Diabetic Neuropathy and Digestive System Dysfunction

Dysfunction of the digestive system in diabetic subjects usually results from complications associated with the disease. Neuropathies are also a common complication of diabetes, with the prevalence after diagnosis approaching 50 at 25 years. Diabetic enteric neuropathy plays an important role in many gastrointestinal abnormalities. The symptoms of nausea and vomiting in diabetic patients may be due to diabetic gastroparesis, which is associated with delayed gastric emptying of foods....

Creatine

Creatine is a physiologically active substance required for muscle contraction. The proper amount of creatine phosphate in the muscle allows high rates of adenosine resynthesis therefore, it plays a vital role in the performance of high-intensity exercise. Creatine supplementation has not consistently been shown to enhance performance in exercise tasks, but it may increase performance in situations in which the availability of creatine phosphate is important 164, 165-168 . Short-term creatine...

Glucose Metabolism Changes in CACS

Glucose is the most important energetic substrate of the human body. Neoplastic cells preferentially metabolise glucose through anaerobic glycolysis. In cancer patients, glucose intake is severely compromised by the presence of symptoms such as nausea, vomiting and anorexia. The reduced glucose intake induces the activation of gluconeo-genesis from lactate, muscle amino acids and free fatty acids, finally leading to depletion of fat and protein stores. The cycle converting lactate to pyruvate...

Treatment of Symptoms and Constipation as Causes for Secondary Anorexia Cachexia

In patients with advanced, progressive, incurable disease, the causes of anorexia, decreased oral intake and loss of weight are complex. Besides the primary (paraneoplastic) catabolic processes, a number of important causes for loss of appetite or weight may occur, such as severe symptoms (i.e. pain, shortness of breath, depression), syndromes (i.e. constipation, mucositis, bowel obstruction) or prolonged bed rest 12 . Poor assessment of interfering symptoms (see Chp. 9.11) by not acknowledging...

Biological Effects of PIF

Since the 24-kDa glycoprotein was originally purified with LMF, it was thought that it may be a lipoly-sis-inducing agent. However, it was found not to have an effect on adipose tissue, but instead induced protein degradation in isolated skeletal muscle 12 . It was therefore given the name proteolysis-inducing factor (PIF), and is likely to be the serum factor previously identified as inducing protein breakdown in skeletal muscle 6 . Biological activity was destroyed by preincubation with...

Activity Efficacy and Safety of Progestagens in Palliative Treatment of Cancer Cachexia

The use of progestagens in the palliative treatment of cancer cachexia has been largely investigated in the past few years, and to date they represent the treatment of choice 1-6,8,9,94 . However, despite the large amount of data about activity, efficacy and safety of medroxyprogesterone acetate or megestrol acetate 95-111 , and the supposed down-regulation of the cytokine cascade as their main mechanism of action 42-44 , some considerations can be made. Unlike what has been observed about the...

References

Yancik R, Ries LA (2000) Aging and cancer in America. Demographic and epidemiologic perspectives. Hematol Oncol Clin N America 14 17-23 2. Balducci L, Extermann M (2004) A practical approach to the older cancer patient. Curr Probl Cancer 25 6-76 3. Balducci L, Extermann M (2003) The assessment of the older cancer patient. In Overcash J, Balducci L (eds) The older cancer Patient. Springer medical Publisher, New York 4. Cohen HJ, Feussner JR, Weinberger M et al (2002) A controlled trial of...

The Meaning of Eating in Terminally Ill Patients Importance of Carers

In patients suffering from terminal disease, such as far-advanced and progressive cancer, the meaning of eating shifts as death becomes close. Gradual cessation of oral intake is part of the natural process of dying, and has been included as one of the few key signs of diagnosing dying (in the Liverpool pathway) 13 . Assessing nutritional status in such patients concentrates increasingly on eating-related distress and on the distress of their carers. The research in this (difficult) field is...

The Human Adipose Organ

As in small mammals, the adult human adipose organ is made up of subcutaneous as well as visceral depots. In normal adult individuals it accounts for about 9-18 of body weight in men and 14-28 in women. Most of the organ is located subcutaneously its distribution is sex-dependent, the mammary and gluteo-femoral subcutaneous depots being more developed in women. The visceral depots are very similar to those described in small mammals. In overweight or obese individuals, the abdominal visceral...

Protein Requirement and Energy Intake

It has been proposed that protein requirement is, within a certain limit, inversely dependent on energy intake, i.e. the more energy is ingested, the less protein is needed (Table 4). This is because proteins can be used also as energy sources (beyond their structural, regulatory and functional role). Therefore, if their use to produce energy varies, their requirement also varies. Furthermore, alternative energy substrates, such as the carbohydrates, can stimulate insulin secretion, which in...

Familial Partial Lipodystrophy Associated with a PPARg Gene Mutation

Garg et al. recently reported on a missense heterozygous mutation, Arg397Cys, in peroxisome-proliferator-activated receptor-gamma (PPARy) gene in a 64-year-old woman with diabetes, hypertriglyceridaemia, hypertension, hirsutism, and marked subcutaneous fat loss, more prominent in her forearms and calves than in her upper arms and thighs 35 . Other heterozygous mutations in the PPARy gene were subsequently recognised in subjects with familial partial LD 36, 37 . PPARy is highly expressed in...

Tumours as Source of PIF

The 24-kDa factor was initially isolated from the murine cachexia-inducing MAC16 tumour 11 , but it was also found to be present in the urine of patients with carcinoma of the pancreas, breast, ovary, lung, colon, rectum, and liver in whom the rate of weight loss was > to about 1 kg per month 16 . Patients who were weight-stable or in whom the rate of weight loss was < 1 kg month showed no evidence for excretion, even though they had the same tumour types. Subjects with weight loss...

Functional Anatomy of White Adipose Tissue

Important discoveries in the 1990s rekindled the interest in white adipose tissue. In December 1994, the team of Friedman at New York Rockefeller University discovered the gene of obesity 8 their subjects were mice, which in the 1950s had developed a spontaneous mutation resulting in hyper-phagia, infertility and reduced activity of the sympathetic nervous system, and consequently in early, massive obesity (ob ob mice) 9 . The alteration - detected on chromosome 6 -consisted of a C to T point...

Chronic Inflammation as a Cause of Cachexia in CKD Patients

Inflammation is defined as a localised adaptive response elicited by injury or destruction of tissues that serves to destroy, dilute, or sequester both the injurious agent and the injured tissue 30, 31 . The acute-phase response (or reaction) is a major pathophysiological phenomenon that accompanies inflammation and is associated with increased activity of pro-inflammatory cytokines 32 . With this reaction, normal homeostatic mechanisms are replaced by new set points that presumably contribute...

TNFa and Cancer Cachexia

The pathogenesis of cancer cachexia has not been fully elucidated. However, numerous cytokines produced by activated lymphocytes, monocytes, macrophages and or tumour cells, including TNF-a, interleukin (IL)-1, IL-6 and interferon (IFN)-a, have been implicated as mediators of the syndrome 18-21 . TNF-a was originally named 'cachectin' when identified as a circulating mediator of wasting in an animal model of chronic parasitic infection 22, 23 . In subsequent studies it was found that continuous...

Omega3 Fatty Acids and Oral Nutritional Support

The eicosanoids are biologically active substances that, in addition to other roles in malignancy, are important mediators of the systemic inflammatory response 52 . Their production can be modulated by dietary polyunsaturated fatty acids (lipids), particularly the omega n-6 and n-3 fatty acids. Omega-6 fatty acids tend to produce highly 'inflammatory' eicosanoids, whereas those derived from n-3 fatty acids are considerably less so 53 . Altering the balance of eicosanoids in vivo through the...

Opioid Peptides Cannabinoids and Cocaine and Amphetamine Regulated Transcript

Opioid peptides, in particular the endogenous agonists of k opioid receptor, increase food intake 37 . It has also been hypothesised that these molecules are involved in reward and pleasure feelings related with food 7 . The appetite-stimulating effect of marijuana in humans has been well known for centuries 38 . Endogenous cannabinoids, in particular anan-damide, increase appetite and food intake via the activation of specific receptors known as CB1 39 , which are expressed in hypothalamic and...

Energy Intake

Resting Energy Expendature

Several factors may contribute to the decreased intake of food in cancer patients. Anorexia, due to the disease itself or its treatment, is commonly recognised. Cancer patients may frequently suffer from symptoms affecting the gastrointestinal tract, for instance due to physical obstruction, constipation, or malabsorption. The effects or consequences of treatment by opiates, radiotherapy, or chemotherapy may all explain decreased food intake in the palliative care of cancer patients. However,...

Causes of Malnutrition in the Elderly

The major causes of weight loss, as determined by several large studies, are summarised in Table 1. In Table 1. Diagnostic spectrum of involuntary weight loss. (Modified from 3 ) Table 1. Diagnostic spectrum of involuntary weight loss. (Modified from 3 ) aOther medical diagnoses neurologic, infectious, alcohol, medication, renal, inflammatory disease n, number of patients aOther medical diagnoses neurologic, infectious, alcohol, medication, renal, inflammatory disease n, number of patients...

The Ubiquitin Proteasome System

Ubiquitin Ligase

Proteins degraded by the ubiquitin proteasome system are first conjugated to multiple molecules of ubiquitin, a 76-amino acid, 8.5-kDa residue that is highly conserved and present in the cytoplasm of all eukaryotic cells 6 . Ubiquitinated proteins are degraded by the proteolytic 26s proteasome, the catalytic core of which is the 20s proteasome, a barrel-shaped particle consisting of four stacked rings with seven subunits in each ring. This complex and tightly regulated process takes place...

Brown Preadipocytes

Brown Adipocytes

In perinatal rat fetuses, the anterior subcutaneous depot contains exclusively brown adipocytes and is recognisable from day 15 of gestation. At the site where the anlage arises, few dilated capillaries are immersed in an extracellular matrix poor in cells and collagen fibrils and rich in amorphous substance. At this stage pericytes - which cannot be defined as 'pure' undifferentiated cells because of their characteristic mitochondria - are already recognisable. They are often numerous, large...

Buccal Fat Reverse

Visceral Fat Surgery

Body silhouette is defined by skeleton framework, muscle masses and fat distribution. All these anatomical components are genetically fixed, related to growth hormones and sex hormones, and modified by extrinsic factors such as age, physical exercise, diet, constrictive garments, way of living and general health conditions. As far as fat distribution is concerned, we recognise the subcutaneous and the central (visceral) fat.

The Spectrum of Malnutrition

Hunger and malnutrition remain among the most devastating problems facing the majority of the world's poor and needy, and continue to dominate the health of the world's poorest nations. Nearly 30 of humanity - infants, children, adolescents, adults and older persons in the developing world - are currently suffering from one or more of the multiple forms of malnutrition. This remains a continuing travesty of the recognised fundamental human right to adequate food and nutrition, and freedom from...

Support of Energy Balance

The best way to improve energy balance is apparently to control tumour progression, which attenuates the metabolic abnormalities induced by the tumour and or tumour-host interactions. When cure cannot be achieved, an obvious next option is to increase nutritional intake by oral nutritional support or artificial nutrition (Fig. 3). A number of studies have tried to achieve this, particularly on a short-term basis. However, few positive effects were reported in terms of anthropometric measures,...

Diseases of the Adrenal Gland

Diseases of the adrenal gland can affect the cortex and or the medulla, with different clinical pictures. The main products of the adrenal cortex, gluco-corticoids (GC) and mineralcorticoids (MC) exert important actions on fluid balance and metabolism. MC regulate electrolyte transport and fluid home-ostasis, with the main target tissues being kidney, colon, and salivary glands. The main effects of GC are exerted on metabolism, immunologic functions, and musculoskeletal and connective tissues....

Immune Activation

Cardiac Cachexia Prognosis

There is evidence that neurohormonal changes and immune activation in CHF patients play a major role in the pathogenesis of cardiac cachexia. While tumour necrosis factor-a (TNF-a) is increased in cardiac cachexia as a sign of immune activation 6, 7, 24 , the levels of this cytokine are not increased in all CHF patients 25 . Keeping the definition of cardiac cachexia as > 7.5 weight loss in 6 months, the TNF-a plasma level is higher in cachectic (Fig. 2), than in non-cachectic CHF patients....

Dimension of the Nutritional Problem in the World

Severely Undernourished People

International organisations (UNO, FAO, WHO, UNICEF, World Bank) have established methods of evaluating available foods, the consumption of food, and nutritional status by taking into consideration parameters of agricultural production, anthropometrical measurements, birth-rate, mortality and morbidity rates, and clinical, immunolog-ical, haematological, and biochemical parameters. One of the most frequently used comprehensive indexes of alimentary and nutritional condi tion is the DES (dietary...

Introduction

Nitrogen is a main body component and is required for both tissue protein synthesis and the production of several nitrogenous compounds involved in a variety of functions (hormones, immune mediators, neurotransmitters, antioxidant defences, etc.). Thus, the body nitrogen content should be both quantitatively and qualitatively normal, as well as normally maintained, to ensure normal body functions. Nitrogen homeostasis is a highly regulated function. Nitrogen balance is commonly referred to as...

Ghrelin and Weight Loss in Obesity

Obesity is a chronic disease that is causally related to serious medical illnesses such as type 2 diabetes mellitus, hypertension, hyperlipidaemia, sleep apnoea and orthopaedic complications. Based on evidence of the potent orexigenic action of ghrelin, its levels were at first expected to be increased in obesity. On the contrary, ghrelin levels turned out to be inversely related to body mass index. At present, the exact peripheral signals leading to a reduced ghrelin secretion in obesity have...

Protein Energy Malnutrition and Cachexia in CKD

Protein-energy malnutrition in CKD patients is a state of decreased body pools of protein with or without fat depletion, or a state of diminished functional capacity. It is caused at least partly by inadequate nutrient intake relative to nutrient demand and is improved by nutritional repletion 31 . Hence, protein-energy malnutrition is engendered when the body's need for protein or energy fuels or both cannot be satisfied by the individual's nutrient intake diet 53 . Protein-energy malnutrition...

Cancer Cachexia

Owing to the difficulties in clearly defining and diagnosing cancer anorexia, its prevalence is yet to be precisely assessed 4 . Based on different diagnostic tools, anorexia has been detected at the point of cancer diagnosis in 13-55 of patients 5 . Nevertheless, consistent evidence suggests that approximately 50 of cancer patients report abnormalities of eating behaviour at the time of first diagnosis 6 and prevalence in terminally ill cancer patients is even higher, at approximately 65 7 ....

Role of Brain Monoamines in Disease Associated Anorexia Cachexia

More data support a role for hypothalamic neurotransmission as an effective therapeutic target in the treatment of anorexia. Using in vivo microdial-ysis, Blaha et al. showed that intrahypothalamic serotonin concentrations are increased in anorec-tic tumour-bearing rats 22 . In the same study, they also showed a more complex derangement of hypothalamic monoaminergic neurotransmission, since dopamine levels were also found to be depressed 22 . This evidence may give the neurochemical explanation...

Overview of Supportive Cancer Care with Melatonin

The therapeutic potential of melatonin is wideranging 54 . Evidence derived from clinical and biological studies has supported our view that melatonin administration should be considered as hormone-replacement therapy aimed at the restoration of the physiological circadian rhythm in cancer patients. The cancer-associated disruption of circadian endocrine, immune, and neurologic systems is still far from being understood 55 , although their prognostic impact on survival has been...

The Functional Impact of Cancer Cachexia

Many of the consequences of cachexia are likely to impact on patient function but as yet this has not been studied in detail. There is, however, a considerable body of knowledge about the importance of weight loss in relation to clinical end-points and treatment variables. Scott 37 studied patients with inoperable non-small-cell lung cancer -about 40 had at least 5 weight loss and almost 80 an elevated CRP. Weight-losing patients had a significantly lower KPS and overall QoL and greater fatigue...

Acquired Generalised Lipodystrophy Lipoatrophic Diabetes or Lawrence Syndrome

Lipo Dostrophy Images

Acquired generalised lipodystrophy (AGLD) is a rare, juvenile-onset lipodystrophy, first fully described by Lawrence in 1946 1 , who reported on a young female subject with 'lipodystrophy, and hepatomegaly with diabetes, lipaemia and other metabolic disturbances.' To date, approximately 80 patients with AGLD have been reported 2 . Like others LDs, AGLD is prevalent in females. Lipoatrophy develops over a number of years, in childhood or in adolescence, so that the onset of the condition is...

Antiserotonergic Therapies Targeting Anorexia and Cachexia

Disease-associated anorexia might be therapeuti-cally approached by interfering with the neuro-chemical events downstream of cytokine activation. Serotonergic hypothalamic neurotransmission represents a suitable example, and it is therefore tempting to speculate that by interfering with hypothalamic serotonin release, food intake might be improved. Hypothalamic serotonin synthesis strictly depends on the brain availability of its precursor, the amino acid tryptophan 10 . An increase of plasma...

Height and Body Weight

Unclothed measurements must be taken using an anthropometer and weight scales. Body weight is the most obvious index of nutritional status, but, taken alone, it is not an accurate measurement. Actual body weight must be compared with ideal body weight (IBW) and other anthropometric parameters. For example, patients with ascites and or oedema may have a normal body weight but severe malnutrition. Several approaches are used for estimating the IBW. One simple method consists of measuring body...

Treatment with Appetite Stimulants Megestrol Acetate

Megestrol acetate (MA) is a synthetic derivative of a naturally occurring progestational agent and is similar to progesterone. MA treatment of patients with cancer increases appetite and non-fluid weight gain in a dose-dependent manner, and is well-tolerated in patients with advanced malignant diseases 39-44 . Von Roenn et al. found that treating patients with MA for AIDS-related anorexia cachexia not only increased weight, but also improved body image, sense of well-being, and pleasure from...

Vitamins Minerals and Electrolytes

A wide array of vitamin, mineral, and electrolyte deficiencies frequently occurs in Crohn's disease patients and with variable clinical significance. These deficiencies may result from extensive inflammation, surgical resection of small bowel, or both, and require haematological and biochemical examination. The prevalence of decreased nutrient levels among patients with Crohn's disease is summarised in Table 2. Of particular clinical relevance is the deficiency in iron, vitamin B12, folate,...

Pheochromocytoma and Weight Loss

Pheochromocytoma is a tumour that produces cat-echolamines and is usually derived from adrenomedullary chromaffin cells. When it arises from extra-adrenal chromaffin cells, the tumours are called extra-adrenal PCC or paragangliomas. Similar clinical manifestations may occur in other related tumours that secrete catecholamines, such as chemodectomas and ganglioneuromas 26, 31 . The rarity of PCCs (fewer than 1 of hypertensive patients) should not reduce the importance of these tumours. In fact,...

The Fate of Dietary Protein Nitrogen During the Postprandial Phase

Nitrogen Balance Study

The diurnal cycle of feeding and fasting is accompanied by concurrent changes in protein turnover. Protein feeding is necessary to replenish the body protein stores that would be wasted during fasting 21-24 . Because of this, nitrogen retention calculated on a daily basis is lower than that derived just from the postprandial phase 21 , and, conversely, dietary protein utilisation calculated as the daily gain is lower than the postprandial gain. Dietary proteins, once ingested, are digested in...

Reversing Cachexia Case Study

Ace Inhibitor Drug Food Interaction

Prevention of the deterioration of CHF, such as occurs with the onset of cachexia, is one of the main goals of therapy. Increasing knowledge about the pathophysiology of CHF and its sequelae has led to an increasing number of therapeutic options. However, there is no specific drug therapy for cachexia associated with CHF. Most of the drugs currently in use, particularly ACE inhibitors, p-blockers, and aldosterone antagonists, have an effect on the neurohormonal system. For instance, ACE...

Causes of Weight Loss and Muscle Wasting

To be able to judge the need for and the effectiveness of nutritional therapy as well as the optimal nutritional support strategy, insight is needed into the underlying mechanisms and contributing factors of overall weight loss and specific tissue wasting in COPD. Weight loss, especially loss of fat mass, occurs if energy expenditure exceeds dietary intake. More specifically, muscle wasting is a consequence of an imbalance between protein synthesis and protein breakdown. Alterations in both...

The Estimate of Life Expectancy

Short-term life-expectancy determines the institution of life-prolonging treatment, long-term life-expectancy that of curative treatment. Simple and reliable ways to calculate mortality risk, from which life-expectancy may be derived, were described by Walter et al. 20-21 . One-year mortality risk may be estimated from a number of parameters Table 3 , such as gender, function, comorbidity, renal function, and nutrition. A score is assigned to each parameter, and the risk of mortality is...

Pituitary Disorders and Weight Loss Hypopituitarism

Total or partial hypopituitarism may occur in patients with pituitary adenomas, following pituitary surgery or radiation, or after head injury. Deficiency of any or all of the six major hormones lutheinising hormone LH , follicle stimulating hormone FSH , thyroid, GH, thyroid stimulating hormone TSH , ACTN, and prolactin can occur. The most common symptom in both men and women is secondary hypogonadism, because of LH and FSH deficiencies or secondary to hyper-prolactinaemia. In children,...

Cannabinoids Dronabinol

The active ingredient of marihuana, dronabinol A-9-tetrahydrocannabinol, THC is known to have a positive effect on appetite, body weight and chemotherapy-induced nausea 73 . Dronabinol was first used as an antiemetic in patients with cancer however, it was reported to have significant neurological and adverse effects including dizziness, euphoria and impairment of cognitive functions. Currently there is only one controlled trial comparing dronabinol vs mege-strol acetate vs combination therapy...

The Standard of Care in Cachexia Trials

When designing an intervention trial it is important to bear in mind the hypothesis that the trial is attempting to prove. Most commonly, an intervention is compared with a placebo the two cohorts of patient subjects should otherwise receive the same standard of care. However, the standard of care pertaining to the general management of cachexia remains currently undefined. The issue of standardisation of care in cancer cachexia is a complex field that can be divided into general medical issues...

Energy Expenditure in Diabetes Mellitus

Urinary glucose loss may be a more important cause of negative energy balance and weight loss in diabetic patients. However, the basal metabolic rate BMR of diabetic patients without glycosuria is higher than that of normal subjects. Increased resting energy expenditure may be another mechanism contributing to weight loss in diabetic subjects, in addition to caloric losses due to glyco-suria. The basal energy expenditure of type 1 diabetic patients 2042 Kcal 24 h was found to be significantly...

Futile Metabolic Cycles of Lipids

Images Lpl And Fat Cells

Lipid metabolism seems to be particularly involved with and affected by cytokines. Early studies 85, 86 pointed out the cachexia-promoting effects of TNF, IL-1,and IFNs. Initially, the cachexia seen in different extreme clinical situations was thought to be due to TNF, which for that reason was also called cachectin. The injection of TNF into animals, while causing hypertriglyceridaemia and reduction of appetite and water intake, does not cause cachexia if the correct amount of calories is...

Fate of Amino Acids Released from Skeletal Muscle

Proteolysis of muscle results in the release of amino acids, particularly alanine and glutamine, which represent more than 50 of the amino acids exported by skeletal muscle 42 . Alanine is channelled to the liver for gluconeogenesis and acute-phase protein APP synthesis see later , while glutamine is taken up by the tumour to sustain the energy and nitrogen demands. The amide nitrogen of glutamine is utilised in the synthesis of purine and pyrimidine bases and for aminosugars. Glutamine is the...

Cytokines

Adiposity Cytokines

Cytokines have a key role as the main humoural factors involved in cancer cachexia Fig. 1 , and a large number of them may be responsible for the metabolic changes associated with cancer wasting. Anorexia may account for malnutrition, invari Fig. 1. Catabolic mediators in cancer. Both tumour-derived and humoural cytokines factors are involved in mediating the anorexia and metabolic changes characteristic of the cachectic state. For abbreviations, see text Fig. 1. Catabolic mediators in cancer....

Definition and Diagnosis

Cachectic heart-failure patients are weaker and fatigue earlier, which is due to both reduced skeletal muscle mass and impaired muscle quality. A simple and fast applicable definition of 'clinical cardiac cachexia' is the following in CHF patients without signs of other primary cachectic states e.g. cancer, thyroid disease, or severe liver disease , cardiac cachexia can be diagnosed when weight loss of gt 6 of the previous normal weight is observed over a period of gt 6 months 4 . The previous...

Metabolic Changes

Enhanced lipid mobilisation, decreased lipogene-sis, and decreased activity of lipoprotein lipase, the enzyme responsible for triglyceride clearance from plasma, in favour of an increased gluconeogenesis and hepatic protido-synthesis are the main biochemical events associated to neoplastic cachexia 6 . The study of body composition in neoplastic patients, carried out with several techniques, shows a loss of fat mass with sparing of the visceral organs and an increase in extracellular mass,...

What are the Dietary Protein Requirements of Cancer Patients

Dietary protein and amino acid requirements of cancer patients have never been formally determined, and we have argued elsewhere that this is an important deficit in the literature that would hopefully draw the attention of nutritional scientists with appropriate expertise 18 . Methods for the determination of human protein requirements continue to advance conceptually and technically, and the subset of these that are minimally invasive merit particular scrutiny for use, since patients with...

Malnutrition Inflammation Complex Syndrome

The foregoing discussion, which is summarised in Tables 1-3, indicates that there is a major overlap among both possible aetiologic factors and the assessment tools for protein-energy malnutrition and inflammation in CKD patients. The link between protein-energy malnutrition and inflammation in CKD population may be an explanation for malnutrition-associated mortality 22, 23, 91 . Indeed, several investigators suggest that protein-energy malnutrition and subsequent wasting syndrome and cachexia...

Management of Short Bowel Syndrome

Comprehensive management of patients with short bowel syndrome involves meticulous attention to meeting their metabolic and nutritional needs. Medical therapies, enteral or parenteral nutritional support, and, in some cases, consideration of surgical intervention are necessary. Patients with short bowel syndrome should receive adequate macronutrients and micronutri-ents to prevent energy malnutrition and specific nutrient deficiencies, and should be provided with sufficient fluids to prevent...

Cachexia and Infectious Diseases

Malnutrition, particularly that related to micronu-trients vitamins, trace minerals, essential amino acids, polyunsaturated fatty acids , is certainly one of the most easily preventable causes of death and disability. The 1995 World Health Organization WHO bulletin shows population-attributable risk for child deaths in 52 developing countries due to interaction between malnutrition and infectious disorders 16 . Malnutrition is a common complication of HIV infection and plays a significant and...

Appetite Stimulants Progestational Agents

Megestrol acetate and medroxyprogesterone acetate are synthetic progestagens that also have some mineralocorticoid activity. Megestrol acetate has been favoured and is one of the most studied therapies in cancer cachexia 80 . Originally used as a therapy in hormone-sensitive tumours, the observation that in a substantial number of patients appetite and weight increased led to it being studied in cancer cachexia 81 . It has been widely promoted as a therapy for cachexia and anorexia, although...

Growth Hormone and Insulin Like Growth Factor1

Growth hormone GH and insulin-like growth factor IGF -1 stimulate amino-acid uptake and protein synthesis in muscle and improve myocyte proliferation and differentiation in animal studies 106, 107 . The FDA recently granted accelerated approval for a form of recombinant human GH rhGH to treat AIDS wasting. Preliminary reports from Schambelan and co-workers in AIDS patients have all been positive 108-112 . The combined GH and IGF-1 doses used in studies in adult males with HIV-associated weight...

Lipid Mobilising Factor

A series of clinical and experimental data have indicated that the changes in lipid metabolism characterising tumour growth are mediated by a LMF produced by the tumour 6,7 . This factor acts directly on adipocytes and stimulates lipolysis in a cyclic-AMP cAMP -dependent manner by a mechanism similar to that of lipolytic hormones 8 . This effect appears peculiar to LMF, since cytokines, which are known to influence lipid metabolism, inhibit the clearing enzyme lipoprotein lipase 9 . This, in...

Physiological Control of Ghrelin Secretion

Circulating ghrelin levels, mostly represented by its acylated form, are rapidly reduced by 80 after total gastrectomy but gradually recover thereafter, indicating that the stomach is the major source of circulating ghrelin but that other tissues can compensate for the loss of ghrelin production after gastrectomy 13 . Ghrelin is secreted in a pulsatile manner 14 . Notably, there is no strict correlation between ghrelin and GH levels, while ghrelin pulses are correlated with food intake episodes...

Therapy of Cachexia

The energetic basis of wasting in HIV infection may help to explain the pathogenesis of AIDS cachexia and the elements of therapy. Energy balance results from calories introduced and calories expended or not absorbed resting energy expenditure REE is reduced accordingly during weight-loss episodes, but the reduction in energy intake exceeds that of REE because of anorexia and other GI symptoms Fig. 1 . The parameters most frequently used at the start of nutritional therapy are weight loss gt 10...

Glucocorticoids

Glucocorticoids freely penetrate cell membranes, and after entering the target cell they bind to a cytosolic glucocorticoid receptor. This receptor eventually serves as a transcription factor. However, the anti-inflammatory action of these substances is not strictly dependent on DNA binding of the hormone-receptor complex. Moreover, glucocorticoids also activate other transcription factors, such as NF-kB 51 , and it appears that side-effects are mostly attributable to the transac-tivating...

Statin Development and Classification

Lipophilic Versus Hydrophilic Statins

In search of a substance that lowers plasma cholesterol levels, Endo et al. tested more than 6000 fungi species, which finally, in 1973, led to the discovery of ML-236B 75 . ML-236B was subsequently termed mevastatin however, due to its severe side-effects, it never reached the market. Nevertheless, mevastatin is still frequently used in in vitro studies. Lovastatin mevinolin was the first statin to be approved by the Food and Drug Administration FDA in 1987. Currently, lovastatin, simvastatin,...

Physiological Regulation

Brown Adipose Tissue And Thermogenesis

Of the total energy expenditure for DIT, about one-third is ascribable to stimulation of BAT or to futile cycles to produce extra heat. Thus, DIT consists of adaptive thermogenesis together with thermogenesis induced by cold exposure. This adaptive thermogenesis, which responds to temperature and diet, is highly variable and is influenced by genetic makeup. It is regulated by brain activity throughout the sympathetic nervous system SNS , an important efferent pathway. p-Adrenergic receptors...

Statins

Hmg Coa Reductase Pathway

Statins are the drugs most often prescribed to treat hypercholesterolaemia. The mechanism by which this class of drugs blocks cholesterol biosynthesis is competitive inhibition of HMG-CoA reductase Fig. 2 . This enzyme catalyses the rate-limiting Fig. 2. Cholesterol biosynthesis. The rate-limiting step of this pathway is 3-hydroxy-3-methylglutaryl-CoA HMG-CoA reductase activity. Statins competitively inhibit this enzyme. Intermediates from cholesterol biosynthesis are used as attachments to...

Refractory Anaemia

Cause And Consequences Stress

Elements of MICS and subsequent cachexia may blunt the responsiveness of anaemia to recombinant human erythropoietin EPO in CKD patients. Refractory anaemia appears to be more common in those dialysis patients who suffer from protein-energy malnutrition and or inflammation 68, 118, 119 . Several previous studies Table 4.Reverse epidemiology of cardiovascular CV risk factors in dialysis patients the effect of CV risk factors in maintenance dialysis patients is the opposite of the general...

Tissue Hypoxia

The observation of constant 'air hunger' brought attention to the role of reduced oxygen supply to the tissues. Cellular hypoxia became the focus of metabolic research at the beginning of the twentieth century. First blood gas analyses were reported as early as 1919 13 and in 1923 it was observed that at high altitudes the study subjects involuntarily lost weight 41 . Evidence for reduced tissue oxygen supply came mostly from indirect observa tions such as increased erythropoietic activity and...

Central

Corpus Adiposum Buccae

Fat is present, in a higher or lesser degree, in almost every anatomical compartment, inside parenchymatous organs, muscles and breasts and it is stored mainly in the omentum intra-abdominal fat this is the so-called 'central' fat and it is the most involved in metabolic variations, increasing in obesity and reducing in the case of weight loss. Intra-abdominal fat contributes to a significant degree, but not exclusively, to the increase of waist circumference and sagittal diameter 1 , altering...

Interferon

IFN-y is secreted by activated T-cells and NK cells. Immunologically, it is the most potent monocyte-macrophage activating factor 39 . The metabolic effects of IFN-y include inhibition of lipoprotein lipase, both in an adipocyte cell line and in vivo 61 . IFN-y also inhibits the production of lipoprotein lipase and glycerol-phosphate dehydrogenase, both of which are involved in lipogenesis in primary cultures of rat adipocytes 62 . In addition, IFN-y stimulates lipolysis in vitro and in vivo 63...

Pathophysiology of Lipodystrophy Mechanisms of Lipodystrophy The Effects of Protease Inhibitors

Lipodystrophy

Different hypotheses have been put forward to explain the putative mechanism of HAART drugs in the development of lipodystrophy syndrome 116-120,122-124,126,134,141,147-152 . The first postulates that PIs primarily block cytochrome P450, which is involved in fat metabolism. The second postulates an interaction between PIs and human proteins. HIV protease has a sequence homology of 12 amino acids with two human proteins playing an important role in fat metabolism, namely, LDL-receptor-related...

Warm Exposure

External Lamina Adiposite

Warm exposure entails a reduction of the orthosympathetic stimulus, resulting in BAT inac-tivation. Morphologically, this corresponds to a transformation of brown fat cells into cells similar to white adipocytes. During this transformation, we have observed a reduced genic expression of UCP1 and increased genic expression of leptin 55 . This suggests that such morphological transformation is accompanied by a new functional situation, with adipocytes losing their thermogenic ability and...

White Preadipocytes

External Lamina Adiposite

The epididymal tissue is recognisable in the fetus in the last days of gestation. At this time, only the capillaries are morphologically visible, immersed in the extracellular matrix together with collagen fibres and undifferentiated cells. Postnatally, a profound rearrangement takes place in rats and mice on days 4-6 marked microanatomically by areas well circumscribed by fibroblast-like cells and by numerous dilated capillaries. Among these vessels a rich cell population is observed, the vast...

Experience with an Ambulatory Physical Activity Meter

Activpal Professional

We are currently undertaking pilot work with an advanced physical activity meter Fig. 2 , the activPAL professional 'physical activity logger' PAL Technologies, Glasgow, Scotland . This records the time that is spent lying sitting, standing and stepping. In addition it will display the number of up-down down-up transitions, the stepping cadence and estimated energy expenditure. From this estimated energy expenditure it is possible to derive an estimated PAL the estimated energy expenditure...

Congenital Generalised Lipodystrophy Berardinelli Seip Syndrome or Lipoatrophic Diabetes

Lawrence Syndrome Lipodystrophy

Congenital generalised lipodystrophy CGLD is an autosomal recessive, transmitted disease characterised by a pronounced loss of subcutaneous and visceral fat tissue manifested since birth. The condition is associated with acromegalic traits Fig. 2 , accelerated growth with normal hGH Fig. 2. A patient with congenital lipodystrophy or lipoatrophic diabetes. There is evidence of a pronounced loss of subcutaneous fat, acromegaloid aspect, and phlebomegaly for details, see Table 3, patient GF Fig....

Proinflammatory Cytokines and Anorexia

Another cause of CACS which, due to its particular aspects and appearance, may be considered specific for the syndrome is decreased food intake. Malnutrition may be considered a hallmark of cancer cachexia and it is associated with anorexia - that is, loss of appetite and or decreased food intake. Nutrition is a complex function resulting from the contribution of peripheral and central nervous afferents in the ventral hypothalamus. Stimulation of the medial hypothalamic nucleus inhibits...

Acquired Localised Lipodystrophies Hemifacial Lipoatrophy

Hemifacial lipoatrophy HFLD asymmetrically involves the left or right half of the face. No peculiar symptoms are associated with HFLD, and aesthetic discomfort is the main consequence. HFLD affects mainly females of any age, from childhood to adulthood. Atrophy of the subcutaneous fat makes the face asymmetrical due to depression of the cheek and the supramandibular region. Cutis, muscles, and bones are unaffected. No renal, neurological, or autoimmune diseases have been reported in association...

Cytokines and Hypermetabolism

Weight Loss Cytokine

Hypermetabolism, i.e. an increase in resting energy expenditure, occurs in many cachectic diseases 46 . Several cytokines, including TNF-a, IL-1 p and IL-6 47-49 , have been shown to stimulate energy expenditure and to induce fever as part of their effects on CNS mechanisms of defence and or energy balance control. Similar to the cytokine anorectic effects see above , cytokine-induced hypermetabolism appears to result from synergistic and sequential interactions 50 and to involve the same...

Endocrine Abnormalities and Cytokines

Weight Loss Cytokine

Several endocrine abnormalities, such as low levels of testosterone and growth hormone and increased production of cytokines, have been correlated with weight loss in AIDS, while adrenal and thyroid hormones show conflicting patterns 63 . The synergic action of TNF and other cytokines is considered the most probable mechanism causing cachexia 8,79,80 Fig. 6,7 . The clinical symptoms of anorexia, nausea, fever, asthenia, fatigue, lethargy, myalgia, sickness, diarrhoea, anaemia, leucocytopaenia,...

Protein Energy Malnutrition

Patients with chronic liver disease exhibit a progressive loss of fat and muscle mass, which leads to mixed protein-energy malnutrition. When investigating whole-body protein metabolism, protein synthesis, degradation, and amino acid oxidation have to be estimated in a specific manner. McCullough and Glamour reported that there appear to be few differences in protein turnover in stable cirrhosis patients and in healthy controls, while oxidation of amino acids in these patients was generally...

Reverse Pharmacology

Ghrelin Structure

Reverse pharmacology is the terminology proposed by Conn and Bowers in 1996 to describe the chemical biological approach utilised in accomplishing the development from unnatural GHRP to natural ghrelin. The first GHRP we developed was the DTrp2 pentapeptide listed in Table 3. DTrp2 was only active in vitro and was low in potency, but released only GH and not prolactin, adrenocorticotropin ACTH , luteinising hormone LH , follicle-stimulating hormone FSH or thyroid-stimulating hormone TSH . The...

Bioelectrical Impedance Analysis

The Fluid Compartments The Body

Bioelectrical impedance analysis is a simple, non-invasive and portable method for estimating fluid compartments and fat-free mass. This method is based on the bioelectrical principle that lean tissues containing the majority of the body's water and electrolytes are good electrical conductors, whereas fat mass which is almost dry acts as an insulator and is a poor electrical conductor Fig. 2 . The human body is considered as a conductor, which opposes an obstruction of defined impedance Z to an...

Lipodystrophic Syndrome

Diabetes with lipodystrophy comprises a heterogeneous group of rare syndromes characterised by insulin-resistant diabetes mellitus associated with an absence of subcutaneous adipose tissue. Several types of lipodystrophy have been reported and are distinguished according to mode of inheritance, and extent and regional distribution of fat loss. Patients with congenital lipoat-rophic diabetes demonstrate insulin resistance, elevated BMR, and hepatomegaly. The absence of subcutaneous fat is noted...

Vitamin B1 or Thiamine

The active form of thiamine, thiamine pyrophosphate, is a coenzyme involved in energy metabolism reactions the requirement for thiamine is therefore related to energy expenditure 56 . Patients at risk for vitamin B1 deficiency include alcoholics, those on chronic peritoneal dialysis, those re-fed after starvation, and thiamine-deplet-ed persons who are given glucose 64 . The RDA of vitamin B1 is 1.1 mg per day for women over 50 years and 1.2 mg per day for men over 50 years Table 3 54 ....

Muscle Mass Changes Sarcopenia

The loss of muscle mass with aging is increasingly recognised as having important consequences in old age because it may be associated with weakness, disability, and morbidity 45-47 . In 1989, Rosenberg focused renewed attention on this phenomenon by giving it a name, sarcopenia 48 . Sarco, from the Greek, denotes flesh muscle , and penia indicates a deficiency thus, sarcopenia translates loosely as muscle deficiency. It is now used to refer specifically to the gradual loss of skeletal muscle...

Proinflammatory Cytokines

Immune response results in a variety of metabolic adjustments that are mediated by cytokines of leukocytic origin. Among cytokines released during an immune response, IL-1, TNF-a and IL-6 are the major mediators of intermediary metabolism. These cytokines act in concert to decrease food intake, increase resting energy expenditure, gluco-neogenesis, glucose oxidation, and hepatic synthesis of fatty acids and acute-phase proteins, decrease fatty acid uptake by adipocytes and alter the...

Lipoatrophy Associated with Multiple Symmetric Lipomatosis Launois Bensaude Syndrome or Madelung Collar

Multiple Lipomatosis Pictures

Multiple symmetric lipomatosis MSL is characterised by the growth of fat masses symmetrically located at the neck, shoulders, deltoid and supras-capular regions, proximal segments of the arms and legs, and at the thoracic inlet, a distribution reminiscent of the location of brown adipose tissue in the foetus. The remaining subcutaneous fat layer is markedly atrophic, allowing MSL to be included in the group of LDs Fig. 3 . MSL is reported to be highly prevalent in men, but several cases of MSL...

Flowchart Nutritional Screening And Therapy

Weight Loss Flowchart

dietary habits -oral supplements -exercise-type oral supplements exercise duration -enteral nutrition of exercise program. Despite optimal implementation of nutritional therapy as part of an integrated treatment approach to COPD, it should be recognised that a sub-group of patients may not respond, due to an underlying mechanism of weight loss that cannot be reversed merely by caloric supplementation. Potential reversibility by means of specific nutrients nutriceuticals or pharmaceuticals will...

Cytokines General Comments

Cytokine activities in brain have a profound impact on neuroregulation, neurochemistry, behavioural manifestations, modulation of the neuroendocrine and autonomic systems, and neu-rophysiological responses 27 . Cytokines also modulate peripheral gastrointestinal, metabolic catabolic and endocrine systems that can impact CNS responses. In diseases associated with wasting and cachexia such as cancer, cytokine deregulation has been extensively studied. Endogenous cytokines are aberrantly produced...

Putative New Natural Ghrelin Hormones and Companion Receptor Subtypes

The seminal chemical-biological role of octanoy-lation as the initial immediate critical chemical step in determining the bioactive receptor conformation of the ghrelin peptide for the GHS type 1a receptor is notable and intriguing. We are currently working with Shaoxing Wu to study the effect of octanoylation on the ghrelin conformation determined from NMR analysis in conjunction with ghrelin conformation as determined from theoretical molecular modelling. The long-term objective is to...

Cytokines in Cancer Anorexia

Cytokines play a key role in the activation of the immune system and the inflammatory response typical of the catabolic state 39-41 . Different experimental approaches have demonstrated that cytokines are able to induce weight loss. They initiate a cascade of events that ultimately leads to a state of wasting, malnourishment, and eventually death. A number of pro-inflammatory cytokines, including IL-1, TNF-a, and interferon IFN -y, have been isolated in tumours, as shown in Fig. 4 7 . These...

Social Causes of Weight Loss

In developing countries, malnutrition takes on different forms of multiple or partial deficiencies, ranging from simple undernourishment to denutrition and cachexia. High rates of malnutrition persist, in spite of progress in the production, preservation, and distribution of food, and in sanitary measures and education. UNO, FAO, WHO and UNICEF data collected in the 1990s Table 2 show that 20 of the popu- Table 2. Prevalence of undernourishment in developing countries source FAO Countries Total...

Voluntary and Involuntary Weight Loss

An intake of protein calories and or any of the 39 essential nutrients that is less than the minimal required threshold leads to disruption of the balance between energy expenditure and nutrient requirements, resulting in various undernutrition syndromes and weight loss. Still, weight loss may be an ambiguous finding, as the presence of oedema may mask depletions in fat or lean body mass, or, conversely, a gain in fat and lean body mass may not be apparent in the presence of massive diuresis....

Adipokines Is Adipose Tissue an Endocrine Organ

Adipose Tisue Asan Endocrine Organe

Although loss of fat tissue during cancer has not been considered as a very important alteration, compared to those affecting the quality of life or the prognosis of the cachectic cancer patient, we now know that adipose tissue is not just a fat reservoir. The concept of the adipocyte as an 'intelligent' cell that is able to communicate directly or indirectly with the brain is revolutionary compared to the previously held view of adipose tissue as a metabolically inactive fat deposit. Nowadays,...

Conclusions

Infectious diseases and drugs, with separate mechanisms, induce fat loss in people infected with HIV. The natural course of HIV infection finally leads to cachexia slim disease . The combined actions of HIV, opportunistic infections, and HAART including NRTIs, NNRTIs, and PIs result in the redistribution of fat throughout the body lipodys-trophy , with simultaneous fat gain and fat loss in peripheral and central sites lipohypertrophy and lipoatrophy . This clinical condition, therefore reflects...

Clinical Outcome and Reverse Epidemiology

Reverse Dialysis

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 Galanin Like 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

Bomb Calorimeter Schematic

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...

Neurohormonal Abnormalities

Increased Afterload Heart Graphics

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...