Clinical Outcome and Reverse Epidemiology
Many recent studies have suggested that protein-energy malnutrition and inflammation in maintenance dialysis patients are associated with a decreased quality of life and increased hospitalisation and mortality, especially from cardiovascular diseases 10,27,28,123 . Epidemiological studies indicate that hypoalbuminaemia and increased serum CRP are strong predictors of poor clinical outcome in the CKD population 36, 37 . Compared to traditional risk factors, such as obesity,...
Functional Anatomy of Brown Adipose Tissue
In the 1990s, advances were also made in the study of brown adipose tissue. Especially following the studies by Stock et al. reported above, a rising num ber of laboratories began to focus on BAT, soon leading to the description of the main mechanisms of action of brown adipocytes. An uncoupling protein UCP1 expressed solely in brown adipocyte mitochondria was identified 23-25 , as an atypical p-adrenergic receptor p3-AR , which appeared to be prevalently expressed by adipose tissue 26, 27 ....
Galanin and GalaninLike Peptide
Galanin is a 30 amino acid peptide with widespread distribution in the CNS 51 . Three distinct galanin receptor subtypes, GalR1, GalR2 and GalR3, have been described at the hypothalamic level 52 , in neurons also expressing leptin receptor 51 . Both galanin and galanin receptor have also been demonstrated in adipose tissue in rats 53 . The intracerebroventricular administration of galanin induces food intake 54 . This effect has been suggested to be mediated by modulation of leptin expression...
Physical Values
The energy values of a single food or nutrient can be directly measured by determining the amount of heat released upon its ignition and total combustion in a bomb calorimeter Fig. 1 . The values obtained with this direct measurement for different foods and nutrients are reported in Table 1 3 . These values do not correspond to the amount of energy utilisable by the body, since they do not take into consideration the amount lost by digestive and metabolic processes, i.e. excretion in the...
References Tml
1. Mattews DE 1999 Proteins and amino acids. In Shills ME, Olson JA, Shine M, Ross AC eds Modern nutrition in health and disease, 9th ed. Lippicott Williams amp Wilkins, Baltimore, pp 11-48 2. Munro HN, Allinson JB 1964 Mammalian protein metabolism. Academic Press, New York, London 3. Papper S 1971 Renal failure. Med Clin North Am 55 335-357 4. Cahill GF Jr 1976 Starvation in man. Clin Endocrinol Metab 5 397-415 5. Bodwell CE, Schuster EM, Kyle E et al 1979 Obligatory urinary and fecal nitrogen...
Conclusions Tlx
PIF is a novel sulphated glycoprotein, secreted only by cachexia-inducing tumours, that may play a major role in muscle atrophy in cancer cachexia. PIF may serve as an appropriate target for the development of anticachectic agents. ma of the mouse colon producing cachexia in recipient animals. J Natl Cancer Inst 78 539-546 8. Beck SA, Tisdale MJ 1987 Production of lipolytic and proteolytic factors by a murine tumor-producing cachexia in the host. Cancer Res 47 5919-5923 9. McDevitt TM, Todorov...
Neurohormonal Abnormalities
Besides activation of the immune system, neurohormonal abnormalities are also important in the pathophysiology of the development of cardiac cachexia. Attributed to impaired cardiac function, a general neurohormonal activation, in which the sympathetic nervous system, the renin-angiotensin-aldosterone axis, and the natriuretic peptide system are stimulated, occurs when heart failure deteriorates to a chronic disease state. Fig. 3. The cardiorenal anaemia syndrome - anaemia as a cause and...
Primary Hyperparathyroidism
Among endocrine disorders inducing weight change, and theoretically weight loss, primary hyperparathyroidism PHPT must be mentioned. PHPT is a common endocrine disorder that predominantly affects post-menopausal women 43 . It is mostly caused by solitary adenomas of the parathyroid gland and is characterised by hypersecretion of parathyroid hormone PTH and consequently by hypercalcaemia. In addition to regu lating calcium concentrations, PTH exerts metabolic effects, including a stimulatory...
Diagnosis and Screening for Cachexia
The rate of detection of cachexia is low among physicians. Even after diagnosis was made, appropriate intervention was instituted in only one-third of the patients, according to one study 84 . The low rates of detection and intervention are most often due to the inability to make the diagnosis 85 thus, there is a need for improved screening for cachexia 85 . The Mini Nutritional Assessment MNA is a well-validated tool that was specifically designed for use with community-dwelling elderly 85 ....
Performance Status as a Functional EndPoint in Oncology
Assigning a 'performance status' PS score to a patient is the most common form of functional assessment in oncology. There are several PS tools in widespread use, providing a formal framework for gathering functional information and influencing treatment decisions. Common examples are the Karnofsky PS score KPS 6 , an 11-point scale from normal score 100 to deceased 0 and the World Health Organisation WHO PS score 7 , a more succinct five-point scale from normal 0 to completely disabled and...
Vitamin B3
Vitamin B3 is niacin, also known as nicotinic acid. The metabolically active forms of niacin are the pyridine nucleotides, nicotinamide adenine dinu-cleotide NAD and nicotinamide adenine dinu-cleotide phosphate NADP 65 . Free forms of the vitamin are white stable crystalline solids 65 . Only small amounts of the free forms of niacin occur in nature 65 . Most of the niacin in food is present as a component of NAD or NADP 65 . Pellagra is the clinical manifestation of niacin deficiency.
Mechanism of Muscle Protein Degradation by PIF
The transcription factor NF-kB may also be important in PIF-induced expression of the ubiquitin-proteasome pathway in skeletal muscle, in addition to its role in liver and endothelial cells 31 . In murine myotubes that were used as a surrogate model of skeletal muscle, PIF produced a transient decrease in the cytosolic NF-kB inhibitor protein IKBa. This was accompanied by increased nuclear migration of NF-kB, at the same concentrations of PIF as those inducing protein degradation, and increased...
Dietary Intake
There are several difficulties in selecting a sample of elderly people for a nutritional study. Some authors 29 suggest the selection of'healthy' elderly. Even if it is possible to obtain an almost homogeneous group, this is not a 'real' sample of an elderly population, which is, on the contrary, characterised by a high heterogeneity of subjects Table 1. Clinical signs in malnutrition Table 1. Clinical signs in malnutrition Thinness, sparseness, easy pluckability Diffuse depigmentation,...
Ghrelin and Cachexia
Cachexia is a clinical condition frequently associated with neoplastic disease and chronic heart failure characterised by loss of body weight, negative nitrogen balance and fatigue that significantly affects patients' quality of life, morbidity and survival. Taking into account the important role of ghrelin in the regulation of food intake and energy metabolism, several studies investigated the possible role of ghrelin as a factor involved in the development of cachexia or as a potential tool...
Lipid Metabolism in Cachexia
In this chapter we will review the alterations of lipoprotein metabolism observed in cachexia. Other aspects of lipid metabolism in cachexia, in particular those regarding adipose tissue, are covered in other chapters. Lipoproteins are macro-molecules circulating in blood and they are quite easily measured in the clinical chemistry laboratory. For this reason lipoproteins can be used to monitor the alterations of lipid metabolism in several clinical conditions, including cachexia. All lipids,...
Changing Patterns of Cachexia in the HAART Era
A familiarity with the information on adipose tissue provided in the previous section is necessary to understand the complex nutritional changes related to HIV infection and its treatments. It has long been known that during the progression of HIV infection, as well as of other chronic infections and tumours, patients may undergo progressive weight loss and changes in body composition, particularly in fat and muscle masses, and in metabolic pathways, particularly lipid metabolism 62, 111 . This...
Strategies To Fight Cachexia Based on Cytokines and Transcriptional Factors
Since both anorexia and metabolic disturbances are involved in cancer cachexia, the development of different therapeutic strategies has focused on these two factors. Unfortunately, counteracting anorexia either pharmacologically or nutritionally has led to rather disappointing results in the treatment of cancer cachexia. It is basically for this reason that the strategies mentioned below rely on neutralising the metabolic changes induced by the tumour, which are ultimately responsible for the...
Cold Exposure
This condition involves the immediate activation of the orthosympathetic system, with the consequent, immediate functional activation of brown adipocytes via the innervation and the neuro-adipocytic junctions described above. In a matter of hours, activated adipocytes exercise their ther-mogenic function by synthesising new mitochondria and UCP1 in the course of a few days new cells develop, giving rise to a new tissue organisation characterised by an increased number of vessels and nerves 59,...
References Lxc
1. Lewis JD, Fisher RL 1994 Nutrition support in inflammatory bowel disease. Med Clin North Am 78 1443-1456 2. Zurita VF, Rawls DE, Dyck WP 1995 Nutritional support in inflammatory bowel disease. Dig Dis 13 92-107 3. Geerling BJ, Badart-Smook A, Stockbrugger RW, Brummer RJ 2000 Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls. Eur J Clin Nutr 54 514-521 4. Charney P 1995 Nutrition assessment in the 1990s where are...
MediumChain Triglycerides
In MAC-16 tumours, an anti-cachectic effect can be obtained, together with a reduction of tumour mass, by administration of amount of MCT gt 80 of the required energy 58, 60 . Cachexia and tumour growth rate 61 can be reduced by replacing a portion of dietary carbohydrates with lipid derivatives of fish oil at 50 of the total calories in the animal diet. Even those neoplastic patients with a weight loss gt 32 , can recover their weight with isocaloric diets in which energy is supplied by MCT at...
Ghrelin as a New Factor in the Control of Energy BalanceAppetite and Food Intake
Among all the biological actions of ghrelin, particular attention has been focused on its role in the regulation of appetite and energy balance. Long before ghrelin was discovered, different reports in rodents indicated that some GHS pos sess orexigenic activity 41 . Moreover, in the last decade, a substantial amount of data showed that GHS were able to activate neurons in hypothalam-ic areas strictly involved in the control of energy balance 41, 42 . Accordingly, ghrelin emerged as one of the...
References Sgo
1. National Kidney Foundation 2002 K DOQI clinical practice guidelines for chronic kidney disease evaluation, classification, and stratification. Am J Kidney Dis 39 S1-S266 2. Keith DS, Nichols GA, Gullion CM et al 2004 Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 164 659-663 3. Jones CA, McQuillan GM, Kusek JW et al 1998 Serum creatinine levels in the US population third National Health and Nutrition...
Mechanisms of Malnutrition in Chronic Pancreatitis
Malnutrition and weight loss in patients with chronic pancreatitis mainly result from maldigestion and abdominal pain Fig. 1 . The loss of aci- Fig.1. Malnutrition in patients with chronic pancreatitis. Modified from 83 Fig.1. Malnutrition in patients with chronic pancreatitis. Modified from 83 nar cells causes insufficient secretion of lipase, col-ipase, amylase, and proteases, which results in maldigestion of lipid, carbohydrates, and protein. Of these nutrients, fat maldigestion is the most...
Role of Ghrelin in Cachexia
Many aspects of appetite regulation that involve peripheral signalling to hypothalamic pathways remain poorly understood. Growth hormone GH secretion from the anterior pituitary is regulated by GH-releasing hormone GHRH , which stimulates the release of GH as well as its inhibitor somatostatin 76 . GH secretagogues are synthetic compounds able to stimulate secretion of the hormone 77 but which act through a receptor different from that for GHRH receptor. Instead, ghrelin was discovered to be...
Deep Layer Fat
The deep layer lamellar fat constitutes blocked reserve fat, easy to gain and difficult to lose, metabolised only when there is starvation. It has a laminar pattern and a horizontal orientation, and is arranged as fat pads localised fat pads, LFP , surrounded by a fascia that is sometimes well identified as a specific capsule and sometimes indistinct from the fascias of the muscles, differently located according to sex, race and genetic Fig. 2. Typical 'Chesterfield sofa' look of the skin of...
In Vivo Measures of Immune Function
The delayed T-cell hypersensitivity DTH response is a widely used in vivo assay for assessing an individual's bacterial host defence capability. Suppression of the response signals a failure of one or more components of the host defence sys tem. In this procedure, a series of antigens ubiquitous antigens derived from bacterial and fungal products as well as 2,4-dinitrochlorobenzene are injected intradermally in the forearm and the area of induration is measured at 24 and 48 h. The rationale is...
Congenital Partial Lipodystrophy Type 1 Dunningam Syndrome
This LD variety was first described by Dunningam in 1974 32 in females belonging to two families in Scotland. An autosomal dominant transmission of the disease was reported in five families. To date, some 200 cases of the disease have been reported, with a higher prevalence in females. Atrophy of the subcutaneous fat layer usually manifests at puberty, involving the arms, legs, and buttocks. The subcutaneous adipose tissue of the face, neck, and intra-abdominal area may be preserved, giving...
Octanoylation of Ghrelin
Collectively, the chemistry-driven conceptualisation of the ghrelin system compellingly fuses the chemistry and biology of bioactive ghrelin into a very special interdependence. The control of regulation of the octanoylating enzyme complex by a potential array of specific metabolic, nutritional and hormonal factors will require elucidating. Octanoylation of the 28 amino acid ghrelin peptide requires the extraordinary specificity of performing three major precise chemical steps presumably by a...
A Complex Picture Emerges
Many studies were carried out in the 1950s and 1960s aiming at investigating special aspects of metabolic malfunction and changes in body composition secondary to chronic diseases. The evidence emerging from these studies made it apparent that multiple mechanisms act in combination, forming a complex web of metabolic imbalance with catabolism dominating the anabolic drive, resulting in weight loss. A first attempt at a comprehensive overview of the complex pathophysiology of cachexia with...
References Ddt
1. Fearon KCH 1992 The mechanisms and treatment of weight loss in cancer. Proc Nutr Soc 51 251-265 2. Kotler DP, Tiemey AR, Culpepper-Morgan JA et al 1990 Effect of home total parenteral nutrition on body composition in patients with acquired immunodeficiency syndrome. J Parent Enteral Nutr 14 454-458 3. Strent SJ, Beddoe AH, Hill GL 1987 Aggressive nutritional support does not prevent protein loss despite fat gain in septic intensive care patients. J Trauma 27 262-266 4. Evans WK, Makuch R,...
Cachexia and Wasting A Modern Approach
Co-editors Stefan D. Anker Akio Inui John E. Morley Filippo Rossi Fanelli Daniele Scevola Michael W. Schuster Shing-Shing Yeh G. Mantovani Editor Department of Medical Oncology University of Cagliari, Cagliari, Italy Imperial College, NHLI, Department of Clinical Cardiology, London, United Kingdom Applied Cachexia Research, Department of Cardiology Charit , Campus Virchow-Klinikum, Berlin, Germany GRECC, VA Medical Center and Division of Geriatric Medicine, Saint Louis University, St. Louis,...
Ghrelin and Anorexia Nervosa
Anorexia nervosa is a psychiatric disorder characterised by patient-induced and maintained weight loss that leads to progressive malnutrition and specific pathophysiological signs disturbance of body image and fear of obesity . Based on the presence or not of bulimic symptoms, anorexia nervosa appears in two specific subtypes, restricting and binge-eating purging 70 . Complications in many organ systems can occur, including cardiovascular, gastrointestinal, haematological, renal, skeletal,...
Conclusions
The older population differs from younger adults not only in age but also in health status. The elderly group is not a homogeneous population, and their many different health and social problems impact on their nutritional status 84 . Optimal nutrient intake not only meets their needs but prevents some chronic diseases and ameliorates others 84 . Besides the biochemical parameters, attention must be paid to environmental and psychological factors in evaluating nutritional status and...
Transdifferentiation
Transdifferentiation is a biological phenomenon by which a differentiated cell turns phenotypically and functionally into a differentiated cell of another type without undergoing dedifferentiation 64 . We believe that brown and white adipocytes can transdifferentiate into one another in the adipose organ. We report some data providing evidence for physiological transdifferentiation of white into brown fat cells. Since Ashwell's pioneering work 1984 , it has been known that, after cold exposure,...
Regulation of Appetite in the Elderly
Regulation of appetite is a sophisticated process that involves feedback from peripheral sensory endings and the interaction of a variety of neurotransmitters in the central nervous system 1 . Numerous studies have shown that food intake declines over the human lifespan, with males having a greater decrease in food intake than females. A large part of the anorexia of aging seems to be related to the changes in gastrointestinal activity that occurs with aging 1 . During a meal, the fundus...
Medroxyprogesterone Acetate and Megestrol Acetate Clinical Experiences
The progestin derivatives MPA and MA have been widely used in the treatment of cancer cachexia, which shows clinical features and, probably, pathological mechanisms similar to those of AIDS wasting syndrome 73, 74 . In anorectic and cachectic AIDS patients, MPA and MA have proved to be particularly effective 65-69,75-80 . Medroxyprogesterone Acetate In two clinical studies 22, 66 , we used MPA 1 g day, os and a hypercaloric diet to correct anorexia and cachexia occurring in HIV-infected...
Therapy of Lipodystrophy Syndrome
No accepted guidelines for the treatment of lipodystrophy syndrome exist, rather, only anecdotal approaches. There is also no validated drug therapy to ameliorate or correct lipodystrophy-associated abnormalities 99 . Instead, treatment must be directed at reducing fat accumulation in visceral adipose tissue VAT , and dorsocervical fat buffalo hump , and or increasing SAT in conditions of lipoatrophy. Thus, prevention is by far the best approach to reverse lipodystrophy. Table 3. Anthropometric...
References Myr
1. Chipkin SR, Kelly KL, Ruderman NB 1994 Hormone-fuel interrelationships fed state, starvation, and diabetes mellitus. In Kahn CR, Weir GC ed Joslin's Diabetes Mellitus 13th ed. Lea amp Febiger, Malvern, Pennsylvania, pp 97-115 2. Petersen KF, Laurent D, Rothman DL et al 1998 Mechanism by which glucose and insulin inhibit net hepatic glycogenolysis in humans. J Clin Invest 101 1203-1209 3. Liu Z, Gardner LB, Barrett EJ 1993 Insulin and glucose suppress hepatic glycogenolysis by distinct...
Leptin Interacts with Ghrelin and Insulin
It is commonly assumed that the effects of leptin and ghrelin on metabolism, including food intake, are exactly opposite. Ghrelin is considered to be a hunger hormone, whereas leptin is a satiety signal 47 . Rising ghrelin levels in concert with falling leptin levels may serve as a critical signal to induce hunger during fasting 48 . It has been observed that leptin exerts a restraint on the orex-igenic effects of ghrelin in two ways, centrally by counteracting its appetite-promoting effects at...
Anatomy
Using anatomical microdissection, our group demonstrated that not only is it possible to excise and isolate nearly the entire adipose content of mammalian organisms, but also that BAT is wholly found in fat depots that are often prevalently white. In other words, in adult rodents kept in standard feeding and environmental conditions there are no totally brown depots distinct from WAT depots, but a single organ articulated into several subcutaneous and visceral depots containing both tissues 39...
Compensatory Mechanisms
The analysis of interactions among endogenous chemical factors also needs to consider compensatory mechanisms that are activated during pro-catabolic activities or overriding anabolic processes. For instance, circulating ghrelin - a positive modulator of energy balance via orexi-genic, adipogenic and growth hormone releaser activities 39, 40 - levels are elevated in patients with wasting and cachexia and this elevation can be associated with increases in TNF-a 41 . The potential anti-cachectic...
References Jat
1. Abbasi AA, Rudman D 1993 Observations on the prevalence of protein-calorie undernutrition in VA nursing homes. J Am Geriatr Soc 41 117-121 2. Abbasi AA, Rudman D 1994 Undernutrition in the nursing home prevalence, consequences, causes and prevention. Nutr Rev 52 113-122 3. Wallace JI, Schwartz RS 2002 Epidemiology of weight loss in humans with special reference to wasting in the elderly. Int J Cardiol 85 15-21 4. Rabinovitz M, Pitlik SD, Leifer M et al 1986 Unintentional weight loss an...
Diagnosis and Management of MICS and Wasting Syndrome in CKD
Since various markers of nutritional state and inflammation may independently predict outcome and assess different aspects of nutritional status, several researchers have tried to develop composite scores to identify the wasting syndrome and MICS in CKD. Ideally, such a scoring system would not only reflect the overall nutritional and inflammatory status of a chronic dialysis patient but would predict outcome. Wolfson et al. 81 introduced a composite score based on body weight, mid-arm muscle...
Micronutrient Metabolism
Deficiencies of water-soluble vitamins, including vitamin C, and the B complex compounds, are particularly common in cirrhotic patients with active alcoholism. Similarly, low plasma concentration of fat-soluble vitamins A, E, D, and K may occur in patients with cirrhosis of any aetiology 72 . Abnormalities in vitamin activation, conversion, release, and transport by carrier molecules all result from hepatocellular injury. Low serum levels of some trace elements, such as zinc and selenium, have...
Conclusions Ayh
Anorexia is a syndrome that is pervasive among patients suffering from acute and chronic diseases. The pathogenesis is multifactorial, but it appears to be related to the hyperactivation of hypothalamic inhibitory pathways, which in turn may be triggered by cytokine-driven stimulation of the hypothalamic serotonergic system. Anorexia can be effectively treated, although it is not known whether amelioration of anorexia results in a long-term benefit for patients, leading to reduced morbidity and...
Energy Metabolism
Much research during the last decade has been focussed on energy expenditure in COPD. Total energy expenditure TEE can be divided into dif ferent components, with the basal metabolic rate usually being the largest component. Physical-activity-induced thermogenesis can vary substantially between different individuals. Other components of TEE are diet-induced thermogenesis DIT , drug-induced thermogenesis, and the thermoregulatory component. Gas-exchange measurements made in patients in the...
Transferrin
Plasma transferrin is a 80 KDa glycoprotein with homologous N-terminal and C-terminal iron-binding domains called the N- and C-lobes 39 . The transferrin gene is on chromosome 3. Transferrin is the product of an ancient intragenic duplication that led to homologous carboxyl and amino domains, each of which has one binding site for trivalent iron and two for bicarbonate 40 . The liver synthesises transferrin and secretes it into the plasma. Transferrin is also produced locally in the testes and...
Peptides
Consistent and convincing evidence suggests that disease-associated anorexia is brought about by derangement of the hypothalamic system regarding its ability to transduce peripheral signals into neuronal responses. Under normal conditions, peripheral signals interact with two separate neuronal populations within the arcuate nucleus the NPY agouti-related peptide AgRP neurons, stimulating food intake, and the pro-opiomelanocortin POMC cocaine- and amphetamine-regulated transcript CART neurons,...
Clinical Impact
The onset of anorexia significantly impacts on the clinical course of the disease. It contributes to the development of malnutrition and cachexia, since it reduces the oral intake of calories, thus further promoting skeletal-muscle wasting. Also, it exacerbates the detrimental effects of disease-related alterations of protein metabolism on nutritional status, eventually leading to increased morbidity and mortality 16 . The metabolic dysregulation associated with cachexia 17 sustains and...
References Ibj
1. Lawrence RD 1946 Lipodystrophy and hepatomegaly with diabetes, lipemia and other metabolic disturbances. Lancet 1 724-731 2. Misra A, Garg A 2003 Clinical features and metabolic derangements in acquired generalized lipodi-strophy case reports and review of the literature. Medicine 82 129-146 3. Garg A 2000 Lipodistrophies. Am J Med 108 143-152 4. Huemer C, Kitson H, Realleson PN et al 2001 Lipodystrophy in patients with juvenile dermatom-yositis. Evaluation of clinical and metabolic...