibres. Immobilization caused minor reduction in size of the D- and I-fibres during the first days and no change thereafter, whereas the L-fibres showed transitory hypertrophy. Cachexia, on the other hand, resulted in progressive atrophy of all three fibre types but a predominant affection of the D- and I-fibres. The different susceptibilities of the various fibre types suggest different mechanisms for atrophy of muscle in these three conditions. PMID:3158148

  12. Detection of Pancreatic Cancer-Induced Cachexia Using a Fluorescent Myoblast Reporter System and Analysis of Metabolite Abundance.

    Science.gov (United States)

    Winnard, Paul T; Bharti, Santosh K; Penet, Marie-France; Marik, Radharani; Mironchik, Yelena; Wildes, Flonne; Maitra, Anirban; Bhujwalla, Zaver M

    2016-03-15

    The dire effects of cancer-induced cachexia undermine treatment and contribute to decreased survival rates. Therapeutic options for this syndrome are limited, and therefore efforts to identify signs of precachexia in cancer patients are necessary for early intervention. The applications of molecular and functional imaging that would enable a whole-body "holistic" approach to this problem may lead to new insights and advances for diagnosis and treatment of this syndrome. Here we have developed a myoblast optical reporter system with the purpose of identifying early cachectic events. We generated a myoblast cell line expressing a dual tdTomato:GFP construct that was grafted onto the muscle of mice-bearing human pancreatic cancer xenografts to provide noninvasive live imaging of events associated with cancer-induced cachexia (i.e., weight loss). Real-time optical imaging detected a strong tdTomato fluorescent signal from skeletal muscle grafts in mice with weight losses of only 1.2% to 2.7% and tumor burdens of only approximately 79 to 170 mm(3). Weight loss in cachectic animals was also associated with a depletion of lipid, cholesterol, valine, and alanine levels, which may provide informative biomarkers of cachexia. Taken together, our findings demonstrate the utility of a reporter system that is capable of tracking tumor-induced weight loss, an early marker of cachexia. Future studies incorporating resected tissue from human pancreatic ductal adenocarcinoma into a reporter-carrying mouse may be able to provide a risk assessment of cachexia, with possible implications for therapeutic development. Cancer Res; 76(6); 1441-50. ©2015 AACR. PMID:26719527

  13. Loss of muscle mass: Current developments in cachexia and sarcopenia focused on biomarkers and treatment.

    Science.gov (United States)

    Drescher, Cathleen; Konishi, Masaaki; Ebner, Nicole; Springer, Jochen

    2016-01-01

    Loss of muscle mass arises from an imbalance of protein synthesis and protein degradation. Potential triggers of muscle wasting and function are immobilization, loss of appetite, dystrophies and chronic diseases as well as aging. All these conditions lead to increased morbidity and mortality in patients, which makes it a timely matter to find new biomarkers to get a fast clinical diagnosis and to develop new therapies. This mini-review covers current developments in the field of biomarkers and drugs on cachexia and sarcopenia. Here, we reported about promising markers, e.g. tartrate-resistant acid phosphatase 5a (TRACP5a), and novel substances like Epigallocatechin-3-gallate (EGCg). In summary, the progress to combat muscle wasting is in full swing and perhaps diagnosis of muscle atrophy and of course patient treatments could be soon supported by improved and more helpful strategies. PMID:26474466

  14. Functional body composition and related aspects in research on obesity and cachexia

    DEFF Research Database (Denmark)

    Müller, M J; Baracos, V; Bosy-Westphal, A;

    2014-01-01

    tissue mass are fixed. Thus an understanding of body weight regulation involves an examination of the relationships between organs and tissues rather than individual organ and tissue masses only. The between organ/tissue mass relationships are associated with and explained by crosstalks between organs......The 12th Stock Conference addressed body composition and related functions in two extreme situations, obesity and cancer cachexia. The concept of 'functional body composition' integrates body components into regulatory systems relating the mass of organs and tissues to corresponding in vivo...... functions and metabolic processes. This concept adds to an understanding of organ/tissue mass and function in the context of metabolic adaptations to weight change and disease. During weight gain and loss, there are associated changes in individual body components while the relationships between organ and...

  15. Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

    International Nuclear Information System (INIS)

    The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. We conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents

  16. Study of morphological alterations of the adrenal glands in the neoplastic cachexia
    Estudo das alterações morfológicas da glândula adrenal na caquexia neoplásica

    OpenAIRE

    Tânia Longo Mazzuco; Karina Garcia Cotrim; Alexandre Yukio Saito; Marcelo Abbá Macioszek; Eveline Aparecida Isquierdo Fonseca

    2009-01-01

    Advanced cancer occurs with nutritional and metabolic alterations that characterize neoplastic cachexia. When homeostasis is compromised, the adrenal glands have a fundamental role in the neuroendocrine response. Our purpose in this research was to study morphological alterations of the adrenal glands in the development of cancer associated to cachexia. Cachexia experimental model induced by Walker 256 tumor in Wistar rats, was used. Animals were sacrificed 12 days after tumor cells inoculati...

  17. STAT3 Activation in Skeletal Muscle Links Muscle Wasting and the Acute Phase Response in Cancer Cachexia

    OpenAIRE

    Andrea Bonetto; Tufan Aydogdu; Noelia Kunzevitzky; Guttridge, Denis C.; Sawsan Khuri; Koniaris, Leonidas G.; Teresa A Zimmers

    2011-01-01

    BACKGROUND: Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6), and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA) are synthesized by hepatocytes in response to IL-6 as part of the i...

  18. Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia-cachexia syndrome: preclinical profile

    OpenAIRE

    Pietra, Claudio; Takeda, Yasuhiro; Tazawa-Ogata, Naoko; Minami, Masashi; Yuanfeng, Xia; Duus, Elizabeth Manning; Northrup, Robert

    2014-01-01

    Background Anamorelin HCl (ANAM) is a novel, orally active, ghrelin receptor agonist in clinical development for the treatment of cancer cachexia. We report in vitro and in vivo studies evaluating the preclinical pharmacologic profile of ANAM. Methods Fluorescent imaging plate reader and binding assays in HEK293 and baby hamster kidney cells determined the agonist and antagonist activity of ANAM, and its affinity for the ghrelin receptor. Rat pituitary cells were incubated with ANAM to evalua...

  19. ROLE OF ANGIOTENSIN-CONVERTING ENZYME AND VITAMIN D RECEPTOR GENE POLYMORPHISMS IN CANCER ANOREXIA-CACHEXIA SYNDROME

    OpenAIRE

    Ariele Fabris; Paolo Biagioni; Tiziana Punzi; Gabriele Morucci; Massimo Gulisano; Stefania Pacini; Marco Ruggiero

    2012-01-01

    The ubiquitin-proteasome pathway is a crucial connection between aberrant immune system activation, systemic inflammation and Cancer Anorexia-Cachexia Syndrome (CACS), a syndrome that culminates in hyper-activation of the ubiquitin-proteasome pathway. Angiotensin directly up-regulates this pathway, while vitamin D down-regulates it indirectly through the insulin-like growth factor-1 pathway. We investigated the genetic predisposition towards CACS in a cancer population, examining Insertion/De...

  20. B-Cell Activating Factor as a Cancer Biomarker and Its Implications in Cancer-Related Cachexia

    Directory of Open Access Journals (Sweden)

    Michal Rihacek

    2015-01-01

    Full Text Available B-cell activating factor (BAFF is a cytokine and adipokine of the TNF ligand superfamily. The main biological function of BAFF in maintaining the maturation of B-cells to plasma cells has recently made it a target of the first FDA-approved selective BAFF antibody, belimumab, for the therapy of systemic lupus erythematosus. Concomitantly, the role of BAFF in cancer has been a subject of research since its discovery. Here we review BAFF as a biomarker of malignant disease activity and prognostic factor in B-cell derived malignancies such as multiple myeloma. Moreover, anti-BAFF therapy seems to be a promising approach in treatment of B-cell derived leukemias/lymphomas. In nonhematologic solid tumors, BAFF may contribute to cancer progression by mechanisms both dependent on and independent of BAFF’s proinflammatory role. We also describe ongoing research into the pathophysiological link between BAFF and cancer-related cachexia. BAFF has been shown to contribute to inflammation and insulin resistance which are known to worsen cancer cachexia syndrome. Taking all the above together, BAFF is emerging as a biomarker of several malignancies and a possible hallmark of cancer cachexia.

  1. Adipose atrophy in cancer cachexia: morphologic and molecular analysis of adipose tissue in tumour-bearing mice.

    Science.gov (United States)

    Bing, C; Russell, S; Becket, E; Pope, M; Tisdale, M J; Trayhurn, P; Jenkins, J R

    2006-10-23

    Extensive loss of adipose tissue is a hallmark of cancer cachexia but the cellular and molecular basis remains unclear. This study has examined morphologic and molecular characteristics of white adipose tissue in mice bearing a cachexia-inducing tumour, MAC16. Adipose tissue from tumour-bearing mice contained shrunken adipocytes that were heterogeneous in size. Increased fibrosis was evident by strong collagen-fibril staining in the tissue matrix. Ultrastructure of 'slimmed' adipocytes revealed severe delipidation and modifications in cell membrane conformation. There were major reductions in mRNA levels of adipogenic transcription factors including CCAAT/enhancer binding protein alpha (C/EBPalpha), CCAAT/enhancer binding protein beta, peroxisome proliferator-activated receptor gamma, and sterol regulatory element binding protein-1c (SREBP-1c) in adipose tissue, which was accompanied by reduced protein content of C/EBPalpha and SREBP-1. mRNA levels of SREBP-1c targets, fatty acid synthase, acetyl CoA carboxylase, stearoyl CoA desaturase 1 and glycerol-3-phosphate acyl transferase, also fell as did glucose transporter-4 and leptin. In contrast, mRNA levels of peroxisome proliferators-activated receptor gamma coactivator-1alpha and uncoupling protein-2 were increased in white fat of tumour-bearing mice. These results suggest that the tumour-induced impairment in the formation and lipid storing capacity of adipose tissue occurs in mice with cancer cachexia. PMID:17047651

  2. The ACT-ONE trial, a multicentre, randomised, double-blind, placebo-controlled, dose-finding study of the anabolic/catabolic transforming agent, MT-102 in subjects with cachexia related to stage III and IV non-small cell lung cancer and colorectal cancer: study design

    OpenAIRE

    Stewart Coats, Andrew J.; Srinivasan, Venkatesan; Surendran, Jayaraman; Chiramana, Haritha; Vangipuram, Shankar R. K. G.; Bhatt, Nirajkumar N.; Jain, Minish; Shah, Sandip; Ali, Irfhan A. B. H.; Fuang, Ho G.; Hassan, Mohammed Z. M.; Beadle, John; Tilson, Julia; Kirwan, Bridget-Anne; Anker, Stefan D.

    2011-01-01

    Aims Cachexia, the wasting disorder associated with a wide range of serious illnesses including cancer, is a major cause of morbidity and mortality. There is currently no widely approved therapeutic agent for treating or preventing cancer-associated cachexia. Colorectal cancer and non-small cell lung cancer have relatively high incidences of cachexia, approximately 28% and 34%, respectively. Neurohormonal overactivity has been implicated in the genesis and progression of cachexia and beta rec...

  3. STAT3 activation in skeletal muscle links muscle wasting and the acute phase response in cancer cachexia.

    Directory of Open Access Journals (Sweden)

    Andrea Bonetto

    Full Text Available BACKGROUND: Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6, and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA are synthesized by hepatocytes in response to IL-6 as part of the innate immune response. To gain insight into the relationships among these observations, we studied mice with moderate and severe Colon-26 (C26-carcinoma cachexia. METHODOLOGY/PRINCIPAL FINDINGS: Moderate and severe C26 cachexia was associated with high serum IL-6 and IL-6 family cytokines and highly similar patterns of skeletal muscle gene expression. The top canonical pathways up-regulated in both were the complement/coagulation cascade, proteasome, MAPK signaling, and the IL-6 and STAT3 pathways. Cachexia was associated with increased muscle pY705-STAT3 and increased STAT3 localization in myonuclei. STAT3 target genes, including SOCS3 mRNA and acute phase response proteins, were highly induced in cachectic muscle. IL-6 treatment and STAT3 activation both also induced fibrinogen in cultured C2C12 myotubes. Quantitation of muscle versus liver fibrinogen and SAA protein levels indicates that muscle contributes a large fraction of serum acute phase proteins in cancer. CONCLUSIONS/SIGNIFICANCE: These results suggest that the STAT3 transcriptome is a major mechanism for wasting in cancer. Through IL-6/STAT3 activation, skeletal muscle is induced to synthesize acute phase proteins, thus establishing a molecular link between the observations of high IL-6, increased acute phase response proteins and muscle wasting in cancer. These results suggest a mechanism by which STAT3 might causally influence muscle wasting by altering the profile of genes expressed and

  4. Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    Mariano Malaguarnera; Corrado Risino; Maria Pia Gargante; Giovanni Oreste; Gloria Barone; Anna Veronica Tomasello; Mario Costanzo; Matteo Angelo Cannizzaro

    2006-01-01

    AIM: To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia.METHODS: Fifthy-five cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations,including examination of the levels of various forms of carnitine present in serum (i.e., long-chain acylcarnitine,short-chain acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects.RESULTS: When the cachectic patients with gastrointestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8 μmol/L in free carnitine (P<0.005), 0.04 μmol/L in long chain acylcarnitine (P<0.05), 8.7 μmol/L in total carnitine (P<0.001). In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2μmol/L in free carnitine (P<0.001), 4.60 μmol/L in short chain acylcarnitine (P<0.001), and 0.60 μmol/L in long-chain acylcarnitine (P<0.005) and 17.4 μmol/L in total carnitine (P<0.001). In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5 μmol/L in free carnitine (P<0.001), 5.2 μmol/L in short-chain acylcarnitine (P< 0.001), 1.0 μmol/L in long chain acylcarnitine (P <0.001), and 21.8μmol/L in total carnitine (P<0.001).CONCLUSION: Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients.

  5. A New Transgenic Mouse Model of Heart Failure and Cardiac Cachexia Raised by Sustained Activation of Met Tyrosine Kinase in the Heart

    Science.gov (United States)

    Sala, Valentina; Gatti, Stefano; Gallo, Simona; Medico, Enzo; Cantarella, Daniela; Cimino, James; Ponzetto, Antonio; Crepaldi, Tiziana

    2016-01-01

    Among other diseases characterized by the onset of cachexia, congestive heart failure takes a place of relevance, considering the high prevalence of this pathology in most European countries and in the United States, and is undergoing a rapid increase in developing countries. Actually, only few models of cardiac cachexia exist. Difficulties in the recruitment and follow-up of clinical trials implicate that new reproducible and well-characterized animal models are pivotal in developing therapeutic strategies for cachexia. We generated a new model of cardiac cachexia: a transgenic mouse expressing Tpr-Met receptor, the activated form of c-Met receptor of hepatocyte growth factor, specifically in the heart. We showed that the cardiac-specific induction of Tpr-Met raises a cardiac hypertrophic remodelling, which progresses into concentric hypertrophy with concomitant increase in Gdf15 mRNA levels. Hypertrophy progresses to congestive heart failure with preserved ejection fraction, characterized by reduced body weight gain and food intake and skeletal muscle wasting. Prevention trial by suppressing Tpr-Met showed that loss of body weight could be prevented. Skeletal muscle wasting was also associated with altered gene expression profiling. We propose transgenic Tpr-Met mice as a new model of cardiac cachexia, which will constitute a powerful tool to understand such complex pathology and test new drugs/approaches at the preclinical level. PMID:27298830

  6. A New Transgenic Mouse Model of Heart Failure and Cardiac Cachexia Raised by Sustained Activation of Met Tyrosine Kinase in the Heart

    Directory of Open Access Journals (Sweden)

    Valentina Sala

    2016-01-01

    Full Text Available Among other diseases characterized by the onset of cachexia, congestive heart failure takes a place of relevance, considering the high prevalence of this pathology in most European countries and in the United States, and is undergoing a rapid increase in developing countries. Actually, only few models of cardiac cachexia exist. Difficulties in the recruitment and follow-up of clinical trials implicate that new reproducible and well-characterized animal models are pivotal in developing therapeutic strategies for cachexia. We generated a new model of cardiac cachexia: a transgenic mouse expressing Tpr-Met receptor, the activated form of c-Met receptor of hepatocyte growth factor, specifically in the heart. We showed that the cardiac-specific induction of Tpr-Met raises a cardiac hypertrophic remodelling, which progresses into concentric hypertrophy with concomitant increase in Gdf15 mRNA levels. Hypertrophy progresses to congestive heart failure with preserved ejection fraction, characterized by reduced body weight gain and food intake and skeletal muscle wasting. Prevention trial by suppressing Tpr-Met showed that loss of body weight could be prevented. Skeletal muscle wasting was also associated with altered gene expression profiling. We propose transgenic Tpr-Met mice as a new model of cardiac cachexia, which will constitute a powerful tool to understand such complex pathology and test new drugs/approaches at the preclinical level.

  7. Cachexia and adiposity in rheumatoid arthritis. Relevance for disease management and clinical outcomes.

    Science.gov (United States)

    Challal, Salima; Minichiello, Emeline; Boissier, Marie-Christophe; Semerano, Luca

    2016-03-01

    Altered body composition is a frequent finding in rheumatoid arthritis and is associated with the two major outcomes of the disease: disability and cardiovascular mortality. It is estimated that up to two thirds of patients may be affected by loss of lean mass, the so-called rheumatoid cachexia. Hence, body weight being equal, the relative amount of lean mass is lower and that of body fat is higher in rheumatoid arthritis patients vs. healthy controls. Both disease-related factors and other factors, like drug treatments, physical activity and nutrition contribute to modify body composition in rheumatoid arthritis. The effect of pharmacological treatments, and notably of anti-TNF drugs, on body composition is controversial. Conversely, training programs to stimulate muscle growth can restore lean mass and reduce adiposity. There is good evidence that amelioration of body composition ameliorates function and reduces disability. Currently, there is no evidence that interventions that modify body composition can reduce cardiovascular morbidity and mortality in rheumatoid arthritis. PMID:26184539

  8. Usefulness of oral medroxyprogesterone acetate in the management of cancer-related cachexia-anorexia syndrome.

    Science.gov (United States)

    Testa, A; Gebbia, V; Borsellino, N; Valenza, R; Cannata, G; Tirrito, M; Verderame, F; Armata, M; Valerio, M; Gebbia, N

    1996-05-01

    A study on the activity and tolerability of high-dose medroxyprogesterone acetate in the treatment of ACS in neoplastic patients was carried out in a series of 103 patients with advanced cancer beyond cure with standard chemotherapeutic or radiotherapeutic treatments. The treatment plan was: medroxyprogesterone acetate (MAP) 1,000 mg/day as liquid suspension orally at a single dose, for at least one month. If there was no improvement in body weight, SSA, performance status therapy was interrupted. An increase in body weight greater than or equal to 5%, in SSA score greater than or equal to 2 points, in performance status and then in quality of life were recorded as positive MAP-related events. Therapy-related toxicity was evaluated according to the WHO criteria. A mean body weight increased from 63 kg recorded before therapy to 67 kg recorded after 30 days of MAP. This difference was statistically significant (pacetate in the management of anorexia-cachexia syndrome in patients with advanced cancer resistant to systemic chemotherapy. PMID:21594399

  9. Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact.

    Science.gov (United States)

    Prado, C M; Cushen, S J; Orsso, C E; Ryan, A M

    2016-05-01

    Our understanding of body composition (BC) variability in contemporary populations has significantly increased with the use of imaging techniques. Abnormal BC such as sarcopenia (low muscle mass) and obesity (excess adipose tissue) are predictors of poorer prognosis in a variety of conditions or clinical situations. As a catabolic illness, a defining feature of cancer is muscle loss. Although the conceptual model of wasting in cancer is typically conceived as involuntary weight loss leading to low body weight, recent studies have shown that both sarcopenia and cachexia can be present with obesity. The combination of low muscle and high adipose tissue (sarcopenic obesity) is an emerging abnormal BC phenotype prevalent across the body weight, and hence BMI spectra. Sarcopenia and sarcopenic obesity in cancer are in most instances occult conditions, which have been independently associated with higher incidence of chemotherapy toxicity, shorter time to tumour progression, poorer outcomes of surgery, physical impairment and shorter survival. Although the mechanisms are yet to be fully understood, the associations with poorer clinical outcomes emphasise the value of nutritional assessment as well as the need to develop appropriate interventions to countermeasure abnormal BC. Sarcopenia and sarcopenic obesity create diverse nutritional requirements, highlighting the compelling need for a more comprehensive and differentiated understanding of energy and protein requirements in this heterogeneous population. PMID:26743210

  10. Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting: potential therapeutic targets for cardiac cachexia.

    Science.gov (United States)

    Yoshida, Tadashi; Tabony, A Michael; Galvez, Sarah; Mitch, William E; Higashi, Yusuke; Sukhanov, Sergiy; Delafontaine, Patrice

    2013-10-01

    Cachexia is a serious complication of many chronic diseases, such as congestive heart failure (CHF) and chronic kidney disease (CKD). Many factors are involved in the development of cachexia, and there is increasing evidence that angiotensin II (Ang II), the main effector molecule of the renin-angiotensin system (RAS), plays an important role in this process. Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme (ACE) inhibitor treatment improves weight loss. In rodent models, an increase in systemic Ang II leads to weight loss through increased protein breakdown, reduced protein synthesis in skeletal muscle and decreased appetite. Ang II activates the ubiquitin-proteasome system via generation of reactive oxygen species and via inhibition of the insulin-like growth factor-1 signaling pathway. Furthermore, Ang II inhibits 5' AMP-activated protein kinase (AMPK) activity and disrupts normal energy balance. Ang II also increases cytokines and circulating hormones such as tumor necrosis factor-α, interleukin-6, serum amyloid-A, glucocorticoids and myostatin, which regulate muscle protein synthesis and degradation. Ang II acts on hypothalamic neurons to regulate orexigenic/anorexigenic neuropeptides, such as neuropeptide-Y, orexin and corticotropin-releasing hormone, leading to reduced appetite. Also, Ang II may regulate skeletal muscle regenerative processes. Several clinical studies have indicated that blockade of Ang II signaling via ACE inhibitors or Ang II type 1 receptor blockers prevents weight loss and improves muscle strength. Thus the RAS is a promising target for the treatment of muscle atrophy in patients with CHF and CKD. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. PMID:23769949

  11. Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBPβ-regulated atrogin1 expression in cancer cachexia.

    Science.gov (United States)

    Sun, Rulin; Zhang, Santao; Hu, Wenjun; Lu, Xing; Lou, Ning; Yang, Zhende; Chen, Shaoyong; Zhang, Xiaoping; Yang, Hongmei

    2016-07-01

    Muscle wasting is the hallmark of cancer cachexia and is associated with poor quality of life and increased mortality. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has important biological effects in the treatment of muscular dystrophy. To verify whether VPA could ameliorate muscle wasting induced by cancer cachexia, we explored the role of VPA in two cancer cachectic mouse models [induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC)] and atrophied C2C12 myotubes [induced by C26 cell conditioned medium (CCM) or LLC cell conditioned medium (LCM)]. Our data demonstrated that treatment with VPA increased the mass and cross-sectional area of skeletal muscles in tumor-bearing mice. Furthermore, treatment with VPA also increased the diameter of myotubes cultured in conditioned medium. The skeletal muscles in cachectic mice or atrophied myotubes treated with VPA exhibited reduced levels of CCAAT/enhancer binding protein beta (C/EBPβ), resulting in atrogin1 downregulation and the eventual alleviation of muscle wasting and myotube atrophy. Moreover, atrogin1 promoter activity in myotubes was stimulated by CCM via activating the C/EBPβ-responsive cis-element and subsequently inhibited by VPA. In contrast to the effect of VPA on the levels of C/EBPβ, the levels of inactivating forkhead box O3 (FoxO3a) were unaffected. In summary, VPA attenuated muscle wasting and myotube atrophy and reduced C/EBPβ binding to atrogin1 promoter locus in the myotubes. Our discoveries indicate that HDAC inhibition by VPA might be a promising new approach for the preservation of skeletal muscle in cancer cachexia. PMID:27122162

  12. Anormalidades neuromuscular no desuso, senilidade e caquexia Neuromuscular abnormalities in disuse, cachexia and ageing

    Directory of Open Access Journals (Sweden)

    João Aris Kouyoumdjian

    1993-09-01

    Full Text Available É feita revisão de literatura sobre as principais alterações do sistema neuromuscular no desuso, senilidade e caquexia no ser humano e em modelos animais. A diminuição do diâmetro das fibras musculares após período de inatividade/imobilidade (desuso deve-se à perda de miofibrilas periféricas não ocorrendo formação de core-targetóides ou diminuição da atividade da miofosforilase, próprias da desnervação; mantêm-se a liberação espontânea de acetilcolina e fatores tróficos na junção mio-neural; em geral são afetadas preferencialmente fibras II, que podem assumir forma angular. Existe um processo contínuo intrínseco de envelhecimento de nervos e músculos, com desnervação e reinervação lenta e progressiva; o número de unidades motoras se reduz após 60 anos, sem ocorrência de atividade elétrica desnervatória; a quantidade de acetilcolina liberada nos neurônios terminais e a capacidade máxima de utilização de oxigênio estão diminuídas; a redução da capacidade oxidativa mitocondrial pode explicar o aumento de fibras I, mantendo-se o equilíbrio energético. Após poucas semanas de caquexia as fibras musculares podem ter o diâmetro reduzido em 30%, essa redução ocorre em ordem decrescente nos músculos dos membros inferiores, superiores e tronco; existe atrofia II preferencial com fibras angulares ocasionais, redução de RNA/síntese proteica, mantendo-se DNA normal.Cachexia, ageing and disuse and their effects on the human and animals neuromuscular system are reviewed. Disuse induces reduction of muscle fibers (mainly II diameter with peripheral myofibrils lost; there is no core-targetoid or even reduction on myophosphorilase activity, both typical of denervation; the acetylcholine spontaneous release and trophic factors on myoneural junction are maintained; muscle fibers could change to angular shape. Ageing affects nerve and muscle by a continuous and progressive process of denervation and reinner

  13. Fisiopatología de la caquexia neoplásica Pathophysiology of neoplasic cachexia

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    J. M. Argilés

    2006-05-01

    , gastrointestinal metabolic, nutritional and endocrine mechanisms. The cancer patient suffers from anorexia which results in early saciety and a reduction of appetite. Sometimes, the causes of the anorectic response are derived from the antitumoral treatment (chemotherapy, radiotherapy or immunotherapy, in some cases vomiting resulting in altered food intake. Alterations in the food taste and smell perception in addition to psychological dearrangements might also lead to the anorexia. Sometimes the tumour may play a direct effect when it is localised in either the hypothalamus or the digestive apparatus. However, in the majority of cases the origin of the anorexia associated with cancer cachexia seems to be due to the metabolic alterations induced by tumour burden. Different factors of both humoral and tumoral origin play a role in cancer anorexia. For instance, tumour necrosis factor (TNF- , a cytokine responsible for a great part of the metabolic alterations characteristic of cancer cachexia seems to be involved. In conclusion, the cancer anorexia seems to be more an effect than the cause of the weight loss and in fact the decrease in food intake might take place after weight loss is evident. In any case, the malnutrition associated with a decrease of food intake worsens the cachectic state, favouring a kind of a positive feed-back mechanism that finally leads to the patient's death.

  14. Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2015.

    Science.gov (United States)

    von Haehling, Stephan; Morley, John E; Coats, Andrew J S; Anker, Stefan D

    2015-12-01

    This article details the principles of ethical authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle (JCSM). At the time of submission to JCSM, the corresponding author, on behalf of all co-authors, needs to certify adherence to these principles. The principles are as follows: (i) all authors listed on a manuscript considered for publication have approved its submission and (if accepted) publication as provided to JCSM; (ii) no person who has a right to be recognized as author has been omitted from the list of authors on the submitted manuscript; (iii) no person who has a right to be recognized as author has been omitted from the list of authors on the submitted manuscript; (iv) the submitted work is original and is neither under consideration elsewhere nor that it has been published previously in whole or in part other than in abstract form; (v) all authors certify that the work is original and does not contain excessive overlap with prior or contemporaneous publication elsewhere, and where the publication reports on cohorts, trials, or data that have been reported on before these other publications must be referenced; (vi) all original research work are approved by the relevant bodies such as institutional review boards or ethics committees; (vii) all conflicts of interest, financial or otherwise, that may affect the authors' ability to present data objectively, and relevant sources of funding have been duly declared in the manuscript; (viii) the manuscript in its published form will be maintained on the servers of JCSM as a valid publication only as long as all statements in the guidelines on ethical publishing remain true; and (ix) If any of the aforementioned statements ceases to be true, the authors have a duty to notify the Editors of JCSM as soon as possible so that the available information regarding the published article can be updated and/or the manuscript can be withdrawn. PMID:26672494

  15. Cancer-associated malnutrition, cachexia and sarcopenia: the skeleton in the hospital closet 40 years later.

    Science.gov (United States)

    Ryan, Aoife M; Power, Derek G; Daly, Louise; Cushen, Samantha J; Ní Bhuachalla, Ēadaoin; Prado, Carla M

    2016-05-01

    An awareness of the importance of nutritional status in hospital settings began more than 40 years ago. Much has been learned since and has altered care. For the past 40 years several large studies have shown that cancer patients are amongst the most malnourished of all patient groups. Recently, the use of gold-standard methods of body composition assessment, including computed tomography, has facilitated the understanding of the true prevalence of cancer cachexia (CC). CC remains a devastating syndrome affecting 50-80 % of cancer patients and it is responsible for the death of at least 20 %. The aetiology is multifactorial and complex; driven by pro-inflammatory cytokines and specific tumour-derived factors, which initiate an energy-intensive acute phase protein response and drive the loss of skeletal muscle even in the presence of adequate food intake and insulin. The most clinically relevant phenotypic feature of CC is muscle loss (sarcopenia), as this relates to asthenia, fatigue, impaired physical function, reduced tolerance to treatments, impaired quality of life and reduced survival. Sarcopenia is present in 20-70 % depending on the tumour type. There is mounting evidence that sarcopenia increases the risk of toxicity to many chemotherapy drugs. However, identification of patients with muscle loss has become increasingly difficult as 40-60 % of cancer patients are overweight or obese, even in the setting of metastatic disease. Further challenges exist in trying to reverse CC and sarcopenia. Future clinical trials investigating dose reductions in sarcopenic patients and dose-escalating studies based on pre-treatment body composition assessment have the potential to alter cancer treatment paradigms. PMID:26786393

  16. Anorexia-cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15.

    Science.gov (United States)

    Tsai, V W W; Lin, S; Brown, D A; Salis, A; Breit, S N

    2016-02-01

    Anorexia-cachexia associated with cancer and other diseases is a common and often fatal condition representing a large area of unmet medical need. It occurs most commonly in advanced cancer and is probably a consequence of molecules released by tumour cells, or tumour-associated interstitial or immune cells. These may then act directly on muscle to cause atrophy and/or may cause anorexia, which then leads to loss of both fat and lean mass. Although the aetiological triggers for this syndrome are not well characterized, recent data suggest that MIC-1/GDF15, a transforming growth factor-beta superfamily cytokine produced in large amounts by cancer cells and as a part of other disease processes, may be an important trigger. This cytokine acts on feeding centres in the hypothalamus and brainstem to cause anorexia leading to loss of lean and fat mass and eventually cachexia. In animal studies, the circulating concentrations of MIC-1/GDF15 required to cause this syndrome are similar to those seen in patients with advanced cancer, and at least some epidemiological studies support an association between MIC-1/GDF15 serum levels and measures of nutrition. This article will discuss its mechanisms of central appetite regulation, and the available data linking this action to anorexia-cachexia syndromes that suggest it is a potential target for therapy of cancer anorexia-cachexia and conversely may also be useful for the treatment of severe obesity. PMID:26620888

  17. Can the Serum Level of Myostatin be Considered as an Informative Factor for Cachexia Prevention in Patients with Medullary Thyroid Cancer?

    Science.gov (United States)

    Hedayati, Mehdi; Nozhat, Zahra; Hannani, Masoomeh

    2016-01-01

    Thyroid cancer, the most common endocrine neoplasia, consists of four main types of carcinomas: papillary, follicular, and anaplastic, all with thyroid follicular origin, and medullary thyroid cancer (MTC) related to para-follicular cells. Cronic diseases such as diverse cancers may be associated with cachexia, especially at advanced stage. Cancer-induced cachexia is associated with diminished quality of life, functional performance, reduced response to antitumor therapy, and increased morbidity and mortality. Myostatin (Mst) is one of the outstanding molecules in the skeletal muscle loss process in cancer and it may be released by both skeletal muscle and cachexia-inducing tumors. Recently changes in serum levels of Mst have been identified as an important factor of cancer-induced cachexia. The goal of this study was to assessserum Mst levels in MTC patients. In this descriptive and case-control study, 90 participants were selected, comprising 45 MTC patients (20 males, 29±13.9 years, 25 females, 29±14.5 years) and 45 control individuals (25 males, 23.1±11.6 years, 20 females, 31.5±14.4 years). Serum Mst was determined using an ELISA kit and body mass index (BMI) was calculated by weight and height measurements. The Kolmogorov Simonov test showed a normal distribution for log transformed Mst serum levels in both case and control groups. Geometric means were 5.9 and 8.2 ng/ml respectively, and a significant difference was found according to the independent t-test results (P<0.01) . There was also a significant difference mean of Mst between females in control and MTC groups, but not for the males. Pearson correlation test showed no correlation between age and BMI with Mst serum levels. The findings of this study support the hypothesis that Mst serum levels may have a potential ability for early diagnosis of cachexia in MTC patients, especially in females. PMID:27165248

  18. CCAAT/enhancer binding protein beta protects muscle satellite cells from apoptosis after injury and in cancer cachexia

    Science.gov (United States)

    Marchildon, F; Fu, D; Lala-Tabbert, N; Wiper-Bergeron, N

    2016-01-01

    CCAAT/enhancer binding protein beta (C/EBPβ), a transcription factor expressed in muscle satellite cells (SCs), inhibits the myogenic program and is downregulated early in differentiation. In a conditional null model in which C/EBPβ expression is knocked down in paired box protein 7+ (Pax7+) SCs, cardiotoxin (CTX) injury is poorly repaired, although muscle regeneration is efficient in control littermates. While myoblasts lacking C/EBPβ can differentiate efficiently in culture, after CTX injury poor regeneration was attributed to a smaller than normal Pax7+ population, which was not due to a failure of SCs to proliferate. Rather, the percentage of apoptotic SCs was increased in muscle lacking C/EBPβ. Given that an injury induced by BaCl2 is repaired with greater efficiency than controls in the absence of C/EBPβ, we investigated the inflammatory response following BaCl2 and CTX injury and found that the levels of interleukin-1β (IL-1β), a proinflammatory cytokine, were robustly elevated following CTX injury and could induce C/EBPβ expression in myoblasts. High levels of C/EBPβ expression in myoblasts correlated with resistance to apoptotic stimuli, while its loss increased sensitivity to thapsigargin-induced cell death. Using cancer cachexia as a model for chronic inflammation, we found that C/EBPβ expression was increased in SCs and myoblasts of tumor-bearing cachectic animals. Further, in cachectic conditional knockout animals lacking C/EBPβ in Pax7+ cells, the SC compartment was reduced because of increased apoptosis, and regeneration was impaired. Our findings indicate that the stimulation of C/EBPβ expression by IL-1β following muscle injury and in cancer cachexia acts to promote SC survival, and is therefore a protective mechanism for SCs and myoblasts in the face of inflammation. PMID:26913600

  19. Metformin treatment modulates the tumour-induced wasting effects in muscle protein metabolism minimising the cachexia in tumour-bearing rats

    OpenAIRE

    André G. Oliveira; Gomes-Marcondes, Maria Cristina C.

    2016-01-01

    Background Cancer-cachexia state frequently induces both fat and protein wasting, leading to death. In this way, the knowledge of the mechanism of drugs and their side effects can be a new feature to treat and to have success, contributing to a better life quality for these patients. Metformin is an oral drug used in type 2 diabetes mellitus, showing inhibitory effect on proliferation in some neoplastic cells. For this reason, we evaluated its modulatory effect on Walker-256 tumour evolution ...

  20. Tratamiento farmacológico de la anorexia-caquexia cancerosa Pharmacological therapy of cancer anorexia-cachexia

    Directory of Open Access Journals (Sweden)

    D. Cardona

    2006-05-01

    megestrol y los corticosteroides serán de primera línea de elección en el síndrome de anorexia-caquexia por incrementar el apetito y el primero el peso y repercutir en la mejoría de la calidad de vida y de confort en los enfermos con cáncer avanzado.Anorexia is one of the most common symptoms of patients with advanced cancer and it presents as loss of appetite due to satiety. On the other hand, cachexia is described in those patients with unwanted weight loss. Cancerous processes produce an energy unbalance by decreased food intake and increased catabolism, resulting in a clearly negative balance. Several factors determining cachexia are observed, from metabolic unbalances produced by tumoral products and endocrine impairments or the inflammatory response produced by cytokines, all of them leading to higher lipolysis, loss of muscle protein, and anorexia. Besides, causes of anorexia are multiple, from chemotherapy agents, radiotherapy, or immunotherapy, which may produce different degrees of nausea, vomiting, diarrhea, and also leading to impairments of taste and smell, to obstruction of the digestive tract, pain, depression, constipation, etc. From the knowledge of the different mechanisms producing the anorexia-cachexia syndrome, hypercaloric diets for artificial nutrition have been studied with varying success, and different drugs with a positive effect on appetite gain such as progestogens, steroids, and with lesser clinical evidence cannabinoids, cyproheptadine, mirtazapine (antidepressant, and olanzapine (antipsychotic. Other drugs have been studied because of their anti-inflammatory properties, anti-cytokine, such as melatonin, polyunsaturated omega-3 fatty acids, pentoxifylline, and thalidomide; with the exception of the latter, clinical data are still scant for daily usage. Similarly happens with testosterone-derived anabolic drugs or with metabolism inhibitors such as hydrazine sulfate. With no doubt, progestogens, especially megestrol, and corticosteroids

  1. Complete reversal of muscle wasting in experimental cancer cachexia: Additive effects of activin type II receptor inhibition and β-2 agonist.

    Science.gov (United States)

    Toledo, Míriam; Busquets, Sílvia; Penna, Fabio; Zhou, Xiaolan; Marmonti, Enrica; Betancourt, Angelica; Massa, David; López-Soriano, Francisco J; Han, H Q; Argilés, Josep M

    2016-04-15

    Formoterol is a highly potent β2-adrenoceptor-selective agonist, which is a muscle growth promoter in many animal species. Myostatin/activin inhibition reverses skeletal muscle loss and prolongs survival of tumor-bearing animals. The aim of this investigation was to evaluate the effects of a combination of the soluble myostatin receptor ActRIIB (sActRIIB) and the β2-agonist formoterol in the cachectic Lewis lung carcinoma model. The combination of formoterol and sActRIIB was extremely effective in reversing muscle wasting associated with experimental cancer cachexia in mice. Muscle weights from tumor-bearing animals were completely recovered following treatment and this was also reflected in the measured grip strength. This combination increased food intake in both control and tumor-bearing animals. The double treatment also prolonged survival significantly without affecting the weight and growth of the primary tumor. In addition, it significantly reduced the number of metastasis. Concerning the mechanisms for the preservation of muscle mass during cachexia, the effects of formoterol and sActRIIB seemed to be additive, since formoterol reduced the rate of protein degradation (as measured in vitro as tyrosine release, using incubated isolated individual muscles) while sActRIIB only affected protein synthesis (as measured in vivo using tritiated phenylalanine). Formoterol also increased the rate of protein synthesis and this seemed to be favored by the presence of sActRIIB. Combining formoterol and sActRIIB seemed to be a very promising treatment for experimental cancer cachexia. Further studies in human patients are necessary and may lead to a highly effective treatment option for muscle wasting associated with cancer. PMID:26595367

  2. Zinc as an appetite stimulator - the possible role of zinc in the progression of diseases such as cachexia and sarcopenia.

    Science.gov (United States)

    Suzuki, Hajime; Asakawa, Akihiro; Li, Jiang B; Tsai, Minglun; Amitani, Haruka; Ohinata, Kousaku; Komai, Michio; Inui, Akio

    2011-09-01

    Zinc is required by humans and animals for many physiological functions, such as growth, immune function, and reproduction. Zinc deficiency induces a number of physiological problems, including anorexia, growth retardation, dermatitis, taste disorder, and hypogonadism. Although it is clear that zinc deficiency produces specific and profound anorexia in experimental animals, the connection between zinc deficiency and anorexia is less certain. We were the first to show that orally, but not intraperitoneally, administered zinc rapidly stimulates food intake through orexigenic peptides coupled to the afferent vagus nerve using rats during early-stage zinc deficiency without decreased zinc concentrations in plasma and tissues. We confirmed that a zinc-sufficient diet containing zinc chloride acutely stimulated food intake after short-term zinc deprivation. We also found that orally administered zinc sulfate increased the expression of NPY and orexin mRNA after administration. Using vagotomized rats, we tested whether the increase in food intake after oral administration of zinc was mediated by the vagus nerve. In sham-operated rats, the oral administration of zinc stimulated food intake, whereas zinc and saline administrations did not exhibit differing effects in vagotomized rats. We conclude that zinc stimulates food intake in short-term zinc-deficient rats through the afferent vagus nerve with subsequent effects on hypothalamic peptides associated with food intake regulation. In this review, we describe recent research investigating the roles of zinc as an appetite stimulator in food intake regulation, along with research about hypothalamus, ghrelin, leptin and zinc receptor, and clinical application about anorexia nervosa, cachexia and sarcopenia. The article also presents some promising patents on zinc. PMID:21846317

  3. ROLE OF ANGIOTENSIN-CONVERTING ENZYME AND VITAMIN D RECEPTOR GENE POLYMORPHISMS IN CANCER ANOREXIA-CACHEXIA SYNDROME

    Directory of Open Access Journals (Sweden)

    Ariele Fabris

    2012-01-01

    Full Text Available The ubiquitin-proteasome pathway is a crucial connection between aberrant immune system activation, systemic inflammation and Cancer Anorexia-Cachexia Syndrome (CACS, a syndrome that culminates in hyper-activation of the ubiquitin-proteasome pathway. Angiotensin directly up-regulates this pathway, while vitamin D down-regulates it indirectly through the insulin-like growth factor-1 pathway. We investigated the genetic predisposition towards CACS in a cancer population, examining Insertion/Deletion (I/D polymorphism of angiotensin-converting enzyme gene and FokI and BsmI polymorphisms of vitamin D receptor gene. Sixty-two cancer patients were recruited and divided into three groups: primary cachectic (C1, n = 14; dysmetabolic body weight loss ≥5% in 6 months; secondary cachectic (C2, n = 34; similar weight loss, mechanic or iatrogenic origin; and non-cachectic (NC, n = 16. C2+NC were merged in the control group. The three groups showed significant differences in average prognostic inflammatory nutritional index (C1: 26.4±23.4; C2: 5.4±5.6; NC: 0.37±0.5, C-reactive protein serum levels (C1: 6.6±2.1; C2: 2.4±2.2; NC: 1.0±2.0 mg/dL, albumin serum levels (C1: 3.1±0.6; C2: 3.5±0.4; NC 3.7±0.6 g/dL, weight loss (C1: 22±8; C2: 15±6.7; NC 5±6% and life expectancy (C1: 6.4±3.3; C2: 25±28; NC: 45±25 months. However, none of the chosen polymorphisms showed any statistically significant correlation with CACS. The complexity of the changes of the immune system in the chronic inflammation state associated with CACS is far greater than expected and further studies are required to identify genetic independent markers of progression toward CACS."

  4. Study of morphological alterations of the adrenal glands in the neoplastic cachexia Estudo das alterações morfológicas da glândula adrenal na caquexia neoplásica

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    Tânia Longo Mazzuco

    2009-01-01

    Full Text Available Advanced cancer occurs with nutritional and metabolic alterations that characterize neoplastic cachexia. When homeostasis is compromised, the adrenal glands have a fundamental role in the neuroendocrine response. Our purpose in this research was to study morphological alterations of the adrenal glands in the development of cancer associated to cachexia. Cachexia experimental model induced by Walker 256 tumor in Wistar rats, was used. Animals were sacrificed 12 days after tumor cells inoculation and adrenal glands removal for histopathologic analysis by means of hematoxylin and eosin stain. Nutritional parameters, cachexia index and adrenal glands weight, were evaluated. Animals with tumor presented cachexia index of 16,6 ± 4%. Adrenal glands average weight was significantly higher in the tumor group (40 mg ± 10 than in the control group (25 mg ± 3. Adrenal cortex of animals with cachexia showed hypertrophy of the zona fasciculata and reticular layer, with voluminous spongiocytes; vascular congestion and stasis were observed in the medullar region. Results were similar in the pair and ad libitum-fed groups. Animals with cancer cachexia showed compromised morphology of the adrenal glands which showed alterations related to stress response, suggesting increased cathecolamine secretion and activation of the hypothalamus-pituitary-adrenal axis.   Advanced cancer occurs with nutritional and metabolic alterations that characterize neoplastic cachexia. When homeostasis is compromised, the adrenal glands have a fundamental role in the neuroendocrine response. Our purpose in this research was to study morphological alterations of the adrenal glands in the development of cancer associated to cachexia. Cachexia experimental model induced by Walker 256 tumor in Wistar rats, was used. Animals were sacrificed 12 days after tumor cells inoculation and adrenal glands removal for histopathologic analysis by means of hematoxylin and eosin stain. Nutritional

  5. The role of long-chain polyunsaturated fatty acids in the treatment of cancer Cachexia and tumour growth in patients with malignant diseases: A review

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    Elizabeth A Symington

    2008-02-01

    Full Text Available Recent studies show that ω-3 polyunsaturated fatty acids (PUFAs have the capacity to modulate cancer outcomes. The body responds to cancer in the same way that it responds to inflammation and wound healing. Nutrients with anti-inflammatory effects could therefore be expected to play a role in cancer treatment. This review focuses on the role of ω-3 PUFAs in tumourigenesis and cancer cachexia. Studies indicate that eicosapentaenoic acid (EPA supplementation may promote arrest of tumour growth and reduce cell proliferation. Patients need to consume at least 2 g of EPA per day for it to have a therapeutic effect. Positive outcomes related to cachexia include diminished weight loss, increased appetite, improved quality of life and prolonged survival, although there is controversy regarding these clinical outcomes. The effects of ω-3 PUFAs on tumourigenesis and cachexia are viewed in the context of altered lipid and protein metabolism. This altered metabolism usually experienced by cancer patients results in increased formation of proinflammatory eicosanoids and cytokines. Cytokines play an indirect role by stimulating the production of arachidonic acid-derived eicosanoids, which support inflammation, cell proliferation and angiogenesis, and inhibit apoptosis. It can be concluded that ω-3 PUFA supplementation offers a means of augmenting cancer therapy, inhibiting tumourigenesis and possibly contributing to cachexia alleviation. Opsomming Onlangse studies toon dat ω-3-poli-onversadigde vetsure (POVSe oor die vermoë beskik om kankeruitkomste te moduleer. Die liggaam reageer op kanker op dieselfde wyse as wat dit op inflammasie en wondgenesing reageer. Daar kan dus verwag word dat voedingstowwe met ‘n anti-inflammatoriese uitwerking ‘n rol in die behandeling van kanker kan speel. In hierdie oorsig word daar op die rol van ω-3-POVSe in tumorigenese en kankerkageksie gefokus. Studies dui daarop dat eikosapentanoënsuur- (EPS

  6. The ghrelin receptor agonist HM01 mimics the neuronal effects of ghrelin in the arcuate nucleus and attenuates anorexia-cachexia syndrome in tumor-bearing rats.

    Science.gov (United States)

    Borner, Tito; Loi, Laura; Pietra, Claudio; Giuliano, Claudio; Lutz, Thomas A; Riediger, Thomas

    2016-07-01

    The gastric hormone ghrelin positively affects energy balance by increasing food intake and reducing energy expenditure. Ghrelin mimetics are a possible treatment against cancer anorexia-cachexia syndrome (CACS). This study aimed to characterize the action of the nonpeptidergic ghrelin receptor agonist HM01 on neuronal function, energy homeostasis and muscle mass in healthy rats and to evaluate its possible usefulness for the treatment of CACS in a rat tumor model. Using extracellular single-unit recordings, we tested whether HM01 mimics the effects of ghrelin on neuronal activity in the arcuate nucleus (Arc). Furthermore, we assessed the effect of chronic HM01 treatment on food intake (FI), body weight (BW), lean and fat volumes, and muscle mass in healthy rats. Using a hepatoma model, we investigated the possible beneficial effects of HM01 on tumor-induced anorexia, BW loss, muscle wasting, and metabolic rate. HM01 (10(-7)-10(-6) M) mimicked the effect of ghrelin (10(-8) M) by increasing the firing rate in 76% of Arc neurons. HM01 delivered chronically for 12 days via osmotic minipumps (50 μg/h) increased FI in healthy rats by 24%, paralleled by increased BW, higher fat and lean volumes, and higher muscle mass. Tumor-bearing rats treated with HM01 had 30% higher FI than tumor-bearing controls and were protected against BW loss. HM01 treatment resulted in higher muscle mass and fat mass. Moreover, tumor-bearing rats reduced their metabolic rate following HM01 treatment. Our studies substantiate the possible therapeutic usefulness of ghrelin receptor agonists like HM01 for the treatment of CACS and possibly other forms of disease-related anorexia and cachexia. PMID:27147616

  7. A trial assessing N-3 as treatment for injury-induced cachexia (ATLANTIC trial): does a moderate dose fish oil intervention improve outcomes in older adults recovering from hip fracture?

    OpenAIRE

    Cleland Leslie; Fraser Robert; Cobiac Lynne; Villani Anthony; Yaxley Alison; Miller Michelle D; James Michael; Crotty Maria

    2010-01-01

    Abstract Background Proximal femoral fractures are associated with increased morbidity and mortality. Pre-existing malnutrition and weight loss amongst this patient group is of primary concern, with conventional nutrition support being largely ineffective. The inflammatory response post proximal femoral fracture surgery and the subsequent risk of cachexia may explain the inability of conventional high energy high protein management to produce an anabolic response amongst these patients. Omega...

  8. Contribución del soporte nutricional a combatir la caquexia cancerosa Contribution of nutritional support to fight cancer cachexia

    Directory of Open Access Journals (Sweden)

    M. Planas

    2006-05-01

    seems necessary. N-3 fatty acids, especially eicosapentaenoic acid may have anticachectic properties. Although further trials are necessary the limited results available suggests that nutritional supplements enriched with EPA may reverse cachexia in cancer patients.

  9. MCG101-induced cancer anorexia-cachexia features altered expression of hypothalamic Nucb2 and Cartpt and increased plasma levels of cocaine- and amphetamine-regulated transcript peptides.

    Science.gov (United States)

    Burgos, Jonathan R; Iresjö, Britt-Marie; Smedh, Ulrika

    2016-04-01

    The aim of the present study was to explore central and peripheral host responses to an anorexia-cachexia producing tumor. We focused on neuroendocrine anorexigenic signals in the hypothalamus, brainstem, pituitary and from the tumor per se. Expression of mRNA for corticotropin-releasing hormone (CRH), cocaine- and amphetamine-regulated transcript (CART), nesfatin-1, thyrotropin (TSH) and the TSH receptor were explored. In addition, we examined changes in plasma TSH, CART peptides (CARTp) and serum amyloid P component (SAP). C57BL/6 mice were implanted with MCG101 tumors or sham-treated. A sham-implanted, pair‑fed (PF) group was included to delineate between primary tumor and secondary effects from reduced feeding. Food intake and body weight were measured daily. mRNA levels from microdissected mouse brain samples were assayed using qPCR, and plasma levels were determined using ELISA. MCG101 tumors expectedly induced anorexia and loss of body weight. Tumor-bearing (TB) mice exhibited an increase in nesfatin-1 mRNA as well as a decrease in CART mRNA in the paraventricular area (PVN). The CART mRNA response was secondary to reduced caloric intake whereas nesfatin-1 mRNA appeared to be tumor-specifically induced. In the pituitary, CART and TSH mRNA were upregulated in the TB and PF animals compared to the freely fed controls. Plasma levels for CARTp were significantly elevated in TB but not PF mice whereas levels of TSH were unaffected. The plasma CARTp response was correlated to the degree of inflammation represented by SAP. The increase in nesfatin-1 mRNA in the PVN highlights nesfatin-1 as a plausible candidate for causing tumor-induced anorexia. CART mRNA expression in the PVN is likely an adaptation to reduced caloric intake secondary to a cancer anorexia-cachexia syndrome (CACS)‑inducing tumor. The MCG101 tumor did not express CART mRNA, thus the elevation of plasma CARTp is host derived and likely driven by inflammation. PMID:26780979

  10. Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia.

    OpenAIRE

    Tracey, K J; Morgello, S; Koplin, B; Fahey, T J; Fox, J; Aledo, A; Manogue, K. R.; Cerami, A

    1990-01-01

    We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weig...

  11. Fisiología de la sarcopenia: Similitudes y diferencias con la caquexia neoplásica Psysiology of sarcopenia: Similarities and differences with neoplasic cachexia (muscle impairments in cancer and aging

    Directory of Open Access Journals (Sweden)

    Josep M. Argilés

    2006-05-01

    Full Text Available Las alteraciones que acontecen durante el proceso canceroso y el envejecimiento comparten bastantes vías metabólicas así como también mediadores. Dado que afectan a gran cantidad de personas, la caquexia cancerosa y la sarcopenia del envejecimiento podrían ser dianas para futuras investigaciones clínicas. La caquexia cancerosa es un síndrome caracterizado por una gran pérdida de peso, anorexia, astenia y anemia. De hecho, muchos de los pacientes que mueren de cáncer avanzado sufren caquexia. El grado de caquexia está inversamente correlacionado con el tiempo de supervivencia de los pacientes y siempre implica una mala prognosis. En los últimos años, las enfermedades e incapacidades relacionadas con la edad han despertado un gran interés e importancia sanitaria. Concretamente, el desgaste muscular, también conocido como sarcopenia, disminuye la calidad de vida de la población geriátrica, aumentando la morbilidad y decreciendo la esperanza de vida. Deberían dedicarse más investigaciones al esclarecimiento de los factores/mediadores del proceso caquéctico (asociados a la pérdida de las reservas grasas y de tejido muscular tanto en caquexia como en sarcopenia, ya que podría ser una buena estrategia terapéutica para la prevención y el tratamiento de la pérdida de masa muscular tanto en la enfermedad como durante el envejecimiento sano.Muscle wasting during cancer and ageing share many common metabolic pathways and mediators. Due to the size of the population involved, both cancer cachexia and ageing sarcopenia may represent targets for future promising clinical investigations. Cancer cachexia is a syndrome characterized by a marked weight loss, anorexia, asthenia and anemia. In fact, many patients who die with advanced cancer suffer from cachexia. The degree of cachexia is inversely correlated with the survival time of the patient and it always implies a poor prognosis. In recent years, age-related diseases and disabilities

  12. Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia.

    Science.gov (United States)

    Tracey, K J; Morgello, S; Koplin, B; Fahey, T J; Fox, J; Aledo, A; Manogue, K R; Cerami, A

    1990-12-01

    We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects. PMID:2254457

  13. Expressão de genes relacionados à função adrenocortical no estado de caquexia neoplásica = Expression of genes related to the adrenocortical function in the neoplastic cachexia process

    Directory of Open Access Journals (Sweden)

    Nicole de Angelis Scripes

    2009-04-01

    Full Text Available A glândula adrenal tem papel fundamental na resposta neuroendócrina,especialmente em situações em que há comprometimento da homeostasia. No processo de caquexia neoplásica, há prejuízo da homeostasia por alterações nutricionais e metabólicas do câncer em estágio avançado, envolvendo a resposta do eixo hipotálamo-hipófise-adrenal. Neste trabalho, foi utilizado um modelo animal de caquexia induzida pelo tumor de Walker-256 em ratos Wistar. Os animais (n=4 foram sacrificados dez dias após a inoculação de células tumorais e a glândula adrenal foi removida. O RNA foi extraído para o estudo da expressão de genes relacionados ao controle da esteroidogênese por RT-PCR semiquantitativa. A análise dos dados demonstrou expressão significativamente reduzida dos genes MC2R (receptor tipo 2 para melacortina, 3ßHSD I (3β-hidroxiesteroidedesidrogenase tipo I e TSPO (proteína translocadora em animais com caquexia neoplásica(valores de P=0,037; 0,0097 e 0,052, respectivamente, revelando falência do córtex da adrenal.The adrenal gland plays a crucial role in the neuroendocrine response, especially in situations where homeostasis is disturbed. In the neoplastic cachexia process, there is homeostasis impairment by nutritional and metabolic alterations of advanced-stage cancer, involving hypothalamus-pituitary-adrenal axis response. In thisassignment, an experimental model of cachexia induced by Walker-256 tumor was performed in Wistar rats. Animals (n=4 were sacrificed 10 days after inoculation of tumor cells, and the adrenal glands were excised. The RNA was isolated for the study of gene expression related to the steroidogenesis control by semi-quantitative RT-PCR. Data analysis showed a significant reduced expression of MC2R (melancortin type 2 receptor, 3ßHSD I (3-beta-hydroxysteroid dehydrogenase type I and TSPO (translocator protein genes in animals with neoplastic cachexia (P=0.037, 0.0097 and 0.052, respectively, revealing

  14. 参附注射液联合甲羟孕酮治疗肿瘤恶病质的临床观察%Clinical observation of Shenfu injection combined with medroxyprogesterone acetate for the treatment of tumor cachexia

    Institute of Scientific and Technical Information of China (English)

    陈红; 曾恩泉

    2015-01-01

    Objective:To observe the clinical efficacy of Shenfu injection combined with medroxyprogesteroneacetate ( MPA) for the treatment of tumor cachexia. Methods:57 cases of cancer cachexia patients were randomly divided into treatment group and control group. Except for giving conventional intravenous nutrition therapy and oral medroxyprogesterone tablet in two groups,the treatment group used Shenfu injection treatment. Before and after one course of treatment (4 weeks) the patients’ intake,body weight,KPS score,serum albumin and hemoglobin values were evaluated. Results:In the treatment group after treatment,food intake and KPS score,peripheral he-moglobin values have increased,compared with before and after treatment in the control group,the difference had statistical significance( P0. 05). Conclusion:Shenfu injection combined with MPA can increase appetite,improve KPS score,increase hemoglobin and im-prove the life quality of patients with tumor cachexia,which is superior to conventional therapy.%目的::观察参附注射液联合甲羟孕酮治疗肿瘤恶病质的临床疗效。方法:将57例肿瘤恶病质患者随机分为治疗组与对照组,两组常规给予静脉营养支持治疗及口服甲羟孕酮分散片,同时治疗组加用参附注射液治疗,治疗前和治疗1个疗程后(共4周)评价患者的进食量、体重、KPS评分、血清白蛋白与血红蛋白值。结果:治疗组在治疗后,进食量、KPS 评分、外周血红蛋白值均有所增加,与治疗前及对照组治疗后相比差异有统计学意义(P0.05)。结论:参附注射液治疗联合甲羟孕酮能增进肿瘤恶病质患者食欲,提高KPS 评分,增加血红蛋白量,改善肿瘤恶病质患者的生活质量,疗效优于常规治疗。

  15. Expressão de genes relacionados à função adrenocortical no estado de caquexia neoplásica - DOI: 10.4025/actascihealthsci.v31i2.6759 Expression of genes related to the adrenocortical function in the neoplastic cachexia process- DOI: 10.4025/actascihealthsci.v31i2.6759

    Directory of Open Access Journals (Sweden)

    Maria Angélica Ehara Watanabe

    2009-09-01

    Full Text Available A glândula adrenal tem papel fundamental na resposta neuroendócrina, especialmente em situações em que há comprometimento da homeostasia. No processo de caquexia neoplásica, há prejuízo da homeostasia por alterações nutricionais e metabólicas do câncer em estágio avançado, envolvendo a resposta do eixo hipotálamo-hipófise-adrenal. Neste trabalho, foi utilizado um modelo animal de caquexia induzida pelo tumor de Walker-256 em ratos Wistar. Os animais (n=4 foram sacrificados dez dias após a inoculação de células tumorais e a glândula adrenal foi removida. O RNA foi extraído para o estudo da expressão de genes relacionados ao controle da esteroidogênese por RT-PCR semiquantitativa. A análise dos dados demonstrou expressão significativamente reduzida dos genes MC2R (receptor tipo 2 para melacortina, 3ßHSD I (3ß-hidroxiesteroide-desidrogenase tipo I e TSPO (proteína translocadora em animais com caquexia neoplásica (valores de P=0,037; 0,0097 e 0,052, respectivamente, revelando falência do córtex da adrenal.The adrenal gland plays a crucial role in the neuroendocrine response, especially in situations where homeostasis is disturbed. In the neoplastic cachexia process, there is homeostasis impairment by nutritional and metabolic alterations of advanced-stage cancer, involving hypothalamus-pituitary-adrenal axis response. In this assignment, an experimental model of cachexia induced by Walker-256 tumor was performed in Wistar rats. Animals (n=4 were sacrificed 10 days after inoculation of tumor cells, and the adrenal glands were excised. The RNA was isolated for the study of gene expression related to the steroidogenesis control by semi-quantitative RT-PCR. Data analysis showed a significant reduced expression of MC2R (melancortin type 2 receptor, 3ßHSD I (3-beta-hydroxysteroid dehydrogenase type I and TSPO (translocator protein genes in animals with neoplastic cachexia (P=0.037, 0.0097 and 0.052, respectively, revealing

  16. Causas e impacto clínico de la desnutrición y caquexia en el paciente oncológico Causes and impact of hyponutrition and cachexia in the oncologic patient

    Directory of Open Access Journals (Sweden)

    P. P. García-Luna

    2006-05-01

    Full Text Available La expresión máxima de desnutrición en el cáncer es la caquexia tumoral, que será responsable directa o indirecta de la muerte en un tercio de los pacientes con cáncer. Las causas de desnutrición en el cáncer están relacionadas con el tumor, con el paciente o con los tratamientos y de forma resumida podemos diferenciar 4 grandes mecanismos por los que puede aparecer desnutrición en el paciente canceroso: • Escaso aporte de energía y nutrientes. • Alteraciones de la digestión y/o absorción de nutrientes. • Aumento de las necesidades. • Alteraciones en el Metabolismo de los nutrientes. El tratamiento oncológico, en cualquiera de sus vertientes induce la aparición de desnutrición, sobre todo en aquellos casos en que se administran varios tratamientos para la curación del cáncer (cirugía, radioterapia y quimioterapia. La desnutrición en el paciente neoplásico produce una disminución de masa muscular que conlleva una pérdida de fuerza que tiene importantes consecuencias sobre el estado funcional del individuo, pues aumenta la dependencia de cuidados por terceros (familiares o cuidadores y disminuye su calidad de vida. La desnutrición se asocia, además, a una menor respuesta a la radioterapia y a la quimioterapia, o a una peor tolerancia a éstas. La desnutrición también altera los mecanismos de cicatrización y aumenta el riesgo de complicaciones quirúrgicas tales como la deshiscencia de suturas e infecciones. Tanto las complicaciones infecciosas como las derivadas de la cirugía comportan un aumento de la estancia hospitalaria, circunstancias que contribuyen a elevar los costes de los tratamientos. En último término, no deben olvidarse los efectos de la desnutrición sobre la mortalidad, asociándose la pérdida de peso severa a una menor supervivencia.The maximal expression of hyponutrition in cancer is tumoral cachexia, which will direct or indirectly account for mortality in one third of cancer patients

  17. Diabetic neuropathic cachexia in a young female

    Directory of Open Access Journals (Sweden)

    Saumik Datta

    2013-01-01

    Full Text Available A 42-year-old lady, a known diabetic presented with generalized body ache, severe burning sensation over her lower limbs, loss of weight (approximately 8 kg, loss of appetite, nausea, frequent vomiting, and altered bowel habits without history of fever or pain abdomen. Symmetrical wasting was noted in all limbs with bilateral proximal muscle weakness, particularly of lower limbs. Ankle jerks were absent with symmetrically decreased reflexes. nerve conduction velocity (NCV revealed symmetrical distal axonal and demyelinating type of sensorimotor polyneuropathy. Hematological and gastrointestinal (GI malignancy were excluded. Patient responded to antidepressants.

  18. 中药消岩汤对肺癌恶病质大鼠摄食的瘦素抵抗机制研究%Mechanism Study on Leptin Resistance in Lung Cancer Cachexia Rats Treated by Xiaoyan Decoction

    Institute of Scientific and Technical Information of China (English)

    张蕴超; 贾英杰; 杨佩颖; 张欣; 李小江; 张莹; 朱津丽; 孙一予; 陈军

    2014-01-01

    resistance mechanism of Xiaoyan Decoction (XD) in lung cancer cachexia (LCC) rats.Methods An LCC rat model was established.Totally 40 rats were randomly divided into the normal control group,the LCC model group,the XD group,and the positive control group,10 in each group.After LCC model was set up,rats in the LCC model group were administered with normal saline,2 mL each time.Rats in the XD group were administered with XD at the daily dose of 2 mL.Those in the positive control group were administered with Medroxyprogesterone Acetate suspension (20 mg/kg) by gastrogavage at the daily dose of 2 mL.All medication lasted for 14 days.The general condition and tumor growth were observed.Serum levels of leptin and leptin receptor in the hypothalamus were detected using enzyme-linked immunosorbent assay.Contents of neuropeptide Y (NPY) and anorexia for genomic POMC were detected using real-time PCR technique.Results Serum leptin levels were lower in the LCC model group than in the normal control group with statistical significance (P < 0.05).Compared with the LCC model groups,serum leptin levels significantly increased in the XD group (P <0.01).Leptin receptor levels in the hypothalamus increased significantly in the LCC model group (P <0.01).Increased receptor levels in the LCG model group indicated that either XD or Medroxyprogesterone Acetate could effectively reduce levels of leptin receptor with statistical significance (P < 0.01).There was also statistical difference between the XD group and the positive control group (P < 0.05).Contents of NPY was higher in the LCC model group than in the other groups with statistical difference (P <0.05).There was no statistical difference in NPY between the normal control group and the rest 2 treatment groups (P >0.05).There was statistical difference in POMC between the normal control group and the LCC model group (P <0.05).POMC could be decreased in the XD group and the positive control group with statistical significance

  19. 表没食子儿茶素没食子酸酯、β-羟基-β甲基丁酸盐联合治疗癌症恶病质%Combined treatment of epigaHocatechin-3-gallate with β-hydroxy-β-methyl butyrate alleviates cancer cachexia in a mouse model

    Institute of Scientific and Technical Information of China (English)

    陈思曾; 宿鲁锋; 季伟涛

    2013-01-01

    Objective To observe the effect of the combination therapy of Epigallocatechin-3-gallate (EGCG) and β-hydroxy-β-methyl butyrate (HMB) on mouse cancer cachexia model.Methods Male BALB/C mice bearing colon 26 adenocarcinoma for 9 days were served as models of cancer cachexia.Seven days after the treatment,body weight and gastrocnemius muscle were documented.Biochemical indicators,serum interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α),C-reactive protein (CRP) levels were evaluated.The expression of nuclear factor-κB (NF-tκB) in tumor was detected,and the expressions of MAFbx and MURF-1 genes were valuated.Results IAD levels of NF-κB in placebo treatment group,EGCG group,HMB group and EGCG + HMB group were 21 247.39 ± 5 482.31,14 512.99 ± 4654.73,7 478.40 ±2 612.45,172.78 ± 173.14;respectively.TNF-αlevels in EGCG group,HMB group and EGCG + HMB group were significantly lower than those in placebo treatment group (P < O.05).The expressions of MAFbx and MURF-1 genes were significantly down-regulated in EGCG group,HMB group and EGCG + HMB group compared with those placebo treatment group (P < O.05).Conclusion The combined treatment of EGCG with HMB is better than EGCG or HMB,its mechanism is probably to improve skeletal muscle metabolism by synergistically inhibiting NF-κB pathway.%目的 观察表没食子儿茶素没食子酸酯(EGCG)、β-羟基-β甲基丁酸盐(HMB)联合应用对小鼠癌症恶病质的治疗作用.方法 于雄性BALB/C小鼠接种小鼠结肠腺癌Colon26(C26)细胞,9d后模型建立.用药7d后,记录小鼠右侧腓肠肌重量、去瘤体质量、血清生化指标、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C-反应性蛋白(CRP)、肿瘤组织核因子-κB(NF-κB)表达、MAFbx及MURF-1基因表达.结果 安慰剂治疗组、EGCG、HMB、EGCG+ HMB组NF-κB积分吸光度(IA)值分别为21 247.39±5482.31、14 512.99±4654.73、7478.40±2612.45、172.78 ± 173.14,均低于安慰剂治疗组(P <0.05),

  20. Systemic administration of ciliary neurotrophic factor induces cachexia in rodents.

    OpenAIRE

    Henderson, J T; Seniuk, N A; Richardson, P.M.; Gauldie, J; Roder, J. C.

    1994-01-01

    Ciliary neurotrophic factor (CNTF) has previously been shown to promote the survival of several classes of neurons and glial. We report here that in addition to its effects on the nervous system, CNTF can induce potent effects in extra-neural tissues. Implantation of C6 glioma cells engineered to secrete CNTF either subcutaneously or into the peritoneal cavity of adult mice, or systemic injections of purified rat or human recombinant CNTF, resulted in a rapid syndrome of weight loss resulting...

  1. Progressive disseminated histoplasmosis presenting with cachexia and hypercalcemia

    Directory of Open Access Journals (Sweden)

    Khasawneh FA

    2013-02-01

    Full Text Available Faisal A Khasawneh,1 Subhan Ahmed,2 Ruba A Halloush31Section of Infectious Diseases, Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, TX, 2Section of Nephrology, Department of Internal Medicine, University of Oklahoma, Tulsa, OK, 3Amarillo Pathology Group, Amarillo, TX, USAAbstract: Histoplasmosis is a common endemic mycosis. The majority of infections involving this dimorphic fungus are asymptomatic. Manifestations in symptomatic patients are diverse, ranging from flu-like illness to a more serious disseminated disease. We present here a case of chronic disseminated histoplasmosis mimicking a metastatic cancer. We reviewed the literature for cases of disseminated histoplasmosis presenting with hypercalcemia, focusing particularly on clinical presentation, risk factors predisposing for fungal infection, and outcome. We report a case of a 65-year-old diabetic male who presented with unexplained weight loss and hypercalcemia. Multiple brain space-occupying lesions and bilateral adrenal enlargement were evident on imaging studies. Biopsies showed caseating granulomas with budding yeast, consistent with histoplasmosis. The patient's symptoms resolved after liposomal amphotericin B and itraconazole therapy. Granulomatous diseases, including fungal infections, should be considered alongside malignancies, in patients with similar presentation.Keywords: disseminated histoplasmosis, hypercalcemia

  2. Effect of Feeding Status on Adjuvant Arthritis Severity, Cachexia, and Insulin Sensitivity in Male Lewis Rats

    Czech Academy of Sciences Publication Activity Database

    Stofková, A.; Železná, Blanka; Romzová, Marianna; Uličná, O.; Kiss, A.; Skurlová, M.; Jurcovicová, J.

    -, ID 398026 (2010), s. 1-12. ISSN 0962-9351 R&D Projects: GA ČR GA305/06/0427; GA ČR GAP303/10/1368 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520701 Keywords : adjuvant arthritis * feeding Subject RIV: CE - Biochemistry Impact factor: 2.059, year: 2010

  3. Refractory cachexia is associated with increased plasma concentrations of fentanyl in cancer patients

    OpenAIRE

    Suno, Manabu

    2015-01-01

    Manabu Suno,1,* Yuriko Endo,1,* Hiroyuki Nishie,2 Makoto Kajizono,3 Toshiaki Sendo,3 Junji Matsuoka4 1Department of Oncology Pharmaceutical Care and Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2Department of Anesthesiology and Resuscitology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 3Department of Pharmacy, Okayama University Hospital, 4Faculty of Health Sciences, Okayama University Medical School, Okayama, Japan ...

  4. Caquexia associada à insuficiência cardíaca Heart failure-induced cachexia

    OpenAIRE

    Marina Politi Okoshi; Fernando G. Romeiro; Paiva, Sergio A.R.; Katashi Okoshi

    2013-01-01

    Pacientes com insuficiência cardíaca frequentemente desenvolvem estado de caquexia, que constitui fator independente de redução da sobrevida. Caquexia pode ser diagnosticada quando ocorre perda de peso corporal maior que 6% do peso habitual, na ausência de outras doenças. Embora sua fisiopatologia não esteja completamente esclarecida, vários fatores parecem estar envolvidos, como diminuição da ingestão alimentar, anormalidades do trato gastrointestinal, ativação imunológica e neuro-hormonal e...

  5. Anormalidades neuromuscular no desuso, senilidade e caquexia Neuromuscular abnormalities in disuse, cachexia and ageing

    OpenAIRE

    João Aris Kouyoumdjian

    1993-01-01

    É feita revisão de literatura sobre as principais alterações do sistema neuromuscular no desuso, senilidade e caquexia no ser humano e em modelos animais. A diminuição do diâmetro das fibras musculares após período de inatividade/imobilidade (desuso) deve-se à perda de miofibrilas periféricas não ocorrendo formação de core-targetóides ou diminuição da atividade da miofosforilase, próprias da desnervação; mantêm-se a liberação espontânea de acetilcolina e fatores tróficos na junção mio-neural;...

  6. Vagus nerve schwannoma presenting with dysphagia and prolonged cachexia: a case report

    OpenAIRE

    Ali Ghafouri; Zhamak Khorgami; Saadat Moulanaei

    2010-01-01

    "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-fon...

  7. Formoterol in the treatment of experimental cancer cachexia: effects on heart function

    OpenAIRE

    Toledo, Míriam; Springer, Jochen; BUSQUETS, SÍLVIA; Tschirner, Anika; López-Soriano, Francisco J.; Anker, Stefan D.; Argilés, Josep M.

    2014-01-01

    Background and aims Formoterol is a highly potent β2-adrenoceptor-selective agonist, which is a muscle growth promoter in many animal species, resulting in skeletal muscle hypertrophy. Previous studies carried out in our laboratory have shown that formoterol treatment in tumour-bearing animals resulted in an amelioration of muscle loss through different mechanisms that include muscle apoptosis and proteolysis. Methods The study presented involved rats bearing the Yoshida AH-130 ascites tumour...

  8. Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia

    OpenAIRE

    Tran, Eric; Chinnasamy, Dhanalakshmi; Yu, Zhiya; Morgan, Richard A.; Lee, Chyi-Chia Richard; Restifo, Nicholas P; Rosenberg, Steven A.

    2013-01-01

    Fibroblast activation protein (FAP) is a candidate universal target antigen because it has been reported to be selectively expressed in nearly all solid tumors by a subset of immunosuppressive tumor stromal fibroblasts. We verified that 18/18 human tumors of various histologies contained pronounced stromal elements staining strongly for FAP, and hypothesized that targeting tumor stroma with FAP-reactive T cells would inhibit tumor growth in cancer-bearing hosts. T cells genetically engineered...

  9. Hypothalamus transcriptome profile suggests an anorexia-cachexia syndrome in the anx/anx mouse model

    OpenAIRE

    Mercader Bigas, Josep Maria; Lozano, Juan Jos??; Sumoy, Lauro; Dierssen, Mara; Visa, Joana; Gratac??s Mayora, M??nica; Estivill, Xavier

    2008-01-01

    The anx/anx mouse displays poor appetite and lean appearance and is considered a good model for the study of anorexia nervosa. To identify new genes involved in feeding behavior and body weight regulation we performed an expression profiling in the hypothalamus of the anx/anx mice. Using commercial microarrays we detected 156 differentially expressed genes and validated 92 of those using TaqMan low-density arrays. The expression of a set of 87 candidate genes selected based on literature evid...

  10. Predicting survival in cancer patients: the role of cachexia and hormonal, nutritional and inflammatory markers

    OpenAIRE

    Utech, Anne E.; Tadros, Eiriny M.; Hayes, Teresa G.; Garcia, Jose M.

    2012-01-01

    Background Cancer can lead to weight loss, anorexia, and poor nutritional status, which are associated with decreased survival in cancer patients. Methods Male cancer patients (n = 136) were followed for a mean time of 4.5 years. Variables were obtained at baseline: cancer stage, albumin, hemoglobin, tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, bioavailable testosterone, appetite questionnaire, and weight change from baseline to 18 months. Primary statistical tests included Kaplan...

  11. Fisiopatología de la caquexia neoplásica Pathophysiology of neoplasic cachexia

    OpenAIRE

    Argilés, J M; Busquets, S; López-Soriano, F J; Figueras, M.

    2006-01-01

    La regulación del apetito y de los patrones alimenticios está mediada por diferentes factores psicológicos, gastrointestinales, metabólicos y nutricionales, así como por distintos mecanismos neuronales y endocrinos. El paciente canceroso anoréxico experimenta una sensación precoz de saciedad y una disminución del apetito. En algunas ocasiones, las causas de esta anorexia pueden derivarse del propio tratamiento anticanceroso (quimioterapia, radioterapia o inmunoterapia), que pueden inducir náu...

  12. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training

    OpenAIRE

    Lenk, Karsten; Schuler, Gerhard; Adams, Volker

    2010-01-01

    Skeletal muscle is the most abundant tissue in the human body, and the maintenance of its mass is essential to ensure basic function as locomotion, strength and respiration. The decision to synthesize or to break down skeletal muscle proteins is regulated by a network of signaling pathways that transmit external stimuli to intracellular factors regulating gene transcription. The tightly regulated balance of muscle protein breakdown and synthesis is disturbed in several distinct myopathies, bu...

  13. Underweight, Markers of Cachexia, and Mortality in Acute Myocardial Infarction: A Prospective Cohort Study of Elderly Medicare Beneficiaries

    OpenAIRE

    Bucholz, Emily M.; Krumholz, Hannah A; Krumholz, Harlan M.

    2016-01-01

    Editors' Summary Background A heart attack, or acute myocardial infarction (AMI), is a potentially fatal medical emergency that occurs when part of the heart muscle dies because the blood supply to the heart becomes blocked, usually by a blood clot. Every year in the US alone, more than three-quarters of a million people have a heart attack—more than one person every minute. Heart attacks are usually caused by coronary artery disease. With age, fatty deposits (atherosclerotic plaque) coat the...

  14. Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock.

    OpenAIRE

    Winter, B. K.; Fiskum, G; Gallo, L. L.

    1995-01-01

    Inappropriate hepatic lipogenesis, hypertriglyceridaemia, decreased fatty acid oxidation and muscle protein wasting are common in patients with sepsis, cancer or AIDS. Given carnitine's role in the oxidation of fatty acids (FAs), we anticipated that carnitine might promote FA oxidation, thus ameliorating metabolic disturbances in lipopolysaccharide (LPS)- and methylcholanthrene-induced sarcoma models of wasting in rats. In the LPS model, rats were injected with LPS (24 mg kg-1 i.p.), and trea...

  15. Lipoprotein lipase expression exclusively in liver. A mouse model for metabolism in the neonatal period and during cachexia.

    OpenAIRE

    Merkel, M.; Weinstock, P H; Chajek-Shaul, T; Radner, H; B. Yin; Breslow, J L; Goldberg, I J

    1998-01-01

    Lipoprotein lipase (LPL), the rate-limiting enzyme in triglyceride hydrolysis, is normally not expressed in the liver of adult humans and animals. However, liver LPL is found in the perinatal period, and in adults it can be induced by cytokines. To study the metabolic consequences of liver LPL expression, transgenic mice producing human LPL specifically in the liver were generated and crossed onto the LPL knockout (LPL0) background. LPL expression exclusively in liver rescued LPL0 mice from n...

  16. Tratamiento farmacológico de la anorexia-caquexia cancerosa Pharmacological therapy of cancer anorexia-cachexia

    OpenAIRE

    D. Cardona

    2006-01-01

    La anorexia es uno de los síntomas más comunes en los enfermos con cáncer avanzado y se manifiesta con pérdida de apetito por saciedad. Por otro lado, la caquexia se describe en aquellos enfermos con pérdida de peso involuntaria. El proceso canceroso produce un desequilibrio en el balance energético al disminuir la ingesta y aumentar el catabolismo, produciéndose un balance netamente negativo. Se observan diferentes factores que determinan a la caquexia, desde los desequilibrios metabólicos p...

  17. Contribución del soporte nutricional a combatir la caquexia cancerosa Contribution of nutritional support to fight cancer cachexia

    OpenAIRE

    M. Planas; C. Puiggrós; S. Redecillas

    2006-01-01

    Habitualmente para incrementar la ingesta de alimentos y combatir la anorexia se adoptan medidas encaminadas a controlar los síntomas que la disminuyen o a administrar los nutrientes por las vías más adecuadas a las alteraciones patológicas existentes. Sin embargo en el caso de la anorexia-caquexia que presentan los pacientes neoplásicos no siempre ello resulta tan lineal ni efectivo. El tratamiento nutritivo debería enfocarse en función de los diversos mecanismos patogénicos implicados en su...

  18. Ghrelin improves body weight loss and skeletal muscle catabolism associated with angiotensin II-induced cachexia in mice.

    Science.gov (United States)

    Sugiyama, Masako; Yamaki, Akira; Furuya, Mayumi; Inomata, Norio; Minamitake, Yoshiharu; Ohsuye, Kazuhiro; Kangawa, Kenji

    2012-10-10

    Ghrelin is a gastric peptide that regulates energy homeostasis. Angiotensin II (Ang II) is known to induce body weight loss and skeletal muscle catabolism through the ubiquitin-proteasome pathway. In this study, we investigated the effects of ghrelin on body weight and muscle catabolism in mice treated with Ang II. The continuous subcutaneous administration of Ang II to mice for 6 days resulted in cardiac hypertrophy and significant decreases in body weight gain, food intake, food efficiency, lean mass, and fat mass. In the gastrocnemius muscles of Ang II-treated mice, the levels of insulin-like growth factor 1 (IGF-1) were decreased, and the levels of mRNA expression of catabolic factors were increased. Although the repeated subcutaneous injections of ghrelin (1.0mg/kg, twice daily for 5 days) did not affect cardiac hypertrophy, they resulted in significant body weight gains and improved food efficiencies and tended to increase both lean and fat mass in Ang II-treated mice. Ghrelin also ameliorated the decreased IGF-1 levels and the increased mRNA expression levels of catabolic factors in the skeletal muscle. IGF-1 mRNA levels in the skeletal muscle significantly decreased 24h after Ang II infusion, and this was reversed by two subcutaneous injections of ghrelin. In C2C12-derived myocytes, the dexamethasone-induced mRNA expression of atrogin-1 was decreased by IGF-1 but not by ghrelin. In conclusion, we demonstrated that ghrelin improved body weight loss and skeletal muscle catabolism in mice treated with Ang II, possibly through the early restoration of IGF-1 mRNA in the skeletal muscle and the amelioration of nutritional status. PMID:22750276

  19. Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity

    OpenAIRE

    Lambert, P. D.; Anderson, K. D.; Sleeman, M. W.; Wong, V.; Tan, J.; Hijarunguru, A.; Corcoran, T L; Murray, J. D.; Thabet, K. E.; Yancopoulos, G D; Wiegand, S J

    2001-01-01

    Ciliary Neurotrophic Factor (CNTF) was first characterized as a trophic factor for motor neurons in the ciliary ganglion and spinal cord, leading to its evaluation in humans suffering from motor neuron disease. In these trials, CNTF caused unexpected and substantial weight loss, raising concerns that it might produce cachectic-like effects. Countering this possibility was the suggestion that CNTF was working via a leptin-like mechanism to cause weight loss, based on the find...

  20. 癌性恶病质的药物治疗进展%Progress on the Treatment of Cancer-related Anorexia and Cachexia Syndrome

    Institute of Scientific and Technical Information of China (English)

    王琳

    2014-01-01

    癌性恶病质是复杂的临床综合征,伴随体重下降、慢性炎症、新陈代谢紊乱、厌食、肌肉消耗、生活质量下降等.癌性恶病质治疗棘手,缺乏有效的治疗手段,目前许多新药的临床前及临床实验正在进行中.本文针对癌性恶病质药物治疗的现状及研究进展作一综述.

  1. P05.07A LOWER-DOSE CISPLATIN-ETOPOSIDE REGIMEN FOR CHILDREN WITH HYPOTHALAMIC/CHIASMATIC TUMOR AND DIENCEPHALIC CACHEXIA

    OpenAIRE

    Cardellicchio, S.; Farina, S.; Bresci, C.; Settimelli, V.; Chiaro, S.; Massimino, M.; Genitori, L.; Sardi, I.

    2014-01-01

    Diencephalic Syndrome (DS) is a rare but potentially lethal condition, which may complicate the clinical course of infants with hypothalamic/chiasmatic tumors, usually low-grade gliomas, either pilocytic (WHO-grade I) or pilomyxoid (WHO-grade II) astrocytomas. The mean survival of DS patients who do not receive any treatment after diagnosis, is usually less than 12 months. Yet, effective therapy is hampered by the tumor location preventing its complete resection, and by significant neurocogni...

  2. Ácido eicosapentanóico no tratamento da caquexia neoplásica : monografia : Eicosapentaenoic acid in the treatment of cancer cachexia

    OpenAIRE

    Marques, Carlos Miguel dos Santos

    2008-01-01

    Contém um relatório de estágio curricular realizado no Serviço de Nutrição e Alimentação do Centro Hospitalar do Alto Ave, Unidade de Guimarães, da licenciatura em Ciências da Nutrição pela Faculdade de Ciências da Nutrição e Alimentação da Universidade do Porto. O exemplar do relatório de estágio existe apenas em formato papel e está disponível para consulta na Biblioteca da FCNAUP Tese de licenciatura em Ciências da Nutrição apresentada à Faculdade de Ciências da Nutrição e Alimentação d...

  3. Nutrition in Cancer Patients

    OpenAIRE

    Dintinjana, Renata Dobrila; Redžović, Arnela; Čubranić, Aleksandar; Dintinjana, Marin; Vanis, Nenad

    2014-01-01

    Cachexia is defi ned as an unintended loss of stable weight exceeding 10%. Patients with advanced cachexia express anorexia, early satiety, severe weight loss, weakness, anemia, and edema. Anorexia represents the result of a failure of the usual appetite signals whereas cachexia is the debilitating state of involuntary weight loss. This syndrome, referred to as the »cancer anorexia-cachexia syndrome« (CACS) and usually consists of a combination of anorexia, tissue wasting, malnutr...

  4. Pioglitazone Treatment Increases Survival and Prevents Body Weight Loss in Tumor–Bearing Animals: Possible Anti-Cachectic Effect

    OpenAIRE

    Beluzi, Mércia; Peres, Sidney B.; Henriques, Felipe S.; Rogério A L Sertié; Franco, Felipe O.; Kaltinaitis B Santos; Knobl, Pâmela; Andreotti, Sandra; Shida, Cláudio S.; Neves, Rodrigo X.; Farmer, Stephen R.; Seelaender, Marília; Fábio B Lima; Batista Jr., Miguel L.

    2015-01-01

    Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglita...

  5. Hypothalamic regulation of food intake during cancer

    OpenAIRE

    Dwarkasing, J. T.

    2015-01-01

    Appetite is often reduced in patients with chronic illness, including cancer. Cancer anorexia, loss of appetite, frequently co-exists with cachexia, and the combined clinical picture is known as anorexia-cachexia syndrome. In patients suffering from this syndrome, anorexia considerably contributes to the progression of cachexia, and strongly impinges on quality of life. Inflammatory processes in the hypothalamus are considered to play a crucial role in the development of disease-related anore...

  6. Nutrition in Head and Neck Cancer Patients

    OpenAIRE

    Varkey, Prashanth; Tang, Wen-Ruay; Tan, Ngian Chye

    2010-01-01

    Anorexia and cachexia frequently complicate the late stages of malignancy and can be a prominent feature of early disease. The resulting weight loss significantly affects the morbidity and mortality of the cancer patient. A fundamental understanding of nutrition and the pathophysiology of cancer cachexia will aid in diligent treatment decisions to achieve optimal results. The pathophysiology of cancer cachexia is discussed, together with methods of nutritional assessment, nutritional requirem...

  7. Fisiología de la sarcopenia: Similitudes y diferencias con la caquexia neoplásica Psysiology of sarcopenia: Similarities and differences with neoplasic cachexia (muscle impairments in cancer and aging)

    OpenAIRE

    Argilés, Josep M.; Silvia Busquets; López-Soriano, Francisco J.; Maite Figueras

    2006-01-01

    Las alteraciones que acontecen durante el proceso canceroso y el envejecimiento comparten bastantes vías metabólicas así como también mediadores. Dado que afectan a gran cantidad de personas, la caquexia cancerosa y la sarcopenia del envejecimiento podrían ser dianas para futuras investigaciones clínicas. La caquexia cancerosa es un síndrome caracterizado por una gran pérdida de peso, anorexia, astenia y anemia. De hecho, muchos de los pacientes que mueren de cáncer avanzado sufren caquexia. ...

  8. Causas e impacto clínico de la desnutrición y caquexia en el paciente oncológico Causes and impact of hyponutrition and cachexia in the oncologic patient

    OpenAIRE

    P. P. García-Luna; J. Parejo Campos; Pereira Cunill, J. L.

    2006-01-01

    La expresión máxima de desnutrición en el cáncer es la caquexia tumoral, que será responsable directa o indirecta de la muerte en un tercio de los pacientes con cáncer. Las causas de desnutrición en el cáncer están relacionadas con el tumor, con el paciente o con los tratamientos y de forma resumida podemos diferenciar 4 grandes mecanismos por los que puede aparecer desnutrición en el paciente canceroso: • Escaso aporte de energía y nutrientes. • Alteraciones de la digestión y/o abs...

  9. Expressão de genes relacionados à função adrenocortical no estado de caquexia neoplásica = Expression of genes related to the adrenocortical function in the neoplastic cachexia process

    OpenAIRE

    Nicole de Angelis Scripes; Marcelo Abbá Macioszek; Larissa Danielle Bahls; Mateus Nóbrega Aoki; Maria Angelica Ehara Watanabe; Tânia Longo Mazzuco

    2009-01-01

    A glândula adrenal tem papel fundamental na resposta neuroendócrina,especialmente em situações em que há comprometimento da homeostasia. No processo de caquexia neoplásica, há prejuízo da homeostasia por alterações nutricionais e metabólicas do câncer em estágio avançado, envolvendo a resposta do eixo hipotálamo-hipófise-adrenal. Neste trabalho, foi utilizado um modelo animal de caquexia induzida pelo tumor de Walker-256 em ratos Wistar. Os animais (n=4) foram sacrificados dez dias após a ino...

  10. 中药合并醋酸甲羟孕酮改善晚期癌症患者恶液质%Traditional Chinese medicine combined with medroxyprogesterone acetate to treat cancerous cachexia in patients with advanced cancer

    Institute of Scientific and Technical Information of China (English)

    陈衍智; 李萍萍; 郭庆志; 孙红

    2002-01-01

    目的观察中药合并醋酸甲羟孕酮对晚期癌症患者的厌食、体重下降、卡氏评分及癌性疼痛的止痛作用.方法 60例晚期肿瘤病人随机分为两组,A组30例为中药加醋酸甲羟孕酮,B组30例为单纯醋酸甲羟孕酮.结果 A组对厌食、体重下降、卡氏评分及癌性疼痛的改善方面优于B组(P<0.05).结论中药合并醋酸甲羟孕酮为改善晚期癌症患者恶液质较为有效的治疗方法.

  11. Ghrelin and Its Analogues, BIM-28131 and BIM-28125, Improve Body Weight and Regulate the Expression of MuRF-1 and MAFbx in a Rat Heart Failure Model

    OpenAIRE

    Palus, Sandra; Schur, Robert; Akashi, Yoshihiro J; Bockmeyer, Barbara; Datta, Rakesh; Halem, Heather; Dong, Jesse,; Culler, Michael D.; Adams, Volker; Anker, Stefan D.; Springer, Jochen

    2011-01-01

    Cardiac cachexia is a serious complication of chronic heart failure with a prevalence of 10–16% and poor prognosis. There are no current therapy options for cardiac cachexia. Ghrelin is the natural ligand for the GHS-1a-receptor and a potential target for conditions associated with cachexia. Ghrelin has been shown to increase weight in several species. The GHS-1a-receptor is not only found in the brain, but also in other tissues, including the myocardium. Human clinical trials with native ghr...

  12. Advance Care Planning: Medical Issues to Consider

    Science.gov (United States)

    ... cancer or end stage chronic illness accompanied by anorexia (lack of appetite) and cachexia (muscles wasting away ... care and administrative program support. Share this: Twitter Facebook Google Search for: Choosing a Hospice: 16 Questions ...

  13. Help for the Caregiver

    Science.gov (United States)

    ... the End of Life Caregivers need help and emotional support. A caregiver responds in his or her ... summaries on Fatigue and Sleep Disorders . Nausea , vomiting , anorexia , and cachexia —See the PDQ summaries on Nausea ...

  14. Roles for the Family Caregiver

    Science.gov (United States)

    ... the End of Life Caregivers need help and emotional support. A caregiver responds in his or her ... summaries on Fatigue and Sleep Disorders . Nausea , vomiting , anorexia , and cachexia —See the PDQ summaries on Nausea ...

  15. Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

    Science.gov (United States)

    2015-03-17

    Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  16. Changes in IGF-I, urinary free cortisol and adipokines during dronabinol therapy in anorexia nervosa: Results from a randomised, controlled trial

    DEFF Research Database (Denmark)

    Andries, Alin; Frystyk, Jan; Flyvbjerg, Allan;

    2015-01-01

    OBJECTIVE: Anorexia nervosa (AN) is characterised by complex neuroendocrine disturbances due to severe underweight, physical hyperactivity and purging behaviour. Cannabinoid agonists are used to palliate cachexia of various causes, but their interactions with the hormonal systems that are involved...

  17. In Reply

    OpenAIRE

    de la Torre-Vallejo, Martha; Turcott, Jenny; Arrieta, Oscar; Baracos, Vickie

    2016-01-01

    The mechanism through which sarcopenia occurs differs between cancer patients and older people. Loss of skeletal muscle mass should be considered the most clinically relevant phenotypic feature of cachexia-related sarcopenia, and it can be identified by computed tomography.

  18. Eicosapentaenoic Acid Enriched Enteral Nutrition Improves Lean Body Mass in Esophageal, Head and Neck Cancer Patients

    OpenAIRE

    Shieh, Christine

    2015-01-01

    OBJECTIVE: Cachexia is a nutrient deficient condition affecting millions of cancer patients. Cancers of the upper gastrointestinal tract, head and neck are often the most severely affected. Currently, there is no established therapy for cachexia, although several potential anti-cachectic agents are being explored. A meta-analysis was conducted to review the effect of eicosapentaenoic acid (EPA) enriched enteral nutrition on lean body mass (LBM) in esophageal, head and neck cancer patients at ...

  19. Is enteral nutrition a primary therapy in cancer patients?

    OpenAIRE

    Bozzetti, F

    1994-01-01

    At present, there is limited evidence for the role of enteral nutrition as a primary therapy in cancer patients. Cachexia commonly occurs in patients with advanced cancer. A consensus view from a large number of studies suggests that cachexia cannot be fully reversed by vigorous enteral nutritional support. A review is included of the available data on the effects of enteral nutritional support on the common indices of nutritional state and on the final outcome of patients receiving enteral n...

  20. Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1

    OpenAIRE

    Ruud, Johan; Nilsson, Anna; Engström Ruud, Linda; Wang, Wenhua; Nilsberth, Camilla; Iresjo, Britt-Marie; Lundholm, Kent; Engblom, David; Blomqvist, Anders

    2013-01-01

    It is well-established that prostaglandins (PGs) affect tumorigenesis, and evidence indicates that PGs also are important for the reduced food intake and body weight loss, the anorexia–cachexia syndrome, in malignant cancer. However, the identity of the PGs and the PG producing cyclooxygenase (COX) species responsible for cancer anorexia–cachexia is unknown. Here, we addressed this issue by transplanting mice with a tumor that elicits anorexia. Meal pattern analysis revealed that the anorexia...

  1. Formoterol treatment downregulates the myostatin system in skeletal muscle of cachectic tumour-bearing rats

    OpenAIRE

    BUSQUETS, SÍLVIA; Toledo, Míriam; Marmonti, Enrica; ORPÍ, MARCEL; CAPDEVILA, EVA; Betancourt, Angelica; López-Soriano, Francisco J.; Argilés, Josep M.

    2011-01-01

    Cachexia is a common systemic manifestation. Additionally, myostatin is known to be a negative regulator of skeletal muscle development. The present study aimed to investigate whether formoterol down-regulates the myostatin system in skeletal muscle of tumour-bearing rats. Real-time PCR and Western blotting were used for the analysis. Results showed that rats bearing the Yoshida AH-130 ascites hepatoma, a cachexia-inducing tumour, exhibited marked muscle wasting that affected the mass of the ...

  2. Cancer cachexia—pathophysiology and management

    OpenAIRE

    Suzuki, Hajime; Asakawa, Akihiro; Amitani, Haruka; NAKAMURA, NORIFUMI; Inui, Akio

    2013-01-01

    About half of all cancer patients show a syndrome of cachexia, characterized by anorexia and loss of adipose tissue and skeletal muscle mass. Cachexia can have a profound impact on quality of life, symptom burden, and a patient’s sense of dignity. It is a very serious complication, as weight loss during cancer treatment is associated with more chemotherapy-related side effects, fewer completed cycles of chemotherapy, and decreased survival rates. Numerous cytokines have been postulated to pla...

  3. The assessment of anorexia in patients with cancer: cut-off values for the FAACT–A/CS and the VAS for appetite

    OpenAIRE

    Blauwhoff-Buskermolen, S.; Ruijgrok, C.; Ostelo, R. W.; de Vet, H. C. W.; Verheul, H.M.W.; de van der Schueren, M. A. E.; Langius, J. A. E.

    2015-01-01

    Purpose Anorexia is a frequently observed symptom in patients with cancer and is associated with limited food intake and decreased quality of life. Diagnostic instruments such as the Anorexia/Cachexia Subscale (A/CS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire and the visual analog scale (VAS) for appetite have been recommended in the assessment of anorexia, but validated cut-off values are lacking. This study aimed to obtain cut-off values of these instrum...

  4. The role of dietary nutrition in stomach cancer

    OpenAIRE

    Stojcev, Zoran; Matysiak, Konrad; Duszewski, Michal; Banasiewicz, Tomasz

    2013-01-01

    Stomach cancer mortality still represents a significant proportion of all cancer deaths. The majority of patients with advanced cancer experience cancer anorexia-cachexia syndrome with weight loss, reduced appetite, fatigue, and weakness. Neoplastic cachexia is a very common clinical manifestation of upper gastrointestinal (GI) tract cancer and is generally assumed to be secondary to the mechanical effects of the tumor on the upper digestive tract. The main reasons are obstruction to swallowi...

  5. Alterations caused by physical training in pulmonary edema and loss of muscle mass in rats with Walker-256 tumor
    Alterações promovidas pelo treinamento físico no edema pulmonar e perda de massa muscular em ratos portadores de tumor Walker-256

    OpenAIRE

    Rubens Cecchini; Eleonora Elísia Abra Blanco; Samantha Bagolan de Abreu; Aida Mehanna; Igor Fernando Scanfelli da Silva; Rosiane Batista Mastelari; Marli Cardoso Martins Pinge

    2008-01-01

    Walker-256 tumor is a fast-growing tumor and has been studied under several metabolic aspects associated or not to cachexia. It was observed in our laboratory that animals with Walker-256 tumor, after spontaneous death (usually around the fifteenth day), showed significant pulmonary edema with fluid in the pleural cavity. Some studies have suggested that physical training improves the survival of animals with tumor and minimizes the effects of cachexia. The purpose of our work was to assess t...

  6. Clinical studies of immunofunction and protein metabolism by combined supplementation of glutamine and recombinant human growth hormone in postoperative patients with cardiogenic cachexia of rheumatic heart disease%风湿性心脏病合并恶病质患者术后应用重组人生长激素的临床观察

    Institute of Scientific and Technical Information of China (English)

    王伟; 吴蔚; 何萍; 王海东; 杨康

    2009-01-01

    Objective To study the effects of recombinant human growth hormone(rhGH) on the treatment for valve replacement postoperative in rheumatic heart disease associated cardiac eaehex.Methods Fortytwo patients with rheumatic heart disease associated cardiac eachexia were divided into two groups.Group one(n=20,rhGH group) received standard enteral nutrition (15 kal·kg-1 · d-1)with rhGH 10U injection subeutaneously from postoperation day 7 to day 14 and group two(n = 22,eontrol group) received standard enteral nutrition (15 kal·kg-1· d-1) for the same period.Haemoglobin, serum total protein, serum albumin, blood glucose, handgrip exercise and triceps skin_fold thickness were determined.Meehanieal ventilation, hypostatie pneumonia incidence rate, and length of stay were observed.Results The levels of serum total protein, serum albumin and blood glucose eoneentration in the rhGH group at the 14th day were inereased significantly compared to that in the control group(P <0.01).Haemoglobin, triceps skinfold thiekness and handgrip exercise in rhGH group were significantly different from those in the control group(P <0.05).Postoperative meehanieal ventilation time, intensive care unit time, hospital stay time were signifieantly shorter than those in the eontrol group (P < 0.05), and hypostatie pneumonia was significantly lower than that in the eontroi group(P < 0.01).Conclusions The rhGH can obviously improve anabolie effects of patients with rheumatic heart disease associated cardiac eachexia whieh can reduce hypostatie pneumonia and shorten postoperative hospital stay time.%目的 探讨风湿性心脏病合并心源性恶病质综合征(SOCC)患者,瓣膜置换术后应用重组人生长激素的效果.方法 42例风湿性心脏病合并SOCC分成重组人生长激素rhGH组(治疗组)和对照组.治疗组(n=20)采用常规营养的肠内营养(总热卡15 kal·kg-1·d-1)+rhGH,其中rhGH每天皮下注射IOU,从术后第7-14 d共计7 d.对照组(n:22)仪采用常规营养的肠内营养(总热量15 kal·kg-1·d-1).术后第7 d和第14 d,分别测定血红蛋白、血浆总蛋白、白蛋白、血糖浓度和双手握力试验,观察机械通气时间、坠积性肺炎发生率,住院时间和营养学测量.结果 治疗组第14 d的血浆总蛋白、白蛋白、血糖浓度比对照组明显升高(P<0.01),血红蛋白、双手握力试验和三头肌皮褶厚度较治疗前明显提高(P<0.05);治疗组呼吸机辅助时间、1CU时间、术后时间(P<0.05)和坠积性肺炎的发生率(P<0.01)较对照组明显降低.结论 相对于单纯的常规营养,rhGH可以明显改善风心病恶病质综合征、瓣膜病换瓣术后患者的蛋白质合成代谢,减少坠积性肺炎的发生,减少住院时间.

  7. Expressão de genes relacionados à função adrenocortical no estado de caquexia neoplásica - DOI: 10.4025/actascihealthsci.v31i2.6759 Expression of genes related to the adrenocortical function in the neoplastic cachexia process- DOI: 10.4025/actascihealthsci.v31i2.6759

    OpenAIRE

    Maria Angélica Ehara Watanabe; Mateus Nóbrega Aoki; Larissa Danielle Bahls; Marcelo Abbá Macioszek; Nicole de Angelis Scripes; Tânia Longo Mazzuco

    2009-01-01

    A glândula adrenal tem papel fundamental na resposta neuroendócrina, especialmente em situações em que há comprometimento da homeostasia. No processo de caquexia neoplásica, há prejuízo da homeostasia por alterações nutricionais e metabólicas do câncer em estágio avançado, envolvendo a resposta do eixo hipotálamo-hipófise-adrenal. Neste trabalho, foi utilizado um modelo animal de caquexia induzida pelo tumor de Walker-256 em ratos Wistar. Os animais (n=4) foram sacrificados dez dias após a in...

  8. Balanço entre ácidos graxos ômega-3 e 6 na resposta inflamatória em pacientes com câncer e caquexia Omega-3 and 6 fatty acids balance in inflammatory response in patients with cancer and cachexia

    OpenAIRE

    Adriana Garófolo; Antônio Sérgio Petrilli

    2006-01-01

    O emagrecimento, associado à perda de massa magra, é um fenômeno observado com freqüência em pacientes com câncer. Tal condição predispõe o paciente ao maior risco de infecções, pior resposta aos tratamentos implantados e, como conseqüência, desfavorece o prognóstico de cura. Além disso, a desnutrição também está associada à pior qualidade de vida. Dessa forma, algumas terapias têm sido propostas na tentativa de reverter o catabolismo, por meio da atenuação da resposta inflamatória, observado...

  9. Balanço entre ácidos graxos ômega-3 e 6 na resposta inflamatória em pacientes com câncer e caquexia Omega-3 and 6 fatty acids balance in inflammatory response in patients with cancer and cachexia

    Directory of Open Access Journals (Sweden)

    Adriana Garófolo

    2006-10-01

    Full Text Available O emagrecimento, associado à perda de massa magra, é um fenômeno observado com freqüência em pacientes com câncer. Tal condição predispõe o paciente ao maior risco de infecções, pior resposta aos tratamentos implantados e, como conseqüência, desfavorece o prognóstico de cura. Além disso, a desnutrição também está associada à pior qualidade de vida. Dessa forma, algumas terapias têm sido propostas na tentativa de reverter o catabolismo, por meio da atenuação da resposta inflamatória, observado em grande porcentagem de pacientes com câncer e caquexia. Entre elas, a suplementação com ácidos graxos da família ômega-3 pode representar uma estratégia na redução da formação de citocinas pró-inflamatórias, favorecendo a tolerância metabólica dos substratos energéticos e atenuando o catabolismo protéico, com o intuito de melhorar o prognóstico de cura de pacientes com câncer. Entretanto, os estudos mostram alguns resultados conflitantes da suplementação com ômega-3 na resposta imunológica. Por outro lado, em pacientes com câncer, os ensaios clínicos mostraram atenuar a resposta inflamatória e melhorar o estado nutricional. O objetivo deste artigo é realizar uma revisão criteriosa do assunto.Emaciation and loss of lean body mass is a frequent phenomenon observed in cancer patients. This condition leads to infection risk and a poor response to treatment, thus reducing the chances of cure. Furthermore, malnutrition is also associated with a poor quality of life. Therefore, therapies have been proposed in attempt to revert the catabolism observed in most of these patients by attenuating the inflammatory response. Among them, omega-3 fatty acid supplementation may be a strategy to reduce the production of pro-inflammatory cytokines and improve metabolic substrate tolerance, decreasing protein catabolism in order to ameliorate the prognosis of cure in cancer patients. However, studies demonstrate some conflicting results of ômega-3 supplementation on immune response. On the other hand, clinical trials in cancer patients demonstrate that the inflammatory response decreases and the nutritional status improves. The aim of this paper is to elaborate a strict review of the subject.

  10. Effects of plasmid-mediated growth hormone-releasing hormone in severely debilitated dogs with cancer.

    Science.gov (United States)

    Draghia-Akli, Ruxandra; Hahn, Kevin A; King, Glen K; Cummings, Kathleen K; Carpenter, Robert H

    2002-12-01

    Cachexia is a common manifestation of late stage malignancy and is characterized by anemia, anorexia, muscle wasting, loss of adipose tissue, and fatigue. Although cachexia is disabling and can diminish the life expectancy of cancer patients, there are still no effective therapies for this condition. We have examined the feasibility of using a myogenic plasmid to express growth hormone-releasing hormone (GHRH) in severely debilitated companion dogs with naturally occurring tumors. At a median of 16 days after intramuscular delivery of the plasmid, serum concentrations of insulin-like growth factor I (IGF-I), a measure of GHRH activity, were increased in 12 of 16 dogs (P intramuscular injection of a GHRH-expressing plasmid is both safe and capable of stimulating the release of growth hormone and IGF-I in large animals. The observed anabolic responses to a single dose of this therapy might be beneficial in patients with cancer-associated anemia and cachexia. PMID:12498779

  11. Nutrition in Pancreatic Cancer: A Review

    Science.gov (United States)

    Gärtner, Simone; Krüger, Janine; Aghdassi, Ali A.; Steveling, Antje; Simon, Peter; Lerch, Markus M.; Mayerle, Julia

    2016-01-01

    Background Pancreatic cancer is the fourth leading cause of cancer-related mortality in both genders. More than 80% of patients suffer from significant weight loss at diagnosis and over time develop severe cachexia. Early nutritional support is therefore essential. Summary This review evaluates the different nutritional therapies, such as enteral nutrition, parenteral nutrition and special nutritional supplements, on nutritional status, quality of life and survival Key Message Due to the high prevalence of malnutrition and the rapid development of anorexia-cachexia-syndrome, early nutritional intervention is crucial and supported by clinical data Practical Implications Enteral nutrition should be preferred over parenteral nutrition. Omega-3 fatty acids and l-carnitine are promising substances for the prevention of severe cachexia, but further randomized controlled trials are needed to establish generally accepted guidelines on nutrition in pancreatic cancer.

  12. Uveitis associated to the infection by Leishmania chagasi in dog from the Olinda city, Pernambuco, Brazil

    Directory of Open Access Journals (Sweden)

    Brito Fábio Luiz da Cunha

    2004-01-01

    Full Text Available Among the parasitic diseases, Canine Visceral Leishmaniasis (CVL is included in the systemic illnesses of chronic evolution that attack men and dogs, presenting varied clinical manifestations as cachexia, dermatologic lesions, peripheral lymphadenopathies, besides the ocular lesions. This work report the case of a dog clinically suspected of having CVL, presenting skin lesions, cachexia, gryphosis, and ocular signs of uveitis. The parasitological diagnosis was accomplished for Canine Leishmaniasis through the visualization of amastigote forms of Leishmania chagasi in smears of bone marrow fluid aspirate, of non-lesioned, and lesioned skin. Alterations in the ocular structures are characterized mainly by mononuclear-plasmocitic infiltrate.

  13. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN) - a randomized multicentre trial

    OpenAIRE

    Kraft Matthias; Kraft Kathleen; Gärtner Simone; Mayerle Julia; Simon Peter; Weber Eckhard; Schütte Kerstin; Stieler Jens; Koula-Jenik Heide; Holzhauer Peter; Gröber Uwe; Engel Georg; Müller Cornelia; Feng You-Shan; Aghdassi Ali

    2012-01-01

    Abstract Background Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia. Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g) or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM)...

  14. Echium oil is not protective against weight loss in head and neck cancer patients undergoing curative radio(chemo)therapy: a randomised-controlled trial

    OpenAIRE

    Pottel, Lies; Lycke, Michelle; Boterberg, Tom; Pottel, Hans; Goethals, Laurence; Duprez, Fréderic; Maes, Alex; Goemaere, Stefan; Rottey, Sylvie; Foubert, Imogen; Debruyne, Philip

    2014-01-01

    Background: Therapy-induced mucositis and dysphagia puts head and neck (H&N) cancer patients at increased risk for developing cachexia. Omega-3 fatty acids (n-3 FA) have been suggested to protect against cachexia. We aimed to examine if echium oil, a plant source of n-3 FA, could reduce weight loss in H&N cancer patients undergoing radio(chemo)therapy with curative intent. Methods: In a double-blind trial, patients were randomly assigned to echium oil (intervention (I) group; 7.5 ml bis in...

  15. [Cancer and Malnutrition].

    Science.gov (United States)

    Tsuzuki, Norimasa; Higashiguchi, Takashi; Ito, Akihiro; Ohara, Hiroshi; Futamura, Akihiko

    2015-07-01

    A Japanese proverb says that a balanced diet leads to a healthy body. However, the relation between healthy life and nutrition has not been established precisely and quantitatively. Cancer cachexia, which is malnutrition in cancer patients, has been studied extensively. Appropriate nutrition support can prevent the progression of malnutrition in cancer patients and advance the tolerance for anticancer therapy. In refractory cachexia (terminally cancer patients), we will judge the necessity of reduction of nutrition support, what it is called "gear-change", because the support is burden for the body. It is important to restrict the quantity of nutrition and to give medical treatment to retain bodily function in these patients. PMID:26197740

  16. Serum levels of human MIC-1/GDF15 vary in a diurnal pattern, do not display a profile suggestive of a satiety factor and are related to BMI

    DEFF Research Database (Denmark)

    Tsai, Vicky Wang-Wei; Macia, Laurence; Feinle-Bisset, Christine;

    2015-01-01

    The TGF-b superfamily cytokine MIC-1/GDF15 circulates in the blood of healthy humans. Its levels rise substantially in cancer and other diseases and this may sometimes lead to development of an anorexia/cachexia syndrome. This is mediated by a direct action of MIC-1/GDF15 on feeding centres in the...

  17. Deletion variant near ZNF389 is associated with control of ovine lentivirus in multiple flocks of sheep

    Science.gov (United States)

    Ovine lentivirus (OvLV) is a macrophage-tropic lentivirus found in many countries that causes interstitial pneumonia, mastitis, arthritis and cachexia in sheep. There is no preventive vaccine and no cure, but breed differences suggest marker-assisted selective breeding might improve odds of infectio...

  18. Weight loss in cancer patients can be offset by aggressive nutritional therapy.

    Science.gov (United States)

    1997-12-01

    Patients with cancer or other debilitating diseases such as AIDS and COPD often have on and off interruptions in care because of cachexia, also known as wasting syndrome. However, managing these patients with "medical foods" can and does get them on their feet faster. Find out how and why some doctors are swearing by this not so well-known management tool. PMID:10176430

  19. Hospital Malnutrition

    OpenAIRE

    Asumadu-Sarkodie, Samuel

    2012-01-01

    Malnutrition seen in hospitals usually occurs as some form of protein-energy malnutrition (PEM). Primary PEM results from an acute or chronic deficiency of both protein and calories. Secondary PEM, or cachexia, results from a disease or medical condition such as cancer or gastrointestinal disease that alters requirements or impairs utilization of nutrients.

  20. Drug: D08856 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08856 Drug Anamorelin hydrochloride (JAN/USAN) C31H42N6O3. HCl 582.3085 583.1645 D08856.gif Tre ... atment of cancer anorexia ... and cancer cachexia Anamorelin is a non-peptidic g ...

  1. Exercise as a Time-conditioning Effector in Chronic Disease: a Complementary Treatment Strategy

    Directory of Open Access Journals (Sweden)

    Luis F. B. P. Costa Rosa

    2004-01-01

    Full Text Available Exercise has been widely believed to be a preventive and therapeutic aid in the treatment of various pathophysiological conditions such as cardiovascular disease and cancer. A common problem associated with such pathologies is cachexia, characterized by progressive weight loss and depletion of lean and fat body mass, and is linked to poor prognosis. As this syndrome comprises changes in many physiological systems, it is tempting to assume that the modulation of the psychoneuroimmunoendocrine axis could attenuate or even prevent cachexia progression in cancer patients. Cancer cachexia is characterized by a disruption in the rhythmic secretion of melatonin, an important time-conditioning effector. This hormone, secreted by the pineal gland, transmits circadian and seasonal information to all organs and cells of the body, synchronizing the organism with the photoperiod. Considering that exercise modulates the immune response through at least two different mechanisms—metabolic and neuroendocrine—we propose that the adoption of a regular exercise program as a complementary strategy in the treatment of cancer patients, with the exercise bouts regularly performed at the same time of the day, will ameliorate cachexia symptoms and increase survival and quality of life.

  2. First report of citrus exocortis viroid and two citrus variants of the hop stunt viroid on lemon in Azerbaijan

    Science.gov (United States)

    Budwood received from a lemon tree growing at the Bioresources Institute Nakhichivan, Azerbaijan, produced symptoms corresponding with citrus viroids and cachexia on biological indicators ‘S-1’ citron and ‘Parson’s Special’ (PSM) mandarin, respectively. Sequential poly acrylamide gel electrophoresis...

  3. Concomitant parenteral nutrition and systemic cytotoxic therapy in a metastatic colorectal cancer patient

    OpenAIRE

    Popov, A.A.; I. L. Chernikovsky; O. L. Fakhrutdinova; E V Tkachenko

    2012-01-01

    Pathologic nutrients metabolism presents a severe problem in metastatic colorectal cancer patients, especially those with canceromatosis. A hypermetabolism-catabolism syndrome frequently develops in in patients with progressing canceromatosis. This leads to cachexia anorexia syndrome, which significantly impedes available treatment options. Artificial nutrition allows to improve available treatment in such patients. We present a successful case of concomitant parenteral nutrition and systemic...

  4. Farber's disease (lysosomal acid ceramidase deficiency).

    OpenAIRE

    Jameson, R. A.; Holt, P.J.; Keen, J H

    1987-01-01

    The patient presented with progressive joint deformity, a hoarse voice, subsequent cachexia, and myoclonic seizures. She was first seen aged 22 months and died aged 6 years. A diagnosis of Farber's disease was made by demonstrating a deficiency of acid ceramidase both in leucocytes and fibroblasts.

  5. Aberrant brain microRNA target and miRISC gene expression in the anx/anx anorexia mouse model

    DEFF Research Database (Denmark)

    Mercader, Josep M; González, Juan R; Lozano, Juan José;

    2012-01-01

    The anorexia mouse model, anx/anx, carries a spontaneous mutation not yet identified and homozygous mutants are characterized by anorexia-cachexia, hyperactivity, and ataxia. In order to test if the microRNA function was altered in these mice, hypothalamus and cortex transcriptomes were evaluated...

  6. A randomized study of the effect of fish oil on n-3 fatty acid incorporation and nutritional status in lung cancer patients

    DEFF Research Database (Denmark)

    Andersen, Jens Rikardt; Dannerfjord, Stina Hjerrild; Nørgaard, Michael; Lauritzen, Lotte; Lange, Peter; Jensen, N Aa; Boisen, L W; Jensen, R G; Andersen, M J; Sørensen, J B

    2015-01-01

    Long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFA) have been proposed to have beneficial effect on cancer cachexia. The aims of the present study were to a) determine the incorporation of n-3 LCPUFA in erythrocytes (RBC) as a measurement of compliance to fish oil (FO)-supplement in lung cancer...

  7. Differentiation of citrus Hop stunt viroid variants by real-time RT-PCR and high resolution melting analysis

    Science.gov (United States)

    Viroids are small, infectious, single-stranded RNA molecules that cause several important citrus diseases. Viroids are transmitted primarily in budwood, however, spread can also occur mechanically on pruning equipment, budding knives, hedging and topping equipment. Exocortis and cachexia are two we...

  8. Development and Validation of an Ovine Progressive Pneumonia Virus Quantitative PCR

    Science.gov (United States)

    Ovine progressive pneumonia virus (OPPV) infects at least one sheep in eighty-one percent of U.S. sheep flocks as measured by serological diagnostic tests and can cause viral-induced mastitis, arthritis, dypsnea, and cachexia. Diagnostic tests that quantify OPP proviral load in peripheral blood leu...

  9. Rapid differentiation of citrus Hop stunt viroid variants by use of real-time RT-PCR and high resolution melting analysis

    Science.gov (United States)

    The RNA genome of Hop stunt viroid (HSVd) contains five to six nucleotides in a variable (V) domain, called the cachexia expression motif, which is associated with pathogenic and non-pathogenic variants in citrus. Current methods to differentiate HSVd variants rely on lengthy greenhouse biological i...

  10. L‑carnitine ameliorates the liver inflammatory response by regulating carnitine palmitoyltransferase I‑dependent PPARγ signaling.

    Science.gov (United States)

    Jiang, Fang; Zhang, Zongqi; Zhang, Yi; Wu, Jianping; Yu, Li; Liu, Su

    2016-02-01

    The liver is crucial for systemic inflammation in cancer cachexia. Previous studies have shown that L‑carnitine, as the key regulator of lipid metabolism, exerts an anti‑inflammatory effect in several diseases, and ameliorates the symptoms of cachexia by regulating the expression and activity of carnitine palmitoyltransferase (CPT) in the liver. However, the effect of L‑carnitine on the liver inflammatory response in cancer cachexia remains to be elucidated. The aim of the present study was to examine the role of the CPT I‑dependent peroxisome proliferator‑activated receptor (PPAR)γ signaling pathway in the ameliorative effect of L‑carnitine on the liver inflammatory response. This was investigated in a colon‑26 tumor‑bearing mouse model with cancer cachexia. Liver sections were immunohistochemically analyzed, and mRNA and protein levels of representative molecules of the CPT-associated PPARγ signaling pathway were assessed using PCR and western blot analysis, respectively. The results showed that oral administration of L‑carnitine in these mice improved hepatocyte necrosis, liver cell cord derangement and hydropic or fatty degeneration of the liver cells in the liver tissues, decreased serum levels of malondialdehyde, increased serum levels of superoxide dismutase and glutathione peroxidase, and elevated the expression levels of PPARα and PPARγ at the mRNA and protein levels. These changes induced by L‑carnitine were reversed by treatment with etomoxir, an inhibitor of CPT I. The inhibitory effect of L‑carnitine on the increased expression level of nuclear factor (NF)‑κB p65 in the peripheral blood mononuclear cells was markedly weakened by GW9662, a selective inhibitor of PPAR‑γ. GW9662 also eliminated the inhibitory effect of L‑carnitine on the expression of cyclooxygenase‑2 (Cox‑2) in the liver, and on the serum expression levels of pro‑inflammatory prostaglandin E2, C-reactive protein, tumor necrosis factor‑α and

  11. Hypolipemia associated with the wasting condition of rabbits infected with Strongyloides papillosus.

    Science.gov (United States)

    Nakamura, Y; Motokawa, M

    2000-02-29

    Rabbits develop a wasting condition in the intestinal stage of Strongyloides papillosus infection. Serum inflammatory cytokine and lipid profiles were investigated in five rabbits infected with S. papillosus and five uninfected pair-fed controls to ascertain whether the disease is inflammatory cytokine-mediated cachexia. Tumor necrosis factor alpha (TNF alpha) was detected in one infected animal at Day 7 after infection. Interleukin (IL)-1 was detected in three infected, and one control, animals at Day 28. IL-6 remained unchanged in both the groups. Infected animals developed hypolipemia, including hypotriglyceridemia in the intestinal stage of infection. Control animals lost body weight in the same manner as the infected animals, but had elevated cholesterols and phospholipids with normal triglyceride concentrations. The results suggested that the wasting condition has no association with cachexia induced by TNF alpha. IL-1 or IL-6, and that hepatic function for lipid synthesis is affected during the intestinal stage of S. papillosus infection. PMID:10681033

  12. Extreme Achalasia Presenting as Anorexia Nervosa

    Directory of Open Access Journals (Sweden)

    P. J. Goldsmith

    2012-01-01

    Full Text Available Background. Achalasia may lead to cachexia if not diagnosed in an early stage. Surgery in cachectic patients is hazardous and complications may result in a protracted recovery or even death. Different treatment options have been described. In this paper, we report a stepwise surgical laparoscopic approach which appears to be safe and effective. Methods. Over a one-year period, a patient with a body mass index (BMI below 17 being treated for anorexia nervosa was referred with dysphagia. Because of the extreme cachexia, a laparoscopic feeding jejunostomy (LFJ was fashioned to enable long-term home enteral feeding. The patient underwent a laparoscopic Heller myotomy (LHM when the BMI was normal. Results. The patient recovered well following this stepwise approach. Conclusion. Patients with advanced achalasia usually present with extreme weight loss. In this small group of patients, a period of home enteral nutrition (HEN via a laparoscopically placed feeding jejunostomy allows weight gain prior to safe definitive surgery.

  13. Polioencephalomalacia and Heart Failure Secondary to Presumptive Thiamine Deficiency, Hepatic Lipidosis, and Starvation in 2 Abandoned Siamese Cats.

    Science.gov (United States)

    Anholt, H; Himsworth, C; Britton, A

    2016-07-01

    Two 4-year-old spayed female Siamese cats were seized by the British Columbia Society for the Prevention of Cruelty to Animals after confinement to an abandoned housing unit without food for 9 weeks. One cat was found dead, and the second was euthanized within 24 hours due to neurologic deterioration despite therapy. Polioencephalomalacia of the caudal colliculus, hepatic lipidosis, cachexia, and congestive heart failure with cardiomyocyte atrophy were identified in both cats through postmortem examination and attributed to a prolonged period of starvation. Brain lesions were likely the result of thiamine deficiency (Chastek paralysis), which can be associated with both malnutrition and liver disease. This case highlights the importance of thiamine supplementation during realimentation of cats with hepatic lipidosis. Heart failure resulting from cachexia may have contributed to the death of the first cat and the morbidity of the second cat. PMID:26792845

  14. Muscle protein waste in tumor-bearing rats is effectively antagonized by a beta 2-adrenergic agonist (clenbuterol). Role of the ATP-ubiquitin-dependent proteolytic pathway.

    OpenAIRE

    Costelli, P; García-Martínez, C; Llovera, M; Carbó, N.; López-Soriano, F J; Agell, N; Tessitore, L.; Baccino, F M; Argilés, J M

    1995-01-01

    Tissue protein hypercatabolism (TPH) is a most important feature in cancer cachexia, particularly with regard to the skeletal muscle. The rat ascites hepatoma Yoshida AH-130 is a very suitable model system for studying the mechanisms involved in the processes that lead to tissue depletion, since it induces in the host a rapid and progressive muscle waste mainly due to TPH (Tessitore, L., G. Bonelli, and F. M. Baccino. 1987. Biochem. J. 241:153-159). Detectable plasma levels of tumor necrosis ...

  15. Nutritional status, body composition and diet in patients with rheumatoid arthritis

    OpenAIRE

    Elkan, Ann-Charlotte

    2009-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease with higher mortality rate than in the general population, which is largely attributed to cardiovascular disease (CVD). Another consequence of the inflammatory process is change in body composition with decreased muscle mass and increased fat mass. This condition has been named rheumatoid cachexia and is difficult to detect in clinical practice, as it is associated with little or no weight loss and with a maintained...

  16. Exploring metabolic dysfunction in chronic kidney disease

    OpenAIRE

    Slee Adrian D

    2012-01-01

    Abstract Impaired kidney function and chronic kidney disease (CKD) leading to kidney failure and end-stage renal disease (ESRD) is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD) risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabol...

  17. Conjugated Linoleic Acid: good or bad nutrient

    Directory of Open Access Journals (Sweden)

    Gonçalves Daniela C

    2010-10-01

    Full Text Available Abstract Conjugated linoleic acid (CLA is a class of 28 positional and geometric isomers of linoleic acid octadecadienoic.Currently, it has been described many benefits related to the supplementation of CLA in animals and humans, as in the treatment of cancer, oxidative stress, in atherosclerosis, in bone formation and composition in obesity, in diabetes and the immune system. However, our results show that, CLA appears to be not a good supplement in patients with cachexia.

  18. Use of Contrast-Enhanced MR Angiography (CE-MRA) for the Diagnosis of a Vascular Ring Anomaly in a Dog

    OpenAIRE

    Silke Hecht; April M. Durant; Adams, William H.; Conklin, Gordon A.

    2012-01-01

    A 4-month-old female mixed breed dog was presented to the University of Tennessee College of Veterinary Medicine with a history of regurgitation and cachexia. Thoracic radiographs revealed focal megaesophagus cranial to the heart base. Magnetic resonance imaging (MRI) was performed. True fast imaging with steady-state precession (TrueFISP), fast low angle shot (FLASH), and short tau inversion recovery (STIR) sequences were acquired prior to contrast medium administration. Contrast-enhanced ma...

  19. The Endocannabinoid System: Role in Energy Regulation

    OpenAIRE

    Gamage, Thomas F; Lichtman, Aron H.

    2012-01-01

    Cannabis sativa has been used since antiquity to treat many ailments, including eating disorders. The primary psychoactive constituent of this plant, Δ9-tetrahydrocannabinol (THC) is an FDA approved medication to treat nausea and emesis caused by cancer chemotherapeutic agents as well as to stimulate appetite in AIDS patients suffering from cachexia. The effects of THC are mediated through the endocannabinoid system (ECS), which promotes a positive energy balance through stimulation of appeti...

  20. Extreme Achalasia Presenting as Anorexia Nervosa

    OpenAIRE

    Goldsmith, P. J.; Decadt, B.

    2012-01-01

    Background. Achalasia may lead to cachexia if not diagnosed in an early stage. Surgery in cachectic patients is hazardous and complications may result in a protracted recovery or even death. Different treatment options have been described. In this paper, we report a stepwise surgical laparoscopic approach which appears to be safe and effective. Methods. Over a one-year period, a patient with a body mass index (BMI) below 17 being treated for anorexia nervosa was referred with dysphagia. Becau...

  1. Molecular mechanisms and treatment options for muscle wasting eiseases

    OpenAIRE

    Rüegg, Markus A.; Glass, David J.

    2010-01-01

    Loss of muscle mass can be the consequence of pathological changes, as observed in muscular dystrophies; or it can be secondary to cachexia-inducing diseases that cause muscle atrophy, such as cancer, heart disease, or chronic obstructive pulmonary disease; or it can be a consequence of aging or simple disuse. Although muscular dystrophies are rare, muscle loss affects millions of people worldwide.Wediscuss the molecular mechanisms involved in muscular dystrophy and in muscle atrophy and pres...

  2. Primary cranial mediastinal hemangiosarcoma in a young dog

    OpenAIRE

    Yoon, Hun-Young; Kang, Hye-Mi; Lee, Mi-Young

    2014-01-01

    Primary cranial mediastinal hemangiosarcomas are uncommon tumors. A 30-kg, 2-year-old, intact female German shepherd was presented for evaluation of cachexia and respiratory distress of a few days’ duration. Lateral radiographic projection of the thorax revealed significant pleural effusion. Computed tomography revealed a cranial mediastinal mass effect adjacent to the heart. On surgical exploration, a pedunculated mass attached to the esophagus, trachea, brachiocephalic trunk, left subclavia...

  3. Myeloid-Specific Tristetraprolin Deficiency in Mice Results in Extreme Lipopolysaccharide Sensitivity in an Otherwise Minimal Phenotype1

    OpenAIRE

    Qiu, Lian-Quan; Stumpo, Deborah J.; Blackshear, Perry J.

    2012-01-01

    Tristetraprolin (TTP) is an mRNA destabilizing protein that binds to AU-rich elements in labile transcripts, such as the mRNA encoding tumor necrosis factor alpha (TNF), and promotes their deadenylation and degradation. TTP-deficient (KO) mice exhibit an early-onset, severe inflammatory phenotype, with cachexia, erosive arthritis, left-sided cardiac valvulitis, myeloid hyperplasia, and autoimmunity, which can be prevented by injections of anti-TNF antibodies, or interbreeding with TNF recepto...

  4. Role of Protein Carbonylation in Skeletal Muscle Mass Loss Associated with Chronic Conditions

    OpenAIRE

    Esther Barreiro

    2016-01-01

    Muscle dysfunction, characterized by a reductive remodeling of muscle fibers, is a common systemic manifestation in highly prevalent conditions such as chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD), cancer cachexia, and critically ill patients. Skeletal muscle dysfunction and impaired muscle mass may predict morbidity and mortality in patients with chronic diseases, regardless of the underlying condition. High levels of oxidants may alter function and structure of ...

  5. Overshadowing as prevention of anticipatory nausea and vomiting in pediatric cancer patients: study protocol for a randomized controlled trial

    OpenAIRE

    Geiger, Friedemann; Wolfgram, Levke

    2013-01-01

    Background Emesis and nausea are side effects induced by chemotherapy. These effects lead to enormous stress and strain on cancer patients. Further consequences may include restrictions in quality of life, cachexia or therapy avoidance. Evidence suggests that cancer patients develop the side effects of nausea and vomiting in anticipation of chemotherapy. Contextual cues such as smell, sounds or even the sight of the clinic may evoke anticipatory nausea and vomiting prior to infusion. Anticipa...

  6. Studies of LXR and CIDEA function in human adipocytes

    OpenAIRE

    Stenson, Britta

    2012-01-01

    Obesity, defined as a body mass index of 30 or above, is the result of an imbalance of energy intake and energy expenditure. In the last decade, the obesity prevalence has truly reached epidemic proportions with major effects on public health. Obesity is closely associated with insulin resistance, type 2 diabetes, hyperlipidemia and atherosclerosis. On the other end of the spectra, cancer cachexia is a poor diagnostic factor in cancer patients. It is characterized by a state of...

  7. Enhanced ZAG production by subcutaneous adipose tissue is linked to weight loss in gastrointestinal cancer patients

    OpenAIRE

    Mracek, T.; Stephens, N. A.; Gao, D.; Bao, Y.; Ross, J A; Rydén, M; Arner, P; Trayhurn, P.; Fearon, K C H; Bing, C

    2011-01-01

    Background: Profound loss of adipose tissue is a hallmark of cancer cachexia. Zinc-α2-glycoprotein (ZAG), a recently identified adipokine, is suggested as a candidate in lipid catabolism. Methods: In the first study, eight weight-stable and 17 cachectic cancer patients (weight loss ⩾5% in previous 6 months) were recruited. Zinc-α2-glycoprotein mRNA and protein expression were assessed in subcutaneous adipose tissue (SAT), subcutaneous adipose tissue morphology was examined and serum ZAG conce...

  8. Pancreatic cancer cell-derived IGFBP-3 contributes to muscle wasting

    OpenAIRE

    Huang, Xiu-yan; Huang, Zi-Li; Yang, Ju-hong; Xu, Yong-Hua; Sun, Jiu-Song; Zheng, Qi; Wei, Chunyao; Song, Wei; Yuan, Zhou

    2016-01-01

    Background: Progressive loss of skeletal muscle, termed muscle wasting, is a hallmark of cancer cachexia and contributes to weakness, reduced quality of life, as well as poor response to therapy. Previous studies have indicated that systemic host inflammatory response regarding tumor development results in muscle wasting. However, how tumor directly regulates muscle wasting via tumor-derived secreted proteins is still largely unknown. Methods: In this study, we performed bioinformatics analys...

  9. Association of sarcopenia and observed physical performance with attainment of multidisciplinary team planned treatment in non-small cell lung cancer: an observational study protocol

    OpenAIRE

    Collins, Jemima T.; Noble, Simon; Chester, John; Davies, Helen E; Evans, William D.; Lester, Jason; Parry, Diane; Pettit, Rebecca J.; Byrne, Anthony

    2015-01-01

    Background Non-small cell lung cancer (NSCLC) frequently presents in advanced stages. A significant proportion of those with reportedly good ECOG performance status (PS) fail to receive planned multidisciplinary team (MDT) treatment, often for functional reasons, but an objective decline in physical performance is not well described. Sarcopenia, or loss of muscle mass, is an integral part of cancer cachexia. However, changes in both muscle mass and physical performance may predate clinically ...

  10. Systemic Inflammation in Chronic Obstructive Pulmonary Disease: May Adipose Tissue Play a Role? Review of the Literature and Future Perspectives

    OpenAIRE

    Ruzena Tkacova

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Low-grade systemic inflammation is considered a hallmark of COPD that potentially links COPD to increased rate of systemic manifestations of the disease. Obesity with/without the metabolic syndrome and cachexia represent two poles of metabolic abnormalities that may relate to systemic inflammation. On one hand systemic inflammatory syndrome likely reflects inflammation in the lungs, i.e. result...

  11. Role of microRNAs in skeletal muscle hypertrophy

    OpenAIRE

    Hitachi, Keisuke; Tsuchida, Kunihiro

    2014-01-01

    Skeletal muscle comprises approximately 40% of body weight, and is important for locomotion, as well as for metabolic homeostasis. Adult skeletal muscle mass is maintained by a fine balance between muscle protein synthesis and degradation. In response to cytokines, nutrients, and mechanical stimuli, skeletal muscle mass is increased (hypertrophy), whereas skeletal muscle mass is decreased (atrophy) in a variety of conditions, including cancer cachexia, starvation, immobilization, aging, and n...

  12. Conditional Activation of Akt in Adult Skeletal Muscle Induces Rapid Hypertrophy

    OpenAIRE

    Lai, Ka-Man V.; Gonzalez, Michael; Poueymirou, William T.; Kline, William O.; Na, Erqian; Zlotchenko, Elizabeth; Stitt, Trevor N.; Economides, Aris N.; Yancopoulos, George D.; Glass, David J.

    2004-01-01

    Skeletal muscle atrophy is a severe morbidity caused by a variety of conditions, including cachexia, cancer, AIDS, prolonged bedrest, and diabetes. One strategy in the treatment of atrophy is to induce the pathways normally leading to skeletal muscle hypertrophy. The pathways that are sufficient to induce hypertrophy in skeletal muscle have been the subject of some controversy. We describe here the use of a novel method to produce a transgenic mouse in which a constitutively active form of Ak...

  13. Nutritional Considerations for Cancer Patients

    OpenAIRE

    Chen, Angela

    1985-01-01

    Although weight loss is a frequent, though not invariable, component of the cancer syndrome, the associated malnutrition is a poor prognostic sign among both children and adults. This article describes the possible mechanisms of cancer cachexia; reviews the present state of nutritional support in cancer patients; identifies nutritional problems and workable approaches during the pre- and post-treatment periods; discusses the unconventional nutritional practices commonly encountered and lists ...

  14. Nutritional Status and Nutritional Support Before and After Pancreatectomy for Pancreatic Cancer and Chronic Pancreatitis

    OpenAIRE

    Karagianni, Vasiliki Th.; Apostolos E. Papalois; Triantafillidis, John K.

    2012-01-01

    Cachexia, malnutrition, significant weight loss, and reduction in food intake due to anorexia represent the most important pathophysiological consequences of pancreatic cancer. Pathophysiological consequences result also from pancreatectomy, the type and severity of which differ significantly and depend on the type of the operation performed. Nutritional intervention, either parenteral or enteral, needs to be seen as a method of support in pancreatic cancer patients aiming at the maintenance ...

  15. A clinical approach to the nutritional care process in protein-energy wasting hemodialysis patients

    OpenAIRE

    Mar Ruperto; Sánchez-Muniz, Francisco J; Guillermina Barril

    2014-01-01

    Introduction: Malnutrition/wasting/cachexia are complex-disease conditions that frequently remain undiagnosed and/or untreated in up to 75% of prevalent hemodialysis (HD) patients. The nutrition care process (NCP) based on assessment, diagnosis, intervention and monitoring of nutritional status is a systematic method that nutrition professionals use to make decisions in clinical practice. Objective: This review examines from a clinical-nutritional practice point of view: a) nutritional status...

  16. Immunological perspectives on nutritional support during cancer

    OpenAIRE

    Faber, J.

    2012-01-01

    Cachexia is a major problem in many cancer patients with a global incidence of malnutrition ranging from 30% to 90% during the course of cancer. The main characteristics of this chronic condition of catabolism include progressive weight loss, anorexia, wasting of muscle and adipose tissue, muscle weakness and fatigue. Tumor-derived factors, therapeutic strategies, but also nutritional status, age and even stress and depression are involved in this process, resulting in a chronic inflammatory ...

  17. New perspective for nutritional support of cancer patients: Enteral/parenteral nutrition

    OpenAIRE

    AKBULUT, GAMZE

    2011-01-01

    Cancer and its treatment result in severe biochemical and physiological alterations associated with a deterioration of quality of life (QoL). Cancer-related malnutrition may evolve into cancer cachexia due to complex interactions between pro-inflammatory cytokines and the host metabolism. Depending on the type of cancer treatment (either curative or palliative), the clinical condition of the patient and nutritional status, adequate and patient-tailored nutritional intervention should be presc...

  18. An infant with hyperalertness, hyperkinesis, and failure to thrive: a rare diencephalic syndrome due to hypothalamic anaplastic astrocytoma

    OpenAIRE

    Stival, Alessia; Lucchesi, Maurizio; Farina, Silvia; Buccoliero, Anna Maria; Castiglione, Francesca; Genitori, Lorenzo; de Martino, Maurizio; Sardi, Iacopo

    2015-01-01

    Background Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas. Case presentation We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy p...

  19. The significance of learned food aversions in the aetiology of anorexia associated with cancer.

    OpenAIRE

    Levine, J A; Emery, P W

    1987-01-01

    The results of 24 h food preference tests have suggested that learned food aversions may be involved in the development of anorexia in tumour bearing rats and in patients with cancer. We have performed similar tests over longer periods, up to 10 days, in male rats implanted with Leydig cell tumours, using semisynthetic diets containing differing proportions of fat, protein and carbohydrate. Tumour growth caused anorexia (16-30% decrease in food intake) and cachexia (78% decrease in body fat a...

  20. Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluorouracil in colon cancer cell-bearing mice

    OpenAIRE

    Perboni, Simona; Bowers, Cyril; Kojima, Shinya; Asakawa, Akihiro; Inui, Akio

    2008-01-01

    The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemotherapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin agonist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluorouracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BA...

  1. Pathophysiology and treatment of inflammatory anorexia in chronic disease

    OpenAIRE

    Braun, Theodore P.; Marks, Daniel L.

    2010-01-01

    Decreased appetite and involuntary weight loss are common occurrences in chronic disease and have a negative impact on both quality of life and eventual mortality. Weight loss in chronic disease comes from both fat and lean mass, and is known as cachexia. Both alterations in appetite and body weight loss occur in a wide variety of diseases, including cancer, heart failure, renal failure, chronic obstructive pulmonary disease and HIV. An increase in circulating inflammatory cytokines has been ...

  2. Effect of ghrelin and anamorelin (ONO-7643), a selective ghrelin receptor agonist, on tumor growth in a lung cancer mouse xenograft model

    OpenAIRE

    Northrup, R.; K. Kuroda; Duus, E. Manning; Barnes, S. Routt; Cheatham, L; Wiley, T.; Pietra, C.

    2013-01-01

    Purpose Anamorelin (ONO-7643) is an orally active ghrelin receptor agonist in development for non-small cell lung cancer (NSCLC)-related anorexia/cachexia. It displays both orexigenic and anabolic properties via ghrelin mimetic activity and transient increases in growth hormone (GH). However, increasing GH and insulin-like growth factor-1 in cancer patients raises concerns of potentially stimulating tumor growth. Therefore, we investigated the effect of ghrelin and anamorelin on tumor growth ...

  3. Treatment of Cancer Pain by Targeting Cytokines

    OpenAIRE

    Vendrell, I.; Macedo, D.; Alho, I.; Dionísio, M. R.; Costa, L.

    2015-01-01

    Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be relate...

  4. Role of nuclear factor-κB-mediated inflammatory pathways in cancer-related symptoms and their regulation by nutritional agents

    OpenAIRE

    Gupta, Subash C.; Kim, Ji Hye; Kannappan, Ramaswamy; Reuter, Simone; Dougherty, Patrick M.; Aggarwal, Bharat B.

    2011-01-01

    Cancer is a disease characterized by dysregulation of multiple genes and is associated with symptoms such as cachexia, anorexia, fatigue, depression, neuropathic pain, anxiety, cognitive impairment, sleep disorders and delirium (acute confusion state) in medically ill patients. These symptoms are caused by either the cancer itself or the cancer treatment. During the past decade, increasing evidence has shown that the dysregulation of inflammatory pathways contributes to the expression of thes...

  5. Treatment of Non Pain-Related Symptoms

    OpenAIRE

    von Gunten, Charles F; Gafford, Ellin

    2013-01-01

    Relieving the suffering associated with cancer and its treatment in the physical, emotional, practical and spiritual domains is impossible without impeccable symptom control. This review summarizes key features essential to the management of: anorexia/cachexia, bowel obstruction, diarrhea, fatigue, mucositis, and nausea/vomiting. Taken together, these are some of the most vexing symptoms for cancer patients. Well-managed symptoms enable the course of overall cancer care to be unimpeded.

  6. Understanding and managing cancer-related weight loss and anorexia: insights from a systematic review of qualitative research

    OpenAIRE

    Cooper, Christine; Burden, Sorrel T; Cheng, Huilin; Molassiotis, Alex

    2015-01-01

    The aim of this study was to summarize the existing qualitative literature in order to develop the evidence base for understanding and managing weight loss and anorexia, in order to make recommendations for clinical practice. A systematic search was performed to retrieve English language studies using electronic search and manual checks of selected reference lists. Keywords included qualitative, cancer cachexia, weight loss, anorexia, appetite, malnutrition, food, eating, and drinking. The se...

  7. Recommendations from SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA on nutrition in the HIV-infected patient Recomendaciones de SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA sobre nutrición en el paciente con infección por VIH

    OpenAIRE

    Polo, R.; C. Gómez-Candela; C Miralles; Locutura, J.; Álvarez, J.; Barreiro, F.; D. Bellido; E. Câncer; D. Cánoves; Domingo, P.; V. Estrada; C. R. Fumaz; M. J. Galindo; T. García-Benayas; IGLESIAS, C

    2007-01-01

    Objective: to make recommendations on the approach to nutritional problems (malnutrition, cachexia, micronutrient deficiency, obesity, lipodystrophy) affecting HIV-infected patients. Methods: these recommendations have been agreed upon by a group of expertes in the nutrition and care of HIV-infected patients, on behalf of the different groups involved in drafting them. Therefore, the latest advances in pathophysiology, epidemiology, and clinical care presented in studies published in medical ...

  8. Medicinal Marijuana: A Legitimate Appetite Stimulant?

    OpenAIRE

    Aquino, Glen

    2005-01-01

    Medicinal marijuana has been at the center of controversy for the treatment of cancer cachexia and AIDS related weight loss. Dronabinol, the oral form of marijuana, was approved for appetite stimulation, but its variability in absorption has led researchers to believe that smoked marijuana may be more effective. The discovery of endocannabinoids and their receptors has drawn attention from the research community, and as a result, marijuana’s role in appetite stimulation is clearer. Marijua...

  9. L'anorexie mentale, une maladie grave specifique de la femme jeune.

    OpenAIRE

    Scheen, André

    1999-01-01

    Anorexia nervosa is characterized by a triad comprising anorexia, weight loss, and amenorrhoea. It is typically present in adolescent or young adult women and its prevalence appears to increase in our society. Eating disorders may lead to cachexia and various severe complications. This disease, which appears to be associated to a particular psychological background, is triggered by conflictual relationships, usually within the family. The anorectic patient should be carefully evaluated, as so...

  10. Concomitant parenteral nutrition and systemic cytotoxic therapy in a metastatic colorectal cancer patient

    Directory of Open Access Journals (Sweden)

    A. A. Popov

    2015-02-01

    Full Text Available Pathologic nutrients metabolism presents a severe problem in metastatic colorectal cancer patients, especially those with canceromatosis. A hypermetabolism-catabolism syndrome frequently develops in in patients with progressing canceromatosis. This leads to cachexia anorexia syndrome, which significantly impedes available treatment options. Artificial nutrition allows to improve available treatment in such patients. We present a successful case of concomitant parenteral nutrition and systemic cytotoxic therapy in metastatic colorectal cancer patient with peritoneal canceromatosis.

  11. Sarcopenia: describing rather than defining a condition

    OpenAIRE

    Alchin, David Rhys

    2014-01-01

    Background Traditional definitions of sarcopenia have described an aging-associated disorder roughly defined as muscle mass two standard deviations below the young adult demographic. In an effort to clear the ambiguity pertaining to such descriptions, two international bodies have put forth working definitions of sarcopenia, namely The Society of Sarcopenia, Cachexia and Wasting Disorders in 2011, and The European Working Group on Sarcopenia in Older People in 2009. Review This paper will loo...

  12. Nutritional Recommendations for the Management of Sarcopenia

    OpenAIRE

    Morley, John E.; Argiles, Josep M.; Evans, William J.; Bhasin, Shalender; Cella, David; Deutz, Nicolaas E. P.; Doehner, Wolfram; Fearon, Ken C. H.; Ferrucci, Luigi; Hellerstein, Marc K.; Kalantar-Zadeh, Kamyar; Lochs, Herbert; MacDonald, Neil; Mulligan, Kathleen; Muscaritoli, Maurizio

    2010-01-01

    The Society for Sarcopenia, Cachexia, and Wasting Disease convened an expert panel to develop nutritional recommendations for prevention and management of sarcopenia. Exercise (both resistance and aerobic) in combination with adequate protein and energy intake is the key component of the prevention and management of sarcopenia. Adequate protein supplementation alone only slows loss of muscle mass. Adequate protein intake (leucine-enriched balanced amino acids and possibly creatine) may enhanc...

  13. Consilience in sarcopenia of cirrhosis

    OpenAIRE

    Dasarathy, Srinivasan

    2012-01-01

    Cirrhosis is the consequence of progression of many forms of necro-inflammatory disorders of the liver with hepatic fibrosis, hepatocellular dysfunction, and vascular remodeling. Reversing the primary hepatic disorder, liver transplantation, and controlling the complications are the major management goals. Since the former options are not available to the majority of cirrhotics, treating complications remains the mainstay of therapy. Sarcopenia and/or cachexia is the most common complication ...

  14. The Many roles of PGC-1α in Muscle – Recent Developments

    OpenAIRE

    Chan, Mun Chun; Arany, Zolt

    2014-01-01

    Skeletal muscle is the largest organ in the body and contributes to innumerable aspects of organismal biology. Muscle dysfunction engenders numerous diseases, including diabetes, cachexia, and sarcopenia. At the same time, skeletal muscle is also the main engine of exercise, one of the most efficacious interventions for prevention and treatment of a wide variety of diseases. The transcriptional coactivator PGC-1α has emerged as a key driver of metabolic programming in skeletal muscle, both in...

  15. A clinical approach to the nutritional care process in protein-energy wasting hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Mar Ruperto

    2014-04-01

    Full Text Available Introduction: Malnutrition/wasting/cachexia are complex-disease conditions that frequently remain undiagnosed and/or untreated in up to 75% of prevalent hemodialysis (HD patients. The nutrition care process (NCP based on assessment, diagnosis, intervention and monitoring of nutritional status is a systematic method that nutrition professionals use to make decisions in clinical practice. Objective: This review examines from a clinical-nutritional practice point of view: a nutritional status as a mortality causative factor; b phenotypic characteristics of malnutri-tion/wasting/cachexia, and c current trends of NCP with special emphasis on nutritional support and novel nutrient and pharmacologic adjunctive therapies in HD patients. Method: A literature review was conducted using the Pubmed, Science Direct, Scielo, Scopus, and Medline electronic scientific basis. Studies which assessing nutritional status and nutritional support published from 1990 to 2013 in HD patients were included and discussed. Results: From all the epidemiological data analyzed, NCP was the suggested method for identifying malnut rition/ wasting or cachexia in clinical practice. Nutrition support as an unimodal therapy was not completely able to reverse wasting in HD patients. Novel experimental therapeutic strategies including the use of appetite stimulants, ghrelin agonist, MC4-R antagonists, anabolic steroids, anti-inflammatory drugs, cholecalciferol, and other components are still under clinical evaluation. Conclusion: Nutritional status is a strong predictor of morbidity and mortality in HD patients. The terms called malnutrition, wasting and cachexia have different nutritional therapeutics implications. The NCP is a necessary tool for assessing and monitoring nutritional status in the current clinical practice. Novel pharmacological therapies or specific nutrient supplementation interventions studies are required.

  16. The emerging role of skeletal muscle oxidative metabolism as a biological target and cellular regulator of cancer-induced muscle wasting.

    Science.gov (United States)

    Carson, James A; Hardee, Justin P; VanderVeen, Brandon N

    2016-06-01

    While skeletal muscle mass is an established primary outcome related to understanding cancer cachexia mechanisms, considerable gaps exist in our understanding of muscle biochemical and functional properties that have recognized roles in systemic health. Skeletal muscle quality is a classification beyond mass, and is aligned with muscle's metabolic capacity and substrate utilization flexibility. This supplies an additional role for the mitochondria in cancer-induced muscle wasting. While the historical assessment of mitochondria content and function during cancer-induced muscle loss was closely aligned with energy flux and wasting susceptibility, this understanding has expanded to link mitochondria dysfunction to cellular processes regulating myofiber wasting. The primary objective of this article is to highlight muscle mitochondria and oxidative metabolism as a biological target of cancer cachexia and also as a cellular regulator of cancer-induced muscle wasting. Initially, we examine the role of muscle metabolic phenotype and mitochondria content in cancer-induced wasting susceptibility. We then assess the evidence for cancer-induced regulation of skeletal muscle mitochondrial biogenesis, dynamics, mitophagy, and oxidative stress. In addition, we discuss environments associated with cancer cachexia that can impact the regulation of skeletal muscle oxidative metabolism. The article also examines the role of cytokine-mediated regulation of mitochondria function, followed by the potential role of cancer-induced hypogonadism. Lastly, a role for decreased muscle use in cancer-induced mitochondrial dysfunction is reviewed. PMID:26593326

  17. Nutrition in Heart Failure

    Directory of Open Access Journals (Sweden)

    Reci Meseri

    2013-10-01

    Full Text Available Heart failure is defined as decreased ability of heart due to various reasons. It%u2019s seen 2-3% but the prevalence increases sharply after the age of seventy. The objectives of nutrition therapy in heart failure are to prevent from water retention and edema, to avoid from hard digestion and to offer a balanced diet. In order to avoid fluid retention and edema, daily sodium and fluid intake must be monitored carefully. Main dilemma of the heart failure patients is the obesity-cachexia dilemma. Since one of the main reasons of heart failure is cardiovascular diseases, in first phase, the patient may be obese. In the later phases, cachexia may show up. It was shown that cachexia is associated with mortality. Within this period, patients should not be over-fed and the patient should pass from catabolic state to anabolic state slowly. If the gastrointestinal track is functional oral/enteral feeding must be preferred. Multi vitamin and mineral supportsmay be beneficial, which may replace the increased loss, increase anti-inflammatory response and be anti-oxidants. Large, controlled and well-designed studies must be conducted in order to evaluate the benefits of nutritional practices such as nutritional assessment, enteral feeding and nutrient supports in heart failure patients.

  18. Circulating carnosine dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer.

    Directory of Open Access Journals (Sweden)

    Peter Arner

    Full Text Available Cancer cachexia (CC is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia.Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32 or without (n = 27 cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer.Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1 was confirmed by sandwich immunoassay to be lower in CC (p = 0.008. In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results.In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC.

  19. Pioglitazone treatment increases survival and prevents body weight loss in tumor-bearing animals: possible anti-cachectic effect.

    Science.gov (United States)

    Beluzi, Mércia; Peres, Sidney B; Henriques, Felipe S; Sertié, Rogério A L; Franco, Felipe O; Santos, Kaltinaitis B; Knobl, Pâmela; Andreotti, Sandra; Shida, Cláudio S; Neves, Rodrigo X; Farmer, Stephen R; Seelaender, Marília; Lima, Fábio B; Batista, Miguel L

    2015-01-01

    Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ) was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107) of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control) and TP5 (tumor + PGZ/5 mg). Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT) depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group). The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01) when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01) on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05) and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT) mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-γ, adiponectin, LPL and C/EBP-α from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT) was entirely re-established due to

  20. Pioglitazone treatment increases survival and prevents body weight loss in tumor-bearing animals: possible anti-cachectic effect.

    Directory of Open Access Journals (Sweden)

    Mércia Beluzi

    Full Text Available Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107 of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control and TP5 (tumor + PGZ/5 mg. Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group. The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01 when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01 on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05 and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-γ, adiponectin, LPL and C/EBP-α from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT was entirely re

  1. Regulation of energy balance by inflammation: common theme in physiology and pathology.

    Science.gov (United States)

    Wang, Hui; Ye, Jianping

    2015-03-01

    Inflammation regulates energy metabolism in both physiological and pathological conditions. Pro-inflammatory cytokines involves in energy regulation in several conditions, such as obesity, aging (calorie restriction), sports (exercise), and cancer (cachexia). Here, we introduce a view of integrative physiology to understand pro-inflammatory cytokines in the control of energy expenditure. In obesity, chronic inflammation is derived from energy surplus that induces adipose tissue expansion and adipose tissue hypoxia. In addition to the detrimental effect on insulin sensitivity, pro-inflammatory cytokines also stimulate energy expenditure and facilitate adipose tissue remodeling. In caloric restriction (CR), inflammatory status is decreased by low energy intake that results in less energy supply to immune cells to favor energy saving under caloric restriction. During physical exercise, inflammatory status is elevated due to muscle production of pro-inflammatory cytokines, which promote fatty acid mobilization from adipose tissue to meet the muscle energy demand. In cancer cachexia, chronic inflammation is elevated by the immune response in the fight against cancer. The energy expenditure from chronic inflammation contributes to weight loss. Immune tolerant cancer cells gains more nutrients during the inflammation. In these conditions, inflammation coordinates energy distribution and energy demand between tissues. If the body lacks response to the pro-inflammatory cytokines (Inflammation Resistance), the energy metabolism will be impaired leading to an increased risk for obesity. In contrast, super-induction of the inflammation activity leads to weight loss and malnutrition in cancer cachexia. In summary, inflammation is a critical component in the maintenance of energy balance in the body. Literature is reviewed in above fields to support this view. PMID:25526866

  2. Influence of dexamethasone on appetite and body weight in lung cancer patients

    Directory of Open Access Journals (Sweden)

    Šarčev Tatjana

    2008-01-01

    Full Text Available Introduction Anorexia and cachexia are the most common symptoms in cancer patients. They increase morbidity and mortality among cancer patients as well as complications of surgery, radiotherapy and chemotherapy. The most common drugs for treatment of cancer cachexia are corticosteroids and megestrol acetate. Material and Methods The purpose of this study was to determine the influence of dexamethasone on appetite loss and weight loss in lung cancer patients treated with chemotherapy. Group A (30 patients was treated with cisplatin, etoposide and standard supportive therapy, while group B (30 patients received, in addition to this treatment, dexamethasone in the dose of 8 mg intravenously per day (1-3 day of chemotherapy. Results There was a statistically significant difference in appetite loss between two groups after the second chemotherapy cycle favoring group A. The analysis of weight loss showed a statistically significant difference between two groups after both chemotherapy cycles, once again in favor of group A. Concerning the improvement of appetite and weight gain, there was no statistically significant difference between two groups after both chemotherapy cycles. Discussion Many double-blind randomized controlled studies showed beneficial symptomatic effect of corticosteroids in cancer cachexia, especially on the improvement of appetite, food intake and performance status. In most of the studies the weight gain was not recorded. The most effective type of corticosteroids, dose and route of administration have not been established. Conclusion Dexamethasone significantly decreases appetite loss and weight loss in lung cancer patients treated with chemotherapy, while it has no influence on appetite improvement and weight gain.

  3. Medical foods: products for the management of chronic diseases.

    Science.gov (United States)

    Morgan, Sarah L; Baggott, Joseph E

    2006-11-01

    Medical foods are a specific category of therapeutic agents created under the Orphan Drug Act of 1988, which separated medical foods from drugs for regulatory purposes. Products in this category share the requirements that they are intended for the nutritional management of a specific disease, are used under the guidance of a physician, and contain ingredients that are generally recognized as safe (GRAS). An example of medical foods are formulations intended to manage patients with inborn errors in amino acid metabolism. Newer medical foods are designed to manage hyperhomocysteinemia, pancreatic exocrine insufficiency, inflammatory conditions, cancer cachexia, and other diseases. PMID:17131945

  4. The relation of muscle protein degradation and 26S proteasome%肌肉蛋白降解与蛋白酶复合体

    Institute of Scientific and Technical Information of China (English)

    谭银玲

    2004-01-01

    The ubiquitin-dependent 20s/26s proteasome system is the capital pathway of exo-lyso-some proteolysis within eukaryotic cell. Under conditions of denervation, starvation, glucocorticoid, infection,tumor, bum and so on, the proteasome system was stimulated tofast. Glucocorticoid, insulin, thyroid honnone,TNFα and IL-1β degrade protein, which results in muscle lose cle protein degradation and the proteasome system. Inhibition or activation of the proteasome system was approved to be a novel means of treatment with cachexia and negative nitrogen balance.

  5. Office management of weight loss in older persons.

    Science.gov (United States)

    Rolland, Yves; Kim, Moon-Jong; Gammack, Julie K; Wilson, Margaret-Mary G; Thomas, David R; Morley, John E

    2006-12-01

    Weight loss in older persons is associated with a variety of deleterious effects, including hip fracture, pressure ulcers, decreasing immune function, decreased functional status, and death. There are 4 major causes of weight loss: anorexia, sarcopenia, cachexia, and dehydration. Many of the reasons for the development of these conditions are treatable. For example, depression is the most common cause of weight loss in the elderly. Early screening for anorexia can be undertaken in the physician's office utilizing the Simplified Nutritional Assessment Questionnaire. An algorithmic approach to the office management of weight loss is provided. PMID:17145241

  6. Characterization of Mycobacterium salmoniphilum as causal agent of mycobacteriosis in Atlantic salmon, Salmo salar L., from a freshwater recirculation system.

    Science.gov (United States)

    Aro, L; Correa, K; Martínez, A; Ildefonso, R; Yáñez, J M

    2014-04-01

    Thirty Atlantic salmon, Salmo salar L., with low corporal condition relative to other fish present in the culture system, were sampled from a freshwater recirculation pisciculture located in Chile. The most characteristic signs and lesions were cachexia and presence of multiple greyish-white granulomas within internal organs. The external and internal lesions, along with the microscopic, histologic and biochemical findings, were consistent with mycobacteriosis. The identification of Mycobacterium salmoniphilum as the causal agent of the lesions was possible through the use of molecular analyses. This study represents the first report of Mycobacterium salmoniphilum in a freshwater recirculation system and the first case of fish mycobacteriosis described in Chile. PMID:23952471

  7. Cryptosporidium varanii infection in leopard geckos (Eublepharis macularius) in Argentina

    Science.gov (United States)

    Dellarupe, A.; Unzaga, J.M.; Moré, G.; Kienast, M.; Larsen, A.; Stiebel, C.; Rambeaud, M.; Venturini, M.C.

    2016-01-01

    Cryptosporidiosis is observed in reptiles with high morbidity and considerable mortality. The objective of this study was to achieve the molecular identification of Cryptosporidium spp. in pet leopard geckos (Eublepharis macularius) from a breeder colony in Buenos Aires, Argentina. Oocysts comparable to those of Cryptosporidium spp. were detected in three geckos with a history of diarrhea, anorexia and cachexia. Molecular identification methods confirmed the presence of Cryptosporidium varanii (syn. C. saurophilum). This agent was considered to be the primary cause of the observed clinical disease. This is the first description of C. varanii infection in pet reptiles in Argentina. PMID:27419102

  8. Desarrollo de una escala numérica para clasificar grados de caquexia en cáncer

    OpenAIRE

    Betancourt Suárez, Angélica Maritza

    2015-01-01

    Cachexia SCOre (CASCO) es una nueva herramienta cuantitativa para la clasificación de la caquexia cancerosa en pacientes. La escala incluye cinco componentes: 1) pérdida de peso y composición corporal, 2) inflamación / alteraciones metabólicas / inmunosupresión, 3) actividad física, 4) anorexia, 5) calidad de vida. En el presente trabajo de tesis doctoral se presenta el desarrollo de CASCO y la validación clínica para el uso de la escala. CASCO clasifica cuatro niveles de severidad de la caqu...

  9. NF-κB Inhibition Protects against Tumor-Induced Cardiac Atrophy in Vivo

    OpenAIRE

    Wysong, Ashley; Couch, Marion; Shadfar, Scott; Li, Lugi; Rodriguez, Jessica E.; Asher, Scott; Yin, Xiaoying; Gore, Mitchell; Baldwin, Al; Patterson, Cam; Willis, Monte S.

    2011-01-01

    Cancer cachexia is a severe wasting syndrome characterized by the progressive loss of lean body mass and systemic inflammation. It occurs in approximately 80% of patients with advanced malignancy and is the cause of 20% to 30% of all cancer-related deaths. The mechanism by which striated muscle loss occurs is the tumor release of pro-inflammatory cytokines, such as IL-1, IL-6, and TNF-α. These cytokines interact with their cognate receptors on muscle cells to enhance NF-κB signaling, which th...

  10. Cryptosporidium varanii infection in leopard geckos (Eublepharis macularius in Argentina

    Directory of Open Access Journals (Sweden)

    A. Dellarupe

    2016-06-01

    Full Text Available Cryptosporidiosis is observed in reptiles with high morbidity and considerable mortality. The objective of this study was to achieve the molecular identification of Cryptosporidium spp. in pet leopard geckos (Eublepharis macularius from a breeder colony in Buenos Aires, Argentina. Oocysts comparable to those of Cryptosporidium spp. were detected in three geckos with a history of diarrhea, anorexia and cachexia. Molecular identification methods confirmed the presence of Cryptosporidium varanii (syn. C. saurophilum. This agent was considered to be the primary cause of the observed clinical disease. This is the first description of C. varanii infection in pet reptiles in Argentina.

  11. Nutrition in Heart Failure

    OpenAIRE

    Reci Meseri

    2013-01-01

    Heart failure is defined as decreased ability of heart due to various reasons. It%u2019s seen 2-3% but the prevalence increases sharply after the age of seventy. The objectives of nutrition therapy in heart failure are to prevent from water retention and edema, to avoid from hard digestion and to offer a balanced diet. In order to avoid fluid retention and edema, daily sodium and fluid intake must be monitored carefully. Main dilemma of the heart failure patients is the obesity-cachexia dilem...

  12. Long-term effects of plasmid-mediated growth hormone releasing hormone in dogs.

    Science.gov (United States)

    Tone, Catherine M; Cardoza, Dawn M; Carpenter, Robert H; Draghia-Akli, Ruxandra

    2004-05-01

    Geriatric and cancer-afflicted patients often experience decreased quality of life with cachexia, anemia, anorexia, and decreased activity level. We have studied the possibility that a myogenic plasmid that expresses growth hormone releasing hormone (GHRH) can prevent and/or treat these conditions. We administered plasmid to 17 geriatric and five cancer-afflicted companion dogs with an average age of 10.5+/-1.0 and 11.3+/-0.6 years at enrollment, respectively. Effects of the treatment were documented for at least 180 days post-treatment, with 10 animals followed for more than 1 year post-treatment, on average 444+/-40 days. Treated dogs showed increased IGF-I levels, and increases in scores for weight, activity level, exercise tolerance, and appetite. No adverse effects associated with the GHRH plasmid treatment were found. Most importantly, the overall assessment of the quality of life of the treated animals increased. Hematological parameters such as red blood cell count, hematocrit, and hemoglobin concentrations were improved and maintained within their normal ranges. We conclude that intramuscular injection of a GHRH-expressing plasmid is both safe and capable of improving the quality of life in animals for an extended period of time in the context of aging and disease. The observed anabolic and hematological responses to a single dose of this plasmid treatment may also be beneficial in geriatric patients or patients with cancer-associated anemia and/or cachexia. PMID:15073611

  13. MRI findings of serous atrophy of bone marrow and associated complications

    International Nuclear Information System (INIS)

    To report the MRI appearance of serous atrophy of bone marrow (SABM) and analyse clinical findings and complications of SABM. A retrospective search of MRI examinations of SABM was performed. Symptoms, underlying conditions, MRI findings, delay in diagnosis and associated complications were recorded. We identified 30 patients (15 male, 15 female; mean age: 46 ± 21 years) with MRI findings of SABM. Underlying conditions included anorexia nervosa (n = 10), cachexia from malignant (n = 5) and non-malignant (n = 7) causes, massive weight loss after bariatric surgery (n = 1), biliary atresia (n = 1), AIDS (n = 3), endocrine disorders (n = 2) and scurvy (n = 1). MRI showed mildly hypointense signal on T1- weighted and hyperintense signal on fat-suppressed fluid-sensitive images of affected bone marrow in all cases and similar signal abnormalities of the adjacent subcutaneous fat in 29/30 cases. Seven patients underwent repeat MRI due to initial misinterpretation of bone marrow signal as technical error. Superimposed fractures of the hips and lower extremities were common (n = 14). SABM occurs most commonly in anorexia nervosa and cachexia. MRI findings of SABM are often misinterpreted as technical error requiring unnecessary repeat imaging. SABM is frequently associated with fractures of the lower extremities. (orig.)

  14. Fish oil-supplementation increases appetite in healthy adults

    DEFF Research Database (Denmark)

    Damsbo-Svendsen, Signe; Rønsholdt, Mia Dybkjær; Lauritzen, Lotte

    2013-01-01

    Marine n-3 fatty acids are hypothesized to have beneficial effects on obesity and cancer cachexia possibly via an effect on appetite. The aim of this study was to investigate, if fish oil-supplementation affects appetite in healthy individuals. In a randomized cross-over study, 20 normal-weight s......Marine n-3 fatty acids are hypothesized to have beneficial effects on obesity and cancer cachexia possibly via an effect on appetite. The aim of this study was to investigate, if fish oil-supplementation affects appetite in healthy individuals. In a randomized cross-over study, 20 normal...... paired design considering oil sequence and gender. All subjects completed both periods with a compliance of 96% and oil sequence did not affect the results. There was no difference between the two supplements in any pre-breakfast appetite scores, but the post-prandial sensation of being full was 1.21. cm...... (0.20; 2.22) lower after the fish oil-period. Furthermore, there was a supplement × gender-interaction on "desire to eat more" due to a score increase of 1.09. cm (0.28; 1.90) in women only. These results suggest that marine n-3 fatty acid may increase appetite. This finding would be potentially...

  15. Exercise training decreases adipose tissue inflammation in cachectic rats.

    Science.gov (United States)

    Lira, F S; Yamashita, A S; Rosa, J C; Koyama, C H; Caperuto, E C; Batista, M L; Seelaender, M C L

    2012-02-01

    Bearing in mind that cancer cachexia is associated with chronic systemic inflammation and that endurance training has been adopted as a nonpharmacological anti-inflammatory strategy, we examined the effect of 8 weeks of moderate intensity exercise upon the balance of anti- and pro-inflammatory cytokines in 2 different depots of white adipose tissue in cachectic tumour-bearing (Walker-256 carcinosarcoma) rats. Animals were assigned to a sedentary control (SC), sedentary tumour-bearing (ST), sedentary pair-fed (SPF) or exercise control (EC), exercise tumour-bearing (ET), and exercise pair-fed (EPF) group. Trained rats ran on a treadmill (60% VO(2)max) 60 min/day, 5 days/week, for 8 weeks. The retroperitoneal (RPAT) and mesenteric (MEAT) adipose pads were excised and the mRNA (RT-PCR) and protein (ELISA) expression of IL-1β, IL-6, TNF-α, and IL-10 were evaluated. The number of infiltrating monocytes in the adipose tissue was increased in cachectic rats. TNF-α mRNA in MEAT was increased in the cachectic animals (preduction of the infiltrating monocytes both in MEAT and RPAT (p<0.05), when compared with ST. We conclude that cachexia is associated with inflammation of white adipose tissue and that exercise training prevents this effect in the MEAT, and partially in RPAT. PMID:22266827

  16. Role of Protein Carbonylation in Skeletal Muscle Mass Loss Associated with Chronic Conditions

    Directory of Open Access Journals (Sweden)

    Esther Barreiro

    2016-05-01

    Full Text Available Muscle dysfunction, characterized by a reductive remodeling of muscle fibers, is a common systemic manifestation in highly prevalent conditions such as chronic heart failure (CHF, chronic obstructive pulmonary disease (COPD, cancer cachexia, and critically ill patients. Skeletal muscle dysfunction and impaired muscle mass may predict morbidity and mortality in patients with chronic diseases, regardless of the underlying condition. High levels of oxidants may alter function and structure of key cellular molecules such as proteins, DNA, and lipids, leading to cellular injury and death. Protein oxidation including protein carbonylation was demonstrated to modify enzyme activity and DNA binding of transcription factors, while also rendering proteins more prone to proteolytic degradation. Given the relevance of protein oxidation in the pathophysiology of many chronic conditions and their comorbidities, the current review focuses on the analysis of different studies in which the biological and clinical significance of the modifications induced by reactive carbonyls on proteins have been explored so far in skeletal muscles of patients and animal models of chronic conditions such as COPD, disuse muscle atrophy, cancer cachexia, sepsis, and physiological aging. Future research will elucidate the specific impact and sites of reactive carbonyls on muscle protein content and function in human conditions.

  17. Pathophysiology and treatment of inflammatory anorexia in chronic disease.

    Science.gov (United States)

    Braun, Theodore P; Marks, Daniel L

    2010-12-01

    Decreased appetite and involuntary weight loss are common occurrences in chronic disease and have a negative impact on both quality of life and eventual mortality. Weight loss in chronic disease comes from both fat and lean mass, and is known as cachexia. Both alterations in appetite and body weight loss occur in a wide variety of diseases, including cancer, heart failure, renal failure, chronic obstructive pulmonary disease and HIV. An increase in circulating inflammatory cytokines has been implicated as a uniting pathogenic mechanism of cachexia and associated anorexia. One of the targets of inflammatory mediators is the central nervous system, and in particular feeding centers in the hypothalamus located in the ventral diencephalon. Current research has begun to elucidate the mechanisms by which inflammation reaches the hypothalamus, and the neural substrates underlying inflammatory anorexia. Research into these neural mechanisms has suggested new therapeutic possibilities, which have produced promising results in preclinical and clinical trials. This review will discuss inflammatory signaling in the hypothalamus that mediates anorexia, and the opportunities for therapeutic intervention that these mechanisms present. PMID:21475703

  18. The relationship among acute-phase response proteins, cytokines and hormones in cachectic patients with colon cancer

    Directory of Open Access Journals (Sweden)

    Dulger Ahmet

    2010-09-01

    Full Text Available Abstract Backgraund Acute-phase response proteins (APRP, cytokines and hormones have been claimed to be an independent prognostic factor of malignancies, however the basis for their association with prognosis remains unexplained. We suggest that in colon malignancies, as similar to pancreatic and lung cancers, changes in APRP are associated with angiogenesis. Methods C-reactive protein (CRP, albumin, IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, midkine, VEGF-A, VEGF-C, leptin, adiponectin, and ghrelin serum levels are studied in 126 colon cancer patients and 36 healthy subjects. Results We found statistically significant difference and correlations between two groups. We found significantly higher serum CRP, IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, VEGF-A, VEGF-C and leptin concentrations in patients relative to controls (p Conclusions Cachexia in patients with colon cancers is associated with changes in APRP, cytokines and hormone concentrations. These biomarkers and cachexia together have a direct relationship with accelerated angiogenesis. This may lead to a connection between the outcomes in malignancies and the biomarkers.

  19. Endogenous lipoid pneumonia in a cachectic patient after brain injury.

    Science.gov (United States)

    Zhang, Ji; Mu, Jiao; Lin, Wei; Dong, Hongmei

    2015-01-01

    Endogenous lipoid pneumonia (EnLP) is an uncommon non-life-threatening inflammatory lung disease that usually occurs in patients with conditions such as lung cancers, primary sclerosing cholangitis, and undifferentiated connective tissue disease. Here we report a case of EnLP in a paralytic and cachectic patient with bronchopneumonia after brain injury. A 40-year-old man experienced a severe brain injury in an automobile accident. He was treated for 1 month and his status plateaued. However, he became paralyzed and developed cachexia and ultimately died 145 days after the accident. Macroscopically, multifocal yellowish firm nodules were visible on scattered gross lesions throughout the lungs. Histologically, many foam cells had accumulated within the alveoli and alveolar walls accompanied by a surrounding interstitial infiltration of lymphocytes. The findings were in accordance with a diagnosis of EnLP. Bronchopneumonia was also noted. To our knowledge, there have been few reports of EnLP associated with bronchopneumonia and cachexia after brain injury. This uncommon pathogenesis should be well recognized by clinicians and forensic pathologists. The case reported here should prompt medical staff to increase the nutritional status and fight pulmonary infections in patients with brain injury to prevent the development of EnLP. PMID:26097618

  20. Protein-energy malnutrition in the rehabilitation setting: Evidence to improve identification.

    Science.gov (United States)

    Marshall, Skye

    2016-04-01

    Methods of identifying malnutrition in the rehabilitation setting require further examination so that patient outcomes may be improved. The purpose of this narrative review was to: (1) examine the defining characteristics of malnutrition, starvation, sarcopenia and cachexia; (2) review the validity of nutrition screening tools and nutrition assessment tools in the rehabilitation setting; and (3) determine the prevalence of malnutrition in the rehabilitation setting by geographical region and method of diagnosis. A narrative review was conducted drawing upon international literature. Starvation represents one form of malnutrition. Inadequate energy and protein intake are the critical factor in the aetiology of malnutrition, which is distinct from sarcopenia and cachexia. Eight nutrition screening tools and two nutrition assessment tools have been evaluated for criterion validity in the rehabilitation setting, and consideration must be given to the resources of the facility and the patient group in order to select the appropriate tool. The prevalence of malnutrition in the rehabilitation setting ranges from 14-65% worldwide with the highest prevalence reported in rural, European and Australian settings. Malnutrition is highly prevalent in the rehabilitation setting, and consideration must be given to the patient group when determining the most appropriate method of identification so that resources may be used efficaciously and the chance of misdiagnosis minimised. PMID:26921933

  1. Outcome research in palliative care: could it represent a new dimension of clinical research or clinical practice?

    Science.gov (United States)

    Tassinari, Davide; Maltoni, Marco; Sartori, Sergio; Fantini, Manuela; Poggi, Barbara; Ravaioli, Alberto

    2005-03-01

    Outcome research is a new dimension of clinical research, and all fields of clinical medicine are involved in this kind of analysis. Overall survival and quality of life are the main outcomes identified in clinical oncology. The former must be the main outcome whenever possible; the latter has to be the main outcome when an improvement of overall survival cannot be expected. It follows that quality of life is the main outcome of palliative care, in which the patient instead of the disease represents the target of the clinical approach. In our critical paper, we review the meaning of clinical outcomes in palliative care, classifying the outcomes as main and surrogate outcomes, and the results of the trials as indexes of activity and efficacy of a treatment. We also review the main randomized clinical trials on the treatment of cancer cachexia, trying to define the role of the treatments in cachexia-related symptom control and quality of life improvement. Strictly related to outcome analysis is the dimension of pharmacoeconomic evaluation. The models of the different designs of pharmacoeconomic analysis are revisited in an attempt to conjugate the pharmacoeconomic evaluation with the particular dimension of palliative care. PMID:15580363

  2. Expression of TRAF6 and ubiquitin mRNA in skeletal muscle of gastric cancer patients

    Directory of Open Access Journals (Sweden)

    Sun Yuan-Shui

    2012-09-01

    Full Text Available Abstract Objective To investigate the prognostic significance of tumor necrosis factor receptor (TNFR,-associated factor 6 (TRAF6,-and ubiquitin in gastric cancer patients. Methods Biopsies of the rectus abdominis muscle were obtained intra operatively from 102 gastric cancer patients and 29 subjects undergoing surgery for benign abdominal diseases, and muscle TRAF6 and ubiquitin mRNA expression and proteasome proteolytic activities were assessed. Results TRAF6 was significantly upregulated in muscle of gastric cancer compared with the control muscles. TRAF6 was upregulated in 67.65% (69/102 muscle of gastric cancer. Over expression of TRAF6 in muscles of gastric cancer were associated with TNM stage, level of serum albumin and percent of weight loss. Ubiquitin was significantly upregulated in muscle of gastric cancer compared with the control muscles. Ubiquitin was upregulated in 58.82% (60/102 muscles of gastric cancer. Over expression of ubiquitin in muscles of gastric cancer were associated with TNM (Tumor-Node-Metastasis stage and weight loss. There was significant relation between TRAF6 and ubiquitin expression. Conclusions We found a positive correlation between TRAF6 and ubiquitin expression, suggesting that TRAF6 may up regulates ubiquitin activity in cancer cachexia. While more investigations are required to understand its mechanisms of TRAF6 and ubiquitin in skeletal muscle. Correct the catabolic-anabolic imbalance is essential for the effective treatment of cancer cachexia.

  3. Association between an inflammatory-nutritional index and nutritional status in cancer patients

    Directory of Open Access Journals (Sweden)

    Carla Alberici Pastore

    2013-02-01

    Full Text Available Introduction: Cachexia is a multifatorial syndrome characterized by loss of body weight, fat and muscle, increasing morbidity and mortality. The use of an index accounting for both serum albumin and C Reactive Protein levels could make early identification of cachexia easier. Objective: To evaluate the variation of an inflammatory nutritional index related to nutritional status in cancer patients. Methods: Cross sectional study including patients with gastrointestinal and lung cancer of a public chemotherapy service in Brazil. Serum albumin and C Reactive Protein were measured and the nutritional status was defined by Subjective Global Assessment. Statistical analyses were performed using Stata 9.2™. Results: A total of 74 patients were evaluated, 58.1% of them were male, mean age 63.4 ± 11.9 years old. Gastrointestinal cancer was the most prevalent type (71.6%. Only 13.7% of the patients were well nourished and 21.9% were severely malnourished. C Reactive Protein significantly increased according to nutritional status decline (p=0.03. When the albumin from patients with systemic inflammation was evaluated, there was no significant variation in relation to nutritional status (p=0.06. The Inflammatory Nutritional Index significantly varied in relation to nutritional status independent of the systemic inflammation (p=0.02. Conclusions: Inflammatory Nutritional Index can be an adjuvant way for biochemical nutritional assessment and follow up in cancer patients with systemic inflammation.

  4. MRI findings of serous atrophy of bone marrow and associated complications

    Energy Technology Data Exchange (ETDEWEB)

    Boutin, Robert D. [Department of Radiology, Sacramento, CA (United States); White, Lawrence M. [University of Toronto, Joint Department of Medical Imaging, Toronto General Hospital, Toronto, ON (Canada); Laor, Tal [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Spitz, Damon J. [New England Baptist Hospital, Department of Radiology, Boston, MA (United States); Lopez-Ben, Robert R. [Carolinas HealthCare System, Charlotte Radiology, Diagnostic Radiology, Charlotte, NC (United States); Stevens, Kathryn J. [Stanford University, Department of Radiology, Stanford, CA (United States); Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States)

    2015-09-15

    To report the MRI appearance of serous atrophy of bone marrow (SABM) and analyse clinical findings and complications of SABM. A retrospective search of MRI examinations of SABM was performed. Symptoms, underlying conditions, MRI findings, delay in diagnosis and associated complications were recorded. We identified 30 patients (15 male, 15 female; mean age: 46 ± 21 years) with MRI findings of SABM. Underlying conditions included anorexia nervosa (n = 10), cachexia from malignant (n = 5) and non-malignant (n = 7) causes, massive weight loss after bariatric surgery (n = 1), biliary atresia (n = 1), AIDS (n = 3), endocrine disorders (n = 2) and scurvy (n = 1). MRI showed mildly hypointense signal on T1- weighted and hyperintense signal on fat-suppressed fluid-sensitive images of affected bone marrow in all cases and similar signal abnormalities of the adjacent subcutaneous fat in 29/30 cases. Seven patients underwent repeat MRI due to initial misinterpretation of bone marrow signal as technical error. Superimposed fractures of the hips and lower extremities were common (n = 14). SABM occurs most commonly in anorexia nervosa and cachexia. MRI findings of SABM are often misinterpreted as technical error requiring unnecessary repeat imaging. SABM is frequently associated with fractures of the lower extremities. (orig.)

  5. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN - a randomized multicentre trial

    Directory of Open Access Journals (Sweden)

    Kraft Matthias

    2012-07-01

    Full Text Available Abstract Background Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia. Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM kg. During treatment body-mass-index increased by 3,4 ± 1,4% under L-Carnitine and decreased (−1,5 ± 1,4% in controls (p  Conclusion While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinically relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine.

  6. Altered energy balance and cytokine gene expression in a murine model of chronic infection with Toxoplasma gondii.

    Science.gov (United States)

    Arsenijevic, D; Girardier, L; Seydoux, J; Chang, H R; Dulloo, A G

    1997-05-01

    The temporal pattern of changes in energy balance and cytokine mRNA expression in spleen and brain were examined in a mouse model of infection with Toxoplasma gondii. During days 1-7 postinfection, food intake was unaltered, but energy expenditure was significantly increased, and this was associated with elevated tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-5, and interferon (IFN)-gamma. The hypermetabolic state persisted during subsequent anorexia, whose onset coincided with elevated IL-2, and at the end of the acute phase of cachexia, the dual anorexic and hypermetabolic states were associated with the cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma. In the chronic phase of the infection, the mice showed either partial weight recovery (gainers) or no weight regain (nongainers). The infected gainers, though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA was no longer elevated, except for TNF-alpha and IL-10. In contrast, the infected nongainers continued to show both anoroxia and hypermetabolism, which were associated with elevations in all cytokines examined and particularly those of the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies reveal a distinct pattern of cytokine mRNA expression underlying 1) hypermetabolism vs. anorexia, 2) acute vs. chronic cachexia, and 3) stable weight loss vs. partial weight recovery. PMID:9176193

  7. Consilience in sarcopenia of cirrhosis.

    Science.gov (United States)

    Dasarathy, Srinivasan

    2012-12-01

    Cirrhosis is the consequence of progression of many forms of necro-inflammatory disorders of the liver with hepatic fibrosis, hepatocellular dysfunction, and vascular remodeling. Reversing the primary hepatic disorder, liver transplantation, and controlling the complications are the major management goals. Since the former options are not available to the majority of cirrhotics, treating complications remains the mainstay of therapy. Sarcopenia and/or cachexia is the most common complication and adversely affects survival, quality of life, development of other complications of cirrhosis, and outcome after liver transplantation. With the increase in number of cirrhotic patients with hepatitis C and nonalcoholic fatty liver disease, the number of patients waiting for a liver transplantation is likely to continue to increase above the currently estimated 72.3/100,000 population. One of the critical clinical questions is to determine if we can treat sarcopenia of cirrhosis without transplantation. No effective therapies exist to treat sarcopenia because the mechanism(s) of sarcopenia in cirrhosis is as yet unknown. The reasons for this include the predominantly descriptive studies to date and the advances in our understanding of skeletal muscle biology and molecular regulation of atrophy and hypertrophy not being translated into the clinical practice of hepatology. Satellite cell biology, muscle autophagy and apoptosis, and molecular signaling abnormalities in the skeletal muscle of cirrhotics are also not known. Aging of the cirrhotic and transplanted population, use of mTOR inhibitors, and the lack of definitive outcome measures to define sarcopenia and cachexia in this population add to the difficulty in increasing our understanding of hepatic sarcopenia/cachexia and developing treatment options. Recent data on the role of myostatin, AMP kinase, impaired mTOR signaling resulting in anabolic resistance in animal models, and the rapidly developing field of

  8. The effect of disease activity on body composition and resting energy expenditure in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Binymin K

    2011-05-01

    Full Text Available K Binymin1,3, AL Herrick1, GL Carlson2, SJ Hopkins21University of Manchester, Rheumatic Diseases Centre, 2Infection Injury and Inflammation Group, and Brain Injury Research Group, Manchester Academic Health Science Centre and University of Manchester Faculty of Medical and Human Sciences, Salford Royal Hospitals NHS Trust, Salford, UK; 3Southport District General Hospital, Southport, UKIntroduction: Cachexia is associated with rheumatoid arthritis (RA, but whether it is attributable primarily to reduced dietary intake or increased metabolism is unclear, as is the association with inflammation. To examine whether rheumatoid cachexia is related to increased energy expenditure, reduced food intake, or an inflammatory cytokine response we undertook a prospective, longitudinal study of patients with RA, during periods of relative relapse and remission of inflammation.Methods: Sixteen patients admitted to hospital with a flare of RA were assessed clinically to determine disease activity and were re-examined 6 weeks later. Their fat-free mass (FFM, dietary intake, resting energy expenditure (REE, and plasma concentrations of interleukin-6 (IL-6 were also measured. Data were compared with those from 16 healthy, age- and sex-matched controls.Results: At baseline the body weight, body mass index, and FFM of patients with RA were significantly lower than those of controls. Disease activity scores of patients (6.39 ± 0.8 were reduced when the patients were re-examined 6 weeks later (5.23 ± 1.26 and FFM was no longer statistically different from that of controls (visit 1 = 25.8 ± 10.1 and visit 2 = 26.8 ± 9.5 versus controls = 32.3 ± 10.9. There were no differences in food intake between patients and controls or between patients studied at the 2 time points, but REE was greater in patients after correcting for FMM (visit 1 = 62.2 ± 24.7, visit 2 = 59.7 ± 26.3 versus controls = 46.0 ± 13.7. Plasma IL-6 concentrations were significantly higher in

  9. Virus-associated haemophagocytic lymphohistiocytosis in a young Filipino man.

    Science.gov (United States)

    Yu, Marc Gregory; Chua, Jamie

    2016-01-01

    Haemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of pathological immune activation characterised by extreme inflammation. We present a case of a young Filipino man consulting for non-specific symptoms of fever, body malaise and weight loss. Prominent physical examination findings included gross pallor, cachexia and hepatosplenomegaly. Laboratory results revealed pancytopaenia, while bone marrow examination revealed haemophagocytosis. Further workup for HLH showed hypertriglyceridaemia, hypofibrinogenaemia and hyperferritinaemia (fulfilling 6 of 8 diagnostic criteria). Exhaustive serological and haematological examinations showed chronic hepatitis B virus infection and past evidence of Epstein-Barr virus infection as possible triggers. The patient was started on antiviral therapy, high-dose steroids and chemotherapy. He initially improved, but eventually succumbed to severe fungal sepsis and pulmonary haemorrhage. An autopsy confirmed the diagnosis of HLH. PMID:27284096

  10. Retrieval-balloon-assisted enterography in post-pancreaticoduodenectomy endoscopic retrograde cholangiopancreatography post-pancreaticoduodenectomy

    Institute of Scientific and Technical Information of China (English)

    Ming Zhuang; Wen-Jie Zhang; Jun Gu; Ying-Bin Liu; Xue-Feng Wang

    2012-01-01

    This case reports an application of conventional duodenoscope in a post pancreaticoduodenectomy patient with the help of retrieval balloon assisted enterography.The 56-year-old woman had pancreaticoduodenectomy with Child reconstruction 9 mo ago because of pancreatic adenocarcinoma and now there are recurrent enlarged lymph nodes in the anastomotic stoma of hepaticojejunostomy.Considering the patient's late-stage cancer,a plastic stent was then successfully placed there to drainage.The main challenge in this case was the extremely long afferent loop and blind cannulation through the anastomotic stoma of hepaticojejunostomy.Retrieval balloon assisted enterography is very helpful for duodenoscope going through the reconstructed intestinal tract and for the cannulation.After two weeks,the patient remained free of painful symptoms and free of fever.Liver function improved well.Four months after the placement of stent,the patient died of cachexia without jaundice,fever and abdominal pain according to her daughter's statement.

  11. MRI demonstration of orbital lipolysis in anorexia nervosa

    International Nuclear Information System (INIS)

    The purpose of this article is to describe the orbital changes due to lipolysis in anorexia nervosa. We examined a cachectic patient with MR imaging using T1-weighted images before and after contrast enhancement. Orbital fat edema has been observed in extreme forms of cachexia and the CT and MR findings have recently been reported. The imaging appearances have been explained by the disappearance of the fat tissue and the appearance of edema due to a disturbance in the electrolyte fluid balance. In the recent literature particular attention has been paid to the increased lipid peroxidation and lipolysis in anorexia nervosa. These metabolic processes result in an increased permeability of the vessel wall endothelium, which can explain the extravasation of the contrast agent in the orbital fat on MR imaging. (orig.)

  12. Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part I.

    Science.gov (United States)

    Aikawa, Katsuji; Miyawaki, Toshio; Hitaka, Takenori; Imai, Yumi N; Hara, Takahito; Miyazaki, Junichi; Yamaoka, Masuo; Kusaka, Masami; Kanzaki, Naoyuki; Tasaka, Akihiro; Shiraishi, Mitsuru; Yamamoto, Satoshi

    2015-05-15

    To develop effective drugs for hypogonadism, sarcopenia, and cachexia, we designed, synthesized, and evaluated selective androgen receptor modulators (SARMs) that exhibit not only anabolic effects on organs such as muscles and the central nervous system (CNS) but also neutral or antagonistic effects on the prostate. Based on the information obtained from a docking model with androgen receptor (AR), we modified a hit compound A identified through high-throughput screening. Among the prepared compounds, 1-(4-cyano-1-naphthyl)-2,3-disubstituted pyrrolidine derivatives 17h, 17m, and 17j had highly potent AR agonistic activities in vitro and good tissue selectivity in vivo. These derivatives increased the weight of the levator ani muscle without influencing the prostate and seminal vesicle. In addition, these compounds induced sexual behavior in castrated rats, indicating that the compounds could also act as agonists on the CNS. PMID:25862209

  13. Regenerating skeletal muscle in the face of aging and disease.

    Science.gov (United States)

    Jasuja, Ravi; LeBrasseur, Nathan K

    2014-11-01

    Skeletal muscle is a fundamental organ in the generation of force and movement, the regulation of whole-body metabolism, and the provision of resiliency. Indeed, physical medicine and rehabilitation is recognized for optimizing skeletal muscle health in the context of aging (sarcopenia) and disease (cachexia). Exercise is, and will remain, the cornerstone of therapies to improve skeletal muscle health. However, there are now a number of promising biologic and small molecule interventions currently under development to rejuvenate skeletal muscle, including myostatin inhibitors, selective androgen receptor modulators, and an activator of the fast skeletal muscle troponin complex. The opportunities for skeletal muscle-based regenerative therapies and a selection of emerging pharmacologic interventions are discussed in this review. PMID:24879554

  14. Body composition as measured by in vivo neutron activation analysis

    International Nuclear Information System (INIS)

    A large scale study is currently underway on the changes in body composition resulting from the cachexia of malignancy. The ultimate objective of the overall project is to assess the changes in body composition associated with hyperalimentation and other modes of nutritional support to cancer patients. The first phase of this study is now in progress. In this phase, a study is being made of a control group of normal patients to provide baseline data against which data from cancer patients can be evaluated. Total body nitrogen and potassium are measured in a group of normal men and women, and are analyzed as a function of age. Additionally, changes in skeletal mass (total body calcium) are also recorded, and body water is measured simultaneously with the use of tritiated water

  15. Primary yolk sac tumor of seminal vesicle: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Yao Xu-Dong

    2012-09-01

    Full Text Available Abstract Background Yolk sac tumor (endodermal sinus tumor is a rare malignant germ cell tumor arising in the testis or ovary. Extragonadal yolk sac tumor is even rarer and has only been described in case reports. Due to the rarity of the tumors, the appropriately optimal treatment remains unclear. We report a case of yolk sac tumor in the seminal vesicle. Case A 38-year-old Asian male presented with gross hematuria and hemospermia. Transrectal ultrasound scan showed a solid mass in the left seminal vesicle and the scrotal sonography showed no abnormalities. Bilateral seminal vesicles were resected, and histopathological examination showed a typical pattern of yolk sac tumor (YST. The patient responded poorly to comprehensive treatment of radiotherapy, chemotherapy and surgeries, developed systemic multiple metastases, and died of cachexia one and half years after diagnosis.

  16. Experimental oral lead toxicity in young dogs

    Energy Technology Data Exchange (ETDEWEB)

    Stowe, H.D.; Goyer, R.A.; Krigman, M.M.; Wilson, M.; Cates, M.

    1973-02-01

    Litter-mate male pups were fed a calcium-and-phosphorus-low purified diet with and without 100 ppm of lead as lead acetate from age 6 to 18 weeks. Lead-toxic dogs exhibited cyclic but terminally severe anorexia and cachexia, significant anemia, normoblastocytosis and leukopenia within six weeks, hypoproteinemia, decreased serum albumin, ..cap alpha../sub 1/-globulin, ..beta../sub 2/-globulin, alkaline phosphatase and lactic dehydrogenase 1, elevated serum glutamic oxaloacetic and pyruvic transaminases, delayed closure of the thoracic vertebral epiphyses, lead lines in the distal radii and thoracic spinous processes, enlargement of liver, kidney, and brain, hepatic fatty metamorphosis, focal proximal renal tubular necrosis, hydropic degeneration of spermatognia, and lead inclusion body formation. Approximately 97% of the tissue lead was estimated to be skeletal; the greatest concentration of lead in the brain was found in the occipital gray matter.

  17. [Specific factors of sex behavior in patients with anorexia nervosa and bulimia].

    Science.gov (United States)

    Oleĭnikov, A N

    2000-01-01

    65 patients were examined. They were divided into three groups. Group 1 consisted of patients with anorexia nervosa (AN) without bulimia, complicated by cachexia and amenorrhea. Epileptoid personality masculinous body built and behaviour, essential disturbances of sexual self-identification prevailed in this group. 3 patients had homoerotic tendencies, while a syndrome of sex negation developed in 5 cases. In group 2 bulimia was a stage of AN development. The patients had frequently initial endocrinopathy (obesity, dysmenorrhea), experiences of phobia and anxiety, asynchronous disharmonious type of psychosexual ontogenesis. Group 3 of patients was characterized by predomination of bulimia symptoms as a variation of the disease course. Normostenic body built, normal somatoendocrine and psychosexual development were combined with hysteric personal characteristics, mood and sexual fluctuations. PMID:10849961

  18. [Anorexia nervosa and bulimia nervosa. II. Somatic complications of undernourishment].

    Science.gov (United States)

    van Rijn, C A

    1998-08-15

    In anorexia nervosa and bulimia nervosa, cachexia and deficient nourishment cause various physical abnormalities, especially of the endocrine and digestive systems and the heart. Disorders in the serotoninergic and dopaminergic systems contribute to development of an eating disorder, whereas an acquired deficiency of tryptophan impairs the serotoninergic system. Any problems of nutritional deficiencies, low blood sugar levels and gastrointestinal disorders disappear after normal nourishment is resumed. Hypotension and sinus bradycardia are manifestations of a physiological adjustment to a lower basal metabolism and need no treatment. Osteoporosis occurs from two years after the onset of weight loss; oestrogen supplementation may protect against this. In patients with infections, symptoms such as fever, leukocytosis and high BSE may be lacking. Hypoglycaemia incidentally leads to coma and death, and a lengthened QT interval to acute cardiac death. During restoration of the nutritional status, the intake of fluid and calories should initially be limited. During the first two weeks, the risk of cardiovascular complications is increased. PMID:9856167

  19. Effect of early psychological intervention on patients with advanced tumors%晚期恶性肿瘤早期心理干预的疗效观察

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ Background: To the terminal stages of esophagus cancer without chance of surgery, radiotherapy has unsatisfactory effect either. It is difficult to swallow for the patients, of whom some even cannot eat anything and lose their weight gradually, and finally, lose the ability to take care of themselves. Even if their lives can be maintained, their life quality is very low. In order to alleviate dysphasia, we have carried out the chemotherapy schemes of CMP and DMB. Objective: By means of united chemotherapy, the following effects are expected: to reduce the focus, to improve the ability to take food, to recover from cachexia, and to reach the target of improving the patients' life quality. Design: Treat the terminal stages of esophagus cancer with united chemotherapy and evaluate the effect in time. Unit: PLA 323 Hospital.

  20. Pathological study on treated and untreated dogs dead after γ-irradiation with 6 Gy

    International Nuclear Information System (INIS)

    Forty dogs γ-irradiated with 6 Gy were divided into three groups: control (8 cases), treated with antibiotics alone (8 cases) and with combined measures (24 cases). The death of dogs in these groups occurred between 8th-12th, 11th-14th and 12th-169th days after irradiation respectively. In the third group, regeneration of hematopoietic cells in sternal bone marrow was first observed in dog dead on 17.5th day after irradiation, and regeneration of lymphoid tissues in spleen on 14th day. The degree of recovery in both of these organs was worse than in dogs irradiated with 3.25 Gy. The complications were varied; for instance, in addition to infection and hemorrhage, there were intussusception, gastric dilation, necrosis and hemorrhage of pancrease, jaundice, cerebral edema, hemorrhage and hernia, cachexia during recovery and so on. The causes of death in these experimental animals were also varied

  1. Pain in Pancreatic Cancer: Does Drug Treatment Still Play a Role?

    Directory of Open Access Journals (Sweden)

    Ilaria Uomo

    2011-09-01

    Full Text Available Disabling pain together with cachexia is the most important symptom in patients with pancreatic cancer. Abdominal pain is a common debilitating symptom quickly leading to deterioration of the quality of life and performance status [1]. Although only 30-40% of patients report moderate to severe pain at the time of diagnosis, more than 80-90% of them with advanced disease experience severe pain before death [2]. Pain is generally transmitted through the celiac plexus which harbors sympathetic fibers carrying nociceptive information from the pancreas and surrounding organs. More infrequently, pain results from pancreatic duct obstruction and associated pancreatitis; this type of pain usually appears after meals, thus increasing the continuous pain related to the infiltration of the peripancreatic nervous plexus [3].

  2. Comorbidity of anorexia nervosa in a male patient with congenital hypogonadism: case report

    Directory of Open Access Journals (Sweden)

    mustafa ozten

    2015-01-01

    Full Text Available Male hypogonadism is a result of insufficient testicular androgen production. In addition to low circulating testosterone levels, patients develop clinical symptoms such as osteopenia, decrease in muscle mass, libido, energy and stamina, decline in cognitive function, increased adiposity, and erectile dysfunction. Anorexia nervosa (AN is quite rarely seen in men, being usually ten times less common than in women, and shows differences in many aspects, from causation to presentation. As AN is connected to hunger physiology, it entails significant medical complications affecting, as in any general medical condition, a number of systems, including the genitourinary system. It is known that a prolonged manifestation of AN or cachexia may cause hypogonadism. This article presents the case of a patient with untreated hypogonadism, diagnosed in his infancy, who at the age of 18 developed AN.

  3. An in Vitro and in Vivo Investigation of Bivalent Ligands That Display Preferential Binding and Functional Activity for Different Melanocortin Receptor Homodimers.

    Science.gov (United States)

    Lensing, Cody J; Freeman, Katie T; Schnell, Sathya M; Adank, Danielle N; Speth, Robert C; Haskell-Luevano, Carrie

    2016-04-14

    Pharmacological probes for the melanocortin receptors have been utilized for studying various disease states including cancer, sexual function disorders, Alzheimer's disease, social disorders, cachexia, and obesity. This study focused on the design and synthesis of bivalent ligands to target melanocortin receptor homodimers. Lead ligands increased binding affinity by 14- to 25-fold and increased cAMP signaling potency by 3- to 5-fold compared to their monovalent counterparts. Unexpectedly, different bivalent ligands showed preferences for particular melanocortin receptor subtypes depending on the linker that connected the binding scaffolds, suggesting structural differences between the various dimer subtypes. Homobivalent compound 12 possessed a functional profile that was unique from its monovalent counterpart providing evidence of the discrete effects of bivalent ligands. Lead compound 7 significantly decreased feeding in mice after intracerebroventricular administration. To the best of our knowledge, this is the first report of a melanocortin bivalent ligand's in vivo physiological effects. PMID:26959173

  4. Paraneoplastic endocrine-metabolic syndromes

    Directory of Open Access Journals (Sweden)

    Marco Grandi

    2013-04-01

    Full Text Available BACKGROUND The paraneoplastic syndromes (PS are characterized by the presence of biochemical alterations, signs and symptoms expressive of cancer distance action into the patient’s organism. Sometimes these syndromes can precede the evidence of malignancy even of some years or can correspond to cancer relapse. PS, even being characterized by general symptoms (fever, anorexia, cachexia, may occur with neurological, rheumathological, osteoarticular, vascular, haematological, nephrological and endocrinological/metabolic symptoms; the latter ones are discussed in this article. AIM OF THE STUDY Here we will focus on the most common PS: paraneoplastic hypercalcemia, inappropriate secretion of antidiuretic hormone (SIADH and paraneoplastic Cushing syndrome. CONCLUSIONS Our work can be useful in the diagnosis and therapeutic management of paraneoplastic syndromes.

  5. Benefits of Exercise in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Jennifer K. Cooney

    2011-01-01

    Full Text Available This paper aims to highlight the importance of exercise in patients with rheumatoid arthritis (RA and to demonstrate the multitude of beneficial effects that properly designed exercise training has in this population. RA is a chronic, systemic, autoimmune disease characterised by decrements to joint health including joint pain and inflammation, fatigue, increased incidence and progression of cardiovascular disease, and accelerated loss of muscle mass, that is, “rheumatoid cachexia”. These factors contribute to functional limitation, disability, comorbidities, and reduced quality of life. Exercise training for RA patients has been shown to be efficacious in reversing cachexia and substantially improving function without exacerbating disease activity and is likely to reduce cardiovascular risk. Thus, all RA patients should be encouraged to include aerobic and resistance exercise training as part of routine care. Understanding the perceptions of RA patients and health professionals to exercise is key to patients initiating and adhering to effective exercise training.

  6. Prognostic value of scores based on malnutrition or systemic inflammatory response in patients with metastatic or recurrent gastric cancer.

    Science.gov (United States)

    Sachlova, Milana; Majek, Ondrej; Tucek, Stepan

    2014-01-01

    Cancer patients are frequently affected by malnutrition and weight loss, which affects their prognosis, length of hospital stay, health care costs, quality of life and survival. Our aim was to assess the prognostic value of different scores based on malnutrition or systemic inflammatory response in 91 metastatic or recurrent gastric cancer patients considered for palliative chemotherapy at the Masaryk Memorial Cancer Institute. We investigated their overall survival according to the following measures: Onodera's Prognostic Nutritional Index (OPNI), Glasgow Prognostic Score (GPS), nutritional risk indicator (NRI), Cancer Cachexia Study Group (CCSG), as previously defined, and a simple preadmission weight loss. The OPNI, GPS, and CCSG provided very significant prognostic values for survival (log-rank test P value evaluation of patients' prognosis and should be part of a routine evaluation of patients to provide a timely nutrition support. PMID:25356861

  7. A phase III study evaluating oral glutamine and transforming growth factor-beta 2 on chemotherapy-induced toxicity in patients with digestive neoplasm

    DEFF Research Database (Denmark)

    Khemissa, Faïza; Mineur, Laurent; Amsellem, Caroline; Assenat, Eric; Ramdani, Mohamed; Bachmann, Patrick; Janiszewski, Chloé; Cristiani, Isabelle; Collin, Fideline; Courraud, Julie; de Forges, Hélène; Dechelotte, Pierre; Senesse, Pierre

    2015-01-01

    efficacy of glutamine and transforming growth factor-β2 (TGF-β2) in the prevention of grade 3-4 non-hematological toxicities induced by chemotherapy in patients with GI cancer. PATIENTS AND METHODS: We designed a double-blind, randomized, controlled and multicenter trial stratified according to center......BACKGROUND: Patients with gastrointestinal (GI) cancer are exposed to cachexia, which is highly correlated with chemotherapy-induced side effects. Research suggests that specific immunonutrients could prevent such toxicities. AIMS: The primary objective of this phase III study was to evaluate the...... interruption. CONCLUSION: This randomized study does not support the hypothesis that oral glutamine and TGF-β2 supplementation is effective to reduce grade 3 or 4 non-hematological toxicities induced by chemotherapy in patients with GI neoplasm....

  8. Lymphoma and broncho-pneumonia in a calf

    International Nuclear Information System (INIS)

    A one and a half month old Holstein calf was presented with a chronic respiratory condition. Clinical examination revealed cachexia and lymphadenopathy and wheezes and crepitations on auscultation. Blood cell count indicated a non-regenerative microcytic anaemia and marked lymphopenia. Broncho-pneumonia due to Mycoplasma bovis was diagnosed after radiography and cytobacteriology of transtracheal lavage. A large cell lymphoma was suspected after finding a high proportion of large lymphocytes in a lymph node puncture aspirate. Serology for bovine leukosis was negative. A diagnosis of juvenile lymphoma associated with M. bovis broncho-pneumonia was established. The diagnosis was confirmed on post-mortem. Juvenile lymphoma is rare. Affected animals are aged between two and six months and systematically present generalised lymphadenopathy. This disease is always fatal. When an animal is presented with generalised lymphadenopathy, this condition should be eliminated by lymph node puncture of a moderately hypertrophied lymph node before other tests are performed

  9. General Survey and Progress in Clinical Trials Abroad over Kanglaite Injection(康莱特注射液)

    Institute of Scientific and Technical Information of China (English)

    李大鹏

    2004-01-01

    @@ Kanglaite (康莱特, KLT) is made of a lipolytic and efficacious anti-cancer ingredient isolated from Chinese herb Semen Coix lacryma-jobi, an anti-cancer emulsion made with international advanced technology for intravenous and intra-arterial injection, which has obvious efficacy in treating many primary malignant tumors such as lung cancer, liver cancer, gastric cancer, breast cancer etc.and could markedly elevate immune function, as it is a biphasic broad spectrum anti-cancer agent;KLT combined with radiotherapy or chemotherapy could alleviate toxicity and raise their efficacy, and before surgical operation could facilitate cancer cell necrosis, apoptosis, prevent diffusion and metastasis, effectively act against cachexia, control cancer pain, increase body weight, improve quality of life and extend survival period of cancer patients in the advanced stage. Since came to market, KLT has been used in over 2 000 large and medium hospitals at home, and 300 000 cancer patients have benefited clinically from it.

  10. Medical image of the week: central pontine myelinolysis

    Directory of Open Access Journals (Sweden)

    Siddiqi TA

    2014-01-01

    Full Text Available A 38-year-old woman with history of alcohol abuse was admitted with generalized weakness, dehydration, alcoholic hepatitis, hyponatremia (serum sodium 116 mM/L, and cachexia (BMI 19 kg/m2. She developed hypoxemic respiratory failure after intravenous fluid resuscitation and required intubation and mechanical ventilation. Neurological exam revealed motor weakness, hyporeflexia, ataxia, and unsustained clonus. Neurology consultation was obtained and MRI revealed hyperintensity in the pons consistent with osmotic demyelination syndrome (1. Review of her records revealed her sodium level increased by 8 mM/L in first 6 hours of presentation, and then a slow increase of 4-6 mM/L daily to the normal range. She received nutritional support and aggressive physical therapy, and was discharged to skilled nursing facility after six weeks of hospitalization.

  11. Visceral leishmaniasis with endobronchial involvement in an immunocompetent adult.

    Science.gov (United States)

    Kotsifas, Konstantinos; Metaxas, Eugenios; Koutsouvelis, Ioannis; Skoutelis, Athanassios; Kara, Panayiota; Tatsis, George

    2011-01-01

    Visceral leishmaniasis is characterized by fever, cachexia, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia. Cough may be a presenting symptom as well. However, pulmonary involvement is considered rare and mainly described in immunocompromised patients. We describe a case of an immunocompetent adult whose clinical presentation was dominated by cough and hemoptysis. Bronchoscopy revealed a discreet polypoid mucosal endobronchial lesion whose biopsy yielded Leishmania amastigotes within histiocytes. Transbronchial needle biopsy of a right paratracheal lymph node was also positive. Leishmania amastigotes were also found on bone marrow and liver biopsies. Treatment with IV Amphotericin B was successful. In conclusion, cough should not be overlooked as a presenting symptom of visceral leishmaniasis and may be a sign of pulmonary involvement. PMID:21577261

  12. Visceral Leishmaniasis with Endobronchial Involvement in an Immunocompetent Adult

    Directory of Open Access Journals (Sweden)

    Konstantinos Kotsifas

    2011-01-01

    Full Text Available Visceral leishmaniasis is characterized by fever, cachexia, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia. Cough may be a presenting symptom as well. However, pulmonary involvement is considered rare and mainly described in immunocompromised patients. We describe a case of an immunocompetent adult whose clinical presentation was dominated by cough and hemoptysis. Bronchoscopy revealed a discreet polypoid mucosal endobronchial lesion whose biopsy yielded Leishmania amastigotes within histiocytes. Transbronchial needle biopsy of a right paratracheal lymph node was also positive. Leishmania amastigotes were also found on bone marrow and liver biopsies. Treatment with IV Amphotericin B was successful. In conclusion, cough should not be overlooked as a presenting symptom of visceral leishmaniasis and may be a sign of pulmonary involvement.

  13. MRI demonstration of orbital lipolysis in anorexia nervosa

    Energy Technology Data Exchange (ETDEWEB)

    Demaerel, Philippe; Dekimpe, Piet; Wilms, Guy [Department of Radiology, University Hospitals, Herestraat 49, 3000 Leuven (Belgium); Muls, Erik [Department of Endocrinology, University Hospitals, Herestraat 49, 3000 Leuven (Belgium)

    2002-07-01

    The purpose of this article is to describe the orbital changes due to lipolysis in anorexia nervosa. We examined a cachectic patient with MR imaging using T1-weighted images before and after contrast enhancement. Orbital fat edema has been observed in extreme forms of cachexia and the CT and MR findings have recently been reported. The imaging appearances have been explained by the disappearance of the fat tissue and the appearance of edema due to a disturbance in the electrolyte fluid balance. In the recent literature particular attention has been paid to the increased lipid peroxidation and lipolysis in anorexia nervosa. These metabolic processes result in an increased permeability of the vessel wall endothelium, which can explain the extravasation of the contrast agent in the orbital fat on MR imaging. (orig.)

  14. Secondary adrenal insufficiency: an overlooked cause of hyponatremia.

    Science.gov (United States)

    Jessani, Naureen; Jehangir, Waqas; Behman, Daisy; Yousif, Abdalla; Spiler, Ira J

    2015-04-01

    Failure to thrive in an elderly patient is often attributed to depression, especially when a patient does not have any chronic diseases or if there is no apparent medical reason to justify poor appetite, cachexia and generalized weakness. Hyponatremia often occurs in such patients and a thorough evaluation as to its etiology should be sought before committing to a premature diagnosis, which at the time may seem more plausible. We report a patient who presented with depression, weight loss and persistent hyponatremia, evaluation of which revealed the cause to be due to secondary adrenal insufficiency, which when treated, resulted in resolution of the symptom complex. Therefore, in our case report, we elucidate the importance of pursuing further evaluation to rule out adrenal insufficiency as a medical cause of depression, especially in the presence of hyponatremia, which is often overlooked and is generally attributed to dehydration in the setting of failure to thrive or SIADH in patients who are on psychotropic medications. PMID:25699130

  15. [Malnutrition due to an extremely 'healthy' diet; a new eating disorder?].

    Science.gov (United States)

    Nauta, K; Toxopeus, K; Eekhoff, E M W

    2016-01-01

    A 71-year-old male was admitted to our hospital with heart failure, cachexia and biochemical disturbances due to a diet consisting of exclusively vegetables, oil and water. Our investigations showed that this diet was a consequence of an excessive preoccupation with health. The patient did not meet criteria for an eating disorder or other DSM-IV psychiatric disorder. We conclude that malnutrition due to health fad diets may be an underestimated medical problem. There is no specific psychopathological disorder that covers this behaviour, and there is no knowledge of its epidemiology. Popular literature is paying a great deal attention to orthorexia nervosa, an alleged eating disorder that describes a pathological obsession with healthy food. In medical literature this concept has been largely neglected, although eating disorder specialists frequently observe this behaviour in their practice. More clinical and scientific attention for this phenomenon is necessary to determine its epidemiology, validity and clinical picture. PMID:27299484

  16. Cockayne syndrome group B protein prevents the accumulation of damaged mitochondria by promoting mitochondrial autophagy

    DEFF Research Database (Denmark)

    Scheibye-Knudsen, Morten; Ramamoorthy, Mahesh; Sykora, Peter;

    2012-01-01

    Cockayne syndrome (CS) is a devastating autosomal recessive disease characterized by neurodegeneration, cachexia, and accelerated aging. 80% of the cases are caused by mutations in the CS complementation group B (CSB) gene known to be involved in DNA repair and transcription. Recent evidence...... indicates that CSB is present in mitochondria, where it associates with mitochondrial DNA (mtDNA). We report an increase in metabolism in the CSB(m/m) mouse model and CSB-deficient cells. Mitochondrial content is increased in CSB-deficient cells, whereas autophagy is down-regulated, presumably as a result...... of defects in the recruitment of P62 and mitochondrial ubiquitination. CSB-deficient cells show increased free radical production and an accumulation of damaged mitochondria. Accordingly, treatment with the autophagic stimulators lithium chloride or rapamycin reverses the bioenergetic phenotype of...

  17. Oxidative stress, redox signaling pathways, and autophagy in cachectic muscles of male patients with advanced COPD and lung cancer.

    Science.gov (United States)

    Puig-Vilanova, Ester; Rodriguez, Diego A; Lloreta, Josep; Ausin, Pilar; Pascual-Guardia, Sergio; Broquetas, Joan; Roca, Josep; Gea, Joaquim; Barreiro, Esther

    2015-02-01

    Muscle dysfunction and wasting are predictors of mortality in advanced COPD and malignancies. Redox imbalance and enhanced protein catabolism are underlying mechanisms in COPD. We hypothesized that the expression profile of several biological markers share similarities in patients with cachexia associated with either COPD or lung cancer (LC). In vastus lateralis of cachectic patients with either LC (n=10) or advanced COPD (n=16) and healthy controls (n=10), markers of redox balance, inflammation, proteolysis, autophagy, signaling pathways, mitochondrial function, muscle structure, and sarcomere damage were measured using laboratory and light and electron microscopy techniques. Systemic redox balance and inflammation were also determined. All subjects were clinically evaluated. Compared to controls, in both cachectic groups of patients, a similar expression profile of different biological markers was observed in their muscles: increased levels of muscle protein oxidation and ubiquitination (p<0.05, both), which positively correlated (r=0.888), redox-sensitive signaling pathways (NF-κB and FoxO) were activated (p<0.05, all), fast-twitch fiber sizes were atrophied, muscle structural abnormalities and sarcomere disruptions were significantly greater (p<0.05, both). Structural and functional protein levels were lower in muscles of both cachectic patient groups than in controls (p<0.05, all). However, levels of autophagy markers including ultrastructural autophagosome counts were increased only in muscles of cachectic COPD patients (p<0.05). Systemic oxidative stress and inflammation levels were also increased in both patient groups compared to controls (p<0.005, both). Oxidative stress and redox-sensitive signaling pathways are likely to contribute to the etiology of muscle wasting and sarcomere disruption in patients with respiratory cachexia: LC and COPD. PMID:25464271

  18. Exploring metabolic dysfunction in chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Slee Adrian D

    2012-04-01

    Full Text Available Abstract Impaired kidney function and chronic kidney disease (CKD leading to kidney failure and end-stage renal disease (ESRD is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabolic factors may play key roles in CKD development and pathogenesis. These include raised proinflammatory cytokines, such as interleukin-1 and −6, tumor necrosis factor, altered hepatic acute phase proteins, including reduced albumin, increased C-reactive protein, and perturbations in normal anabolic hormone responses with reduced growth hormone-insulin-like growth factor-1 axis activity. Others include hyperactivation of the renin-angiotensin aldosterone system (RAAS, with angiotensin II and aldosterone implicated in hypertension and the promotion of insulin resistance, and subsequent pharmacological blockade shown to improve blood pressure, metabolic control and offer reno-protective effects. Abnormal adipocytokine levels including leptin and adiponectin may further promote the insulin resistant, and proinflammatory state in CKD. Ghrelin may be also implicated and controversial studies suggest activities may be reduced in human CKD, and may provide a rationale for administration of acyl-ghrelin. Poor vitamin D status has also been associated with patient outcome and CVD risk and may indicate a role for supplementation. Glucocorticoid activities traditionally known for their involvement in the pathogenesis of a number of disease states are increased and may be implicated in CKD-associated hypertension, insulin resistance, diabetes risk and cachexia, both directly and indirectly through effects on other systems including activation of the mineralcorticoid

  19. Theodor Kocher (1841-1917 Nobel Prize Centenary 2009 Theodor Kocher (1841-1917 Centenário de Prêmio Nobel 2009

    Directory of Open Access Journals (Sweden)

    Peter Kopp

    2009-12-01

    Full Text Available One hundred years ago, in 1909, Theodor Kocher was awarded the Nobel Prize in Physiology and Medicine for his work on the physiology, pathology, and surgery of the thyroid gland. In the late 19th century, the resection of the thyroid was feared because of its high mortality rate. Kocher's innovative techniques resulted in safe outcomes. His observations that radical resection of the thyroid results in "cachexia strumipriva" contributed to the recognition that the thyroid is essential for normal growth, development and metabolism. He made many other seminal contributions to the field of surgery and medicine, and his expertise was internationally recognized. Kocher served as the chairman of surgery at the University of Bern in Switzerland, his alma mater, until his death in 1917.Há 100 anos, em 1909, Theodor Kocher foi agraciado com o Prêmio Nobel de Fisiologia e Medicina pelo seu trabalho na fisiologia, na patologia e na cirurgia da glândula tireoide. No final do século XIX, a ressecção da tireoide era temida pelo alto índice de mortalidade. As técnicas inovadoras de Kocher resultaram como procedimento seguro. Suas observações de que a ressecção radical da tireoide resulta em cachexia strumipriva contribuiu no reconhecimento de que a tireoide é essencial no crescimento normal, no desenvolvimento e no metabolismo. Ele realizou muitas outras contribuições seminais no campo da cirurgia e da medicina, e seu conhecimento foi reconhecido internacionalmente. Kocher foi chefe da cirurgia da Universidade de Berna na Suíça, sua alma mater, até sua morte em 1917.

  20. Sipjeondaebo-tang in patients with cancer with anorexia: a protocol for a pilot, randomised, controlled trial

    Science.gov (United States)

    Cheon, Chunhoo; Park, Sunju; Park, Yu Lee; Huang, Ching-Wen; Ko, Youme; Jang, Bo-Hyoung; Shin, Yong-Cheol; Ko, Seong-Gyu

    2016-01-01

    Introduction Cancer-related anorexia is the loss of appetite or desire to eat in patients with cancer. Although treatments for cancer-related anorexia do exist, patients have sought complementary and alternative medicine including herbal remedies, due to safety concerns. Sipjeondaebo-tang is one among other popular herbal medicines that are beneficial to management of anorexia in Korea. The purpose of this study is to examine the feasibility for a full randomised clinical trial of Sipjeondaebo-tang for cancer-related anorexia. Methods and analysis This study is a randomised, double-blinded and placebo-controlled trial of Sipjeondaebo-tang. For the study, 40 patients with cancer, aged 20–80 years, who reported anorexia, will be recruited. The participants will receive either 3 g of Sipjeondaebo-tang or a placebo, 3 times a day for 4 weeks. The primary end point is a change in the anorexia/cachexia subscale (A/CS) of Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary end points include changes in the visual analogue scale (VAS) of appetite, cortisol and ghrelin. The outcomes will be measured on every visit. Each participant will visit once a week during 4 weeks. Ethics and dissemination The present study has been approved by the Institutional Review Board of the Dunsan Korean Medicine Hospital of Daejeon University (reference DJDSKH-15-03-2 (V.2.0)). The results will be disseminated in a peer-reviewed journal and scientific conference. Trial registration number NCT02468141; Pre-results. PMID:27173813

  1. Skeletal muscle atrophy: disease-induced mechanisms may mask disuse atrophy.

    Science.gov (United States)

    Malavaki, C J; Sakkas, G K; Mitrou, G I; Kalyva, A; Stefanidis, I; Myburgh, K H; Karatzaferi, C

    2015-12-01

    Disuse atrophy is the loss of skeletal muscle mass due to inactivity or lower than 'normal' use. It is not only a furtive component of the 'modern' sedentary lifestyle but also a part of numerous pathologies, where muscle loss is linked to disease specific and/or other toxicity factors, eventually leading to wasting (cachexia). Whether disuse-or-disease induced, muscle loss leads to weakness and metabolic comorbidities with a high societal and financial cost. This review discusses the intricate network of interacting signalling pathways including Atrogin-1/MAFbx, IGF1-Akt, myostatin, glucocorticoids, NF-kB, MAPKs and caspases that seem to regulate disuse atrophy but also share common activation patterns in other states of muscle loss such as sarcopenia or cachexia. Reactive oxygen species are also important regulators of cell signalling pathways that can accelerate proteolysis and depress protein synthesis. Exercise is an effective countermeasure and antioxidants may show some benefit. We discuss how the experimental model used can crucially affect the outcome and hence our understanding of atrophy. Timing of sampling is crucial as some signalling mechanisms reach their peak early during the atrophy process to rapidly decline thereafter, while other present high levels even weeks and months after study initiation. The importance of such differences lays in future consideration of appropriate treatment targets. Apart from attempting to correct defective genes or negate their effects, technological advances in new rational ways should aim to regulate specific gene expression at precise time points for the treatment of muscle atrophy in therapeutic protocols depending on the origin of atrophy induction. PMID:26728748

  2. Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluoruracil in colon cancer cell-bearing mice

    Institute of Scientific and Technical Information of China (English)

    Simona Perboni; Cyril Bowers; Shinya Kojima; Akihiro Asakawa; Akio Inui

    2008-01-01

    The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemo-therapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin ago-nist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluoruracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BALB/c female tumour-bearing mice were randomized to receive a solution containing: (a) placebo; (b) GHRP-2; (c) 5-FU; or (d) 5-FU + GHRP-2. Ten BALB/c no tumour-bearing mice received placebo solution. Food intake and survival were checked. Six hours after the drug injection the cumulative food intake was significantly increased in mice treated with the combination of 5-FU + GHRP-2 versus the 5-FU alone (P = 0.0096). On day 3, the cumulative food intake of mice treated with GHRP-2, 5-FU and 5-FU + GHRP-2 significantly increased com-pared with naive and vehicle groups (P = 0.0007, P = 0.0038 and P = 0.0166, respectively). The median survival time was longer in 5-FU + GHRP-2 treated mice than in those with 5-FU, although it was not significant (18 d versus 15.5 d, P = 0.7). For the first time, we demonstrated that the addition of GHRP-2 to cytotoxic therapy with 5-FU improved appetite in tumour-bearing mice with anorexia/cachexia syndrome in early stage. These data suggest that GHRP-2 may improve the efficacy of therapy and the quality of life of cancer patients thank to the amelioration of their nutritional state.

  3. Food effect on the bioavailability of two distinct formulations of megestrol acetate oral suspension

    Directory of Open Access Journals (Sweden)

    Benoit Deschamps

    2009-09-01

    Full Text Available Benoit Deschamps1, Naomi Musaji2, John A Gillespie21SFBC Anapharm, Montreal, Canada; 2Strativa Pharmaceuticals, a division of Par Pharmaceutical, Inc., Woodcliff Lake, NJ, USAObjective: Megestrol acetate oral suspension (MAOS is an appetite stimulant indicated for cachexia in patients with AIDS. It is available in its original formulation, Megace® (MAOS, and as a nanocrystal dispersion, Megace® ES (MA-ES. Three studies were conducted to evaluate the pharmacokinetic properties of these formulations under fed and fasting conditions.Methods: An open-label, crossover trial was conducted in 24 healthy males randomized to MA-ES 625 mg/5 mL given with a high-calorie, high-fat meal, or after an overnight fast. Blood samples were drawn at multiple time points and pharmacokinetic parameters were determined. Two separate, open-label reference studies evaluated MAOS 800 mg/20 mL in 40 fed or 40 fasting healthy male volunteers.Results: In fasting MA-ES subjects, the average maximum concentration (Cmax was 30% less than the fed Cmax value. For MAOS, fasting Cmax was 86% less than fed Cmax. In fasting subjects, the area under the curve was 12,095 ng⋅h/mL for MA-ES, and 8,942 ng⋅h/mL for MAOS. In fed subjects, the absorption of the two formulations was comparable.Conclusion: Bioavailability and absorption are greater for MA-ES than MAOS in fasting subjects. MA-ES may be a preferred formulation of megestrol acetate when managing cachectic patients whose caloric intake is reduced.Keywords: megestrol acetate, bioavailability, cachexia, nanocrystal technology, appetite stimulant

  4. Subclinical myopathy in patients with colorectal cancer: clinical-pathological characterization and search for tissue markers

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    Massimo Vecchiato

    2012-03-01

    Full Text Available Skeletal muscle in patients with cancer undergoes many morphological changes due to immuno-inflammatory factors of tumor origin or treatment.T he latest event of these changes is cancer cachexia. Aim of the study is to identify myopathic features in skeletal muscle biopsies from weight stable patients with colorectal cancer and without cachexia or asthenia / weakness, that could possibly provide new diagnostic and prognostic cancer biomarkers. Morphometric analyses and immunohistochemical studies were performed on intraoperative muscle biopsies from patients with colorectal cancer and from weight stable patients undergoing surgery for benign non-inflammatory conditions. A rectus abdominis biopsy was taken in all patients and controls.A correlation between histopathologic findings and clinical characteristics, circulating inflammatory biomarkers and markers of muscle necrosis,surgery data and cancer phenotype were investigated.. Forty four patients (21male/23 female and 17 controls (6 male/11 female (p=NS were studied. In cancer patients’biopsies we observed asubclinical myopathy characterized by an abnormal distribution of myonuclei, which are localized inside the myofiber rather than at the periphery, and by the presence of regenerating muscle fibers. The percentage of myofibers with internalized nuclei is significantly higher in patients (median= 9%, IQR= 3.7-18.8 than in controls (median= 2.7%, IQR= 1.7-3.2 ( p=0.0002. In patients we observed an inverse correlation between the number of centronucleated fibers and the presence of node metastasis (N+(ρ=-0.64 (p=0.002. Patients affected with colorectal cancer display early sign of a myopathy, characterized by centronucleated and regenerating myofibers. This myopathy appears to be associated with an early stage of neoplasia and it could be an adaptive response of muscle to cancer. We hope a future application of these findings as a possible early diagnostic and prognostic biomarker of

  5. Molecular and cell-based therapies for muscle degenerations: a road under construction

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    Maurilio eSampaolesi

    2014-04-01

    Full Text Available There are no specific treatments for muscular degeneration caused by muscular dystrophies and for muscle wasting caused by cachexia or sarcopenia. Corticosteroid medications for dystrophic patients only helps to control inflammatory process and slightly delay the progression of the disease. Walkers and wheel chairs are the only options to maintain patients’ independence and walking capabilities until respiratory muscles become weak and mechanical ventilation is mandatory. On the other hand myostatin inhibition, melanocortin-4 receptor antagonists, β-blockers, IL-6 antagonism, and synthetic ghrelin are promising treatments for cachectic animal models. Although in both cases muscular degeneration is relevant the translational therapeutic attempts to find a possible cure are well defined. Molecular treatments are common options to explore beneficial treatments for cachexia, and gene/cell therapies are mostly employed to induce the phenotypic improvement of dystrophic muscles. This review deals with the use of molecular administrations and gene/stem cell therapy to treat muscular degenerations. It reviews previous trials using cell delivery protocols in mice and patients starting with the use of donor myoblasts, outlining the likely causes for their poor results and briefly focusing on satellite cell studies that raise new hope. Then it proceeds to describe recently identified stem/progenitor cells in relationship to their ability to home within a dystrophic muscle and to differentiate into skeletal muscle cells. Different known features of various stem cells are compared in this perspective, and the few available examples of their use in animal models of muscular degeneration are reported. This review also provides an outline of the role of microRNAs to control myogenic commitment. Finally, based on our current knowledge and the rapid advance in stem cell biology a prediction of clinical translation for cell therapy protocols combined with

  6. Serum and tissue markers of myopathy in patients with colorectal cancer

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    Nicoletta Adami

    2012-09-01

    Full Text Available Skeletal muscles in patients with cancer undergo many changes due to immuno-inflammatory factors of tumor origin, or to chemotherapy and irradiation. Aim of the present study is to identify serological biomarkers and early myopathic features in skeletal muscle biopsies from weight stable patients bearing colorectal cancer at the onset of disease. Morphometric analyses by histochemistry and immunohistochemistry were performed on intraoperative muscle biopsies from patients with early colorectal cancer and from weight stable patients undergoing surgery for benign non-inflammatory conditions. Serological analyses for testing markers of inflammation (C Reactive Protein, CRP, muscle enzymes, (Creatin Kinase, CK, soluble isoforms of adhesion molecules (Neural Cell Adhesion Molecule, NCAM, and a marker of protein turnover (prealbumin, a typical indicator of caloric and protein malnutrition were also performed. Fifty oncologic patients (28 male/22 female and 25 non oncologic patients (18 male/7 female (p=N.S. were studied. In muscles from cancer patients we observed a subclinical myopathy characterized by an abnormal distribution of myonuclei. The percentage of myofibers with internalized nuclei was significantly higher in oncologic (median= 13.1%, IQR= 6.0-20.3 than in non oncologic patients (median= 3%, IQR= 2.5-6.1 (p<0.0001. The frequency of these internally nucleated myofibers is even higher in a subgroup of oncologic patients taking myotoxic drugs. In cancer patients, we observed an inverse correlation between the number of internally nucleated fibers and the presence of node metastasis (N+ (ρ=-0.30 (p=0.03. Moreover, in patients with colorectal cancer, low serum levels of preoperative prealbumin (median= 167,7 mg/L, normal range 200-400 mg/L, were detected. The link between the observed early myopathy and long-term cachexia is supported also by the altered expression of sarcolemma associated proteins, in particular laminin and dystrophin

  7. Parenteral nutrition support for patients with pancreatic cancer. Results of a phase II study

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    Riess Hanno

    2010-03-01

    Full Text Available Abstract Background Cachexia is a common problem in patients (pts suffering from upper gastrointestinal cancer. In addition, most of these patients suffer from malabsorption and stenosis of the gastrointestinal tract due to their illness. Various methods of supplementary nutrition (enteral, parenteral are practised. In patients with advanced pancreatic cancer (APC, phase angle, determined by bio-electrical impedance analysis (BIA, seems to be a survival predictor. The positive influence of BIA determinate predictors by additional nutrition is currently under discussion. Methods To examine the impact of additional parenteral nutrition (APN we assessed outpatients suffering from APC and progressive cachexia. The assessment based on the BIA method. Assessment parameters were phase angle, ECM/BCM index (ratio of extracellular mass to body cell mass, and BMI (body mass index. Patients suffering from progressive weight loss in spite of additional enteral nutritional support were eligible for the study. Results Median treatment duration in 32 pts was 18 [8-35] weeks. Response evaluation showed a benefit in 27 pts (84% in at least one parameter. 14 pts (43.7% improved or stabilised in all three parameters. The median ECM/BCM index was 1.7 [1.11-3.14] at start of APN and improved down to 1.5 [1.12-3.36] during therapy. The median BMI increased from 19.7 [14.4-25.9] to 20.5 [15.4-25.0]. The median phase angle improved by 10% from 3.6 [2.3-5.1] to 3.9 [2.2-5.1]. Conclusions We demonstrated the positive impact of APN on the assessed parameters, first of all the phase angle, and we observed at least a temporary benefit or stabilisation of the nutritional status in the majority of the investigated patients. Based on these findings we are currently investigating the impact of APN on survival in a larger patient cohort. Trial registration ClinicalTrials.gov Identifier: NCT00919659

  8. 大麻素系统在骨科中的应用进展%Recent progress in the application of cannabinoid system in orthopaedics

    Institute of Scientific and Technical Information of China (English)

    杨豪; 王建儒; 郑召民

    2013-01-01

    Cannabinoids have been implicated in many physiological processes, ranging from appetite regulation and pain perception to motor function development and immune response regulation. And cannabinoids have been approved for clinical use in the treatment of the following symptoms, such as nausea and vomiting caused by cytostatic therapy, loss of appetite in HIV/Aids-related cachexia, refractory spasticity caused by multiple sclerosis, the side effects of chemotherapy in cancer patients, chronic pain and so on. Recent studies found the expressions of cannabinoids and cannabinoid receptors in the bone and synovial tissues, and their important roles in bone metabolism were conifrmed. Preclinical testing in animal models demonstrated that cannabinoids could alleviate the development of arthritis, prevent osteoporosis and improve the neurological function following spinal cord injury. So the recent progress in the application of cannabinoid system in orthopaedics was reviewed in this paper, with the expectation to provide a new direction for orthopaedic research and apply cannabinoid drugs in the clinical treatment of orthopaedic diseases.

  9. Clinical and laboratory investigation of experimentaly infected broilers with CIAV

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    Kapetanov Miloš C.

    2004-01-01

    Full Text Available Chicken infectious anemia (CIA is widespread viral disease in countries with the intensive poultry industry. In susceptible birds CIAV causes anemia subcutaneous and intramuscular hemorrhages, lymphoid tissue atrophy immunosuppression, cachexia and increased mortality. Protection of progeny relies not only on age resistance but also on maternally delivered antibodies (Mabs so possessing the information on level and persistence of Mabs is of great significance. In our study experimental infection with CIAV was performed on one and seven days old broiler chickens from naturally infected parent flock during the rearing period. In infected birds, clinical signs hematological findings and humoral immune response were examined. After euthanasia, we looked for specific pathomorphological and histopathological changes that indicate the presence of CIAV infection. In all one and seven days old chickens maternally derived antibodies were established. No clinical signs of CIA were observed, hematological findings showed no deviation from referent values, and there were no specific pathomorphological and histopathological changes at postmortem examination. According to previous knowledge, only serological negative flock if infected in time of laying represent risk for vertical transmission to progeny where typical disease with mortality will appear. The absence of Mabs in one day old chickens is critical point in break of disease. Typical clinical picture in day old chickens rises only when vertical transmission occurs.

  10. Lack of CFTR in skeletal muscle predisposes to muscle wasting and diaphragm muscle pump failure in cystic fibrosis mice.

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    Maziar Divangahi

    2009-07-01

    Full Text Available Cystic fibrosis (CF patients often have reduced mass and strength of skeletal muscles, including the diaphragm, the primary muscle of respiration. Here we show that lack of the CF transmembrane conductance regulator (CFTR plays an intrinsic role in skeletal muscle atrophy and dysfunction. In normal murine and human skeletal muscle, CFTR is expressed and co-localized with sarcoplasmic reticulum-associated proteins. CFTR-deficient myotubes exhibit augmented levels of intracellular calcium after KCl-induced depolarization, and exposure to an inflammatory milieu induces excessive NF-kB translocation and cytokine/chemokine gene upregulation. To determine the effects of an inflammatory environment in vivo, sustained pulmonary infection with Pseudomonas aeruginosa was produced, and under these conditions diaphragmatic force-generating capacity is selectively reduced in Cftr(-/- mice. This is associated with exaggerated pro-inflammatory cytokine expression as well as upregulation of the E3 ubiquitin ligases (MuRF1 and atrogin-1 involved in muscle atrophy. We conclude that an intrinsic alteration of function is linked to the absence of CFTR from skeletal muscle, leading to dysregulated calcium homeostasis, augmented inflammatory/atrophic gene expression signatures, and increased diaphragmatic weakness during pulmonary infection. These findings reveal a previously unrecognized role for CFTR in skeletal muscle function that may have major implications for the pathogenesis of cachexia and respiratory muscle pump failure in CF patients.

  11. The importance of glycemic load of the diet in the development of cancer 

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    Katarzyna Dudziak

    2013-05-01

    Full Text Available Treatment of cancer involves not only appropriate pharmacological or psychological therapy and rehabilitation, but also diet aimed at prevention of the process of cachexia. Postprandial hyperglycemia exerts a significant effect on the growth and proliferation of tumor cells. It promotes formation of a number of metabolic changes in every tissue of the organism. Chronic postprandial hyperglycemia, occurring in type 2 diabetes, enhances all these changes. Although the results of epidemiological studies on the relationship between the overall risk of cancer development, or tumors in different parts of the organism, are heterogeneous, most of them indicate that the risk increases with an increase in glycemic load of the examined population’s diets. Researchers also suggest a beneficial effect of limiting the amount of easily assimilable carbohydrate in the diet to stabilize the disease and for better tolerance of chemoor radiation therapy. However, further studies are required.

  12. Involvement of Ghrelin-Growth Hormone Secretagogue Receptor System in Pathoclinical Profiles of Digestive System Cancer

    Institute of Scientific and Technical Information of China (English)

    Zhigang WANG; Weigang WANG; Wencai QIU; Youben FAN; Jun ZHAO; Yu WANG; Qi ZHENG

    2007-01-01

    Ghrelin receptor has been shown to be expressed along the human gastrointestinal tract.Recent studies showed that ghrelin and a synthetic ghrelin receptor agonist improved weight gain and lean body mass retention in a rat model of cancer cachexia by acting on ghrelin receptor, that is, growth hormone secretagogue receptor (GHS-R). This study aims to explore the expression and the distribution of ghrelin receptor in human gastrointestinal tract cancers and to investigate the possible involvement of the ghrelin-GHS-R system in human digestive cancers. Surgical human digestive cancer specimens were obtained from various portions of the gastrointestinal tract from different patients. The expression of ghrelin receptor in these tissues was detected by tissue microarray technique. Our results showed that ghrelin receptor was expressed in cancers throughout the gastrointestinal tract, mainly in the cytoplasm of mucosal layer cells.Its expression level possibly correlated with organ type, histological grade, tumor-nodes-metastases stage,and nutrition status (weight loss) of the patients. For the first time, we identified the distribution of ghrelin receptor in digestive system cancers. Our results implied that the ghrelin-GHS-R system might be involved in the pathoclinical profiles of digestive cancers.

  13. An outbreak of bovine tuberculosis in a fallow deer herd (Dama dama) in Sicily.

    Science.gov (United States)

    Amato, Benedetta; Mignacca, Sebastian Alessandro; Pacciarini, Maria Lodovica; Vitale, Maria; Antoci, Salvatore; Cucinotta, Salvatore; Puleio, Roberto; Biasibetti, Elena; Fiasconaro, Michele; Capucchio, Maria Teresa; Di Marco Lo Presti, Vincenzo

    2016-06-01

    Wild ruminants have an important role in the epidemiology of bovine tuberculosis (bTB). This study describes an outbreak of bovine tuberculosis occurring in a fallow deer herd in Sicily. In 2012 a Sicilian herd of 47 animals was referred for cachexia. Pathological examination of 2 dead animals revealed disseminated granulomas predominantly involving the skin and subcutaneous tissues. Tissue samples were submitted for histological analysis, bacteriological culture, and biomolecular assay. PCR analysis identified Mycobacterium strains. Genotyping by spoligotyping and MIRU-VNTR profiles identified Mycobacterium bovis spoligotype SB0120 in both animals. In 2014, bTB skin testing of 28 fallow deer from the same group was positive in 4 and inconclusive in another 4. All 8 positive/inconclusive reactors were euthanized. Disseminated granulomatous lesions were noted in 6 of these animals, 3 of which (2 positive and 1 negative to skin tests) also presented cutaneous lesions. M. bovis spoligotype SB0120 was identified from all animals in which tuberculous-like lesions were observed, including 2 negative reactors. Many of the animals involved in this outbreak presented diffuse skin lesions, a potential route of transmission of M. bovis infection. Given the epidemiological role wildlife play in the maintenance of bTB infection and its potential risk for humans, a comprehensive monitoring plan for this zoonosis in wildlife species in Sicily is needed. PMID:27234548

  14. Toxic effects of oral 2-amino-4,6-dinitrotoluene in the Western fence lizard (Sceloporus occidentalis)

    International Nuclear Information System (INIS)

    The compound 2-amino-4,6-dinitrotoluene (2A-DNT) was evaluated under laboratory conditions in the Western fence lizard (Sceloporus occidentalis) to assess the potential for reptile toxicity. Oral LD50 values were 1406 and 1867 mg/kg for male and female lizards, respectively. Based on responses from a 14-day subacute study, a 60-day subchronic experiment followed where lizards were orally dosed at 0, 5, 15, 20, 25, 30 mg/kg-d. At day 60, number of days and survivors, food consumption, and change in body weight were inversely related to dose. Signs of toxicity were characterized by anorexia and generalized cachexia. Significant adverse histopathology was observed in hepatic tissue at ≥15 mg/kg-d, consistent with hepatocellular transdifferentiation. Based on survival, loss of body weight, diminished food intake, changes in liver, kidney, and testes, and increased blood urea nitrogen, these data suggest a LOAEL of 15 mg/kg-d and a NOAEL of 5 mg/kg-d in S. occidentalis. - Research highlights: → Oral LD50 (mg/kg) values were 1406 for male and 1867 for female lizards. → Dose-dependent hepatocellular transdifferentiation was observed at ≥5 mg/kg-d. → Chromaturia in 2A-DNT and the parent TNT suggest biomarkers of exposure and effect. → Health effects of metabolites support comprehensive ecological risk assessments. - The Western fence lizard (Sceloporus occidentalis) is a suitable reptile model for assessing the toxicity of energetic compounds and their metabolites.

  15. The pentapeptide RM-131 promotes food intake and adiposity in wildtype mice but not in mice lacking the ghrelin receptor

    Directory of Open Access Journals (Sweden)

    Katrin eFischer

    2015-01-01

    Full Text Available The gastrointestinal peptide hormone ghrelin is the endogenous ligand of the growth hormone secretagogue receptor (GHSR, a.k.a. ghrelin receptor, GHR. Currently, ghrelin is the only circulating peripheral hormone with the ability to promote a positive energy balance by stimulating food intake while decreasing energy expenditure and body fat utilization, as defined in rodents. Based on these and additional, beneficial effects on metabolism, the endogenous ghrelin system is considered an attractive target to treat diverse pathological conditions including those associated with eating/wasting disorders and cachexia. As the pharmacological potential of ghrelin is hampered by its relatively short half-life, ghrelin analogs with enhanced pharmacokinetics offer the potential to sustainably improve metabolism. One of these ghrelin analogs is the pentapeptide RM-131, which promotes food intake and adiposity with higher potency as compared to native ghrelin in rodents. Whereas the effect of RM-131 on energy metabolism is solidly confirmed in rodents, it remains elusive whether RM-131 exerts its effect solely via the ghrelin receptor. Accordingly, we assessed the receptor specificity of RM-131 to promote food intake and adiposity in mice lacking the GHR. Our data show that in wildtype mice RM-131 potently promotes weight gain and adiposity through stimulation of food intake. However, RM-131 fails to affect food intake and body weight in mice lacking the GHR, underlining that the anabolic effects of RM-131 are mediated via the ghrelin receptor in mice.

  16. Molecular insights into mitochondrial dysfunction in cancer-related muscle wasting.

    Science.gov (United States)

    Antunes, Diana; Padrão, Ana Isabel; Maciel, Elisabete; Santinha, Deolinda; Oliveira, Paula; Vitorino, Rui; Moreira-Gonçalves, Daniel; Colaço, Bruno; Pires, Maria João; Nunes, Cláudia; Santos, Lúcio L; Amado, Francisco; Duarte, José Alberto; Domingues, Maria Rosário; Ferreira, Rita

    2014-06-01

    Alterations in muscle mitochondrial bioenergetics during cancer cachexia were previously suggested; however, the underlying mechanisms are not known. So, the goal of this study was to evaluate mitochondrial phospholipid remodeling in cancer-related muscle wasting and its repercussions to respiratory chain activity and fiber susceptibility to apoptosis. An animal model of urothelial carcinoma induced by exposition to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) and characterized by significant body weight loss due to skeletal muscle mass decrease was used. Morphological evidences of muscle atrophy were associated to decreased respiratory chain activity and increased expression of mitochondrial UCP3, which altogether highlight the lower ability of wasted muscle to produce ATP. Lipidomic analysis of isolated mitochondria revealed a significant decrease of phosphatidic acid, phosphatidylglycerol and cardiolipin in BBN mitochondria, counteracted by increased phosphatidylcholine levels. Besides the impact on membrane fluidity, this phospholipid remodeling seems to justify, at least in part, the lower oxidative phosphorylation activity observed in mitochondria from wasted muscle and their increased susceptibility to apoptosis. Curiously, no evidences of lipid peroxidation were observed but proteins from BBN mitochondria, particularly the metabolic ones, seem more prone to carbonylation with the consequent implications in mitochondria functionality. Overall, data suggest that bladder cancer negatively impacts skeletal muscle activity specifically by affecting mitochondrial phospholipid dynamics and its interaction with proteins, ultimately leading to the dysfunction of this organelle. The regulation of phospholipid biosynthetic pathways might be seen as potential therapeutic targets for the management of cancer-related muscle wasting. PMID:24657703

  17. Advances in the neurorehabilitation of severe disorder of consciousness

    Directory of Open Access Journals (Sweden)

    Giuliano Dolce

    2014-09-01

    Full Text Available Introduction. The paper describes the evolution of knowledge concerning severe brain injury which determines the Vegetative State/Unresponsive Wakefulness Syndrome. Background. The term Vegetative State was proposed by Jennet and Plum in 1972. Later on, the Intensive Care Units progresses increased the survival of these patients and, contemporary, decreased their characteristic conditions of cachexia and severe dystonia. In 1994, the disease was conceived as a disconnection syndrome of the hemispheres from the brainstem, mainly due to a temporary or permanent deficit of the functions of the white matter. From 2005 on, the psychophysiological parameters relative to an emotional consciousness, albeit submerged, were described. Since then, it has been recognized that the brain of these patients was not only to be considered living but also working. Conclusion. The latest studies that have greatly improved the knowledge of the physiopathology of this particular state of consciousness. These new insights have led to the formation of a European Union Task Force, which has proposed in 2009 to change the name from a Vegetative State to Unresponsive Wakefulness Syndrome, outlining the character of syndrome and not that of state, as forms of even late recovery in consciousness levels have been observed and described.

  18. Clinical and Pathological Findings in Green Turtles (Chelonia mydas) from Gladstone, Queensland: Investigations of a Stranding Epidemic.

    Science.gov (United States)

    Flint, Mark; Eden, Paul A; Limpus, Colin J; Owen, Helen; Gaus, Caroline; Mills, Paul C

    2015-06-01

    An investigation into the health of green turtles was undertaken near Gladstone, Queensland, in response to a dramatic increase in stranding numbers in the first half of 2011. A total of 56 live turtles were subject to clinical examination and blood sampling for routine blood profiles, and 12 deceased turtles underwent a thorough necropsy examination. This population of green turtles was found to be in poor body condition and a range of infectious and non-infectious conditions were identified in the unhealthy turtles, including hepato-renal insufficiency (up to 81%, 27/33 based on clinical pathology), cachexia (92%, 11/12), parasitism (75%, 9/12), cardiopulmonary anomalies (42%, 5/12), gastroenteritis (25%, 3/12), masses (25%, 3/12) and mechanical impediments (17%, 2/12 based on necropsy). Overall, there was no evidence to indicate a unifying disease as a primary cause of the mass mortality. Recent adverse weather events, historic regional contamination and nearby industrial activities are discussed as potential causative factors. PMID:25256011

  19. Association of plasma hormones, nutritional status, and stressful life events in anorexia nervosa patients

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    Małgorzata Śmiarowska

    2014-02-01

    Full Text Available Objective: The aim of the current study was to analyze the relationships between plasma hormones, body weight parameters and stressful life events in anorexia nervosa (AN. Material and Methods: 72 females in the active phase of AN were evaluated. 52 healthy women constituted the control group. RIA kits were used to measure plasma hormone levels. Results: The concentrations of leptin, insulin, IGF-1, triiodothyronine, LH, FSH, estradiol, and testosterone were significantly lower and those of cortisol and growth hormone significantly higher in the AN than the control group. No hormonal differences between restrictive and binge-purging AN subtypes were found. Leptin, IGF-1, gonadotropins, and sex steroids correlated significantly negatively and growth hormone positively with total reduction of body weight or the degree of undernutrition. Associations were also found between lower insulin concentration and family violence, lower cortisol and psychiatric diseases in the family, higher testosterone and patient’s alcohol or drug abuse. Discussion: The changed activity of the somatotropin-somatomedin, gonadal, and corticotrophin axes corresponds to the clinical stage of AN. Plasma IGF-1 seems to be the most sensitive and useful independent hormonal marker of cachexia.

  20. Molecular imaging of brown adipose tissue in health and disease

    International Nuclear Information System (INIS)

    Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, 18F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to 18F-FDG, other radiopharmaceuticals such as 99mTc-sestamibi, 123I-metaiodobenzylguanidine (MIBG), 18F-fluorodopa and 18F-14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity. (orig.)

  1. Deletion variant near ZNF389 is associated with control of ovine lentivirus in multiple sheep flocks.

    Science.gov (United States)

    White, S N; Mousel, M R; Reynolds, J O; Herrmann-Hoesing, L M; Knowles, D P

    2014-04-01

    Ovine lentivirus (OvLV) is a macrophage-tropic lentivirus found in many countries that causes interstitial pneumonia, mastitis, arthritis and cachexia in sheep. There is no preventive vaccine and no cure, but breed differences suggest marker-assisted selective breeding might improve odds of infection and control of OvLV post-infection. Although variants in TMEM154 have consistent association with odds of infection, no variant in any gene has been associated with host control of OvLV post-infection in multiple animal sets. Proviral concentration is a live-animal diagnostic measure of OvLV control post-infection related to severity of OvLV-induced lesions. A recent genome-wide association study identified a region including four zinc finger genes associated with proviral concentration in one Rambouillet flock. To refine this region, we tested additional variants and identified a small insertion/deletion variant near ZNF389 that showed consistent association with proviral concentration in three animal sets (P sheep from multiple locations and management conditions. Strikingly, one flock had exceptionally high prevalence (>87%, including yearlings) and mean proviral concentration (>950 copies/μg), possibly due to needle sharing. The best estimate of proviral concentration by genotype, obtained from all 1310 OvLV-positive animals tested, showed insertion homozygotes had less than half the proviral concentration of other genotypes (P sheep flocks. PMID:24303974

  2. Cannabinoids: new promising agents in the treatment of neurological diseases.

    Science.gov (United States)

    Giacoppo, Sabrina; Mandolino, Giuseppe; Galuppo, Maria; Bramanti, Placido; Mazzon, Emanuela

    2014-01-01

    Nowadays, Cannabis sativa is considered the most extensively used narcotic. Nevertheless, this fame obscures its traditional employ in native medicine of South Africa, South America, Turkey, Egypt and in many regions of Asia as a therapeutic drug. In fact, the use of compounds containing Cannabis and their introduction in clinical practice is still controversial and strongly limited by unavoidable psychotropic effects. So, overcoming these adverse effects represents the main open question on the utilization of cannabinoids as new drugs for treatment of several pathologies. To date, therapeutic use of cannabinoid extracts is prescribed in patients with glaucoma, in the control of chemotherapy-related vomiting and nausea, for appetite stimulation in patients with anorexia-cachexia syndrome by HIV, and for the treatment of multiple sclerosis symptoms. Recently, researcher efforts are aimed to employ the therapeutic potentials of Cannabis sativa in the modulation of cannabinoid receptor activity within the central nervous system, particularly for the treatment of neurodegenerative diseases, as well as psychiatric and non-psychiatric disorders. This review evaluates the most recent available data on cannabinoids utilization in experimental and clinical studies, and highlights their beneficial effects in the prevention of the main neurological diseases and for the clinical treatment of symptoms with them correlated. PMID:25407719

  3. Cannabinoids: New Promising Agents in the Treatment of Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Sabrina Giacoppo

    2014-11-01

    Full Text Available Nowadays, Cannabis sativa is considered the most extensively used narcotic. Nevertheless, this fame obscures its traditional employ in native medicine of South Africa, South America, Turkey, Egypt and in many regions of Asia as a therapeutic drug. In fact, the use of compounds containing Cannabis and their introduction in clinical practice is still controversial and strongly limited by unavoidable psychotropic effects. So, overcoming these adverse effects represents the main open question on the utilization of cannabinoids as new drugs for treatment of several pathologies. To date, therapeutic use of cannabinoid extracts is prescribed in patients with glaucoma, in the control of chemotherapy-related vomiting and nausea, for appetite stimulation in patients with anorexia-cachexia syndrome by HIV, and for the treatment of multiple sclerosis symptoms. Recently, researcher efforts are aimed to employ the therapeutic potentials of Cannabis sativa in the modulation of cannabinoid receptor activity within the central nervous system, particularly for the treatment of neurodegenerative diseases, as well as psychiatric and non-psychiatric disorders. This review evaluates the most recent available data on cannabinoids utilization in experimental and clinical studies, and highlights their beneficial effects in the prevention of the main neurological diseases and for the clinical treatment of symptoms with them correlated.

  4. [Suspicion of anorexia nervosa as a cause of delayed diagnosis of brain tumor. A case report].

    Science.gov (United States)

    Niedzielska, Ewa; Węcławek-Tompol, Jadwiga; Kazanowska, Bernarda; Barg, Ewa

    2015-01-01

    Tumors of the central nervous system (CNS) are the most common solid tumors diagnosed in children. The most frequent symptoms of brain tumors in this age group are headaches and vomiting, regardless of the location of the lesions. These symptoms are non-specific, and in each case require differential diagnosis, especially if there is no gradual improvement in the patient's condition or progression. The most common signs of anorexia nervosa are chronic vomiting, weakness of the body, pain and in extreme cases cachexia. These symptoms are similar to the clinical image of CNS tumor. Teenager, described in our case report presented the following signs for several weeks prior to the diagnosis of a brain tumor: vomiting (especially after meals), non-specific headache and epigastric pain. No significant progression in the patient's condition oriented the diagnostic process towards anorexia nervosa. Although anorexia in this age group is much more common disease, compared to a brain tumor, it is vital to ruled out/ exclude organic disorders prior to diagnosis of psychogenic disorder. At the same time the waiting for the specialist consultations (ophthalmologist, neurologist) and test results (head CT, head NMR) should not prolong the patients referral to a specialist center. PMID:26615049

  5. Intravenous Mistletoe Treatment in Integrative Cancer Care: A Qualitative Study Exploring the Procedures, Concepts, and Observations of Expert Doctors

    Directory of Open Access Journals (Sweden)

    Gunver S. Kienle

    2016-01-01

    Full Text Available Background. Mistletoe therapy (MT is widely used in patient-centered integrative cancer care. The objective of this study was to explore the concepts, procedures, and observations of expert doctors, with a focus on intravenous MT. Method. A qualitative interview study was conducted with 35 highly experienced doctors specialized in integrative and anthroposophic medicine. Structured qualitative content analysis was applied. For triangulation, the results were compared with external evidence that was systematically collected, reviewed, and presented. Results. Doctors perform individualized patient assessments that lead to multimodal treatment approaches. The underlying goal is to help patients to live with and overcome disease. Mistletoe infusions are a means of accomplishing this goal. They are applied to stabilize disease, achieve responsiveness, induce fever, improve quality of life, and improve the tolerability of conventional cancer treatments. The doctors reported long-term disease stability and improvements in patients’ general condition, vitality, strength, thermal comfort, appetite, sleep, pain from bone metastases, dyspnea in pulmonary lymphangitis carcinomatosa, fatigue, and cachexia; chemotherapy was better tolerated. Also patients’ emotional and mental condition was reported to have improved. Conclusion. Individualized integrative cancer treatment including MT aims to help cancer patients to live well with their disease. Further research should investigate the reported observations.

  6. What do we really know about the ubiquitin-proteasome pathway in muscle atrophy?

    Science.gov (United States)

    Jagoe, R. T.; Goldberg, A. L.

    2001-01-01

    Studies of many different rodent models of muscle wasting have indicated that accelerated proteolysis via the ubiquitin-proteasome pathway is the principal cause of muscle atrophy induced by fasting, cancer cachexia, metabolic acidosis, denervation, disuse, diabetes, sepsis, burns, hyperthyroidism and excess glucocorticoids. However, our understanding about how muscle proteins are degraded, and how the ubiquitin-proteasome pathway is activated in muscle under these conditions, is still very limited. The identities of the important ubiquitin-protein ligases in skeletal muscle, and the ways in which they recognize substrates are still largely unknown. Recent in-vitro studies have suggested that one set of ubquitination enzymes, E2(14K) and E3(alpha), which are responsible for the 'N-end rule' system of ubiquitination, plays an important role in muscle, especially in catabolic states. However, their functional significance in degrading different muscle proteins is still unclear. This review focuses on the many gaps in our understanding of the functioning of the ubiquitin-proteasome pathway in muscle atrophy, and highlights the strengths and limitations of the different experimental approaches used in such studies.

  7. Effect of N-Terminal Acylation on the Activity of Myostatin Inhibitory Peptides.

    Science.gov (United States)

    Takayama, Kentaro; Nakamura, Akari; Rentier, Cédric; Mino, Yusaku; Asari, Tomo; Saga, Yusuke; Taguchi, Akihiro; Yakushiji, Fumika; Hayashi, Yoshio

    2016-04-19

    Inhibition of myostatin, which negatively regulates skeletal muscle growth, is a promising strategy for the treatment of muscle atrophic disorders, such as muscular dystrophy, cachexia and sarcopenia. Recently, we identified peptide A (H-WRQNTRYSRIEAIKIQILSKLRL-NH2 ), the 23-amino-acid minimum myostatin inhibitory peptide derived from mouse myostatin prodomain, and highlighted the importance of its N-terminal tryptophan residue for the effective inhibition. In this study, we synthesized a series of acylated peptide derivatives focused on the tryptophan residue to develop potent myostatin inhibitors. As a result of the investigation, a more potent derivative of peptide A was successfully identified in which the N-terminal tryptophan residue is replaced with a 2-naphthyloxyacetyl moiety to give an inhibitory peptide three times (1.19±0.11 μm) more potent than parent peptide A (3.53±0.25 μm). This peptide could prove useful as a new starting point for the development of improved inhibitory peptides. PMID:26954624

  8. Primary cranial mediastinal hemangiosarcoma in a young dog.

    Science.gov (United States)

    Yoon, Hun-Young; Kang, Hye-Mi; Lee, Mi-Young

    2014-01-01

    Primary cranial mediastinal hemangiosarcomas are uncommon tumors. A 30-kg, 2-year-old, intact female German shepherd was presented for evaluation of cachexia and respiratory distress of a few days' duration. Lateral radiographic projection of the thorax revealed significant pleural effusion. Computed tomography revealed a cranial mediastinal mass effect adjacent to the heart. On surgical exploration, a pedunculated mass attached to the esophagus, trachea, brachiocephalic trunk, left subclavian artery and cranial vena cava without attachment to the right atrium and auricular appendage was removed and debrided by use of blunt dissection and dry gauzes, respectively. Histopathology results described the cranial mediastinal mass as hemangiosarcoma. At 8 months and 5 days post-operatively, the patient died. Primary cranial mediastinal hemangiosarcomas, although a seemingly rare cause of thoracic pathology in young dogs, should be considered in the differential diagnosis for pleural effusion and soft tissue mass effect in the cranial mediastinum. This is the first case report in a dog to describe primary cranial mediastinal hemangiosarcoma. PMID:25089185

  9. Failure-to-thrive syndrome associated with tumor formation by Madin-Darby canine kidney cells in newborn nude mice.

    Science.gov (United States)

    Brinster, Lauren R; Omeir, Romelda L; Foseh, Gideon S; Macauley, Juliete N; Snoy, Philip J; Beren, Joel J; Teferedegne, Belete; Peden, Keith; Lewis, Andrew M

    2013-08-01

    Tumors that formed in newborn nude mice that were inoculated with 10(7) Madin-Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 10(2.8) to 10(7.5)); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor-derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases. PMID:24209967

  10. Adenocarcinoma of the small bowel

    International Nuclear Information System (INIS)

    Adenocarcinoma of small bowel is generally a rather rare primary tumour of small bowel with a prevalence rate of 0.5 - 3.0 / 100.000 population, but the most frequent tumour of small intestine. It more often involves the duodenum and jejunum than the ileum. The aim of this paper is also to point out the value of small bowel follow through (SBFT) in the diagnosis of stenosing lesions. An 83 - year old male patient suffered from abdominal pain, malaise, vomiting, cachexia and diarrhoea for 3 months. The result of occult blood testing was negative. Haemoglobin level was normal. Proctoscopy, colonoscopy, upper gastrointestinal (GI) endoscopy, and ultrasonography (US) did not explain the patient's problems. Ileus of the small bowel was established with abdominal plain film. Small bowel follow through (SBFT) and computer tomography (CT) showed a stenosing tumour in the jejunum. Adenocarcinoma of the small bowel was established with histological examination after resection of the tumor. SBFT, with manual compression of all segments of the small bowel, can be a very accurate diagnostic investigation for evaluation of stenosing lesions in this part of the intestine. (author)

  11. The Complex Role of Branched Chain Amino Acids in Diabetes and Cancer

    Directory of Open Access Journals (Sweden)

    Thomas M. O'Connell

    2013-10-01

    Full Text Available The obesity and diabetes epidemics are continuing to spread across the globe. There is increasing evidence that diabetes leads to a significantly higher risk for certain types of cancer. Both diabetes and cancer are characterized by severe metabolic perturbations and the branched chain amino acids (BCAAs appear to play a significant role in both of these diseases. These essential amino acids participate in a wide variety of metabolic pathways, but it is now recognized that they are also critical regulators of a number of cell signaling pathways. An elevation in branched chain amino acids has recently been shown to be significantly correlated with insulin resistance and the future development of diabetes. In cancer, the normal demands for BCAAs are complicated by the conflicting needs of the tumor and the host. The severe muscle wasting syndrome experience by many cancer patients, known as cachexia, has motivated the use of BCAA supplementation. The desired improvement in muscle mass must be balanced by the need to avoid providing materials for tumor proliferation. A better understanding of the complex functions of BCAAs could lead to their use as biomarkers of the progression of certain cancers in diabetic patients.

  12. Malakoplakia of the colon associated with colonic adenocarcinoma diagnosed in colonic biopsies

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Malakoplakia, typically involving the urinary tract, is an uncommon form of chronic inflammation caused by chronic nfections and characterized by accumulation of macrophages. It has also been found in many other sites such as the gastrointestinal tract, pancreas, liver, lymph Snodes, skin, respiratory tract, adrenal gland, vagina and brain. We present a case of a 64-year-old man referred to our hospital with cachexia and radiologic evidence of metastatic tumor of the liver.Colonoscopy revealed a large malignant-appearing polypoid mass of the ascending colon and multiple distinct polyps throughout the rest of the colon. Biopsies of the ascending colon mass confirmed the diagnosis of adenocarcinoma.Histological examination of two of the other polyps revealed malakoplakia which was characterized by aggregates of granular histiocytes with Michaelis-Gutmann bodies and histochemically confirmed with periodic acid-Schiff and von Kossa stains. This is a rare case diagnosed on endoscopic samples. The majority of reported cases were found in surgical specimens. In addition, the endoscopic appearance of multiple polyps is unusual in malakoplakia.

  13. Immunoproliferative Small Intestinal Disease Associated with Overwhelming Polymicrobial Gastrointestinal Infection with Transformation to Diffuse Large B-cell Lymphoma.

    Science.gov (United States)

    Ewers, Evan C; Sheffler, Robert L; Wang, James; Ngauy, Viseth

    2016-05-01

    Immunoproliferative small intestinal disease (IPSID) is an extra-nodal B-cell lymphoma most commonly described in the Mediterranean, Africa, and Asia. It is associated with poverty and poor sanitation, and is rarely encountered in developed countries. A 26-year-old previously healthy, Marshallese male was transferred to our facility with a 6-month history of watery diarrhea, weakness, and cachexia refractory to multiple short courses of oral antibiotics. Stool cultures grew Campylobacter jejuni and Vibrio fluvialis. Endoscopic evaluation showed histologic evidence of Helicobacter pylori gastritis and gross evidence of whipworm infection found in the colon. Mesenteric lymph node biopsy cultures grew Escherichia coli. Histopathology and immunohistochemical stains of the small intestine were consistent with IPSID. He subsequently transformed to diffuse large B-cell lymphoma (DLBCL) with tonsillar involvement despite treatment with rituximab and an extended course of antibiotics. Systemic chemotherapy with six cycles of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone, and lenalidomide, resulted in remission of his diffuse B cell lymphoma. This case is illustrative of IPSID developing in a previously healthy individual due to overwhelming polymicrobial gastrointestinal infection by C. jejuni and other enteric pathogens with subsequent transformation to an aggressive DLBCL. IPSID should be considered in residents of developing countries presenting with refractory chronic diarrhea, weight loss, and mesenteric lymphadenopathy. PMID:26903604

  14. [Huge dorsolumbar cold abscess associated with Pott's disease].

    Science.gov (United States)

    Rakotoson, J L; Rakotomizao, J R; Andrianarisoa, A C F

    2010-12-01

    Pott's disease, or tuberculosis of the spine, is the most common osteoarticular tuberculosis. Among them, dorsolumbar impairment is predominant. The authors report the case of a patient with a huge cold lumbar abscess associated with Pott's disease. The patient is a 32-year-old man presenting dorsolumbar tumefaction associated with an alteration in his general condition and fever for three months. Treatment by "traditional healers" did not provide any improvement. He consulted for mild lumbar pain triggered by fatigue appearing one week before and after the failure of the traditional practitioner. The clinical examination found a temperature of 38.5°C, cachexia, mild lumber kyphosis and impressive, soft, painless and non inflammatory dorsolumbar bruised tumefaction, 40 cm high, 15 cm wide and 7 cm deep. He did not present any neurological signs. The dorsolumbar X-ray of the spine revealed a lesion associated with Pott's disease in the first and second lumbar vertebrae with pinching of the disc, punched-out lesions and osteocondensation. The ultrasound examination of the soft tissue revealed the presence of a laterovertebral collection of fluid diffusing in the subcutaneous region. The psoas major and the paravertebral muscles were not affected. A scan or MRI of the spine was not carried out. Examination of the tissue sample and drainage of the abscess confirmed the tubercular origin. Treatment with tuberculostatic drugs for 12 months associated with immobilisation resulted in a cure with sequelae of mild kyphoscoliosis vertebral statics. PMID:21167445

  15. Physical activity counteracts tumor cell growth in colon carcinoma C26-injected muscles: an interim report

    Directory of Open Access Journals (Sweden)

    Charlotte Hiroux

    2016-06-01

    Full Text Available Skeletal muscle tissue is a rare site of tumor metastasis but is the main target of the degenerative processes occurring in cancer-associated cachexia syndrome. Beneficial effects of physical activity in counteracting cancer-related muscle wasting have been described in the last decades. Recently it has been shown that, in tumor xeno-transplanted mouse models, physical activity is able to directly affect tumor growth by modulating inflammatory responses in the tumor mass microenvironment. Here, we investigated the effect of physical activity on tumor cell growth in colon carcinoma C26 cells injected tibialis anterior muscles of BALB/c mice. Histological analyses revealed that 4 days of voluntary wheel running significantly counteracts tumor cell growth in C26-injected muscles compared to the non-injected sedentary controls. Since striated skeletal muscle tissue is the site of voluntary contraction, our results confirm that physical activity can also directly counteract tumor cell growth in a metabolically active tissue that is usually not a target for metastasis.

  16. Pulmonary Kaposi sarcoma and disseminated Mycobacterium genavense infection in an HIV-infected patient.

    Science.gov (United States)

    Tribuna, Cindy; Ângela, Cristina; Eira, Isabel; Carvalho, Alexandre

    2015-01-01

    We report a case of Kaposi sarcoma (KS) and disseminated infection by Mycobacterium genavense in a 40-year-old HIV-positive man with CD4+ T-cell count 5/µL. He presented with anorexia, diarrhoea, cachexia and multiple firm violaceous nodules distributed over the face, neck and upper and lower extremities. Biopsy of a skin nodule was performed, confirming KS. Immunoperoxidase staining for human herpesvirus 8 was strongly positive. Endoscopic examination revealed erosive duodenopathy. Multiple biopsy samples showed numerous acid-fast bacilli at direct microscopic examination. Real-time PCR (RT-PCR) identified M. genavense. A CT scan showed diffuse pulmonary infiltrates with a 'tree-in-bud' appearance, striking splenomegaly and abdominal lymphadenopathy. A bronchoscopy was performed, revealing typical Kaposi's lesions in the upper respiratory tract. RT-PCR of bronchial aspirate identified M. genavense and Pneumocystis jirovecii. Despite treatment with highly active antiretroviral therapy, antimycobacterial therapy and trimethoprim/sulfamethoxazole, the outcome was fatal. PMID:26452414

  17. LY293111 Improves Efficacy of Gemcitabine Therapy on Pancreatic Cancer in a Fluorescent Orthotopic Model in Athymic Mice

    Directory of Open Access Journals (Sweden)

    Rene Hennig

    2005-04-01

    Full Text Available Pancreatic cancer has an abysmal prognosis because of late diagnosis and lack of effective therapeutics. New drugs are desperately needed. The present study determined the effect of the LTB4 receptor antagonist, LY293111, on tumor growth and metastases in a fluorescent orthotopic model of pancreatic cancer. Pancreatic cancer cells (S2-013 with stable expression of enhanced green fluorescent protein were implanted into the duodenal pancreatic lobe of athymic mice. Animals were allocated to four groups (eight mice per group: control (no treatment; LY293111; gemcitabine; and LY293111 + gemcitabine. Monitoring of the surgical procedure and follow-up examinations at 2, 3, and 4 weeks after implantation to monitor tumor growth and metastases were performed using a fluorescence microscope and the reversible skin-flap technique. A staging and scoring system was developed to evaluate tumor progression, based on the TNM classification. Control animals developed end-stage disease with invasive cancer, metastases, and cachexia. Tumor growth and incidence of metastases were significantly reduced in all treated mice. However, combined treatment with LY293111 and gemcitabine was most effective. LY293111 is a novel therapeutic agent for pancreatic cancer, which improves the efficacy of gemcitabine. It is well tolerated and can be administered orally and, therefore, provides a new hope for patients suffering from pancreatic adenocarcinoma.

  18. Gastrointestinal motility disorders in patients with anorexia nervosa – a review of the literature

    Directory of Open Access Journals (Sweden)

    Katarzyna Agnieszka Weterle- Smolińska

    2015-08-01

    Full Text Available Anorexia nervosa is a disease carrying havoc on many levels of the body functioning. The presence of numerous somatic complications as a consequence of starvation is an important part of the clinical picture of this disease. Symptoms of the gastrointestinal tract are one of the most common complaints reported by patients, especially in the initial period of realimentation. Most common symptoms are associated with gastrointestinal motility disorders. The available data show that as many as half of patients suffering from anorexia nervosa manifest significant gastrointestinal motility disorders (incomplete relaxation of the upper and lower oesophageal sphincter, impaired compliance of the stomach, delayed gastric emptying, intestinal transit extension, decreased motility of the rectum and anus. These disorders along with gastrointestinal tract ailments may impede the restoration of proper diet, if not detected early and treated. There are relatively few studies on gastrointestinal motility disorders in patients suffering from anorexia nervosa, which do not clearly answer the question whether these disorders are genetic, or result from cachexia and whether they disappear along with the restoration of the normal body weight. No reference of research results to the clinical practice, and the lack of standard procedures for diagnosis and treatment of gastrointestinal disorders in patients with anorexia nervosa are significant problems for specialists in the field of psychiatry and gastroenterology.

  19. Novel Approaches to the Diagnosis of Sarcopenia.

    Science.gov (United States)

    Edwards, Mark H; Buehring, Bjoern

    2015-01-01

    Sarcopenia is common in older people and is associated with disability, reduced mobility, hospitalization, and various comorbidities. Although it has been recognized for over a quarter of a century, we do not currently have a universally adopted definition. This limits our ability to compare results from different studies and impedes the development of novel therapies. Although sarcopenia was initially defined purely based on low muscle mass, the importance of measures of muscle function has been realized and these have been included in recent operational definitions. These continue to evolve with some including an assessment of adiposity and others adding further components of musculoskeletal health in a score-based approach. This review describes the importance of reaching a widely accepted method to define sarcopenia in both research and clinical practice. It details the ways in which the definition has changed since its initial inception and explores how it may continue to evolve in the future. The different methods by which components of sarcopenia can be measured are described, and the various advantages and disadvantages of these techniques are evaluated. Clearly, there are several other similar syndromes in older people, such as frailty and cachexia; their relationships and overlap with sarcopenia are also explored. PMID:26059568

  20. Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome.

    Directory of Open Access Journals (Sweden)

    Ingrid van der Pluijm

    2007-01-01

    Full Text Available Cockayne syndrome (CS is a photosensitive, DNA repair disorder associated with progeria that is caused by a defect in the transcription-coupled repair subpathway of nucleotide excision repair (NER. Here, complete inactivation of NER in Csb(m/m/Xpa(-/- mutants causes a phenotype that reliably mimics the human progeroid CS syndrome. Newborn Csb(m/m/Xpa(-/- mice display attenuated growth, progressive neurological dysfunction, retinal degeneration, cachexia, kyphosis, and die before weaning. Mouse liver transcriptome analysis and several physiological endpoints revealed systemic suppression of the growth hormone/insulin-like growth factor 1 (GH/IGF1 somatotroph axis and oxidative metabolism, increased antioxidant responses, and hypoglycemia together with hepatic glycogen and fat accumulation. Broad genome-wide parallels between Csb(m/m/Xpa(-/- and naturally aged mouse liver transcriptomes suggested that these changes are intrinsic to natural ageing and the DNA repair-deficient mice. Importantly, wild-type mice exposed to a low dose of chronic genotoxic stress recapitulated this response, thereby pointing to a novel link between genome instability and the age-related decline of the somatotroph axis.

  1. Key Roles of Glutamine Pathways in Reprogramming the Cancer Metabolism

    Science.gov (United States)

    Michalak, Krzysztof Piotr; Maćkowska-Kędziora, Agnieszka; Sobolewski, Bogusław; Woźniak, Piotr

    2015-01-01

    Glutamine (GLN) is commonly known as an important metabolite used for the growth of cancer cells but the effects of its intake in cancer patients are still not clear. However, GLN is the main substrate for DNA and fatty acid synthesis. On the other hand, it reduces the oxidative stress by glutathione synthesis stimulation, stops the process of cancer cachexia, and nourishes the immunological system and the intestine epithelium, as well. The current paper deals with possible positive effects of GLN supplementation and conditions that should be fulfilled to obtain these effects. The analysis of GLN metabolism suggests that the separation of GLN and carbohydrates in the diet can minimize simultaneous supply of ATP (from glucose) and NADPH2 (from glutamine) to cancer cells. It should support to a larger extent the organism to fight against the cancer rather than the cancer cells. GLN cannot be considered the effective source of ATP for cancers with the impaired oxidative phosphorylation and pyruvate dehydrogenase inhibition. GLN intake restores decreased levels of glutathione in the case of chemotherapy and radiotherapy; thus, it facilitates regeneration processes of the intestine epithelium and immunological system. PMID:26583064

  2. Effect of a high-intensity exercise training on the metabolism and function of macrophages and lymphocytes of walker 256 tumor bearing rats.

    Science.gov (United States)

    Bacurau, Aline Villa Nova; Belmonte, Mônica Aparecida; Navarro, Francisco; Moraes, Milton Rocha; Pontes, Francisco Luciano; Pesquero, Jorge Luiz; Araújo, Ronaldo Carvalho; Bacurau, Reury Frank Pereira

    2007-11-01

    Epidemiologic studies suggest that moderately intense training promotes augmented immune function, whereas strenuous exercise can cause immunosupression. Because the combat of cancer requires high immune function, high-intensity exercise could negatively affect the host organism; however, despite the epidemiologic data, there is a lack of experimental evidence to show that high-intensity training is harmful to the immune system. Therefore, we tested the influence of high-intensity treadmill training (10 weeks, 5 days/week, 30 mins/day, 85% VO(2)max) on immune system function and tumor development in Walker 256 tumor-bearing Wistar rats. The metabolism of glucose and glutamine in lymphocytes and macrophages was assessed, in addition to some functional parameters such as hydrogen peroxide production, phagocytosis, and lymphocyte proliferative responses. The metabolism of Walker 256 cells was also investigated. Results demonstrated that high-intensity training increased the life span of tumor-bearing rats, promoted a reduction in tumor mass, and prevented indicators of cachexia. Several changes, such as a reduction in body weight and food intake and activation of glutamine metabolism in macrophages and lymphocytes induced by the presence of Walker 256 tumor, were prevented by high intensity training. The reduction in tumor growth was associated with an impairment of tumor cell glucose and glutamine metabolism. These data suggest that high-intensity exercise training may be a viable strategy against tumors. PMID:17959841

  3. Evaluation of a rabbit rectal VX2 carcinoma model using computed tomography and magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Xin-Mei Liang; Guang-Yu Tang; Ying-Sheng Cheng; Bi Zhou

    2009-01-01

    AIM: To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma. METHODS: A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to observe tumor growth and metastasis at different phases. Pathological changes and spontaneous survival time of the rabbits were recorded. RESULTS: Two weeks after VX2 cell implantation, the tumor diameter ranged 4.1-5.8 mm and the success implantation rate was 81.8%. CT scanning showed low-density foci of the tumor in the rectum wall, while enhanced CT scanning demonstrated asymmetrical intensification in tumor foci. MRI scanning showed a low signal of the tumor on T1-weighted imaging and a high signal of the tumor on T2-weighted imaging. Both types of signals were intensified with enhanced MRI. Metastases to the liver and lung could be observed 6 wk after VX2 cell implantation, and a large area of necrosis appeared in the primary tumor. The spontaneous survival time of rabbits with cachexia and multiple organ failure was about 7 wk after VX2 cell implantation. CONCLUSION: The rabbit rectal VX2 carcinoma model we established has a high stability, and can be used in the study of rectal carcinoma.

  4. Clinical features of human intestinal capillariasis in Taiwan

    Institute of Scientific and Technical Information of China (English)

    Ming-Jong Bair; Kao-Pin Hwang; Tsang-En Wang; Tai-Cherng Liou; Shee-Chan Lin; Chin-Roa Kao; Tao-Yeuan Wang; Kwok-Kuen Pang

    2004-01-01

    Human intestinal capillariasis is a rare parasitosis that was first recognized in the Philippines in the 1960 s. Parasitosis is a life threatening disease and has been reported from Thailand, Japan, South of Taiwan (Kaoh-Siung), Korea,Tran, Egypt, Italy and Spain. Its clinical symptoms are characterized by chronic diarrhea, abdominal pain,borborygmus, marked weight loss, protein and electrolyte loss and cachexia. Capillariasis may be fatal if early treatment is not given. We reported 14 cases living in rural areas of Taiwan. Three cases had histories of travelling to Thailand. They might have been infected in Thailand while stayed there. Two cases had the diet of raw freshwater fish before. Three cases received emergency laparotomy due to peritonitis and two cases were found of enteritis cystica profunda. According to the route of transmission,freshwater and brackish-water fish may act as the intermediate host of the parasite. The most simple and convenient method of diagnosing capillariasis is stool examination. Two cases were diagnosed by histology.Mebendazole or albendezole 200 mg orally twice a day for 20-30 d is the treatment of choice. All the patients were cured, and relapses were not observed within 12 mo.

  5. Narrative review of the safety and efficacy of marijuana for the treatment of commonly state-approved medical and psychiatric disorders.

    Science.gov (United States)

    Belendiuk, Katherine A; Baldini, Lisa L; Bonn-Miller, Marcel O

    2015-01-01

    The present investigation aimed to provide an objective narrative review of the existing literature pertaining to the benefits and harms of marijuana use for the treatment of the most common medical and psychological conditions for which it has been allowed at the state level. Common medical conditions for which marijuana is allowed (i.e., those conditions shared by at least 80 percent of medical marijuana states) were identified as: Alzheimer's disease, amyotrophic lateral sclerosis, cachexia/wasting syndrome, cancer, Crohn's disease, epilepsy and seizures, glaucoma, hepatitis C virus, human immunodeficiency virus/acquired immunodeficiency syndrome, multiple sclerosis and muscle spasticity, severe and chronic pain, and severe nausea. Post-traumatic stress disorder was also included in the review, as it is the sole psychological disorder for which medical marijuana has been allowed. Studies for this narrative review were included based on a literature search in PsycINFO, MEDLINE, and Google Scholar. Findings indicate that, for the majority of these conditions, there is insufficient evidence to support the recommendation of medical marijuana at this time. A significant amount of rigorous research is needed to definitively ascertain the potential implications of marijuana for these conditions. It is important for such work to not only examine the effects of smoked marijuana preparations, but also to compare its safety, tolerability, and efficacy in relation to existing pharmacological treatments. PMID:25896576

  6. Adrenal metastasis as first presentation of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Zacharakis Evangelos

    2005-07-01

    Full Text Available Abstract Background Metastases from hepatocellular carcinoma (HCC can be found in the lung and adrenal gland. We report case of a patient who presented with adrenal metastasis as the first clinical manifestation of HCC. Case presentation A patient was referred for surgical treatment for a tumor in retro-peritoneal space. The computerized tomography (CT scan revealed a mass originating from the left adrenal gland. The patient underwent left adrenalectomy and the exploration of abdominal cavity did not reveal any other palpable lesions. Histologically, the resected lesion was a poorly differentiated metastatic tumor from HCC. Seven months later patient was readmitted complaining of cachexia, icterus, and significant weight loss. CT scan revealed hyperdense lesions of the liver Conclusion HCC may have atypical presentations like in present case. Fine needle aspiration/tru-cut® biopsy might be useful in the investigation of an accidentally discovered adrenal mass regardless of the size and can lead to the detection of a primary tumor.

  7. Oral Administration of Aloe vera (L.) Burm. f. (Xanthorrhoeaceae) and Honey Improves the Host Body Composition and Modulates Proteolysis Through Reduction of Tumor Progression and Oxidative Stress in Rats.

    Science.gov (United States)

    Tomasin, Rebeka; de Andrade, Rafael Siqueira; Gomes-Marcondes, Maria Cristina Cintra

    2015-10-01

    Oxidative stress has a dual role in cancer; it is linked with tumorigenic events and host wasting, as well as senescence and apoptosis. Researchers have demonstrated the importance of coadjuvant therapies in cancer treatment, and Aloe vera and honey have immunomodulatory, anticancer, and antioxidant properties. The preventive and therapeutic effects of Aloe vera (L.) Burm. f. (Xanthorrhoeaceae) and honey in tumor progression and host wasting were analyzed in Walker 256 carcinoma-bearing rats. The animals were distributed into the following groups: C=control-untreated, W=tumor-untreated, WA=treated after tumor induction, A=control-treated, AW=treated before tumor induction, and AWA=treated before and after tumor induction. Proteolysis and oxidative stress were analyzed in the tumor, liver, muscle, and myocardial tissues. The results suggest that the Aloe vera and honey treatment affect the tumor and host by different mechanisms; the treatment-modulated host wasting and cachexia, whereas it promoted oxidative stress and damage in tumor tissues, particularly in a therapeutic context (WA). PMID:25856497

  8. Emergence of co-infection of visceral leishmaniasis in HIV-positive patients in northeast Iran: a preliminary study.

    Science.gov (United States)

    Shafiei, Reza; Mohebali, Mehdi; Akhoundi, Behnaz; Galian, Meysam Sharifdini; Kalantar, Fathollah; Ashkan, Saeedeh; Fata, Abdolmajid; Farash, Bibi Razieh Hosseini; Ghasemian, Mehrdad

    2014-01-01

    Visceral leishmaniasis (VL) serosurvey was carried out on 49 HIV/AIDS patients among 500 asymptomatic HIV/infected patients who registered in the Khorasan Razavi Province during the last 14 years. HIV infections were detected by ELISA and confirmed using western blot assay at the AIDS centre of the Khorasan Razavi Province. All collected sera were screened using the direct agglutination test (DAT). The sera with anti-Leishmania infantum antibodies at a titre of 1:100 were considered positive for VL infection and serum titration was performed from 1:100 to 1:102,400. Nine (18.4%) patients were sero-positive according to DAT. The distribution of sera titrations were as follows: 1:100 (n = 6) 1:1600 (n = 1); 1:25,600 (n = 1) and 1:102,400 (n = 1). All sero-positive cases showed clinical signs and symptoms. The most predominant signs and symptoms of co-infection of visceral leishmaniasis in HIV-positive patients were pneumonia (n = 2), hepatosplenomegaly (n = 2), lymphadenopathy (n = 2), anaemia (n = 1), prolonged fever (n = 1) and cachexia (n = 1). Our finding shows that VL (or kala-azar) is an opportunistic disease in HIV-positive patients that may be occurred in VL endemic areas of Iran. PMID:24100200

  9. MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity

    Science.gov (United States)

    Moretti, Irene; Ciciliot, Stefano; Dyar, Kenneth A.; Abraham, Reimar; Murgia, Marta; Agatea, Lisa; Akimoto, Takayuki; Bicciato, Silvio; Forcato, Mattia; Pierre, Philippe; Uhlenhaut, N. Henriette; Rigby, Peter W. J.; Carvajal, Jaime J.; Blaauw, Bert; Calabria, Elisa; Schiaffino, Stefano

    2016-01-01

    The myogenic regulatory factor MRF4 is highly expressed in adult skeletal muscle but its function is unknown. Here we show that Mrf4 knockdown in adult muscle induces hypertrophy and prevents denervation-induced atrophy. This effect is accompanied by increased protein synthesis and widespread activation of muscle-specific genes, many of which are targets of MEF2 transcription factors. MEF2-dependent genes represent the top-ranking gene set enriched after Mrf4 RNAi and a MEF2 reporter is inhibited by co-transfected MRF4 and activated by Mrf4 RNAi. The Mrf4 RNAi-dependent increase in fibre size is prevented by dominant negative MEF2, while constitutively active MEF2 is able to induce myofibre hypertrophy. The nuclear localization of the MEF2 corepressor HDAC4 is impaired by Mrf4 knockdown, suggesting that MRF4 acts by stabilizing a repressor complex that controls MEF2 activity. These findings open new perspectives in the search for therapeutic targets to prevent muscle wasting, in particular sarcopenia and cachexia. PMID:27484840

  10. Taurine Rescues Cisplatin-Induced Muscle Atrophy In Vitro: A Morphological Study

    Directory of Open Access Journals (Sweden)

    Alessandra Stacchiotti

    2014-01-01

    Full Text Available Cisplatin (CisPt is a widely used chemotherapeutic drug whose side effects include muscle weakness and cachexia. Here we analysed CisPt-induced atrophy in C2C12 myotubes by a multidisciplinary morphological approach, focusing on the onset and progression of autophagy, a protective cellular process that, when excessively activated, may trigger protein hypercatabolism and atrophy in skeletal muscle. To visualize autophagy we used confocal and transmission electron microscopy at different times of treatment and doses of CisPt. Moreover we evaluated the effects of taurine, a cytoprotective beta-amino acid able to counteract oxidative stress, apoptosis, and endoplasmic reticulum stress in different tissues and organs. Our microscopic results indicate that autophagy occurs very early in 50 μM CisPt challenged myotubes (4 h–8 h before overt atrophy but it persists even at 24 h, when several autophagic vesicles, damaged mitochondria, and sarcoplasmic blebbings engulf the sarcoplasm. Differently, 25 mM taurine pretreatment rescues the majority of myotubes size upon 50 μM CisPt at 24 h. Taurine appears to counteract atrophy by restoring regular microtubular apparatus and mitochondria and reducing the overload and the localization of autophagolysosomes. Such a promising taurine action in preventing atrophy needs further molecular and biochemical studies to best define its impact on muscle homeostasis and the maintenance of an adequate skeletal mass in vivo.

  11. Marijuana Legalization: Impact on Physicians and Public Health.

    Science.gov (United States)

    Wilkinson, Samuel T; Yarnell, Stephanie; Radhakrishnan, Rajiv; Ball, Samuel A; D'Souza, Deepak Cyril

    2016-01-01

    Marijuana is becoming legal in an increasing number of states for both medical and recreational use. Considerable controversy exists regarding the public health impact of these changes. The evidence for the legitimate medical use of marijuana or cannabinoids is limited to a few indications, notably HIV/AIDS cachexia, nausea/vomiting related to chemotherapy, neuropathic pain, and spasticity in multiple sclerosis. Although cannabinoids show therapeutic promise in other areas, robust clinical evidence is still lacking. The relationship between legalization and prevalence is still unknown. Although states where marijuana use is legal have higher rates of use than nonlegal states, these higher rates were generally found even prior to legalization. As states continue to proceed with legalization for both medical and recreational use, certain public health issues have become increasingly relevant, including the effects of acute marijuana intoxication on driving abilities, unintentional ingestion of marijuana products by children, the relationship between marijuana and opioid use, and whether there will be an increase in health problems related to marijuana use, such as dependence/addiction, psychosis, and pulmonary disorders. In light of this rapidly shifting legal landscape, more research is urgently needed to better understand the impact of legalization on public health. PMID:26515984

  12. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    International Nuclear Information System (INIS)

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis

  13. ITA-MNGIE: an Italian regional and national survey for mitochondrial neuro-gastro-intestinal encephalomyopathy.

    Science.gov (United States)

    D'Angelo, Roberto; Rinaldi, Rita; Carelli, Valerio; Boschetti, Elisa; Caporali, Leonardo; Capristo, Mariantonietta; Casali, Carlo; Cenacchi, Giovanna; Gramegna, Laura Ludovica; Lodi, Raffaele; Pinna, Antonio Daniele; Pironi, Loris; Stanzani, Marta; Tonon, Caterina; D'Alessandro, Roberto; De Giorgio, Roberto

    2016-07-01

    Mitochondrial neuro-gastro-intestinal encephalomyopathy (MNGIE) is a rare and unavoidably fatal disease due to mutations in thymidine phosphorylase (TP). Clinically it is characterized by gastrointestinal dysfunction, malnutrition/cachexia and neurological manifestations. MNGIE diagnosis remains a challenge mainly because of the complexity and rarity of the disease. Thus, our purposes were to promote a better knowledge of the disease in Emilia-Romagna region (ERR) by creating an accurate and dedicated network; to establish the minimal prevalence of MNGIE in Italy starting from ERR. Blood TP activity level was used as screening test to direct candidates to complete diagnostic work-up. During the study period of 1 year, only 10/71 units of ERR recruited 14 candidates. Their screening did not show TP activity changes. An Italian patient not resident in ERR was actually proved to have MNGIE. At the end of study in Italy there were nine cases of MNGIE; thus, the Italian prevalence of the disease is ~0.15/1,000,000 as a gross estimation. Our study confirms that MNGIE diagnosis is a difficult process which reflects the rarity of the disease and, as a result, a low level of awareness among specialists and physicians. Having available novel therapeutic options (e.g., allogenic hematopoietic stem cell transplantation and, more recently, liver transplantation) and an easy screening test, an early diagnosis should be sought before tissue damage occurs irreversibly. PMID:27007276

  14. Causes of mortality in green turtles from Hawaii and the insular Pacific exclusive of fibropapillomatosis

    Science.gov (United States)

    Work, Thierry M.; Balazs, George H.; Summers, Tammy M.; Hapdei, Jessy R.; Tagarino, Alden P.

    2015-01-01

    Fibropapillomatosis (FP) comprises a majority of green turtle stranding in Hawaii; however, green turtles in the Pacific are also susceptible to non-FP related causes of death. We present here necropsy findings from 230 free-ranging green turtles originating from Hawaii, the Mariana archipelago, Palmyra Atoll, American Samoa, and Johnston Atoll that died from non-FP related causes. Most turtles died from fishing-induced or boat strike trauma followed by infectious/inflammatory diseases, nutritional problems (mainly cachexia), and an array of physiologic problems. Infectious/inflammatory problems included bacterial diseases of the lungs, eyes, liver or intestines, spirorchid fluke infection, or polyarthritis of unknown origin. Likelihood of a successful diagnosis of cause of death was a function of post-mortem decomposition. Fibropapillomatosis was not seen in turtles submitted from outside Hawaii. The preponderance of anthropogenic causes of mortality offers some management opportunities to mitigate causes of death in these animals by, for example, implementing measures to decrease boating and fishing interactions.

  15. Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

    International Nuclear Information System (INIS)

    Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C2C12 muscle cells. WF decreased the viability of C2C12 myotubes, especially at concentrations of 20–25 μg.mL-1. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model

  16. [Bilateral phrenic nerve paralysis, dysautonomia and restrictive cardiomyopathy in a case of POEMS syndrome].

    Science.gov (United States)

    Delalande, S; Stojkovic, T; Rose, C; Millaire, A; Hurtevent, J F; Vermersch, P

    2002-07-01

    We report a case of POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M protein and Skin changes) with unusual clinical features. A 62-year-old woman presented a severe polyneuropathy with dysphonia and vegetative symptoms, including bradycardia and sphincterial disorders. The clinical examination showed facial hyperpigmentation, cachexia, anasarca and splenomegaly. She also presented restrictive cardiomyopathy and endocrine disturbances. Nerve conduction studies revealed a severe demyelinating sensorimotor neuropathy. Cerebrospinal fluid analysis showed an elevated protein level. We detected a biclonal gammapathy (Ig G and Ig A with lambda light chain) and lytic pelvic bone lesions. Later, she developed a severe ventilatory failure due to a bilateral phrenic nerve paralysis leading to a mechanical ventilation. Steroids followed by localized radiotherapy partially improved the respiratory status and stabilized the neuropathy. Phrenic nerve paralysis, restrictive cardiomyopathy, vegetative symptoms and cranial nerve palsy are exceptional in POEMS syndrome. Moreover, this case emphasizes the importance of radiological investigations since the discover of plasmocytoma may improve the prognosis of POEMS syndrome. PMID:12486906

  17. Molecular events and signalling pathways involved in skeletal muscle disuse-induced atrophy and the impact of countermeasures.

    Science.gov (United States)

    Chopard, Angèle; Hillock, Steven; Jasmin, Bernard J

    2009-09-01

    Disuse-induced skeletal muscle atrophy occurs following chronic periods of inactivity such as those involving prolonged bed rest, trauma and microgravity environments. Deconditioning of skeletal muscle is mainly characterized by a loss of muscle mass, decreased fibre cross-sectional area, reduced force, increased fatigability, increased insulin resistance and transitions in fibre types. A description of the role of specific transcriptional mechanisms contributing to muscle atrophy by altering gene expression during muscle disuse has recently emerged and focused primarily on short period of inactivity. A better understanding of the transduction pathways involved in activation of proteolytic and apoptotic pathways continues to represent a major objective, together with the study of potential cross-talks in these cellular events. In parallel, evaluation of the impact of countermeasures at the cellular and molecular levels in short- and long-term disuse experimentations or microgravity environments should undoubtedly and synergistically increase our basic knowledge in attempts to identify new physical, pharmacological and nutritional targets to counteract muscle atrophy. These investigations are important as skeletal muscle atrophy remains an important neuromuscular challenge with impact in clinical and social settings affecting a variety of conditions such as those seen in aging, cancer cachexia, muscle pathologies and long-term space exploration. PMID:19656243

  18. Therapeutic approaches for muscle wasting disorders.

    Science.gov (United States)

    Lynch, Gordon S; Schertzer, Jonathan D; Ryall, James G

    2007-03-01

    Muscle wasting and weakness are common in many disease states and conditions including aging, cancer cachexia, sepsis, denervation, disuse, inactivity, burns, HIV-acquired immunodeficiency syndrome (AIDS), chronic kidney or heart failure, unloading/microgravity, and muscular dystrophies. Although the maintenance of muscle mass is generally regarded as a simple balance between protein synthesis and protein degradation, these mechanisms are not strictly independent, but in fact they are coordinated by a number of different and sometimes complementary signaling pathways. Clearer details are now emerging about these different molecular pathways and the extent to which these pathways contribute to the etiology of various muscle wasting disorders. Therapeutic strategies for attenuating muscle wasting and improving muscle function vary in efficacy. Exercise and nutritional interventions have merit for slowing the rate of muscle atrophy in some muscle wasting conditions, but in most cases they cannot halt or reverse the wasting process. Hormonal and/or other drug strategies that can target key steps in the molecular pathways that regulate protein synthesis and protein degradation are needed. This review describes the signaling pathways that maintain muscle mass and provides an overview of some of the major conditions where muscle wasting and weakness are indicated. The review provides details on some therapeutic strategies that could potentially attenuate muscle atrophy, promote muscle growth, and ultimately improve muscle function. The emphasis is on therapies that can increase muscle mass and improve functional outcomes that will ultimately lead to improvement in the quality of life for affected patients. PMID:17258813

  19. MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity.

    Science.gov (United States)

    Moretti, Irene; Ciciliot, Stefano; Dyar, Kenneth A; Abraham, Reimar; Murgia, Marta; Agatea, Lisa; Akimoto, Takayuki; Bicciato, Silvio; Forcato, Mattia; Pierre, Philippe; Uhlenhaut, N Henriette; Rigby, Peter W J; Carvajal, Jaime J; Blaauw, Bert; Calabria, Elisa; Schiaffino, Stefano

    2016-01-01

    The myogenic regulatory factor MRF4 is highly expressed in adult skeletal muscle but its function is unknown. Here we show that Mrf4 knockdown in adult muscle induces hypertrophy and prevents denervation-induced atrophy. This effect is accompanied by increased protein synthesis and widespread activation of muscle-specific genes, many of which are targets of MEF2 transcription factors. MEF2-dependent genes represent the top-ranking gene set enriched after Mrf4 RNAi and a MEF2 reporter is inhibited by co-transfected MRF4 and activated by Mrf4 RNAi. The Mrf4 RNAi-dependent increase in fibre size is prevented by dominant negative MEF2, while constitutively active MEF2 is able to induce myofibre hypertrophy. The nuclear localization of the MEF2 corepressor HDAC4 is impaired by Mrf4 knockdown, suggesting that MRF4 acts by stabilizing a repressor complex that controls MEF2 activity. These findings open new perspectives in the search for therapeutic targets to prevent muscle wasting, in particular sarcopenia and cachexia. PMID:27484840

  20. Cancer cell: using inflammation to invade the host

    Directory of Open Access Journals (Sweden)

    Aller María-Angeles

    2007-04-01

    Full Text Available Abstract Background Inflammation is increasingly recognized as an important component of tumorigenesis, although the mechanisms involved are not fully characterized. The invasive capacity of cancers is reflected in the classic metastatic cascade: tumor (T, node (N and metastasis (M. However, this staging system for cancer would also have a tumoral biological significance. Presentation of the hypothesis To integrate the mechanisms that control the inflammatory response in the actual staging system of cancer. It is considered that in both processes of inflammation and cancer, three successive phenotypes are presented that represent the expression of trophic functional systems of increasing metabolic complexity for using oxygen. Testing the hypothesis While a malignant tumor develops it express phenotypes that also share the inflammatory response such as: an ischemic phenotype (anoxic-hypoxic, a leukocytic phenotype with anaerobic glycolysis and migration, and an angiogenic phenotype with hyperactivity of glycolytic enzymes, tumor proliferation and metastasis, and cachexia of the host. The increasing metabolic complexity of the tumor cell to use oxygen allows for it to be released, migrate and proliferate, thus creating structures of growing complexity. Implication of the hypothesis One aim of cancer gene therapy could be the induction of oxidative phosphorylation, the last metabolic step required by inflammation in order to differentiate the tissue that it produces.

  1. Anorexia, serum zinc, and immunologic response in small cell lung cancer patients receiving chemotherapy and prophylactic cranial radiotherapy.

    Science.gov (United States)

    Lindsey, A M; Piper, B F

    1986-01-01

    Anorexia is a major clinical problem for patients with certain types of cancer. The specific mechanisms that result in this spontaneous decline in food intake remain unknown. In noncancer populations, zinc has been shown to play a role in maintaining normal appetite, taste acuity, and immunocompetence. One purpose of this prospective, longitudinal study of cachexia in ten males with small cell lung carcinoma was to determine if anorexia (caloric intake), perceived taste changes, zinc intake, and impaired cellular immunity were associated with serum zinc concentrations. The average daily caloric intake declined 490 kcal from time of diagnosis to seven months after diagnosis (mean caloric intake = 72% of RDA). Daily zinc intake ranged from 6.5 to 25.4 mg over the seven months. During this period, the mean serum zinc concentrations, although low (71 micrograms/dl), remained within the normal range. The average weight declined from 81.7 to 74.1 kg. There was no identifiable pattern of perceived taste changes; most of the perceived changes were recorded during the period coinciding with prophylactic cranial radiation. At the initial testing, four of nine subjects were anergic to a battery of skin test antigens (mumps, candida, tuberculin purified protein derivative). The only subject who remained responsive to two antigens throughout the study remained alive at 12 months. Caloric intake was inadequate to maintain weight. While zinc intake was low, low normal serum zinc concentrations were maintained; thus in this sample, serum zinc does not appear to be the anorexigenic factor. PMID:3022247

  2. Persistent release of IL-1s from skin is associated with systemic cardio-vascular disease, emaciation and systemic amyloidosis: the potential of anti-IL-1 therapy for systemic inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Keiichi Yamanaka

    Full Text Available The skin is an immune organ that contains innate and acquired immune systems and thus is able to respond to exogenous stimuli producing large amount of proinflammatory cytokines including IL-1 and IL-1 family members. The role of the epidermal IL-1 is not limited to initiation of local inflammatory responses, but also to induction of systemic inflammation. However, association of persistent release of IL-1 family members from severe skin inflammatory diseases such as psoriasis, epidermolysis bullosa, atopic dermatitis, blistering diseases and desmoglein-1 deficiency syndrome with diseases in systemic organs have not been so far assessed. Here, we showed the occurrence of severe systemic cardiovascular diseases and metabolic abnormalities including aberrant vascular wall remodeling with aortic stenosis, cardiomegaly, impaired limb and tail circulation, fatty tissue loss and systemic amyloid deposition in multiple organs with liver and kidney dysfunction in mouse models with severe dermatitis caused by persistent release of IL-1s from the skin. These morbid conditions were ameliorated by simultaneous administration of anti-IL-1α and IL-1β antibodies. These findings may explain the morbid association of arteriosclerosis, heart involvement, amyloidosis and cachexia in severe systemic skin diseases and systemic autoinflammatory diseases, and support the value of anti-IL-1 therapy for systemic inflammatory diseases.

  3. Heart valve surgery in hemodialysis-dependent patients: nutrition status impact on surgical outcome.

    Science.gov (United States)

    Kawahito, Koji; Aizawa, Kei; Oki, Shinichi; Saito, Tsutomu; Misawa, Yoshio

    2016-06-01

    Valve surgery in hemodialysis-dependent patients is associated with postoperative complications and a high mortality rate, and such patients frequently suffer cachexia. This study aimed to determine pre- and intraoperative risk factors associated with in-hospital mortality and long-term survival in hemodialysis-dependent patients undergoing heart valve surgery from the viewpoint of nutrition status. Eighty-seven hemodialysis-dependent patients who underwent valve surgery between January 1998 and October 2015 were retrospectively reviewed. Thirty-seven potential perioperative risk factors were evaluated. The in-hospital mortality rate was 12.6 % (11 patients). Univariate analysis identified New York Heart Association Functional Classification III or IV, emaciation (body mass index 3000 ml as predictors of in-hospital death. Multivariate logistic regression analysis confirmed low serum albumin death. The 1- and 3-year actuarial survival rates were 64.9 ± 5.4 and 51.8 ± 5.8 %, respectively. Long-term survival estimated by log-rank test was negatively impacted by anemia (hemoglobin death. Hypoalbuminemia and emergent/urgent operation are strong predictors of in-hospital and remote death. Malnutrition before surgery should be considered for operative risk estimation, and adequate preoperative nutrition management may improve surgical outcomes for hemodialysis-dependent patients. PMID:26749145

  4. Cystatin C Falsely Underestimated GFR in a Critically Ill Patient with a New Diagnosis of AIDS

    Directory of Open Access Journals (Sweden)

    Caitlin S. Brown

    2016-01-01

    Full Text Available Cystatin C has been suggested to be a more accurate glomerular filtration rate (GFR surrogate than creatinine in patients with acquired immunodeficiency syndrome (AIDS because it is unaffected by skeletal muscle mass and dietary influences. However, little is known about the utility of this marker for monitoring medications in the critically ill. We describe the case of a 64-year-old female with opportunistic infections associated with a new diagnosis of AIDS. During her course, she experienced neurologic, cardiac, and respiratory failure; yet her renal function remained preserved as indicated by an eGFR ≥ 120 mL/min and a urine output > 1 mL/kg/hr without diuresis. The patient was treated with nephrotoxic agents; therefore cystatin C was assessed to determine if cachexia was resulting in a falsely low serum creatinine. Cystatin C measured 1.50 mg/L which corresponded to an eGFR of 36 mL/min. Given the >60 mL/min discrepancy, serial 8-hour urine samples were collected and a GFR > 120 mL/min was confirmed. It is unclear why cystatin C was falsely elevated, but we hypothesize that it relates to the proinflammatory state with AIDS, opportunistic infections, and corticosteroids. More research is needed before routine use of cystatin C in this setting can be recommended.

  5. El factor de necrosis de los tumores o caquectina

    Directory of Open Access Journals (Sweden)

    Jorge Eliécer Ossa Londoño

    1988-02-01

    Full Text Available

    Se presenta una revisión de la literatura sobre el Factor de Necrosis de los Tumores o Caquectina, con base en artículos publicados durante los anos 1986-1987, haciendo hincapié en las diferencias funcionales y moleculares entre el FNT Alfa, la Linfotoxina o FNT Beta y la Caquectina. Se enfatizan los mecanismos del shock, de la necrosis tumoral y de la caquexia; se Indican las propiedades antitumorales del FNT in vivo e in vitro y se esbozan esquemas terapéuticos experimentales que permiten colegir que el FNT tendrá un papel Importante en la Inmunoterapia del cáncer en el hombre.

    This is a review of the 1986-1987 Literature on the Tumor Necrosis Factor (TNF or Cachectin, emphasizing functional and molecular differences among TNF alpha, Iymphotoxin or TNF beta and Cachectin. Mechanisms of shock, tumor necrosis and cachexia are discussed. In vivo and ín vítro antitumoral properties of TNF are indicated, as well as some experimental therapeutic regimens. These facts allow the suggestion that TNF might become an Important aid for Immunotherapy of cancer In humans.

  6. Cyclosporin safety in a simplified rat brain tumor implantation model

    Directory of Open Access Journals (Sweden)

    Francisco H. C. Felix

    2012-01-01

    Full Text Available Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate. This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

  7. Effect of medroxyprogesterone acetate on the quality of life of the oncologic patient: a multicentric cooperative study.

    Science.gov (United States)

    Neri, B; Garosi, V L; Intini, C

    1997-06-01

    Anorexia and cachexia, major problems in patients with cancer, lead to decreased caloric intake and weight loss. Successful treatment of these conditions has a positive effect on patients' quality of life. Among the pharmacologic treatments, partial effects have been observed following administration of corticosteroids, anabolizing drugs and synthetic progestogens such as megestrol acetate and medroxyprogesterone acetate (MPA). The aim of the present study was to evaluate whether MPA is able to influence the quality of life of neoplastic patients undergoing different chemotherapeutic regimens and/or radiotherapy for different tumor types. A series of 279 cancer patients undergoing either chemotherapy and/or radiotherapy treatment for different tumor types was randomly allocated to receive either MPA or no treatment. We explored the effect of MPA oral suspension at the daily dose of 1000 mg for 12 weeks (group A) or no treatment (group B). Our data show an increase of body weight in group A patients and improvement in performance status. The outcome of the present study strongly demonstrates that therapy with MPA plays a fundamental role in ameliorating the complex symptomatology of cancer patients in intermediate or advanced stage of the disease undergoing casual treatment with chemotherapy and/or radiotherapy. PMID:9215608

  8. Globular adiponectin induces differentiation and fusion of skeletal muscle cells

    Institute of Scientific and Technical Information of China (English)

    Tania Fiaschi; Domenico Cirelli; Giuseppina Comito; Stefania Gelmini; Giampietro Ramponi; Maria Serio; Paola Chiarugi

    2009-01-01

    The growing interest in skeletal muscle regeneration is associated with the opening of new therapeutic strategies for muscle injury after trauma, as well as several muscular degenerative pathologies, including dystrophies, muscu-lar atrophy, and cachexia. Studies focused on the ability of extracellular factors to promote myogenesis are therefore highly promising. We now report that an adipocyte-derived factor, globular adiponectin (gAd), is able to induce mus-cle gene expression and cell differentiation, gAd, besides its well-known ability to regulate several metabolic func-tions in muscle, including glucose uptake and consumption and fatty acid catabolism, is able to block cell cycle entry of myoblasts, to induce the expression of specific skeletal muscle markers such as myosin heavy chain or eaveolin-3, as well as to provoke cell fusion into multinucleated syneytia and, finally, muscle fibre formation, gAd exerts its pro-differentiative activity through redox-dependent activation of p38, Akt and 5'-AMP-activated protein kinase path-ways. Interestingly, differentiating myoblasts are autocrine for adiponectiu, and the mimicking of pro-inflammatory settings or exposure to oxidative stress strongly increases the production of the hormone from differentiating cells. These data suggest a novel function of adiponectin, directly coordinating the myogenic differentiation program and serving an autocrine function during skeletal myogenesis.

  9. A metabolic link to skeletal muscle wasting and regeneration

    Directory of Open Access Journals (Sweden)

    René eKoopman

    2014-02-01

    Full Text Available Due to its essential role in movement, insulating the internal organs, generating heat to maintain core body temperature, and acting as a major energy storage depot, any impairment to skeletal muscle structure and function may lead to an increase in both morbidity and mortality. In the context of skeletal muscle, altered metabolism is directly associated with numerous pathologies and disorders, including diabetes, and obesity, while many skeletal muscle pathologies have secondary changes in metabolism, including cancer cachexia, sarcopenia and the muscular dystrophies. Furthermore, the importance of cellular metabolism in the regulation of skeletal muscle stem cells is beginning to receive significant attention. Thus, it is clear that skeletal muscle metabolism is intricately linked to the regulation of skeletal muscle mass and regeneration. The aim of this review is to discuss some of the recent findings linking a change in metabolism to changes in skeletal muscle mass, as well as describing some of the recent studies in developmental, cancer and stem-cell biology that have identified a role for cellular metabolism in the regulation of stem cell function, a process termed ‘metabolic reprogramming’.

  10. Molecular imaging of brown adipose tissue in health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Bauwens, Matthias [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Maastricht University, Research School NUTRIM, Maastricht (Netherlands); Wierts, Roel; Brans, Boudewijn [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Royen, Bart van; Backes, Walter [MUMC, Department of Medical Imaging, Division of Radiology, Maastricht (Netherlands); Bucerius, Jan [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Uniklinikum Aachen, Division of Nuclear Medicine, Aachen (Germany); Maastricht University, Research School CARIM, Maastricht (Netherlands); Mottaghy, Felix [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Uniklinikum Aachen, Division of Nuclear Medicine, Aachen (Germany)

    2014-04-15

    Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, {sup 18}F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to {sup 18}F-FDG, other radiopharmaceuticals such as {sup 99m}Tc-sestamibi, {sup 123}I-metaiodobenzylguanidine (MIBG), {sup 18}F-fluorodopa and {sup 18}F-14(R,S)-[{sup 18}F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity. (orig.)

  11. Skeletal muscle mass and quality: evolution of modern measurement concepts in the context of sarcopenia.

    Science.gov (United States)

    Heymsfield, Steven B; Gonzalez, M Cristina; Lu, Jianhua; Jia, Guang; Zheng, Jolene

    2015-11-01

    The first reports of accurate skeletal muscle mass measurement in human subjects appeared at about the same time as introduction of the sarcopenia concept in the late 1980s. Since then these methods, computed tomography and MRI, have been used to gain insights into older (i.e. anthropometry and urinary markers) and more recently developed and refined methods (ultrasound, bioimpedance analysis and dual-energy X-ray absorptiometry) of quantifying regional and total body skeletal muscle mass. The objective of this review is to describe the evolution of these methods and their continued development in the context of sarcopenia evaluation and treatment. Advances in these technologies are described with a focus on additional quantifiable measures that relate to muscle composition and 'quality'. The integration of these collective evaluations with strength and physical performance indices is highlighted with linkages to evaluation of sarcopenia and the spectrum of related disorders such as sarcopenic obesity, cachexia and frailty. Our findings show that currently available methods and those in development are capable of non-invasively extending measures from solely 'mass' to quality evaluations that promise to close the gaps now recognised between skeletal muscle mass and muscle function, morbidity and mortality. As the largest tissue compartment in most adults, skeletal muscle mass and aspects of muscle composition can now be evaluated by a wide array of technologies that provide important new research and clinical opportunities aligned with the growing interest in the spectrum of conditions associated with sarcopenia. PMID:25851205

  12. Candidate SNP Markers of Gender-Biased Autoimmune Complications of Monogenic Diseases Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

    Science.gov (United States)

    Ponomarenko, Mikhail P.; Arkova, Olga; Rasskazov, Dmitry; Ponomarenko, Petr; Savinkova, Ludmila; Kolchanov, Nikolay

    2016-01-01

    Some variations of human genome [for example, single nucleotide polymorphisms (SNPs)] are markers of hereditary diseases and drug responses. Analysis of them can help to improve treatment. Computer-based analysis of millions of SNPs in the 1000 Genomes project makes a search for SNP markers more targeted. Here, we combined two computer-based approaches: DNA sequence analysis and keyword search in databases. In the binding sites for TATA-binding protein (TBP) in human gene promoters, we found candidate SNP markers of gender-biased autoimmune diseases, including rs1143627 [cachexia in rheumatoid arthritis (double prevalence among women)]; rs11557611 [demyelinating diseases (thrice more prevalent among young white women than among non-white individuals)]; rs17231520 and rs569033466 [both: atherosclerosis comorbid with related diseases (double prevalence among women)]; rs563763767 [Hughes syndrome-related thrombosis (lethal during pregnancy)]; rs2814778 [autoimmune diseases (excluding multiple sclerosis and rheumatoid arthritis) underlying hypergammaglobulinemia in women]; rs72661131 and rs562962093 (both: preterm delivery in pregnant diabetic women); and rs35518301, rs34166473, rs34500389, rs33981098, rs33980857, rs397509430, rs34598529, rs33931746, rs281864525, and rs63750953 (all: autoimmune diseases underlying hypergammaglobulinemia in women). Validation of these predicted candidate SNP markers using the clinical standards may advance personalized medicine. PMID:27092142

  13. Toxic effects of oral 2-amino-4,6-dinitrotoluene in the Western fence lizard (Sceloporus occidentalis)

    Energy Technology Data Exchange (ETDEWEB)

    McFarland, Craig A., E-mail: craig.a.mcfarland@us.army.mi [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Quinn, Michael J. [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Boyce, John [Biotechnics, LLC, Hillsborough, NC 27278 (United States); LaFiandra, Emily M.; Bazar, Matthew A. [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Talent, Larry G. [Oklahoma State University, Department of Natural Resource Ecology and Management, Stillwater, OK 74078 (United States); Johnson, Mark S. [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States)

    2011-02-15

    The compound 2-amino-4,6-dinitrotoluene (2A-DNT) was evaluated under laboratory conditions in the Western fence lizard (Sceloporus occidentalis) to assess the potential for reptile toxicity. Oral LD{sub 50} values were 1406 and 1867 mg/kg for male and female lizards, respectively. Based on responses from a 14-day subacute study, a 60-day subchronic experiment followed where lizards were orally dosed at 0, 5, 15, 20, 25, 30 mg/kg-d. At day 60, number of days and survivors, food consumption, and change in body weight were inversely related to dose. Signs of toxicity were characterized by anorexia and generalized cachexia. Significant adverse histopathology was observed in hepatic tissue at {>=}15 mg/kg-d, consistent with hepatocellular transdifferentiation. Based on survival, loss of body weight, diminished food intake, changes in liver, kidney, and testes, and increased blood urea nitrogen, these data suggest a LOAEL of 15 mg/kg-d and a NOAEL of 5 mg/kg-d in S. occidentalis. - Research highlights: Oral LD{sub 50} (mg/kg) values were 1406 for male and 1867 for female lizards. Dose-dependent hepatocellular transdifferentiation was observed at {>=}5 mg/kg-d. Chromaturia in 2A-DNT and the parent TNT suggest biomarkers of exposure and effect. Health effects of metabolites support comprehensive ecological risk assessments. - The Western fence lizard (Sceloporus occidentalis) is a suitable reptile model for assessing the toxicity of energetic compounds and their metabolites.

  14. A role for oleoylethanolamide in chronic lymphocytic leukemia.

    Science.gov (United States)

    Masoodi, M; Lee, E; Eiden, M; Bahlo, A; Shi, Y; Ceddia, R B; Baccei, C; Prasit, P; Spaner, D E

    2014-07-01

    Oleoylethanolamide (OEA) is a bioactive lipid that stimulates nuclear and G protein-coupled receptors and regulates appetite and fat metabolism. It has not previously been shown to have a role in cancer. However, a mass spectrometry-based lipidomics platform revealed the presence of high amounts of OEA in the plasma of chronic lymphocytic leukemia (CLL) patients compared with normal donors. CLL cells produced OEA and the magnitude of plasma OEA levels was related directly to the circulating leukemic cell number. OEA from CLL cells was increased by URB-597, an inhibitor of fatty acid amide hydrolase (FAAH), and decreased by inflammatory mediators that downregulate expression of N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD). These enzymes degrade and synthesize OEA, respectively. Nonphysiologic doses of OEA prevented spontaneous apoptosis of CLL cells in a receptor-independent manner that was mimicked by its free fatty acid (FFA) derivative oleate. However, OEA-containing supernatants from CLL cells induced lipolysis in adipocytes, lipid products from adipocytes protected CLL cells from cytotoxic chemotherapy, and increased levels of FFAs were found in CLL plasma that correlated with OEA. We suggest OEA is a lipolytic factor produced by CLL cells to fuel their growth with a potential role in drug resistance and cancer cachexia. PMID:24413323

  15. Evaluation of the efficacy of palliative irradiation with high fractionated doses and planned intervals of patients with advanced cancer of the oral cavity and pharynx

    International Nuclear Information System (INIS)

    200 patients, previously not treated, with advanced highly differentiated cancer of the oral cavity and pharynx have been palliatively irradiated in the Oncology Center in Cracow in the years 1976-1985. Megavoltage irradiation with fractionated doses 4-5 Gy up to the dose of 20 Gy to the tumor with 4-5 fractions during 4-7 days has been applied. 64 patients received 20 Gy as simple dose, in 65 cases such dose has been repeated after month. 71 patients have been irradiated for the third time with similar dose after another 1 month interval. Partial regression of 25-50% of the tumor volume has been obtained after the first series of irradiation in 19% of patients and more than 50% in 28% of patients, complete regression in 4% of patients. 15,5% of the total number of patients survived 1 year since the initiation of the irradiation, 5% without symptoms of the neoplasm. Worse prognosis is connected with major advancement of the tumor (T4, N2), poor general condition, cachexia and alcohol addition. Absence of improvement after the first series of irradiations indicates the non-effectiveness of the treatment. Palliative treatment by irradiation with high fractionated doses and planned interval is a safe and efficacious method. 1 fig., 6 tabs., 14 refs. (author)

  16. Metabolic Dysfunction in Heart Failure: Diagnostic, Prognostic, and Pathophysiologic Insights From Metabolomic Profiling.

    Science.gov (United States)

    Hunter, Wynn G; Kelly, Jacob P; McGarrah, Robert W; Kraus, William E; Shah, Svati H

    2016-06-01

    Metabolic impairment is an intrinsic component of heart failure (HF) pathophysiology. Although initially conceived as a myocardial defect, metabolic dysfunction is now recognized as a systemic process with complex interplay between the myocardium and peripheral tissues and organs. Specifically, HF-associated metabolic dysfunction includes alterations in substrate utilization, insulin resistance, defects in energy production, and imbalanced anabolic-catabolic signaling leading to cachexia. Each of these metabolic abnormalities is associated with significant morbidity and mortality in patients with HF; however, their detection and therapeutic management remains challenging. Given the difficulty in obtaining human cardiac tissue for research purposes, peripheral blood metabolomic profiling, a well-established approach for characterizing small-molecule metabolite intermediates from canonical biochemical pathways, may be a useful technology for dissecting biomarkers and mechanisms of metabolic impairment in HF. In this review, metabolic abnormalities in HF will be discussed with particular emphasis on the application of metabolomic profiling to detecting, risk stratifying, and identifying novel targets for metabolic therapy in this heterogeneous population. PMID:27216948

  17. Palliation of the patient with cancer: Treatment of mind and body

    International Nuclear Information System (INIS)

    It can reasonably be assumed that on any given day in any radiation therapy facility 30% or more of the patients are being treated with palliative intent. Usually half of these patients were previously treated in anticipation of cure or for palliative procedures. The need for repetitive palliative intervention may increase as newer chemotherapeutic agents prolong control and survival of patients with metastatic cancer. There is evidence of a changing pattern of metastatic disease as primary tumors once considered more immediately lethal are now better controlled. This may be true of certain forms of head and neck cancer, as well as of advanced gynecologic cancers. Palliative radiation therapy is directed toward the most oppressive immediate symptoms of the incurable cancer patient, symptoms that do much to destroy the quality of life for what time the patient may have to live in the expected course of his disease. These may include pain, usually severe and incapacitating owing to destruction or fracture of bone, compression of nerve, and vascular occlusion; respiratory and digestive obstruction, hemorrhage; ulceration; malodorous discharge; soft tissue infiltration; disfigurement; obstructive edema; ascites; and severe cachexia. We often lose sight of the fact that although definitive radiation therapy may fail to cure or influence survival, it often does provide the best means of preventing the extreme and flagrant unchecked potentials of the disease

  18. Distance learning in the Applied Sciences of Oncology

    International Nuclear Information System (INIS)

    Background: The major impediment to the expansion of oncology services is a shortage of personnel. Purpose: To develop a distance learning course for radiation oncology trainees. Materials: Under the sponsorship of the Asia Pacific Regional Cooperative Agreement administered by the International Atomic Energy Agency (IAEA), a CD ROM-based Applied Sciences of Oncology (ASOC) distance learning course of 71 modules was created. The course covers communications, critical appraisal, functional anatomy, molecular biology, pathology. The materials include interactive text and illustrations that require students to answer questions before they can progress. The course aims to supplement existing oncology curricula and does not provide a qualification. It aims to assist students in acquiring their own profession's qualification. The course was piloted in seven countries in Asia, Africa and Latin America during 2004. After feedback from the pilot course, a further nine modules were added to cover imaging physics (three modules), informed consent, burnout and coping with death and dying, Economic analysis and cancer care, Nutrition, cachexia and fatigue, radiation-induced second cancers and mathematical tools and background for radiation oncology. The course was widely distributed and can be downloaded from (http://www.iaea.org/Publications/Training/Aso/register.html). ASOC has been downloaded over 1100 times in the first year after it was posted. There is a huge demand for educational materials but the interactive approach is labour-intensive and expensive to compile. The course must be maintained to remain relevant.

  19. Indwelling intrathecal catheter with subcutaneous abdominal reservoir: a viable baclofen delivery system in severely cachectic patients.

    Science.gov (United States)

    Waqar, Mueez; Ellenbogen, Jonathan R; Kumar, Ram; Sneade, Christine; Zebian, Bassel; Williams, Dawn; Pettorini, Benedetta L

    2014-10-01

    Intrathecal baclofen (ITB) is a reversible treatment that reduces muscle tone to ameliorate spasticity and dystonia in patients with cerebral palsy (CP). The resulting decrease in energy expenditure allows patients to gain much-needed weight, albeit temporarily. Modern techniques require sufficient abdominal musculature and subcutaneous fat to permit the implantation of an indwelling pump. In patients with extremely low muscle bulk, visceral pumps may be impractical or impossible, with increased risks of dehiscence and infection. The authors describe a variation of the classical procedure in a young patient with severe cachexia. A 10-year-old boy with spastic-dystonic quadriplegic CP was admitted to the neuromedical unit. Numerous drug trials had failed, and surgical intervention was deemed necessary but was complicated by his cachectic body habitus. The authors inserted a lumbar intrathecal catheter and subcutaneously tunneled it to the anterolateral abdomen, where it was connected to a subcutaneous injection port. Baclofen was continuously infused into the subcutaneous port using a noncoring needle connected to an external pump. The needle and line were changed every 5 days to minimize the risk of sepsis. Although other techniques, such as intraventricular baclofen delivery, have been described, these are largely dependent upon sufficient musculature to support a visceral pump. A subcutaneous injection port system represents an alternative approach that reduces the risk of sepsis and may be better tolerated in cachectic patients. PMID:25084089

  20. Protein energy wasting in chronic kidney disease: An update with focus on nutritional interventions to improve outcomes

    Directory of Open Access Journals (Sweden)

    Yashpal P Jadeja

    2012-01-01

    Full Text Available Protein-energy wasting (PEW is common in patients with chronic kidney disease (CKD. PEW is one of the strongest predictors of mortality in patients with CKD. The International Society of Renal Nutrition and Metabolism (ISRNM expert panel has defined PEW as a, "state of decreased body stores of protein and energy fuels (body protein and fat masses". The ISRNM panel has also proposed diagnostic criteria of PEW with four categories. Cachexia is a severe form of PEW. The proposed causes of PEW are multi-factorial and include nutritional and non-nutritional mechanisms. The literature indicates that PEW can be mitigated or corrected with an appropriate diet and enteral nutritional support that targets dietary protein intake. Dietary requirements and enteral nutritional support must also be considered in patients with CKD and diabetes mellitus and in children with CKD, in addition to dialysis patients. Features of ideal dietary supplement have also been discussed. Dietary interventions such as enteral feeding with high-protein meals or supplements might improve the nutritional status and outcomes in dialysis patients.

  1. The role of E3 ubiquitin-ligases MuRF-1 and MAFbx in loss of skeletal muscle mass.

    Science.gov (United States)

    Rom, Oren; Reznick, Abraham Z

    2016-09-01

    The ubiquitin-proteasome system (UPS) is the main regulatory mechanism of protein degradation in skeletal muscle. The ubiquitin-ligase enzymes (E3s) have a central role in determining the selectivity and specificity of the UPS. Since their identification in 2001, the muscle specific E3s, muscle RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx), have been shown to be implicated in the regulation of skeletal muscle atrophy in various pathological and physiological conditions. This review aims to explore the involvement of MuRF-1 and MAFbx in catabolism of skeletal muscle during various pathologies, such as cancer cachexia, sarcopenia of aging, chronic kidney disease (CKD), diabetes, and chronic obstructive pulmonary disease (COPD). In addition, the effects of various lifestyle and modifiable factors (e.g. nutrition, exercise, cigarette smoking, and alcohol) on MuRF-1 and MAFbx regulation will be discussed. Finally, evidence of potential strategies to protect against skeletal muscle wasting through inhibition of MuRF-1 and MAFbx expression will be explored. PMID:26738803

  2. Nutritional supplementation in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Hsieh, Meng-Jer; Yang, Tsung-Ming; Tsai, Ying-Huang

    2016-08-01

    Malnutrition in patients with chronic obstructive pulmonary disease (COPD) is associated with cachexia, sarcopenia, and weight loss, and may result in poorer pulmonary function, decreased exercise capacity, and increased risk of exacerbations. Providing nutritional supplementation is an important therapeutic intervention, particularly for severely ill COPD patients with malnutrition. Higher calorie intake through nutritional supplementation significantly increases body weight and muscle strength, and improves quality of life in malnourished COPD patients. Difficulties may be experienced by these COPD patients, who are struggling to breathe and eliminate CO2 from the lungs, resulting in dyspnea, hypercapnia, hypoxia, and respiratory acidosis, which exacerbates muscle loss through oxidative stress and inflammatory responses. To overcome these problems, nutritional supplements should aim to reduce metabolic CO2 production, lower respiratory quotient, and improve lung function. Several studies have shown that high-fat supplements produce less CO2 and have lower respiratory quotient value than high-carbohydrate supplements. In addition, high-fat supplements may be the most efficient means of providing a low-volume, calorie-dense supplement to COPD patients, and may be most beneficial to patients with prolonged mechanical ventilation where hypercapnia and malnutrition are most pronounced. Further studies are required to investigate the optimal nutritional supplements for COPD patients according to their disease severity. PMID:26822811

  3. GC-MS Based Plasma Metabolomics for Identification of Candidate Biomarkers for Hepatocellular Carcinoma in Egyptian Cohort.

    Directory of Open Access Journals (Sweden)

    Mohammad R Nezami Ranjbar

    Full Text Available This study evaluates changes in metabolite levels in hepatocellular carcinoma (HCC cases vs. patients with liver cirrhosis by analysis of human blood plasma using gas chromatography coupled with mass spectrometry (GC-MS. Untargeted metabolomic analysis of plasma samples from participants recruited in Egypt was performed using two GC-MS platforms: a GC coupled to single quadruple mass spectrometer (GC-qMS and a GC coupled to a time-of-flight mass spectrometer (GC-TOFMS. Analytes that showed statistically significant changes in ion intensities were selected using ANOVA models. These analytes and other candidates selected from related studies were further evaluated by targeted analysis in plasma samples from the same participants as in the untargeted metabolomic analysis. The targeted analysis was performed using the GC-qMS in selected ion monitoring (SIM mode. The method confirmed significant changes in the levels of glutamic acid, citric acid, lactic acid, valine, isoleucine, leucine, alpha tocopherol, cholesterol, and sorbose in HCC cases vs. patients with liver cirrhosis. Specifically, our findings indicate up-regulation of metabolites involved in branched-chain amino acid (BCAA metabolism. Although BCAAs are increasingly used as a treatment for cancer cachexia, others have shown that BCAA supplementation caused significant enhancement of tumor growth via activation of mTOR/AKT pathway, which is consistent with our results that BCAAs are up-regulated in HCC.

  4. Fatal Paratanaisia bragai (Digenea: Eucotylidae) infection in scarlet macaws (Ara macao) in Costa Rica.

    Science.gov (United States)

    Alfaro-Alarcón, Alejandro; Morales, Juan Alberto; Veneziano, Vincenzo; Santoro, Mario

    2015-09-01

    We report on four fatal cases of renal infection due to Paratanaisia bragai in scarlet macaws (Ara macao) from two rescue centres in Costa Rica. At necropsy, birds had severe dehydration and cachexia. Two birds had hydropericardium, oedematous lungs, and liver lipidic degeneration. All birds had enlarged kidneys with brown pale discoloration and diffuse white spots on the cortical and sliced surfaces. Ureters were filled with many specimens of P. bragai. Histopathologically, the urinary system revealed multifocal interstitial lymphocytic-plasmacytic nephritis, multifocal mineralization of renal tubules, and interstitial fibrosis associated with flukes. Death of all scarlet macaws was related to severe nephritis leading to chronic renal failure due to P. bragai infection. It is plausible that P. bragai infection of scarlet macaws was accidental due to ingestion of the gastropod intermediate host inside the cages during the rainy season when humidity is higher and gastropods are more active. This represents the second report of parasitism by Eucotylidae digeneans in birds of Psittaciformes and the first in scarlet macaws. PMID:26204012

  5. Hyperammonaemic encephalopathy secondary to selective cobalamin deficiency in a juvenile Border collie.

    Science.gov (United States)

    Battersby, I A; Giger, U; Hall, E J

    2005-07-01

    An eight-month-old Border collie was presented with anorexia, cachexia, failure to thrive and stupor. Laboratory tests demonstrated a mild anaemia, neutropenia, proteinuria and hyperammonaemia. Serum bile acid concentrations were normal, but an ammonia tolerance test (ATT) was abnormal. The dog responded to symptomatic therapy for hepatoencephalopathy. When a low serum cobalamin (vitamin B12) concentration and methylmalonic aciduria were noted, the dog was given a supplement of parenteral cobalamin. Two weeks later, a repeat ATT was normal. Cobalamin supplementation was continued every two weeks, and all clinical signs, except for proteinuria, resolved despite withdrawing all therapy for hepatoencephalopathy. A presumptive diagnosis of hereditary selective cobalamin malabsorption was made, based on the young age, Border collie breed, low serum cobalamin concentration and methylmalonic aciduria. Although hereditary selective cobalamin malabsorption in Border collies, giant schnauzers, Australian shepherd dogs and beagles has previously been reported in North America, to the authors' knowledge this is the first report of the condition in the UK and the first to document an abnormal ATT in a cobalamin-deficient dog. PMID:16035451

  6. Nutrition for Space Exploration

    Science.gov (United States)

    Smith, Scott M.

    2005-01-01

    during space flight. Omega3 fatty acids are currently being studied as a means of protecting against radiation-induced cancer. They have also recently been implicated as having a role in mitigating the physical wasting, or cachexia, caused by cancer. The mechanism of muscle loss associated with this type of cachexia is similar to the mechanism of muscle loss during disuse or space flight. Omega3 fatty acids have already been shown to have protective effects on bone and cardiovascular function. Omega3 fatty acids could be an ideal countermeasure for space flight because they have protective effects on multiple systems. A definition of optimal nutrient intake requirements for long-duration space travel should also include antioxidants. Astronauts are exposed to numerous sources of oxidative stress, including radiation, elevated oxygen exposure during extravehicular activity, and physical and psychological stress. Elevated levels of oxidative damage are related to increased risk for cataracts, cardiovascular disease, and cancer. Many groundbased studies show the protective effects of antioxidants against oxidative damage induced by radiation or oxygen. Balancing the diet with foods that have high levels of antioxidants would be another ideal countermeasure because it should have minimal side effects on crew health. Antioxidant supplements, however, are often used without having data on their effectiveness or side effects. High doses of supplements have been associated with bone and cardiovascular problems, but research on antioxidant effects during space flight has not been conducted. Much work must be done before we can send crews on exploration missions. Nutrition is often assumed to be the simple provision of food items that will be stable throughout the mission. As outlined briefly above, the situation is much more complex than food provision. As explorers throughout history have found, failure to truly understand the role of nutrition can be catastrophic. When huns are

  7. Killing of trypanosomatid parasites by a modified bovine host defense peptide, BMAP-18.

    Directory of Open Access Journals (Sweden)

    Lee R Haines

    -induced secretion of tumour necrosis factor alpha (TNF-alpha, a cytokine that is associated with inflammation and cachexia (wasting in sleeping sickness patients. As a prelude to in vivo applications, high affinity antibodies to BMAP-18 were produced in rabbits and used in immuno-mass spectrometry assays to detect the intact peptide in human blood and plasma. CONCLUSIONS/SIGNIFICANCE: BMAP-18, a truncated form of the potent antimicrobial BMAP-27, showed low toxicity to mammalian cells, insect cells and the tsetse bacterial symbiont Sodalis glossinidius while retaining an ability to kill a variety of species and life cycle stages of pathogenic kinetoplastid parasites in vitro. BMAP-18 also inhibited secretion of TNF-alpha, an inflammatory cytokine that plays a role in the cachexia associated with African sleeping sickness. These findings support the idea that BMAP-18 should be explored as a candidate for therapy of economically important trypanosome-infected hosts, such as cattle, fish and humans, and for paratransgenic expression in Sodalis glossinidius, a bacterial symbiont in the tsetse vector, as a strategy for interference with trypanosome transmission.

  8. Enhanced activity of hormone sensitive lipase (HSL) in mesenteric but not epididymal fat correlates with higher production of epinephrine in mesenteric adipocytes in rat model of cachectic rheumatoid arthritis.

    Science.gov (United States)

    Stofkova, Andrea; Krskova, Katarina; Vaculin, Simon; Jurcovicova, Jana

    2016-06-01

    Cachectic rheumatoid arthritis, the less frequent form of the disease, is associated with loss of fat mass and often more severe course of the disease. Its experimental model represents rat adjuvant arthritis (AA) characterized by edema, lack of appetite, sharp body weight and fat loss. As individual fat depots display functional differences, here we studied lipolytic activity and sensitivity to lipolytic stimuli of nodeless epididymal fat (eWAT) and perinodal mesenteric fat (mWAT) depots at the peak of AA. We also examined changes in catecholamine and cytokine levels involved in lipolysis in plasma and/or isolated adipocytes from both WATs to identify the contribution of local, adipocyte-based processes and/or systemic events to adiposity loss in cachectic rheumatoid arthritis. AA was induced to male Lewis rats by complete Freund's adjuvant. Groups of ad libitum-fed and pair-fed controls were used to distinguish the effects of food restriction from inflammation-induced cachexia. Adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and its phosphorylated form (pHSL) were analyzed by western blot. CRP and catecholamine levels in plasma or adipocyte lysates were determined using ELISA kits. Cytokine-induced neutrophil chemoattractant-1 (CINC-1/CXCL1), monocyte chemoattractant protein-1 (MCP-1/CCL2), IL-1β, IL-6, IL-10 and leptin in adipocyte lysate were analyzed by quantitative protein microarray. Plasma glycerol and FFA were measured spectrophotometrically. AA rats developed severe cachexia, with lower adiposity in mWAT compared to normal and pair-fed controls, whereas in eWAT the adiposity was similarly reduced in AA and pair-fed groups. ATGL levels in both WATs were not affected by AA or pair feeding. AA upregulated levels of HSL, pHSL and pHSL/HSL ratio in mWAT, whereas none of these parameters has changed in eWAT of AA rats or in either WATs of pair-fed rats. In AA rats plasma glycerol was elevated, whereas FFA concentration was reduced. Plasma

  9. Study Design and Rationale for the Phase 3 Clinical Development Program of Enobosarm, a Selective Androgen Receptor Modulator, for the Prevention and Treatment of Muscle Wasting in Cancer Patients (POWER Trials).

    Science.gov (United States)

    Crawford, Jeffrey; Prado, Carla M M; Johnston, Mary Ann; Gralla, Richard J; Taylor, Ryan P; Hancock, Michael L; Dalton, James T

    2016-06-01

    Muscle wasting in cancer is a common and often occult condition that can occur prior to overt signs of weight loss and before a clinical diagnosis of cachexia can be made. Muscle wasting in cancer is an important and independent predictor of progressive functional impairment, decreased quality of life, and increased mortality. Although several therapeutic agents are currently in development for the treatment of muscle wasting or cachexia in cancer, the majority of these agents do not directly inhibit muscle loss. Selective androgen receptor modulators (SARMs) have the potential to increase lean body mass (LBM) and hence muscle mass, without the untoward side effects seen with traditional anabolic agents. Enobosarm, a nonsteroidal SARM, is an agent in clinical development for prevention and treatment of muscle wasting in patients with cancer (POWER 1 and 2 trials). The POWER trials are two identically designed randomized, double-blind, placebo-controlled, multicenter, and multinational phase 3 trials to assess the efficacy of enobosarm for the prevention and treatment of muscle wasting in subjects initiating first-line chemotherapy for non-small-cell lung cancer (NSCLC). To assess enobosarm's effect on both prevention and treatment of muscle wasting, no minimum weight loss is required. These pivotal trials have pioneered the methodological and regulatory fields exploring a therapeutic agent for cancer-associated muscle wasting, a process hereby described. In each POWER trial, subjects will receive placebo (n = 150) or enobosarm 3 mg (n = 150) orally once daily for 147 days. Physical function, assessed as stair climb power (SCP), and LBM, assessed by dual-energy X-ray absorptiometry (DXA), are the co-primary efficacy endpoints in both trials assessed at day 84. Based on extensive feedback from the US Food and Drug Administration (FDA), the co-primary endpoints will be analyzed as a responder analysis. To be considered a physical function responder, a

  10. Field performance of "marsh seedless" grapefruit on trifoliate orange inoculated with viroids in Brazil Desempenho do pomeleiro "marsh seedles" enxertado em trifoliata inoculado com viróides no Brasil

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    Eduardo Sanches Stuchi

    2007-12-01

    Full Text Available Some viroids reduce citrus tree growth and may be used for tree size control aiming the establishment of orchards with close tree spacing that may provide higher productivity than conventional ones. To study the effects of citrus viroids inoculation on vegetative growth, yield and fruit quality of 'Marsh Seedless' grapefruit (Citrus paradisi Macf. grafted on trifoliate orange [Poncirus trifoliata (L. Raf.], an experiment was set up in January 1991, in Bebedouro, São Paulo State, Brazil. The experimental design was randomized blocks with four treatments with two plants per plot: viroid isolates Citrus Exocortis Viroid (CEVd + Hop stunt viroid (HSVd - CVd-II, a non cachexia variant + Citrus III viroid (CVd-III and Hop stunt viroid (HSVd - CVd-II, a non cachexia variant + Citrus III viroid (CVd-III and controls: two healthy buds (control, and no grafting (absolute control. Inoculation was done in the field, six months after planting by bud grafting. Both isolates reduced tree growth (trunk diameter, plant height, canopy diameter and volume. Trees not inoculated yielded better (average of eleven harvests than inoculated ones but the productivity was the same after 150 months. Fruit quality was affected by viroids inoculation but not in a restrictive way. The use of such severe dwarfing isolates for high density plantings of grapefruit on trifoliate orange rootstock is not recommended.Alguns viróides reduzem o crescimento dos citros e podem ser usados para o controle do tamanho das plantas objetivando a instalação de pomares adensados que podem ter maior produtividade que os pomares com espaçamentos convencionais. Para estudar o efeito da inoculação de viróides no desenvolvimento vegetativo, produção e qualidade dos frutos de pomeleiro 'Marsh Seedless' (Citrus paradisi Macf. enxertado em trifoliata [Poncirus trifoliata (L. Raf.], foi instalado um experimento em Janeiro de 1991, em Bebedouro, Estado de São Paulo, Brasil. O delineamento

  11. Recommendations from SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA on nutrition in the HIV-infected patient Recomendaciones de SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA sobre nutrición en el paciente con infección por VIH

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    R. Polo

    2007-04-01

    Full Text Available Objective: to make recommendations on the approach to nutritional problems (malnutrition, cachexia, micronutrient deficiency, obesity, lipodystrophy affecting HIV-infected patients. Methods: these recommendations have been agreed upon by a group of expertes in the nutrition and care of HIV-infected patients, on behalf of the different groups involved in drafting them. Therefore, the latest advances in pathophysiology, epidemiology, and clinical care presented in studies published in medical journals or at scientific meetings were evaluated. Results: there is no single method of evaluating nutrition, and diferent techniques -CT, MRI, and DXA-must be combined. The energy requirements of symptomatic patients increase by 20-30%. There is no evidence to support the increase in protein or fat intake. Micronutrient supplementation in only necessary in special circumstances (vitamin A in children and pregnant woman. Aerobic and resistance excercise is beneficial both for cardiovascular health and for improving lean mass and muscular strength. It is important to follow the rules of food safety at every stage in the chain. Therapeutic intervention in anorexia and cachexia must be tailored, by combining nutritional and pharmacological support (appetite stimulants, anabolic steroids, and, in some cases, testosterone. Artificial nutrition (oral supplementation, enteral or parenteral nutrition is safe and efficacious, and improves nutritional status and response to therapy. In children, nutritional recommendations must be made early, and are a necessary component of therapy. Conclusion: appropriate nutritional evaluation and relevant therapeutic action are an essential part of the care of HIV-infected patients.Objetivo: realizar recomendaciones sobre el abordaje de los problemas nutricionales (malnutrición, caquexia, déficit de micronutrientes, obesidad, lipodistrofia presentes en la infección VIH. Métodos: estas recomendaciones se han consensuado por un

  12. [Cannabinoid drugs for neurological diseases: what is behind?].

    Science.gov (United States)

    Fernández-Ruiz, Javier

    2012-05-16

    In recent years progress has been made in the development of pharmaceuticals based on the plant Cannabis sativa or on synthetic molecules with a similar action. Some of these pharmaceuticals, such as the mouth spray Sativex, have recently been approved for the treatment of spasticity in multiple sclerosis, but they are not the first and others, such as Marinol or Cesamet for the treatment of vomiting and nausea, and anorexia-cachexia syndrome, had already been approved. This incipient clinical use of cannabinoid drugs confirms something that was already known from fairly ancient times up to practically the last century, which is the potential use of this plant for medicinal applications - something which was brought to a standstill by the abusive use of preparations of the plant for recreational purposes. In any case, this incipient clinical use of cannabinoid drugs is not backed just by the anecdote of the medicinal use of cannabis since ancient times, but instead the boost it has been given by scientific research, which has made it possible to identify the target molecules that are activated or inhibited by these substances. These targets are part of a new system of intercellular communication that is especially active in the central nervous system, which is called the 'endogenous cannabinoid system' and, like many other systems, can be manipulated pharmacologically. The aim of this review is to probe further into the scientific knowledge about this system generated in the last few years, as a necessary step to justify the development of pharmaceuticals based on its activation or inhibition and which can be useful in different neurological diseases. PMID:22573509

  13. Hypothalamic CaMKKβ mediates glucagon anorectic effect and its diet-induced resistance

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    Quiñones, Mar; Al-Massadi, Omar; Gallego, Rosalía; Fernø, Johan; Diéguez, Carlos; López, Miguel; Nogueiras, Ruben

    2015-01-01

    Objective Glucagon receptor antagonists and humanized glucagon antibodies are currently studied as promising therapies for obesity and type II diabetes. Among its variety of actions, glucagon reduces food intake, but the molecular mechanisms mediating this effect as well as glucagon resistance are totally unknown. Methods Glucagon and adenoviral vectors were administered in specific hypothalamic nuclei of lean and diet-induced obese rats. The expression of neuropeptides controlling food intake was performed by in situ hybridization. The regulation of factors of the glucagon signaling pathway was assessed by western blot. Results The central injection of glucagon decreased feeding through a hypothalamic pathway involving protein kinase A (PKA)/Ca2+-calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMP-activated protein kinase (AMPK)-dependent mechanism. More specifically, the central injection of glucagon increases PKA activity and reduces protein levels of CaMKKβ and its downstream target phosphorylated AMPK in the hypothalamic arcuate nucleus (ARC). Consistently, central glucagon significantly decreased AgRP expression. Inhibition of PKA and genetic activation of AMPK in the ARC blocked glucagon-induced anorexia in lean rats. Genetic down-regulation of glucagon receptors in the ARC stimulates fasting-induced hyperphagia. Although glucagon was unable to decrease food intake in DIO rats, glucagon sensitivity was restored after inactivation of CaMKKβ, specifically in the ARC. Thus, glucagon decreases food intake acutely via PKA/CaMKKβ/AMPK dependent pathways in the ARC, and CaMKKβ mediates its obesity-induced hypothalamic resistance. Conclusions This work reveals the molecular underpinnings by which glucagon controls feeding that may lead to a better understanding of disease states linked to anorexia and cachexia. PMID:26909312

  14. The Level of Serum Cholesterol is Negatively Associated with Lean Body Mass in Korean non-Diabetic Cancer Patients

    Science.gov (United States)

    2016-01-01

    Due to poor nutrition and abnormal energy metabolism, cancer patients typically experience the loss of muscle mass. Although the diabetic conditions or dyslipidemia have been reported as a causal link of cancer but the consequence of such conditions in relation to gain or loss of skeletal muscle mass in cancer patients has not been well documented. The purpose of this study was to investigate the relationship of lean body mass and systemic parameters related to lipid metabolism in non-diabetic cancer patients using data from the Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2011. As results the level of serum total cholesterol (total-C) was negatively associated with both total lean body mass and appendicular lean body mass in cancer patients after adjustment for sex, physical activity, energy intake and comorbidity. The associations between consumption of dietary factors (energy, carbohydrate, protein and fat) and lean body mass were disappeared after adjusting comorbidities of cancer patients. Multivariate-adjusted linear regression analysis by quartiles of serum total-C showed that higher quartile group of total-C had significantly lower percent of lean body mass than reference group in cancer patients. The data indicate that serum lipid status can be the potential estimate of loss of skeletal muscle mass in cancer patients and be referenced in nutrition care of cancer patients under the onset of cachexia or parenteral/enteral nutrition. This data need to be confirmed with large pool of subjects and should be specified by stage of cancer or the site of cancer in future studies. PMID:27152302

  15. Myelofibrosis-associated complications: pathogenesis, clinical manifestations, and effects on outcomes

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    Mughal TI

    2014-01-01

    Full Text Available Tariq I Mughal,1 Kris Vaddi,2 Nicholas J Sarlis,2 Srdan Verstovsek31Tufts University School of Medicine, Boston, MA, 2Incyte Corporation, Wilmington, DE, 3Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USAAbstract: Myelofibrosis (MF is a rare chronic BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homologue 1-negative myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, inefficient hematopoiesis, and shortened survival. The clinical manifestations of MF include splenomegaly, consequent to extramedullary hematopoiesis, cytopenias, and an array of potentially debilitating abdominal and constitutional symptoms. Dysregulated Janus kinase (JAK-signal transducer and activator of transcription signaling underlies secondary disease-associated effects in MF, such as myeloproliferation, bone marrow fibrosis, constitutional symptoms, and cachexia. Common fatal complications of MF include transformation to acute leukemia, thrombohemorrhagic events, organ failure, and infections. Potential complications from hepatosplenomegaly include portal hypertension and variceal bleeding, whereas extramedullary hematopoiesis outside the spleen and liver – depending on the affected organ – may result in intracranial hypertension, spinal cord compression, pulmonary hypertension, pleural effusions, lymphadenopathy, skin lesions, and/or exacerbation of abdominal symptoms. Although allogeneic stem cell transplantation is the only potentially curative therapy, it is suitable for few patients. The JAK1/JAK2 inhibitor ruxolitinib is effective in improving splenomegaly, MF-related symptoms, and quality-of-life measures. Emerging evidence that ruxolitinib may be associated with a survival benefit in intermediate- or high-risk MF suggests the possibility of a disease-modifying effect. Consequently, ruxolitinib could provide a treatment backbone to which other (conventional and novel

  16. Is Growth Differentiation Factor 11 a Realistic Therapeutic for Aging-Dependent Muscle Defects?

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    Harper, Shavonn C; Brack, Andrew; MacDonnell, Scott; Franti, Michael; Olwin, Bradley B; Bailey, Beth A; Rudnicki, Michael A; Houser, Steven R

    2016-04-01

    This "Controversies in Cardiovascular Research" article evaluates the evidence for and against the hypothesis that the circulating blood level of growth differentiation factor 11 (GDF11) decreases in old age and that restoring normal GDF11 levels in old animals rejuvenates their skeletal muscle and reverses pathological cardiac hypertrophy and cardiac dysfunction. Studies supporting the original GDF11 hypothesis in skeletal and cardiac muscle have not been validated by several independent groups. These new studies have either found no effects of restoring normal GDF11 levels on cardiac structure and function or have shown that increasing GDF11 or its closely related family member growth differentiation factor 8 actually impairs skeletal muscle repair in old animals. One possible explanation for what seems to be mutually exclusive findings is that the original reagent used to measure GDF11 levels also detected many other molecules so that age-dependent changes in GDF11 are still not well known. The more important issue is whether increasing blood [GDF11] repairs old skeletal muscle and reverses age-related cardiac pathologies. There are substantial new and existing data showing that GDF8/11 can exacerbate rather than rejuvenate skeletal muscle injury in old animals. There is also new evidence disputing the idea that there is pathological hypertrophy in old C57bl6 mice and that GDF11 therapy can reverse cardiac pathologies. Finally, high [GDF11] causes reductions in body and heart weight in both young and old animals, suggestive of a cachexia effect. Our conclusion is that elevating blood levels of GDF11 in the aged might cause more harm than good. PMID:27034276

  17. New uses for old drugs in HIV infection: the role of hydroxyurea, cyclosporin and thalidomide.

    Science.gov (United States)

    Ravot, E; Lisziewicz, J; Lori, F

    1999-12-01

    The tenacious effort to develop new, specific agents to treat HIV infection is currently accompanied by a reconsideration of existing drugs on the basis of their known or putative effects on the retroviral life cycle and/or the tuning of immune mechanisms. Three specific 'older' compounds that interfere with HIV infection by both a direct antiviral activity, and a modulation of T-cell activation and proliferation have received the most attention. Hydroxurea, a classical chemotherapeutic agent, inhibits retroviral reverse transcription by targeting a cellular enzyme responsible for the synthesis of deoxynucleoside triphosphates. It may also have a role in reducing viral load while maintaining low numbers of potential target T cells. Beneficial effects of hydroxyurea in combination with didanosine and/or stavudine on viral load have been shown in a number of clinical trials. Cyclosporin, a known immunosuppressant, blocks the activation of T cells, hence reducing the permissivity to HIV, and also prevents proper HIV virion maturation. However, clinical studies have produced conflicting results in HIV-infected patients with regard to immunological and disease effects and toxicity. Thalidomide may have antiretroviral effects as a result of its primarily inhibitory effects on the production of tumour necrosis factor alpha (TNFalpha). TNFalpha induces expression of HIV from chronically infected cell lines by stimulating a cellular transcription factor, and blocking of TNFalpha-stimulated HIV replication by thalidomide has been shown in vitro and ex vivo. However, the effects on TNFalpha production in vivo have been inconsistent. Thalidomide has shown potential in treating some AIDS-related conditions [cachexia (weight loss and muscle wasting), and aphtous oral, oesophageal or genital ulcers]. However, because of its numerous and major adverse effects, thalidomide should always be used cautiously. In summary, some older drugs have potential as anti-HIV agents and offer the

  18. Thalidomide for erythema nodosum leprosum and other applications.

    Science.gov (United States)

    Okafor, Mark C

    2003-04-01

    Thalidomide, administered as a sedative and antiemetic decades ago, was considered responsible for numerous devastating cases of birth defects and consequently was banned from markets worldwide. However, the drug remarkably has resurfaced with promise of immunomodulatory benefit in a wide array of immunologic disorders for which available treatments were limited. It is approved by the Food and Drug Administration for erythema nodosum leprosum (ENL). Although the relative paucity of leprosy and ENL worldwide may perceivably limit interest in and knowledge about thalidomide, increasing numbers of new and potential uses expand its applicability widely beyond ENL. Thalidomide, an inhibitor of tumor necrosis factor a, is the best known agent for short-term treatment of ENL skin manifestations, as well as postremission maintenance therapy to prevent recurrence. For this indication, it is effective as monotherapy and as part of combination therapy with corticosteroids. Studies of thalidomide in chronic graft-versus-host disease showed benefit in children and adults as treatment, but not as prophylaxis. The agent has been administered successfully for treatment of cachexia related to cancer, tuberculosis, and human immunodeficiency virus infection, although evidence of efficacy is inconclusive. Thalidomide monotherapy effectively induced objective response in trials in patients with both newly diagnosed and advanced or refractory multiple myeloma. Combination therapy with thalidomide and corticosteroids was also effective in these patients, as well as in treatment of aphthous and genital ulcers. Limited evidence supports the drug's benefit in treatment of Kaposi's sarcoma. Other thalidomide applications include Crohn's disease, rheumatoid arthritis, and multiple sclerosis. Somnolence, constipation, and rash were the most frequently cited adverse effects in studies, but thalidomide-induced neuropathy and idiopathic thromboembolism were critical causes for drug

  19. A retrospective study of pathologic findings in the Amazon and Orinoco river dolphin (Inia geoffrensis) in captivity.

    Science.gov (United States)

    Bonar, Christopher J; Boede, Ernesto O; Hartmann, Manuel García; Lowenstein-Whaley, Joanne; Mujica-Jorquera, Esmeralda; Parish, Scott V; Parish, James V; Garner, Michael M; Stadler, Cynthia K

    2007-06-01

    River dolphins are especially susceptible to negative human impacts. For their conservation, attempts of relocation or procreation ex situ may become important in the future to avoid their extinction. Additional knowledge and medical experiences of river dolphin management in captivity may aid such conservation efforts. The medical records and necropsy and histopathology reports on 123 captive Amazon River dolphins (Inia geoffrensis) were re-viewed. Of these 123 animals, 105 were necropsied and 70 necropsies were supported with histopathology. Eighteen animals were not necropsied. Among wild-born animals, mortality was highest in the first 2 mo immediately postcapture and transport, accounting for 32 of 123 deaths. Pneumonia and skin lesions (cutaneous and subcutaneous ulcerations and abscesses) were the most common findings, found in 44 of 105 (42%) and 38 of 105 (36%) of gross diagnoses, respectively. At least 10 of 44 cases of pneumonia diagnosed grossly included a verminous component. Cachexia, from a variety of causes, was a major gross finding in 21 animals. Fifteen animals had histologic evidence of significant renal pathology, and this was the primary cause of death in 13 cases. Hepatic pathology was found in 18 cases, and bacterial sepsis was confirmed via histology in 16 cases. Based on these findings, it may be concluded that keys to successful maintenance of this species include 1) prophylactic anthelminthic and antibiotic therapy immediately post-capture; 2) maintenance of animals in larger enclosures than in past attempts, in compatible groups, and in facilities capable of separating aggressive animals; 3) maintenance in microbiologically hygienic water quality at all times; and 4) a proactive program of preventive medicine during the immediate postcapture, quarantine, and maintenance period of captivity. PMID:17679501

  20. Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs.

    Science.gov (United States)

    Straub, Rainer H; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3-8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID:26817483

  1. Loss of p53 attenuates the contribution of IL-6 deletion on suppressed tumor progression and extended survival in Kras-driven murine lung cancer.

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    Xiaohong Tan

    Full Text Available Interleukin-6 (IL-6 is involved in lung cancer tumorigenesis, tumor progression, metastasis, and drug resistance. Previous studies show that blockade of IL-6 signaling can inhibit tumor growth and increase drug sensitivity in mouse models. Clinical trials in non-small cell lung cancer (NSCLC reveal that IL-6 targeted therapy relieves NSCLC-related anemia and cachexia, although other clinical effects require further study. We crossed IL-6(-/- mice with Kras(G12D mutant mice, which develop lung tumors after activation of mutant Kras(G12D, to investigate whether IL-6 inhibition contributes to tumor progression and survival time in vivo. Kras(G12D; IL-6(-/- mice exhibited increased tumorigenesis, but slower tumor growth and longer survival, than Kras(G12D mice. Further, in order to investigate whether IL-6 deletion contributes to suppression of lung cancer metastasis, we generated Kras(G12D; p53(flox/flox; IL-6(-/- mice, which developed lung cancer with a trend for reduced metastases and longer survival than Kras(G12D; p53(flox/flox mice. Tumors from Kras(G12D; IL-6(-/- mice showed increased expression of TNFα and decreased expression of CCL-19, CCL-20 and phosphorylated STAT3(pSTAT3 than Kras(G12D mice; however, these changes were not present between tumors from Kras(G12D; p53(flox/flox; IL-6(-/- and Kras(G12D; p53(flox/flox mice. Upregulation of pSTAT3 and phosphorylated AKT(pAKT were observed in Kras(G12D tumors with p53 deletion. Taken together, these results indicate that IL-6 deletion accelerates tumorigenesis but delays tumor progression and prolongs survival time in a Kras-driven mouse model of lung cancer. However, these effects can be attenuated by p53 deletion.

  2. Neuroactive peptides as putative mediators of antiepileptic ketogenic diets

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    GiuseppeBiagini

    2014-04-01

    Full Text Available Various ketogenic diet (KD therapies, including classic KD, medium chain triglyceride administration, low glycemic index treatment, and a modified Atkins diet, have been suggested as useful in patients affected by pharmacoresistant epilepsy. A common goal of these approaches is to achieve an adequate decrease in the plasma glucose level combined with ketogenesis, in order to mimic the metabolic state of fasting. Although several metabolic hypotheses have been advanced to explain the anticonvulsant effect of KDs, including changes in the plasma levels of ketone bodies, polyunsaturated fatty acids, and brain pH, direct modulation of neurotransmitter release, especially purinergic (i.e., adenosine and γ-aminobutyric acidergic neurotransmission, was also postulated. Neuropeptides and peptide hormones are potent modulators of synaptic activity, and their levels are regulated by metabolic states. This is the case for neuroactive peptides such as neuropeptide Y, galanin, cholecystokinin and peptide hormones such as leptin, adiponectin, and growth hormone-releasing peptides (GHRPs. In particular, the GHRP ghrelin and its related peptide des-acyl ghrelin are well-known controllers of energy homeostasis, food intake, and lipid metabolism. Notably, ghrelin has also been shown to regulate the neuronal excitability and epileptic activation of neuronal networks. Several lines of evidence suggest that GHRPs are upregulated in response to starvation and, particularly, in patients affected by anorexia and cachexia, all conditions in which also ketone bodies are upregulated. Moreover, starvation and anorexia nervosa are accompanied by changes in other peptide hormones such as adiponectin, which has received less attention. Adipocytokines such as adiponectin have also been involved in modulating epileptic activity. Thus, neuroactive peptides whose plasma levels and activity change in the presence of ketogenesis might be potential candidates for elucidating the

  3. A simplified surveillance case definition of AIDS derived from empirical clinical data. The Clinical AIDS Study Group, and the Working Group on AIDS case definition.

    Science.gov (United States)

    Weniger, B G; Quinhões, E P; Sereno, A B; de Perez, M A; Krebs, J W; Ismael, C; Sion, F S; Ramos-Filho, C F; de Sá, C A; Byers, R H

    1992-12-01

    A clinical AIDS case definition is needed for surveillance in countries where the CDC case definition is not practical. To derive such a definition, we compared 110 HIV-seropositive and 135 randomly selected HIV-seronegative adult medical-ward inpatients in Brazil. Multivariate analysis of clinical signs and symptoms and simple diagnoses resulted in a discriminant function with sensitivity of 89% and specificity of 96% in predicting for AIDS. These data were the empirical basis for a clinical definition of AIDS in adults drafted in a Caracas, Venezuela, workshop sponsored by the Pan American Health Organization. The revised "Caracas" definition presented here requires a positive HIV serology, the absence of cancer or other cause of immunosuppression, plus > or = 10 cumulative points, as follows: Kaposi's sarcoma (10 points); extrapulmonary/noncavitary pulmonary tuberculosis (10); oral candidiasis or hairy leukoplakia (5); cavitary pulmonary/unspecified tuberculosis (5); herpes zoster or = 1 month (2); fever > or = 1 month (2); cachexia or > 10% weight loss (2); asthenia > or = 1 month (2); persistent dermatitis (2); anemia, lymphopenia, or thrombocytopenia (2); persistent cough or any pneumonia except TB (2); and lymphadenopathy > or = 1 cm at > or = 2 noninguinal sites for > or = 1 month (2). This definition has a sensitivity of 95% and a specificity of 100% (91% without HIV serology) when applied to the Brazilian patients in this study. The Caracas definition has been adopted by Brazil, Honduras, and Surinam, and is in validation elsewhere. The use of a reasonably sensitive and specific case definition commensurate with available diagnostic resources should facilitate AIDS surveillance in developing countries. PMID:1453332

  4. Imatinib binding to human serum albumin modulates heme association and reactivity.

    Science.gov (United States)

    Di Muzio, Elena; Polticelli, Fabio; Trezza, Viviana; Fanali, Gabriella; Fasano, Mauro; Ascenzi, Paolo

    2014-10-15

    Imatinib, an inhibitor of the Bcr-Abl tyrosine kinase, is approximately 95% bound to plasma proteins, α1-acid glycoprotein (AGP) being the primary carrier. However, human serum albumin (HSA) may represent the secondary carrier of imatinib in pathological states characterized by low AGP levels, such as pancreatic cancer, hepatic cirrhosis, hepatitis, hyperthyroidism, nephrotic syndrome, malnutrition, and cachexia. Here, thermodynamics of imatinib binding to full-length HSA and its recombinant Asp1-Glu382 truncated form (containing only the FA1, FA2, FA6, and FA7 binding sites; trHSA), in the absence and presence of ferric heme (heme-Fe(III)), and the thermodynamics of heme-Fe(III) binding to HSA and trHSA, in the absence and presence of imatinib, has been investigated. Moreover, the effect of imatinib on kinetics of peroxynitrite detoxification by ferric human serum heme-albumin (HSA-heme-Fe(III)) and ferric truncated human serum heme-albumin (trHSA-heme-Fe(III)) has been explored. All data were obtained at pH 7.0, and 20.0 °C and 37.0 °C. Imatinib binding to the FA7 site of HSA and trHSA inhibits allosterically heme-Fe(III) association to the FA1 site and vice versa, according to linked functions. Moreover, imatinib binding to the secondary FA2 site of HSA-heme-Fe(III) inhibits allosterically peroxynitrite detoxification. Docking simulations and local structural comparison with other imatinib-binding proteins support functional data indicating the preferential binding of imatinib to the FA1 and FA7 sites of HSA, and to the FA2 and FA7 sites of HSA-heme-Fe(III). Present results highlight the allosteric coupling of the FA1, FA2, and FA7 sites of HSA, and may be relevant in modulating ligand binding and reactivity properties of HSA in vivo. PMID:25057771

  5. Chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    V K Vijayan

    2013-01-01

    Full Text Available The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD in adults aged >40 yr is approximately 9-10 per cent. Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent. The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors. Pathological changes in COPD are observed in central airways, small airways and alveolar space. The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair. Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec to FVC (forced vital capacity ratio <0.70. COPD is characterized by an accelerated decline in FEV1. Co morbidities associated with COPD are cardiovascular disorders (coronary artery disease and chronic heart failure, hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity, bone disease (osteoporosis and osteopenia, stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline. The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death and this is essential to guide therapy. COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor. Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support. Lung volume reduction surgery and lung transplantation are advised in selected severe patients. Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease

  6. Salvage of Theileria infected calves with clinical manifestation of exophthalmia.

    Science.gov (United States)

    Singh, Shanker K; Sudan, Vikrant; Sachan, Pratibha; Srivastava, Ashish

    2015-09-01

    Two crossbred female calves aged between 30 and 35 days were presented with bilateral exophthalmia, inappetence, pyrexia and cachexia since last 15 days. Clinical examination revealed mainly bilateral exophthalmia with dry and pulpy cornea, generalized enlargement of superficial lymph nodes, pallor mucous, petechiae, high rectal temperature and sternal recumbency. The calves were severely infested with Hyalomma anatolicum anatolicum ticks and thin layer blood smears revealed presence of piroplasm in the RBCs, while lymph nodes aspirate smear examination revealed presence schizonts in the mononuclear cells. The calves were treated with buparvaquone; meloxicam, nandrolone decanoate and vitamins A, D3, E and H. From day second post-therapy a remarkable improvement in the clinical condition was noticed and substantial reduction in the both protruded eyeballs was noticed by 7 days post-therapy in the both calves. Further at day 47 post-therapy the one calf was free from the parasite on blood smear examination and right eye was retracted in its orbits with full of sight. Moreover the left eye was also retracted in its orbit but there was loss of sight and opacity developed in this eye. While, the other calf also revealed remarkable improvement in the clinical condition and both eye balls retracted completely into the orbit at day 30 post-therapy. But, at day 86 the calf developed microphthalmia and complete loss of sight in both eyes. It can be concluded that adjunction of antioxidants and hematopoietic agents may salvage the calves suffering from fatal theileriosis. PMID:26345050

  7. Muscle-bone interactions: From experimental models to the clinic? A critical update.

    Science.gov (United States)

    Laurent, Michaël R; Dubois, Vanessa; Claessens, Frank; Verschueren, Sabine M P; Vanderschueren, Dirk; Gielen, Evelien; Jardí, Ferran

    2016-09-01

    Bone is a biomechanical tissue shaped by forces from muscles and gravitation. Simultaneous bone and muscle decay and dysfunction (osteosarcopenia or sarco-osteoporosis) is seen in ageing, numerous clinical situations including after stroke or paralysis, in neuromuscular dystrophies, glucocorticoid excess, or in association with vitamin D, growth hormone/insulin like growth factor or sex steroid deficiency, as well as in spaceflight. Physical exercise may be beneficial in these situations, but further work is still needed to translate acceptable and effective biomechanical interventions like vibration therapy from animal models to humans. Novel antiresorptive and anabolic therapies are emerging for osteoporosis as well as drugs for sarcopenia, cancer cachexia or muscle wasting disorders, including antibodies against myostatin or activin receptor type IIA and IIB (e.g. bimagrumab). Ideally, increasing muscle mass would increase muscle strength and restore bone loss from disuse. However, the classical view that muscle is unidirectionally dominant over bone via mechanical loading is overly simplistic. Indeed, recent studies indicate a role for neuronal regulation of not only muscle but also bone metabolism, bone signaling pathways like receptor activator of nuclear factor kappa-B ligand (RANKL) implicated in muscle biology, myokines affecting bone and possible bone-to-muscle communication. Moreover, pharmacological strategies inducing isolated myocyte hypertrophy may not translate into increased muscle power because tendons, connective tissue, neurons and energy metabolism need to adapt as well. We aim here to critically review key musculoskeletal molecular pathways involved in mechanoregulation and their effect on the bone-muscle unit as a whole, as well as preclinical and emerging clinical evidence regarding the effects of sarcopenia therapies on osteoporosis and vice versa. PMID:26506009

  8. Trichostatin A, a histone deacetylase inhibitor, modulates unloaded-induced skeletal muscle atrophy.

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    Dupré-Aucouturier, Sylvie; Castells, Josiane; Freyssenet, Damien; Desplanches, Dominique

    2015-08-15

    Skeletal muscle atrophy is commonly associated with immobilization, ageing, and catabolic diseases such as diabetes and cancer cachexia. Epigenetic regulation of gene expression resulting from chromatin remodeling through histone acetylation has been implicated in muscle disuse. The present work was designed to test the hypothesis that treatment with trichostatin A (TSA), a histone deacetylase inhibitor, would partly counteract unloading-induced muscle atrophy. Soleus muscle atrophy (-38%) induced by 14 days of rat hindlimb suspension was reduced to only 25% under TSA treatment. TSA partly prevented the loss of type I and IIa fiber size and reversed the transitions of slow-twitch to fast-twitch fibers in soleus muscle. Unloading or TSA treatment did not affect myostatin gene expression and follistatin protein. Soleus protein carbonyl content remained unchanged, whereas the decrease in glutathione vs. glutathione disulfide ratio and the increase in catalase activity (biomarkers of oxidative stress) observed after unloading were abolished by TSA treatment. The autophagy-lysosome pathway (Bnip3 and microtubule-associated protein 1 light chain 3 proteins, Atg5, Gabarapl1, Ulk1, and cathepsin B and L mRNA) was not activated by unloading or TSA treatment. However, TSA suppressed the rise in muscle-specific RING finger protein 1 (MuRF1) caused by unloading without affecting the forkhead box (Foxo3) transcription factor. Prevention of muscle atrophy by TSA might be due to the regulation of the skeletal muscle atrophy-related MuRF1 gene. Our findings suggest that TSA may provide a novel avenue to treat unloaded-induced muscle atrophy. PMID:26112243

  9. Hypothalamic inflammation is reversed by endurance training in anorectic-cachectic rats

    Directory of Open Access Journals (Sweden)

    Lira Fábio S

    2011-08-01

    Full Text Available Abstract Aim We tested the effects of a cancer cachexia-anorexia sydrome upon the balance of anti and pro-inflammatory cytokines in the hypothalamus of sedentary or trained tumour-bearing (Walker-256 carcinosarcoma rats. Methods Animals were randomly assigned to a sedentary control (SC, sedentary tumour-bearing (ST, and sedentary pair-fed (SPF groups or, exercised control (EC, exercised tumour-bearing (ET and exercised pair-fed (EPF groups. Trained rats ran on a treadmill (60%VO2max for 60 min/d, 5 days/wk, for 8 wks. We evaluated food intake, leptin and cytokine (TNF-α, IL1β levels in the hypothalamus. Results The cumulative food intake and serum leptin concentration were reduced in ST compared to SC. Leptin gene expression in the retroperitoneal adipose tissue (RPAT was increased in SPF in comparison with SC and ST, and in the mesenteric adipose tissue (MEAT the same parameter was decreased in ST in relation to SC. Leptin levels in RPAT and MEAT were decreased in ST, when compared with SC. Exercise training was also able to reduce tumour weight when compared to ST group. In the hypothalamus, IL-1β and IL-10 gene expression was higher in ST than in SC and SPF. Cytokine concentration in hypothalamus was higher in ST (TNF-α and IL-1β, p Conclusion Cancer-induced anorexia leads towards a pro-inflammatory state in the hypothalamus, which is prevented by endurance training which induces an anti-inflammatory state, with concomitant decrease of tumour weight.

  10. CURRENT APPROACHES TO THERAPY OF RETT’S SYNDROME (A REVIEW OF LITERATURE

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    N. Yu. Borovikova

    2016-01-01

    Full Text Available Antiepileptic therapy is one of the most urgent problems in the treatment of Rett’s syndrome. By taking into account a common concurrence of generalized and focal seizures with diffuse epileptiform activity on the electroencephalogram (EEG in Rett’s syndrome, there are effective broad-spectrum antiepileptic drugs (AEDs: valproates, topiramate, levetiracetam, lamotrigine. Carbamazepine is effective for focal seizures and in the absence of diffuse EEG changes. For atypical absences, ethosuximide may be added to valproates, topiramate, or levetiracetam. Reflex seizures show a high resistance; their frequency is occasionally reduced by AEDs in combination with neuroleptics. Sleep hygiene, as well as medication (clonidine, zolpidem, trazodone, melatonin, risperidone are recommended to correct various sleep disorders. Dopamine agonists, as well as L-carnitine are used for the drug correction of movement disorders in Rett’s syndrome. Therapeutic exercises are one of the most optimal ways to correct movement disorders. Orthopedic correction, including surgery, is indicated for skeletal deformities. Vitamin D used for long periods of time is beneficial, by considering its deficiency and osteoporosis at a fracture risk in Rett’s syndrome patients who receive AEDs particularly long. A special high-fat diet and a fractional diet in small portions are used in the therapy of cachexia and growth retardation due to oral dysfunction and malnutrition. A cardiological follow-up is needed in abnormalities, such as prolonged Q interval, tachyarrhythmia, and cardiac structural anomalies. Systematic learning to maintain communication and motor skills are of importance. In this case a special role is played by music therapy that exerts a calming effect on patients and partially compensates for loss of contact with the environment.

  11. The concept of rehabilitation of cancer patients.

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    Body, J J; Lossignol, D; Ronson, A

    1997-07-01

    The scope of supportive care and cancer rehabilitation is very wide and heterogeneous. In this review we focus on nutritional aspects, sexual and gonadal function, psychological rehabilitation, treatment of cancer pain, and rehabilitation of patients with bone metastases. The anorexia-cachexia syndrome is a particularly frequent manifestation of cancer that profoundly affects body image and significantly impairs quality of life of cancer patients. However, enteral feeding through nasogastric tubes, gastrostomies, or jejunostomies is an efficient method for providing long-term enteral nutrition at home and for contributing to complete rehabilitation after cancer therapy. Recent effort has focused on nutritional pharmacology and on the optimalization of the use of appetite-stimulating drugs, such as progestational agents. The psychological components of cancer, anticancer therapy, and quality of life have now been widely recognized and studied. Effective pharmacological and psychotherapeutic interventions help patients and their family to better adjust to the chronic stress of cancer, but more specific determinants of psychological morbidity should be developed. In particular, the safe and efficient use of the most recent classes of antidepressants and anxiolytics should be urgently studied. More than 90% of cancer patients present one or more pain syndromes during their illness. The adequate use of drugs is the cornerstone of treatment. The development on new molecules and new routes of administration opens interesting perspectives for cancer pain control. Bone metastases are the source of considerable morbidity. Intravenous bisphosphonates have been successfully used for the treatment of the symptoms of metastatic bone disease, especially bone pain. Moreover, monthly pamidronate infusions in addition to chemotherapy reduce the mean skeletal morbidity rate by more than one third and contribute to the rehabilitation of cancer patients with bone metastases from breast

  12. Ghrelin gene products and the regulation of food intake and gut motility.

    Science.gov (United States)

    Chen, Chih-Yen; Asakawa, Akihiro; Fujimiya, Mineko; Lee, Shou-Dong; Inui, Akio

    2009-12-01

    A breakthrough using "reverse pharmacology" identified and characterized acyl ghrelin from the stomach as the endogenous cognate ligand for the growth hormone (GH) secretagogue receptor (GHS-R) 1a. The unique post-translational modification of O-n-octanoylation at serine 3 is the first in peptide discovery history and is essential for GH-releasing ability. Des-acyl ghrelin, lacking O-n-octanoylation at serine 3, is also produced in the stomach and remains the major molecular form secreted into the circulation. The third ghrelin gene product, obestatin, a novel 23-amino acid peptide identified from rat stomach, was found by comparative genomic analysis. Three ghrelin gene products actively participate in modulating appetite, adipogenesis, gut motility, glucose metabolism, cell proliferation, immune, sleep, memory, anxiety, cognition, and stress. Knockdown or knockout of acyl ghrelin and/or GHS-R1a, and overexpression of des-acyl ghrelin show benefits in the therapy of obesity and metabolic syndrome. By contrast, agonism of acyl ghrelin and/or GHS-R1a could combat human anorexia-cachexia, including anorexia nervosa, chronic heart failure, chronic obstructive pulmonary disease, liver cirrhosis, chronic kidney disease, burn, and postsurgery recovery, as well as restore gut dysmotility, such as diabetic or neurogenic gastroparesis, and postoperative ileus. The ghrelin acyl-modifying enzyme, ghrelin O-Acyltransferase (GOAT), which attaches octanoate to serine-3 of ghrelin, has been identified and characterized also from the stomach. To date, ghrelin is the only protein to be octanylated, and inhibition of GOAT may have effects only on the stomach and is unlikely to affect the synthesis of other proteins. GOAT may provide a critical molecular target in developing novel therapeutics for obesity and type 2 diabetes. PMID:20038570

  13. Nutritional demands in acute and chronic illness.

    Science.gov (United States)

    Richardson, Rosemary A; Davidson, H Isobel M

    2003-11-01

    Common to both acute and chronic disease are disturbances in energy homeostasis, which are evidenced by quantitative and qualitative changes in dietary intake and increased energy expenditure. Negative energy balance results in loss of fat and lean tissue. The management of patients with metabolically-active disease appears to be simple; it would involve the provision of sufficient energy to promote tissue accretion. However, two fundamental issues serve to prevent nutritional demands in disease being met. The determination of appropriate energy requirements relies on predictive formulae. While equations have been developed for critically-ill populations, accurate energy prescribing in the acute setting is uncommon. Only 25-32% of the patients have energy intakes within 10% of their requirements. Clearly, the variation in energy expenditure has led to difficulties in accurately defining the energy needs of the individual. Second, the acute inflammatory response initiated by the host can have profound effects on ingestive behaviour, but this area is poorly understood by practising clinicians. For example, nutritional targets have been set for specific disease states, i.e. pancreatitis 105-147 kJ (25-35 kcal)/kg; chronic liver disease 147-168 kJ (35-40 kcal)/kg, but given the alterations in gut physiology that accompany the acute-phase response, targets are unlikely to be met. In cancer cachexia attenuation of the inflammatory response using eicosapentaenoic acid results in improved nutritional intake and status. This strategy poses an attractive proposition in the quest to define nutritional support as a clinically-effective treatment modality in other disorders. PMID:15018475

  14. Obesity might be a good prognosis factor for COPD patients using domiciliary noninvasive mechanical ventilation

    Science.gov (United States)

    Altinoz, Hilal; Adiguzel, Nalan; Salturk, Cuneyt; Gungor, Gokay; Mocin, Ozlem; Berk Takir, Huriye; Kargin, Feyza; Balci, Merih; Dikensoy, Oner; Karakurt, Zuhal

    2016-01-01

    Cachexia is known to be a deteriorating factor for survival of patients with chronic obstructive pulmonary disease (COPD), but data related to obesity are limited. We observed that obese patients with COPD prescribed long-term noninvasive mechanical ventilation (NIMV) had better survival rate compared to nonobese patients. Therefore, we conducted a retrospective observational cohort study. Archives of Thoracic Diseases Training Hospital were sought between 2008 and 2013. All the subjects were prescribed domiciliary NIMV for chronic respiratory failure secondary to COPD. Subjects were grouped according to their body mass index (BMI). The first group consisted of subjects with BMI between 20 and 30 kg/m2, and the second group consisted of subjects with BMI >30 kg/m2. Data obtained at the first month’s visit for the following parameters were recorded: age, sex, comorbid diseases, smoking history, pulmonary function test, 6-minute walk test (6-MWT), and arterial blood gas analysis. Hospital admissions were recorded before and after the domiciliary NIMV usage. Mortality rate was searched from the electronic database. Overall, 118 subjects were enrolled. Thirty-eight subjects had BMI between 20 and 30 kg/m2, while 80 subjects had BMI >30 kg/m2. The mean age was 65.8±9.4 years, and 81% were male. The median follow-up time was 26 months and mortality rates were 32% and 34% for obese and nonobese subjects (P=0.67). Improvement in 6-MWT was protective against mortality. In conclusion, survival of obese patients with COPD using domiciliary NIMV was found to be better than those of nonobese patients, and the improvement in 6-MWT in such patients was found to be related to a better survival.

  15. Pythiosis in sheep from Paraná, southern Brazil

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    Fábio D. Bernardo

    2015-06-01

    Full Text Available Abstract: This paper reports pythiosis in a sheep from southwestern Paraná, Brazil, confirmed by indirect ELISA (Enzime-Linked Immunosorbent Assay and immunohistochemistry, as well as it describes the macro and microscopic injuries, in order to understand the pathogenicity. A 4-year-old ewe from a flock of 30 Santa Inês sheep, raised semi-extensively with access to a weir, showed cachexia, bilateral enlargement in nasal region, a serous and bloody secretion with a fetid odor from its nose and swollen submandibular and retropharyngeal lymph nodes. Blood collection was performed trough jugular vein puncture in order to make complete blood cell count (CBC and to obtain serum for the subsequent serological examination. As the hematological counts were within the normal range for sheep, the animal was euthanized and submitted to necropsy. Indirect ELISA resulted positive for pythiosis. Necropsy revealed necrosis of the hard palate with a diameter of 3.5cm and extending up to the nasal cavity, forming a fistula. Submandibular and retropharyngeal lymph nodes were enlarged and edematous on section. Microscopic findings for submandibular and retropharyngeal lymph nodes consisted in moderate infiltration of eosinophils mainly in the subcapsular sinus, characterizing reactive eosinophilic lymphadenitis. The nasal cavity revealed rhinitis and oral cavity stomatitis with necro-eosinophilic and pronounced multifocal granulomatous infiltration and presence of hyphae. Hyphae found in palate and nasal cavity were positive for Pythium insidiosum by Grocott's method and immunohistochemistry, the last one considered to be confirmatory for the pathogen diagnostic. This report has an important epidemiological aspect, as it is the first case of pythiosis in sheep confirmed by serology in South Brazil and an alert of possible infection by the pathogen in floodplains.

  16. Pathological changes of suspected tetrachloro dibenzo-p-dioxins/tetrachloro dibenzofurans toxication in beef cattle

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    Yulvian Sani

    2015-09-01

    Full Text Available The contamination of tetrachlorodibenzo-r-dioxins (TCDDs and tetra chlorinated dibenzofurans (TCDFs may affect human or animal health such as cancer, reproductive failure, dermaltoxicities and neurologic effects. The present study describes the effects of TCDD/TCDFs contamination in feed to various tissues of beef cattle to which TCDD/TCDFs were detected byGC MS/MS. The results revealed that POPs (DDT, heptachlor, aldrin, dieldrin and endrin as a precursor for dioxins were detected in all samples except drinking water. The total concentration of OC in soils was Nd – 42.73 mg/kg, grasses (3.30 – 27.66 mg/kg, well water (0.82 – 1.00 mg/kg, feed mill (3.90 mg/kg, sera (Nd – 13.08 mg/kg and meats (Nd – 100.72 mg/kg. Futhermore, the TEQ residues of TCDDs/TCDFs in beef were 4496.66 - 20642.40 pg/g from Yogyakarta, and 717.13pg/g (beef and 0.037 pg/g (brain tissues from Solo (Central Java. The concentration of TCDD/TCDFs residues in beef was above the maximum residue limit (MRL at 2 pg/g. Animal feeds is regarded as the main source of dioxins contamination in meats. Macroscopic changes were general anaemia, cachexia, fibrotic liver, athropic heart, ruminal impaction, constipated intestinal, haemorrhagic kidney, and ptechiae in the brain. Microscopically were depleted spleen vacuolation of interseptum, haemorrhages and accumulation of hemosiderin. Heart shows degeneration, fragmentation and pale cardiac muscle and swollen nuclei. Liver was pale, degeneration of epithelial cells and congestion. Lungs were pneumonia, oedema pulmonum and mild haemorrhage. Intestines showed haemorrhage and infiltration of mononuclear cells, neutrophyls and eosinophyls. Brain was haemorrhage, perivascular cuffs and intranuclear inclusion bodies. The animal was suffering from haemorrhagic enteritis, encephalitis, and hepatic degeneration.

  17. The Role of Serum Leptin and IL-6 Levels in Post Viral Hepatitis Cirrhotic patients

    International Nuclear Information System (INIS)

    Chronic liver disease is characterized by numerous metabolic alterations resulting in the clinical picture of malnutrition or even cachexia and contributing to complications such as hepatic encephalopathy and ascites. Leptin is a hormone that plays an important role in regulating energy intake and expenditure including appetite and metabolism. Interleukin-6 (IL-6), on the other hand, is generally considered to be one of the important cytokines that regulate immunologic and metabolic actions. The aim of the present study was to investigate serum leptin and IL-6 levels in liver cirrhosis, as well as to determine their levels in relation to liver functions and lipid profile. This study was conducted on 25 patients with post- viral hepatic cirrhosis compared to 20 healthy matched individuals served as controls with the same age and sex. The severity of the disease assessed with Child-Pugh criteria yielded 8 patients (3 women, 5 men) with stage A, 10 patients (4 women, 6 men) with stage B and 7 patients (2 women, 5 men) with stage C. Compared to controls, body mass index (BMI) was decreased and reached statistical significance in group C liver cirrhosis (P< 0.05). Also, serum leptin level was highly significantly decreased in the three groups, while IL-6 level showed highly significant increase. Leptin level negatively correlated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin and positively correlated with serum albumin, triglycerides (TG), cholesterol and low density lipoprotein (LDL). In contrast, serum IL-6 level positively correlated with parameters of liver functions and negatively correlated with parameters of lipid profile. Additionally, there was highly significant negative correlation between serum leptin and IL-6 levels (P < 0.001) in post-hepatic cirrhotic patients. We concluded that leptin and IL-6 have important role in diagnosis and prognosis of patients with post-hepatic liver cirrhosis

  18. Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations.

    Science.gov (United States)

    Behrens, Maria I; Brüggemann, Norbert; Chana, Pedro; Venegas, Pablo; Kägi, Marianne; Parrao, Teresa; Orellana, Patricia; Garrido, Cristian; Rojas, Cecilia V; Hauke, Jan; Hahnen, Eric; González, Rafael; Seleme, Nicolas; Fernández, Verónica; Schmidt, Alexander; Binkofski, Ferdinand; Kömpf, Detlef; Kubisch, Christian; Hagenah, Johann; Klein, Christine; Ramirez, Alfredo

    2010-09-15

    We report the clinical features of the original Chilean family with Kufor-Rakeb syndrome (KRS) that led to the discovery of the ATP13A2 gene at the PARK9 locus. KRS is a rare juvenile-onset autosomal recessive disease characterized by progressive Parkinsonism, pyramidal signs, and cognitive decline in addition to vertical gaze palsy and facial-faucial-finger minimyoclonus. Neurological and neuropsychological examination during a 10-year period, videotaping, neuroimaging, and measurement of DNA methylation of the ATP13A2 promoter region were performed. The youngest 5 of 17 children of nonconsanguineous parents, carrying compound-heterozygous ATP13A2 mutations, had normal development until ages ∼10 to 12 years, when school performance deteriorated and slowness, rigidity, and frequent falls developed. Examination revealed bradykinesia, subtle postural/action tremor, cogwheel rigidity, spasticity, upward gaze palsy, smooth pursuit with saccadic intrusions, and dementia. Additional signs included facial-faucial-finger minimyoclonus, absent postural reflexes, visual/auditory hallucinations, and insomnia. Levodopa response could not be fully judged in this family. T2* magnetic resonance imaging sequences revealed marked diffuse hypointensity of the caudate (head and body) and lenticular nucleus bilaterally. Disease progression was slow including epilepsy, cachexia, and anarthria. Four affected members died after 28.5 ± 5.5 (mean ± SD) years of disease. Two heterozygous carriers, the mother and eldest sibling, showed jerky perioral muscle contractions and clumsiness of hand movements. There was no significant correlation between DNA methylation of the ATP13A2 promoter region and disease progression. The marked caudate and lenticular nucleus T2*-hypointensity suggests that KRS might belong to the family of neurodegenerative diseases associated with brain iron accumulation. PMID:20683840

  19. Development of a high throughput screen for allosteric modulators of melanocortin-4 receptor signaling using a real time cAMP assay.

    Science.gov (United States)

    Pantel, Jacques; Williams, Savannah Y; Mi, Dehui; Sebag, Julien; Corbin, Jackie D; Weaver, C David; Cone, Roger D

    2011-06-11

    The melanocortin MC(4) receptor is a potential target for the development of drugs for both obesity and cachexia. Melanocortin MC(4) receptor ligands known thus far are orthosteric agonists or antagonists, however the agonists, in particular, have generally exhibited unwanted side effects. For some receptors, allosteric modulators are expected to reduce side-effect profiles. To identify allosteric modulators of the melanocortin MC(4) receptor, we created HEK293 cell lines coexpressing the human melanocortin MC(4) receptor and a modified luciferase-based cAMP sensor. Monitoring luminescence as a readout of real-time intracellular cAMP concentration, we demonstrate that this cell line is able to report melanocortin agonist responses, as well as inverse agonist response to the physiological AgRP peptide. Based on the MC4R-GLO cell line, we developed an assay that was shown to meet HTS standards (Z'=0.50). A pilot screen run on the Microsource Spectrum compound library (n=2000) successfully identified 62 positive modulators. This screen identified predicted families of compounds: β(2)AR agonists - the β(2)AR being endogenously expressed in HEK293 cells, an adenylyl cyclase activator and finally a distribution of phosphodiesterase (PDE) inhibitors well characterized or recently identified. In this last category, we identified a structural family of coumarin-derived compounds (imperatorin, osthol and prenyletin), along with deracoxib, a drug in veterinary use for its COX2 inhibitory properties. This latter finding unveiled a new off-target mechanism of action for deracoxib as a PDE inhibitor. Overall, these data are the first report of a HTS for allosteric modulators for a Gs protein coupled receptor. PMID:21296065

  20. Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease.

    Science.gov (United States)

    Argilés, Josep M; Campos, Nefertiti; Lopez-Pedrosa, José M; Rueda, Ricardo; Rodriguez-Mañas, Leocadio

    2016-09-01

    Skeletal muscle is recognized as vital to physical movement, posture, and breathing. In a less known but critically important role, muscle influences energy and protein metabolism throughout the body. Muscle is a primary site for glucose uptake and storage, and it is also a reservoir of amino acids stored as protein. Amino acids are released when supplies are needed elsewhere in the body. These conditions occur with acute and chronic diseases, which decrease dietary intake while increasing metabolic needs. Such metabolic shifts lead to the muscle loss associated with sarcopenia and cachexia, resulting in a variety of adverse health and economic consequences. With loss of skeletal muscle, protein and energy availability is lowered throughout the body. Muscle loss is associated with delayed recovery from illness, slowed wound healing, reduced resting metabolic rate, physical disability, poorer quality of life, and higher health care costs. These adverse effects can be combatted with exercise and nutrition. Studies suggest dietary protein and leucine or its metabolite β-hydroxy β-methylbutyrate (HMB) can improve muscle function, in turn improving functional performance. Considerable evidence shows that use of high-protein oral nutritional supplements (ONS) can help maintain and rebuild muscle mass and strength. We review muscle structure, function, and role in energy and protein balance. We discuss how disease- and age-related malnutrition hamper muscle accretion, ultimately causing whole-body deterioration. Finally, we describe how specialized nutrition and exercise can restore muscle mass, strength, and function, and ultimately reverse the negative health and economic outcomes associated with muscle loss. PMID:27324808