bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitric Oxide Suppresses Cerebral Vasomotion by sGC-Independent Effects on Ryanodine Receptors and Voltage-Gated Calcium Channels
Authors: Yuill Kathryn H. , McNeish Alister J. , Kansui Yasuo , Garland Christopher J. , Dora Kim A.
Published: September 2009

Background/Aims: In cerebral arteries, nitric oxide (NO) release plays a key role in suppressing vasomotion. Our aim was to establish the pathways affected by NO in rat middle cerebral arteries. Methods: In isolated segments of artery, isometric tension and simultaneous measurements of either smooth muscle membrane potential or intracellular [Ca2+] ([Ca2+]SMC) changes were recorded. Results: In the absence of L-NAME, asynchronous propagating Ca2+ waves were recorded that were sensitive to block with ryanodine, but not nifedipine. L-NAME stimulated pronounced vasomotion and synchronous Ca2+ oscillations with close temporal coupling between membrane potential, tone and [Ca2+]SMC. If nifedipine was applied together with L-NAME, [Ca2+]SMC decreased and synchronous Ca2+ oscillations were lost, but asynchronous propagating Ca2+ waves persisted. Vasomotion was similarly evoked by either iberiotoxin, or by ryanodine, and to a lesser extent by ODQ. Exogenous application of NONOate stimulated endothelium-independent hyperpolarization and relaxation of either L-NAME-induced or spontaneous arterial tone. NO-evoked hyperpolarization involved activation of BKCa channels via ryanodine receptors (RYRs), with little involvement of sGC. Further, in whole cell mode, NO inhibited current through L-type voltage-gated Ca2+ channels (VGCC), which was independent of both voltage and sGC. Conclusion: NO exerts sGC-independent actions at RYRs and at VGCC, both of which normally suppress cerebral artery myogenic tone.
Mast Cells and Basophils: A Potential Link in Promoting Angiogenesis during Allergic Inflammation
Authors: Crivellato E. , Travan L. , Ribatti D.
Published: September 2009

Mast cells and basophils are granulated metachromatic cells which possess complex and partially overlapping roles in acquired and innate immunity, including both effector and regulatory activities. Mast cells and basophils cooperate in exacerbating and/or modulating inflammation as well as in mediating subsequent tissue repair. Mast cells release a series of potent proangiogenic molecules during inflammation that stimulate vessel sprouting and new vessel formation. Recent data suggest that basophils may also play a role in inflammation-related angiogenesis, principally but not exclusively through the expression of several forms of vascular endothelial growth factors and their receptors. This review focuses on the potential cooperative link between mast cells and basophils in promoting angiogenesis during allergic inflammation. We discuss the multifaceted roles of mast cells and basophils in inflammatory mechanisms of allergic diseases and whether these cells can be both source and target of proangiogenic mediators.
Participation of CD11b and F4/80 Molecules in the Conjunctival Eosinophilia of Experimental Allergic Conjunctivitis
Authors: Fukushima Atsuki , Ishida Waka , Ojima Ayako , Kajisako Mina , Sumi Tamaki , Yamada Jun , Tsuru Emi , Miyazaki Jun-ichi , Tominaga Akira , Yagita Hideo
Published: September 2009

Background: CD11b and F4/80 are macrophage surface markers. How these molecules participate in allergic eosinophil infiltration remains unclear. We examined the roles CD11b and F4/80 play in the conjunctival eosinophil infiltration associated with experimental allergic conjunctivitis. Methods: Ragweed-immunized BALB/c mice were challenged with ragweed in eye drops to induce conjunctival eosinophil infiltration. The effect of challenge on conjunctival CD11b+ and F4/80+ cell numbers was determined by immunohistochemistry. In the same model, blocking anti-CD11b and anti-F4/80 Abs were injected intraperitoneally during the induction or the effector phase, or subconjunctivally 2 h before challenge, to determine their effect on challenge-induced conjunctival eosinophilia. To examine whether eosinophils express CD11b and F4/80 molecules, splenocytes from IL-5 gene-electroporated mice were subjected to flow cytometric analysis. To clarify the involvement of CD11b and F4/80 in conjunctival eosinophil infiltration, mice were intraperitoneally injected with anti-CD11b and anti-F4/80 Abs and then subconjunctivally injected with eotaxin to induce conjunctival eosinophilia. Results: Ragweed challenge elevated conjunctival CD11b+ and F4/80+ cell numbers. Systemic anti-CD11b and anti-F4/80 Ab treatments during the effector phase, but not in either the induction phase or the local injection of Ab, suppressed conjunctival eosinophil infiltration in ragweed-induced conjunctivitis. Most splenic eosinophils from IL-5 gene-introduced mice expressed CD11b and F4/80. Systemic anti-CD11b and anti-F4/80 Ab treatment suppressed conjunctival eosinophilia induced by subconjunctival eotaxin injection. Conclusions: CD11b and F4/80 appear to participate in conjunctival eosinophil infiltration in allergic conjunctivitis. Their involvement in conjunctival eosinophilia appears to be due to their expression on eosinophils rather than on macrophages.
Who Is Caring for Kidney Transplant Patients? Variation by Region, Transplant Center, and Patient Characteristics
Authors: Israni Ajay K. , Snyder Jon J. , Skeans Melissa A. , Tuomari Anne V. , Maclean J. Ross , Kasiske Bertram L.
Published: September 2009

Background/Aims: Despite implications for long-term care, little is known about outpatient care for kidney transplant patients. Methods: In this retrospective observational cohort study, outpatient claims were examined for 42,078 Medicare kidney transplant patients using United States Renal Data System data to ascertain location and timing of outpatient visits and type of physician seen. Logistic regression with generalized estimating equations was used to determine the odds and clinical correlates of visits in 4 post-transplant time periods. Results: In months 1–3, 88% of patients visited their transplant centers, but this declined to 69% in months 25–36. In the adjusted analysis, Native Americans (odds ratio 0.56, 95% confidence interval 0.48–0.65) and Hispanics (OR 0.86, 95% CI 0.80–0.92) were less likely than whites to visit their transplant centers. Centers performing 18–34 (OR 1.44, 95% CI 1.30–1.59) and 35–61 transplants per year (OR 1.30, 95% CI 1.18–1.43) were more likely to see patients than centers performing <18 or >61. Almost 80% of patients saw nephrologists in months 1–3 after transplant. African-Americans (OR 0.85, 95% CI 0.80–0.90), Asians (OR 0.87, 95% CI 0.77–0.97), and Native Americans (OR 0.63, 95% CI 0.53–0.75) were less likely than whites to see nephrologists, as were Hispanics (OR 0.78, 95% CI 0.72–0.84) compared with non-Hispanics. Conclusion: Frequency of visits to transplant centers varied by center and region; most visits were to nephrologists. Patients from minority groups were less likely to visit transplant centers and nephrologists, with possibly significant public health implications.
Systemic Cardiac Amyloidoses
Authors: Rapezzi Claudio , Merlini Giampaolo , Quarta Candida C. , Riva Letizia , Longhi Simone , Leone Ornella , Salvi Fabrizio , Ciliberti Paolo , Pastorelli Francesca , Biagini Elena , Coccolo Fabio , Cooke Robin M.T. , Bacchi-Reggiani Letizia , Sangiorgi Diego , Ferlini Alessandra , Cavo Michele , Zamagni Elena , Fonte Maria Luisa , Palladini Giovanni , Salinaro Francesco , Musca Francesco , Obici Laura , Branzi Angelo , Perlini Stefano
Published: September 2009

Background—

Most studies of amyloidotic cardiomyopathy consider as a single entity the 3 main systemic cardiac amyloidoses: acquired monoclonal immunoglobulin light-chain (AL); hereditary, mutated transthyretin-related (ATTRm); and wild-type transthyretin-related (ATTRwt). In this study, we compared the diagnostic/clinical profiles of these 3 types of systemic cardiac amyloidosis.

Methods and Results—

We conducted a longitudinal study of 233 patients with clear-cut diagnosis by type of cardiac amyloidosis (AL, n=157; ATTRm, n=61; ATTRwt, n=15) at 2 large Italian centers providing coordinated amyloidosis diagnosis/management facilities since 1990. Average age at diagnosis was higher in AL than in ATTRm patients; all ATTRwt patients except 1 were elderly men. At diagnosis, mean left ventricular wall thickness was higher in ATTRwt than in ATTRm and AL. Left ventricular ejection fraction was moderately depressed in ATTRwt but not in AL or ATTRm. ATTRm patients less often displayed low QRS voltage (25% versus 60% in AL;
P
<0.0001) or low voltage-to-mass ratio (1.1±0.5 versus 0.9±0.5;
P
<0.0001). AL patients appeared to have greater hemodynamic impairment. On multivariate analysis, ATTRm was a strongly favorable predictor of survival, and ATTRwt predicted freedom from major cardiac events.

Conclusions—

AL, ATTRm, and ATTRwt should be considered 3 different cardiac diseases, probably characterized by different pathophysiological substrates and courses. Awareness of the diversity underlying the cardiac amyloidosis label is important on several levels, ranging from disease classification to diagnosis and clinical management.
Mac-1 (CD11b/CD18) Links Inflammation and Thrombosis After Glomerular Injury
Authors: Hirahashi Junichi , Hishikawa Keiichi , Kaname Shinya , Tsuboi Naotake , Wang Yunmei , Simon Daniel I. , Stavrakis George , Shimosawa Tatsuo , Xiao Ling , Nagahama Yutaka , Suzuki Kazuo , Fujita Toshiro , Mayadas Tanya N.
Published: September 2009

Background—

Inflammation and thrombosis coexist in several disorders. Although it is recognized that leukocytes may induce a procoagulant state at sites of inflammation, the critical molecular determinants of this process remain largely unknown.

Methods and Results—

To examine mechanisms of inflammation-induced thrombosis, we developed a murine model of thrombotic glomerulonephritis (TGN), a known cause of acute renal failure in patients. This model, induced by lipopolysaccharide and antibody to the glomerular basement membrane, led to rapid glomerular neutrophil recruitment, thrombotic glomerular lesions with endothelial cell injury, and renal dysfunction. In mice immunodepleted of neutrophils or lacking the leukocyte-specific integrin Mac-1, neutrophil recruitment, endothelial injury, glomerular thrombosis, and acute renal failure were markedly attenuated despite the robust generation of renal cytokines. Neutrophil elastase is a likely effector of Mac-1 because its activity was reduced in Mac-1–deficient mice and the phenotype in mice deficient in Mac-1 or neutrophil elastase was similar. Platelets accumulated in glomerular capillaries within 4 hours of TGN before evidence of thrombosis. Platelet immunodepletion before TGN markedly exacerbated hematuria (hemorrhage), inflammation, and injury, whereas thrombocytopenic Mac-1–deficient mice remained resistant to disease, indicating that initial glomerular platelet deposition protects the vessel wall from neutrophil-mediated sequelae. The subsequent thrombosis relied on the interaction of Mac-1 on recruited neutrophils with glycoprotein Ibα on platelets as antibody-mediated disruption of this interaction attenuated TGN without affecting renal neutrophil accumulation.

Conclusions—

These observations establish Mac-1 on neutrophils as a critical molecular link between inflammation and thrombosis and suggest it as an attractive target for antithrombotic therapy.
Universal Cognitive Maps and the Search for Intelligent Life in the Universe
Authors: Lemarchand Guillermo A. , Lomberg Jon
Published: September 2009

For almost 50 years the Search for Extraterrestrial Intelligence (SETI) research program was pursued under the hypothesis of the universality of the physical laws in the cosmos. The authors call attention to some epistemological issues that make it necessary to seek other aesthetic, spiritual and ethical “cognitive universals.” They propose the participation of a broader community of scholars from natural, social, artistic and humanistic disciplines to explore all the possible “universal cognitive maps” that eventually might favor the detection of extraterrestrial intelligent life.
Ground-breaking: Scientific and Sonic Perceptions of Environmental Change in the African Sahel
Authors: Adderley W. Paul , Young Michael
Published: September 2009

Soils surrounding ancient settlements can hold evidence of the activities of past societies. To seek an understanding of how past societies have reacted and contributed to environmental change requires many data sources. The real-time audiovisual installation Ground-breaking problematizes the presentation of such data, gained in this case through the image-analysis of soil materials. These data are used to connote environmental events and consequent human responses. By combining these data with audiovisual synthesis and environmental recordings, the authors present a basis for developing conceptualizations of new locales undergoing environmental change; the visual and sonic narratives that are developed allow the art-science interface to be explored.
Conversion of Minors to Islam in Malaysia
Authors: Muda Mohd Zamro , Kusrin Zuliza Mohd
Published: September 2009

Malaysia constitutes a multicultural, multi-ethnic and multi-religious society and legally recognizes the right of freedom of religion among its subjects who have reached the age of maturity, that is, eighteen years of age. There are cases where minors change their religion due to their parents' conversion or through their own choice and this needs special consideration. This article aims to focus and discuss some issues of conversion of minors to Islam, commencing from the definition of minor, the law that relates to the conversion and some relevant cases.
Class, Race, and the Spousal Income Gap
Authors: Huato Julio , Woodbury Zeno Kathryn
Published: September 2009

The literature on gender economics has largely ignored the striking variation of the gender income gap across socioeconomic classes and racial and ethnic groups. Our article reports the effects of family income, educational attainment, and race-ethnicity on the ratio of the individual incomes of husbands and wives, the spousal gap, in the United States, using regression analysis on the PUMS data. We find that the higher the family income and the educational gap between husbands and wives, the larger the spousal gap. Non-White husbands (especially Blacks) are associated with significantly lower spousal gaps. Conditions shaping wives' choices --especially in relation to allocating more or less labor to their homes—have a larger impact on the spousal gap than those shaping husbands’ choices. This underscores the importance of industrial and occupational desegregation, antidiscrimination in the workplace, and the provision of services that relieve wives from domestic labor in improving gender equity.
Political Groups, Leader Change, and the Pattern of International Cooperation
Authors: Smith Alastair
Published: September 2009

Nations are politically heterogeneous and which group is in political ascendency shapes the nature of interstate cooperation through two mechanisms. First, groups differ in the benefits they receive from cooperation. This affects which groups can commit to cooperate. Second, a nation may selectively withhold cooperation from one group to influence the domestic political competition between groups in another nation. By integrating political competition between leaders of different groups under different institutional rules into a prisoner’s dilemma model of international cooperation, the theory generates hypotheses relating leader turnover, group membership, and patterns of cooperation.
Clinical Manifestations of Nutrient Deficiency
Authors: Jensen Gordon L. , Binkley Jeff
Published: September 2009

Background: Clinical manifestations of nutrient deficiencies are often overlooked by practitioners caring for patients receiving home nutritional therapies. Methods: Literature review was conducted placing priority on identifying practical history and physical examination elements that may represent clinical manifestations of nutrient deficiency. Results: Summary tables are presented that highlight key history and physical examination elements. Conclusions: Appropriate care of the patient receiving home enteral or parenteral nutrition therapies requires routine surveillance of these elements. (Journal of Parenteral and Enteral Nutrition26:S29—S33, 2002)
Detection of Aspiration in Enterally Fed Patients: A Requiem for Bedside Monitors of Aspiration
Authors: Maloney James P. , Ryan Tracey A.
Published: September 2009

Background: Pulmonary aspiration of gastric and oropharyngeal contents is common in enterally fed patients. Detection of early aspiration in these patients has relied on clinical impression, the coloring of enteral feedings with dyes, and less commonly the detection of elevated glucose in tracheal aspirates. The potential benefits, risks, and clinical use of bedside monitors of aspiration are under increasing scrutiny. Methods: Literature review. Although this review reflects the opinions of the authors, recommendations of an expert consensus panel (North American Summit on Aspiration, which included one author, J. P. Maloney) were also used to guide recommendations. The specific recommendations of that panel are presented elsewhere. Results: No large prospective clinical trials have been done to evaluate the use and safety of bedside monitors for aspiration. Clinical impression remains a poor “gold standard” of aspiration diagnosis in enterally fed patients. The coloring of enteral feedings with blue dyes (chiefly FD&C Blue No.1) is ubiquitous in hospitals despite evidence that it is not sensitive and potentially harmful. Cases of absorption of blue dye from enteral feedings in patients with critical illness have raised concern about the safety of the blue dye method, particularly in light of apparent toxic effects of these dyes on mitochondria. The glucose detection method has not been embraced; it too has little use and is labor intensive. Conclusions: Use of colored dyes in enteral feedings and glucose detection methods should be abandoned. Nonrecumbent positioning is an evidenced‐based method for aspiration prevention that needs to be re‐emphasized. Novel bedside methods of detecting early aspiration are needed to supplement preventative strategies. (Journal of Parenteral and Enteral Nutrition 26:S34‐S42, 2002)
North American Summit on Aspiration in the Critically Ill Patient: Consensus Statement
Authors: McClave Stephen A. , DeMeo Mark T. , DeLegge Mark H. , DiSario James A. , Heyland Daren K. , Maloney James P. , Metheny Norma A. , Moore Frederick A. , Scolapio James S. , Spain David A. , Zaloga Gary P.
Published: September 2009

Aspiration is the leading cause of pneumonia in the intensive care unit and the most serious complication of enteral tube feeding (ETF). Although aspiration is common, the clinical consequences are variable because of differences in nature of the aspirated material and individual host responses. A number of defense mechanisms normally present in the upper aerodigestive system that protect against aspiration become compromised by clinical events that occur frequently in the critical care setting, subjecting the patient to increased risk. The true incidence of aspiration has been difficult to determine in the past because of vague definitions, poor assessment monitors, and varying levels of clinical recognition. Standardization of terminology is an important step in helping to define the problem, design appropriate research studies, and develop strategies to reduce risk. Traditional clinical monitors of glucose oxidase strips and blue food coloring (BFC) should no longer be used. A modified approach to use of gastric residual volumes and identification of clinical factors that predispose to aspiration allow for risk stratification and an algorhythm approach to the management of the critically ill patient on ETF. Although the patient with confirmed aspiration should be monitored for clinical consequences and receive supportive pulmonary care, ETF may be continued when accompanied by appropriate steps to reduce risk of further aspiration. Management strategies for treating aspiration pneumonia are based on degree of diagnostic certainty, time of onset, and host factors. (Journal of Parenteral and Enteral Nutrition26:S80‐S85, 2002)
Anthropometric Assessment of the Adult Hospitalized Patient
Authors: Heymsfield Steven B. , Casper Katie
Published: September 2009

Anthropometry is a technique in which simple measuring instruments are used to describe human form. By applying the measurement directly or through use of additional calculations, the practitioner can partition the body into fat and fat‐free components. Quantifying these two body spaces provides information on the amount and rate of change over time in whole body energy supply and protein mass. These data can then be used in association with other indices of energy and protein metabolism. Whereas anthropometry is simple, practical, and inexpensive, the technique is limited to a qualitative tool by several sources of error. A thorough understanding of the strengths, limitations, and appropriate applications of anthropometry is essential when applying the method in clinical practice. (Journal of Parenteral and Enteral Nutrition 11:36S‐41S,1987)
Determination of Water and Electrolytes in Muscle Biopsies in the Nutritional Assessment of Clinical Disorders
Authors: Bergstrom Jonas , Hultman Eric
Published: September 2009

Nutritional inadequacies profoundly affect the content and distribution of water and electrolytes in muscle tissue. However, most changes in tissue water and electrolytes are nonspecific and reflect the degree of sickness; they cannot be used for evaluation of malnutrition, except to indicate whether there is a loss or excess of intracellular ions, such as potassium and magnesium. In patients without disturbances in potassium metabolism, muscle cell potassium and protein are strongly correlated, but this relationship does not hold true in patients with potassium depletion. Accumulation and loss of potassium occur in parallel with changes in muscle glycogen, independent of other muscle constituents, eg, magnesium. Potassium depletion and excess, as well as changes in muscle glycogen, must be considered when evaluating the relation of lean body mass and total body protein content to total body potassium. (Journal of Parenteral and Enteral Nutrition 11:51S‐54S, 1987)
Proteinases in Catabolism and Malnutrition
Authors: Hörl Walter H. , Wanner Christoph , Schollmeyer Peter
Published: September 2009

Protein synthesis and degradation are particularly sensitive to malnutrition and catabolic states. Intracellular protein degradation is determined by the conformation, molecular weight, isoelectric point, and carbohydrate content of the proteins. ATP‐stimulated endoproteases appear to catalyse the rate‐limiting steps. In the liver, proteolysis is reduced by amino acids and/or insulin, whereas glucagon stimulates protein degradation, probably due to depletion of intracellular gluconeogenic amino acids. In the muscle, protein degradation is promoted by interleukin‐1 and inhibited by Ep‐475, which specifically inactivates cathepsin B,H, and L. Myofibrillar alkaline protemase activity increases postoperatively and in patients suffering from malignant tumors, whereas normal proteinase values were observed in these patients following total parenteral nutrition. Increased alkaline proteinase activity is also observed in diabetes mellitus and is normalized by insulin. Extracellular proteolysis has been reported in patients with hypercatabolic acute renal failure and in patients with sepsis or acute pancreatitis. Plasma fractions obtained from hypercatabolic patients with postoperative acute renal failure were proteolytic. Plasma proteinase activity decreases during hemodialysis due to elimination of a metallo‐proteinase. Plasma α2‐macroglobulin decreases in patients with acute renal failure and also during acute pancreatitis. Proteolytic degradation of parathyroid hormone by sera obtained from patients with acute pancreatitis has been observed. Also, there is a decrease of high molecular weight kininogen during experimental acute pancreatitis. Granulocyte elastase increases postoperatively, mainly in patients with sepsis. Sepsis also causes increased proteolytic activity in the urine.

In conclusion, intracellular protein degradation can supply important precursors for hepatic and renal gluconeogenesis during malnutrition. Selective and nonspecific proteolysis may occur in patients with severe injury, sepsis, or acute renal failure, and result in the consumption of various plasma proteins. (Journal of Parenteral and Enteral Nutrition 11:98S‐103S, 1987)
Determinants of Nutritional Status in Hospital Patients in Italy
Authors: Mobarhan S. , Maiani G. , Ferro‐Luzzi A. , Pitassi F. , Trentini P. , Pappalardo G. , Nicastro A. , Azzini E. , Dalla Torre S. , Jama M.A. , Spigliati P. , Toico G. , Morabito S.
Published: September 2009

The prevalence of protein‐calorie malnutrition (PCM) and micronutrient deficiency (MND) at the time of admission and discharge from hospital was evaluated in 91 patients consecutively admitted to the Surgery Clinic of the University Hospital of Rome.

Anthropometric parameters and circulating levels of vitamins (A, E, C, B1, and B2) and visceral proteins [retinol‐binding protein (RBP, prealbumin (PA), and transferrin] were measured. Twenty‐one patients (23%) had moderate to severe PCM, and 70 patients (77%) had normal nutritional status (NNS) at admission. Two patients with PCM died in the hospital. At discharge, the prevalence of PCM was unchanged in the remaining 19 patents. Single or multiple MND was observed initially in 71% of patients with PCM and in 36% with apparently normal nutritional status. Despite vitamin supplementation, MND was present at the time of discharge in 73% of patients with PCM and 44% with NNS.

Nutritional status at the time of admission was assessed in hospitals in six different Italian cities. The criterion for admission to the study was the diagnosis of chronic (>1 yr duration) illness (excluding cancer and multiple organ disorders). Two hundred eighty‐four patients (145 males, 139 females), ages 25–88 yr, were selected. The findings indicated a high prevalence of MND (64%). Also, in disorders that usually do not have significant alterations of digestion or absorption, such as uncomplicated cardiorespiratory disease, the prevalence of MND was high (9–38%). The prevalence of MND was not related to body mass index (BMI). PCM was more common among patients with chronic gastrointestinal disease. There was a high level of obesity among cardiac patients (BMI>24–25), even though one‐third of them had MND. The prevalence of MND was not related to anthropometric indicators of PCM. (Journal of Parenteral and Enteral Nutrition 11:122S‐125S, 1987)
Optimal Nutritional Indexes in Gastroenterology
Authors: Miglioli Mario , Pironi Loris , Luca Cornia Gian , Salera Marcello , Barbara Luigi
Published: September 2009

Malnutrition in gastrointestinal disease can result from several pathogenetic mechanisms. The resulting clinical and laboratory features of malnutrition vary according to the specific pathogenetic factors involved. Many of the causes of malnutrition in gastroenterology are similar to those found in other acute and chronic diseases. However, certain disorders, specific to gastroenterology, may alter nutritional indices independent of the usual causes of malnutrition. These include small bowel bacterial overgrowth and protein‐losing enteropathy. The impact of these disorders on the indexes of nutritional status is discussed. (Journal of Parenteral and Enteral Nutrition 11:126S‐129S, 1987)
Optimal Nutritional Indexes in Cancer Patients
Authors: Lundholm Kent G. , Drott Christer
Published: September 2009

This paper reviews various parameters that are used to assess the nutritional and functional status of cancer patients. Available information shows that the nutritional status of cancer patients is correlated with their overall prognosis and outcome. However, little information exists concerning the use of nutritional indexes to evaluate the effectiveness of nutritional rehabilitation of cancer patients. It is emphasized that we should concentrate on developing nutritional parameters to assess the functional improvement of patients rather than their body structure and composition. (Journal of Parenteral and Enteral Nutrition11:13S‐137S, 1987)
Cachectin/TNF: A Macrophage Protein That Induces Cachexia and Shock
Authors: Yuman Fong  , Lowry Stephen F. , Cerami Anthony
Published: September 2009

Infection may elicit a clinical picture of metabolic and hemodynamic compromise that can deteriorate acutely to shock and death. Alternatively, injury or infection can lead a more indolent course, resulting in a progressive catabolic state that in time may advance to cachexia, organ failure, and death. Recent data suggest a complex array of endogenous humoral‐ and immunomodulators may orchestrate many of these detrimental responses. It has become clear that cachectin/tumor necrosis factor, a protein secreted by monocytes in response to many inflammatory, and injurious stimuli, holds a pivotal role in these host responses to injury. Circulating levels of this monokine is found in greater abundance and in higher frequency in seriously ill patients. The cellular metabolic response to cachectin/TNF simulates many of the pathophysiologic changes seen in injury and infection. Administration of cachectin/TNF to animals and man can mimic the clinical syndromes of cachexia or endotoxic shock, and neutralization of circulating activity of this protein protects experimental animals against the detrimental consequences of otherwise lethal infection. (Journal of Parenteral and Enteral Nutriton12:072S‐077S, 1988)
Immunonutrition
Authors: Van Buren Charles T.
Published: September 2009

“Clinical nutrition therapy stands poised upon the threshold of a new era — an era in which we shall approach the goal of providing our patients with diets which maintain normal immune defenses.” 1
Glutamine Nutrition and Requirements
Authors: Smith Robert J. , Wilmore Douglas W.
Published: September 2009

Glutamine is the most abundant free amino acid in plasma and tissue pools and an important intermediate in a number of metabolic pathways. Glutamine levels decline markedly in the course of many different catabolic disease states and it has recently been suggested that glutamine may be a conditionally essential dietary nutrient rather than a nonessential amino acid. Changes in tissue glutamine concentrations have been shown to correlate with net protein turnover, and there is evidence that glutamine may both stimulate protein synthesis and inhibit protein degradation. In experimental animals, we have shown that the fall in glutamine concentrations in plasma and tissue pools that occurs in the postoperative state can be prevented or reversed by providing large quantities of exogenous glutamine. In gastrointestinal tissues, the provision of glutamine‐free total parenteral nutrition solutions is associated with atrophy of mucosal cells and pancreatic exocrine cells. Glutamine‐supplemented parenteral formulas result in diminished atrophy of intestinal mucosal and pancreatic exocrine cells; both intravenous and enteral glutamine promote gastrointestinal tissue regeneration following toxic injury. In animals undergoing partial small intestine resection, glutamine feeding leads to increased adaptive hyperplasia in remaining intestinal segments and results in earlier postoperative weight gain. All of these trophic, anabolic effects of glutamine require the administration of quantities that exceed the glutamine content of normal dietary protein. These findings in experimental animals support the hypothesis that glutamine is a conditionally essential nutrient and suggest a potentially important role for glutamine‐supplemented nutrition in catabolic disease states. (Journal of Parenteral and Enteral Nutrition14:945–995, 1990)
Glutamine‐Containing Dipeptides in Parenteral Nutrition
Authors: Fürst P. , Albers S. , Stehle P.
Published: September 2009

Of the total pool of muscle free intracellular amino acids, glutamine represents about 60%. During catabolic stress, a marked reduction (50%) of this pool occurs; the depletion is not reversible by therapeutic efforts or conventional nutritional means. If maintenance of the intracellular glutamine pool promotes conservation of muscle protein, there is a theoretical case for use of glutamine supplements in the parenteral nutrition of patients with injury and infection. Glutamine is too unstable and poorly soluble for addition to existing preparations in its native form, but this drawback can be overcome by the use of synthetic stable and highly soluble glutamine‐containing dipeptides. In vivo studies in humans and animals provide firm evidence that a synthetic glutamine‐containing dipeptide, L‐alanyl‐L‐glutamine (Ala‐Gln), is readily hydrolyzed following its intravenous administration. The results also indicate a safe and efficient use of Ala‐Gln as a source of free glutamine in parenteral nutrition. In clinical studies, nitrogen balance was more positive in catabolic patients receiving a peptide‐supplemented solution than in control patients given isonitrogenous, isoenergetic total parenteral nutrition. Muscle glutamine concentrations were markedly decreased in the control groups. The intracellular concentrations were not influenced following severe injury, but were maintained in postoperative trauma. It is inferred that the increased intestinal requirement and cellular demand for metabolic fuel during catabolic stress is matched by an enhanced demand on muscle glutamine, resulting in intracellular glutamine depletion. Thus, the delivery of adequate amounts of glutamine is essential to maintain the integrity of intestinal mucosa and rapidly proliferating cells, to preserve the muscle glutamine pool, and to improve overall nitrogen economy during conditions of stress. (Journal of Parenteral and Enteral Nutrition14:118S‐124S, 1990)
Lipids, Membrane Receptors, and Enzymes: Effects of Dietary Fatty Acids
Authors: Kinsella J.E.
Published: September 2009

Dietary polyunsaturated fatty acids can significantly affect many biochemical and physiologic functions that are related to inflammatory, immune, and protective reactions. The different types of fatty acids can impact on energy metabolism, determine the lipid composition of membranes, and influence eicosanoid synthesis, all of which are relevant to prevention of and recovery from illness. In this paper, the effects of dietary polyunsaturated fatty acids on membrane composition, membrane‐associated enzyme and receptor functions, signal transduction, second messenger, and eicosanoid generation are summarized. The differential effects of the polyunsaturated fatty acids of the n‐6 and n‐3 families are reviewed in the context of optimizing levels in diets. (Journal of Parenteral and Enteral Nutrition 14:20OS‐217S, 1990)
The Role of Cytokines in Cancer Cachexia
Authors: Moldawer Lyle L. , Rogy Michael A. , Lowry Stephen F.
Published: September 2009

There is, at present, considerable interest in the possible role for the proinflammatory cytokines, tumor necrosis factor‐α, interleukin‐1, interleukin‐6, and interferon‐γ in the pathogenesis of cancer cachexia. Indirect evidence for such a role is based on the observation that chronic administration of many of these cytokines, either alone or in combination, can reproduce the myriad of host responses seen in experimental and human cancer cachexia. Elevated plasma levels of tumor necrosis factor‐α, interleukin‐1, and inteferon‐γ have rarely been detected in patients or experimental animals with cancer, although interleukin‐6 levels appear to correlate with tumor progression in animal models. The strongest evidence for a causal role for cytokines has come from rodent studies in which tumor‐bearing animals have been passively immunized with antibodies directed against individual cytokines. Several groups have shown modest but significant improvements in food intake and lean tissue retention with antibodies directed against tumor necrosis factor‐α, interleukin‐1, interleukin‐6, and interferon‐γ. However, there has been no consistent finding that one cytokine is universally involved in cancer cachexia in histologically distinct tumor models. One ominous finding in several tumor models has been that the endogenous production of cytokines appears to support tumor growth. Such findings raise the intriguing possibility that these cytokines, although contributors to tissue wasting and anorexia, may also serve the tumor as either direct or indirect cell growth factors. We conclude, however, that because of redundancy in the cytokine network and differential cytokine production in histologically distinct tumors, efforts to block the development of cancer cachexia with anticytokine therapies will require the inhibition of several proinflammatory cytokines simultaneously. (Journal of Parenteral and Enteral Nutrition16:43S‐49S, 1992)
The Early Cancer Anorexia Paradigm: Changes in Plasma Free Tryptophan and Feeding Indexes
Authors: Meguid Michael M. , Muscaritoli Maurizio , Lee Beverly J. , Yang Zhong‐Jin , Cangiano Carlo , Rossi‐Fanelli Filippo
Published: September 2009

Tumor growth is accompanied by an anorexia mediated by humoral factors that appear to influence appetitive mechanisms in the brain. Because tumor resection is followed by resumption of normal food intake, the circulating anorexigenic substance(s) are produced either by the neoplastic tissue or by the host in response to the tumor. Increased levels of plasma free tryptophan and plasma ammonia have been proposed to mediate cancer anorexia. With animal models, it is often difficult to ascertain whether changes in food intake depend upon metabolic changes or the progressively increasing tumor mass per se. The feeding patterns and biochemical changes that occur during tumor growth were evaluated in 96 male Fischer rats that were inoculated with 10 6 methylcholanthrene sarcoma cells or saline (controls). Rats were placed into metabolic cages equipped with an Automated Computerized Rat Eater Meter to continuously determine meal size and meal number. Plasma free tryptophan and ammonia were evaluated 6, 10, 16, 18, 22, and 26 days after tumor inoculation. Anorexia developed by day 17–18, when food intake started to decrease via a decrease in meal size but not meal number and reached 60% of control by day 26. However, long before anorexia developed, free tryptophan was significantly higher 6 days after tumor inoculation, and the greatest increase occurred after 18 days. Ammonia did not differ from control at any time. Data confirm tumor‐associated increases in plasma free tryptophan that occurred before the manifestation of anorexia and support a possible role of brain serotonin in cancer anorexia. (Journal of Parenteral and Enteral Nutrition 16:56S‐59S, 1992)
Hormonal and Metabolic Abnormalities in the Malnourished Cancer Patient: Effects on Host‐Tumor Interaction
Authors: Heber David , Byerley Lauri O. , Tchekmedyian N. Simon
Published: September 2009

Many common metastatic cancers are associated with marked weight loss at the time of diagnosis. Anorexia clearly plays a major role in weight loss in the cancer patient, but cannot explain all of the weight loss noted. Malnourished patients with localized cancers under metabolic ward conditions fail to gain weight when given apparently adequate calories for anabolism, thus suggesting that these patients are hypermetabolic. Increased whole body protein breakdown, increased lipolysis, and increased gluconeogenesis have been repeatedly demonstrated in malnourished cancer patients. Protein and glucose metabolism are closely linked, and both are regulated by a number of the same hormones and metabolites. For example, when increased glucose production in malnourished cancer patients is inhibited pharmacologically, protein catabolism is proportionally decreased. Studies of glucose, growth hormone, cortisol, and insulin secretion following an oral glucose load in well‐nourished cancer patients are consistent with insulin resistance but no other hormonal abnormalities. Malnourished cancer patients have elevated levels of growth hormone that are further stimulated by arginine and insulin infusion. No abnormalities of thyroid function were noted in cancer patients. Current studies are underway to determine the mechanisms and effects of progestational steroids and cytokines on both food intake and intermediary lipid metabolism. (Journal of Parenteral and Enteral Nutrition 16:60S‐64S, 1992)
Cytokines and Inflammatory Bowel Disease: A Review
Authors: McClane Steven J. , Rombeau John L.
Published: September 2009

The etiology and pathogenesis of inflammatory bowel disease (IBD) remains an area under intense investigation. Cytokine secretion, which is important in the regulation of normal gastrointestinal immune responses, appears to be dysregulated in IBD. In Crohn's disease, there appears to be an excessive TH1 T‐cell response to an antigenic stimulus, leading to increased levels of proinflammatory cytokines, such as interferon‐γ (IFN‐γ), interleukin (IL)‐12, IL‐1, IL‐6, and tumor necrosis factor‐α (TNFa). In ulcerative colitis, a TH2 T‐cell response appears to be the pathological process responsible for the inflammatory disease. New and innovative therapeutic strategies targeting cytokines, such as TNF‐α, are producing some promising results in animal and human studies. As more is learned about the complex cytokine interactions in IBD, more effective treatments will undoubtedly ensue. (Journal of Parenteral and Enteral Nutrition23:S20‐S24, 1999)
Glutamine Signaling in Intestinal Cells
Authors: Rhoads Marc
Published: September 2009

Glutamine (Gln) is a “competence factor” necessary for intestinal cell proliferation, intestinal fluid/ electrolyte absorption, and mitogenic response to growth factors. Gln deprivation produces apoptosis. Gln stimulation of quiescent cells produces immediate‐early gene expression and MAP kinase activation. However, EGF signals more powerfully through MAPKs than Gln. Interestingly, EGF‐stimulated mitogenesis is ineffective in the absence of Gln. In the intact intestinal epithelia in vivo, Gln has powerful effects on absorption of sodium and chloride. Gln‐stimulated absorption is greater than and additive to glucose‐stimulated absorption in cryptosporidial enteritis. In the piglet ileum, Gln metabolism stimulates apical amiloride‐inhibitable Na+/H+ exchange. Although one might predict powerful effects of oral Gln on absorption in babies with diarrhea, 3 clinical trials to date (one published) have not shown an advantage of GIn‐supplemented oral rehydration solutions (ORS) compared to standard glucose ORS. Severely dehydrated subjects have not been studied. More important effects of Gln treatment may be seen with (1) co‐administration with a growth factor and (2) in patients with severe intestinal damage, such as protracted diarrhea of infancy or AIDS enteropathy. (Journal of Parenteral and Enteral Nutrition 23:S38‐S40, 1999)
Physiological and Anti‐Inflammatory Roles of Dietary Fiber and Butyrate in Intestinal Functions
Authors: Andoh Akira , Bamba Tadao , Sasaki Masaya
Published: September 2009

Background: We investigated the effects of pectin, a soluble dietary fiber, on the morphological parameters of the small intestine. In addition, we tested the effects of butyrate enemas on dextran sulfate sodium (DSS)‐induced experimental colitis. Methods: Male Wistar rats were fed an elemental diet containing 2.5% pectin for 14 days, and several parameters were then determined. DSS‐induced colitis was evoked by the oral administration of water containing 3% DSS for 10 days. The butyrate enema (3 mL of 100 mmol/L butyrate per day) was begun 7 days before the DSS treatment. Interleukin (IL)‐8 secretion in the human intestinal epithelial cell line HT‐29 was determined by enzyme‐linked immunosorbent assay (ELISA). Results: Pectin feeding induced a significant increase in the villus height and crypt depth in the small intestine. These effects correlated with a significant increase in plasma enteroglucagon levels. Pretreatment with a butyrate enema significantly blocked the development of DSS‐induced experimental colitis. In the in vitro experiment, sodium butyrate dose‐dependently inhibited tumor necrosis factor (TNF)‐α‐induced IL‐8 secretion in HT‐29 cells. Conclusions: A trophic effect due to dietary fiber was directly observed. The generation of short‐chain fatty acids and the induction of enteroglucagon release might play an important role in this process. Butyrate, one of the major metabolites of dietary fiber, exerted a potent anti‐inflammatory effect both in vivo and in vitro. Dietary fiber may therefore play important roles in the regulation of normal and pathological conditions in the intestine. (Journal of Parenteral and Enteral Nutrition23:S70‐S73, 1999)
Glutamate in Enteral Nutrition: Can Glutamate Replace Glutamine in Supplementation to Enteral Nutrition in Burned Rats?
Authors: Hasebe Masaharu , Suzuki Hiromasa , Mori Eigo , Furukawa Junko , Kobayashi Kunio , Ueda Yoshitsugu
Published: September 2009

Background: Glutamine (GLN) plays many important roles for the enterocytes in health and disease, but no liquid enteral products contain GLN because of its instability. We hypothesized that glutamate (GLU) may replace GLN in supplementation to an enteral diet, and compared the metabolic effect of GLU and GLN on the gut to each other. Methods: Rats suffering from a 30% burn received an enteral diet containing 30% GLU (m/w to total amino acids; GLU group), 30% GLN (GLN group), or a standard amino acid formula (CTR group). After a 64‐hour feeding period, the small intestine and the portal and arterial blood were harvested to observe portal and arterial amino acid levels, and glutaminase activity and glutathione in the jejunal mucosa. In another study, 3H uptake into the mucosal protein was examined after a massive dose injection of 3H‐phenylalanine. Results: Alanine, a product of GLN or GLU catabolism, significantly increased in the portal blood of the GLU group compared with the GLN group. In the gut mucosa of the GLU group, 3H uptake into protein and total glutathione were higher than those of other two groups. GLN did not elevate the glutaminase activity. Arterial GLU levels increased in the GLU group, however remained within safety limits. Conclusions: Enterally delivered GLU may be a preferable fuel for the enterocytes and enhance the mucosal protein synthesis. GLU probably can substitute for GLN in supplementation to an enteral diet regarding many roles GLN plays in the intestinal mucosa under stress situations. (Journal of Parenteral and Enteral Nutrition23:S78‐S82, 1999)
Effect of IGF‐1 on Protein Metabolism in Burned Rats
Authors: Tashiro Tsuguhiko , Sugiura Toshiyuki , Morishima Yuuichi , Shimoda Naoshi , Yamamori Hideo , Takagi Kazuya , Nakajima Nobuyuki
Published: September 2009

The effects of insulin‐like growth factor‐1 (IGF‐1) on the catabolic and immune response induced by thermal injury were studied in burned rats fed by TPN. An increase of synthesis greater than the increase of breakdown resulted in improved nitrogen retention in the IGF‐1 group. There was no effect on the mRNA in the structural proteins of the skeletal muscle and liver. However, the gene expression of albumin and the structural proteins of the diaphragm increased significantly in the rats receiving IGF‐1. The proliferation of the gut mucosa and the fractional protein synthesis rate of the small intestine increased, and the endotoxin content of the liver and spleen were smaller in the burned rats that received IGF‐1. Delayed type hypersensitivity increased significantly (p <.01) in the IGF‐1 group. In conclusion, IGF‐1 improved the whole‐body protein metabolism, and albumin and respiratory muscle protein synthesis in the burned rats. It significantly promoted the proliferation of the intestinal mucosa, and reduced the intestinal translocation of endotoxin. Cellular immunity was also enhanced. (Journal of Parenteral and Enteral Nutrition23:S93‐S97, 1999)