Protein Imbalance Research Articles

Nutrition therapy in the critically ill child

Malnutrition and obesity are prevalent in children admitted to the pediatric intensive care unit. Nutritional deterioration secondary to suboptimal nutrient delivery can adversely affect outcomes during pediatric critical illness. This review highlights the recent investigations of nutrition assessment, energy balance, indirect calorimetry, nutrition therapy, barriers to nutrient delivery, monitoring during enteral feeding, and the role of nutrition guidelines in critically ill children. Critically ill children are at high risk for energy and protein imbalance. Indirect calorimetry remains the only accurate method to assess energy requirements in this population. Intensive insulin therapy to achieve glycemic control may reduce morbidity and mortality in adults, but risks hypoglycemia in critically ill children. Early enteral nutrition improves nutrition outcomes and adherence to nutrition guidelines can overcome barriers to optimal nutrition therapy. Timely and adequate nutrition therapy is essential to improve nutrition outcomes in critically ill children. Further research is required to determine clinical outcome benefits with indirect calorimetry and enteral nutrition guidelines, and to identify optimal glucose targets.

Imbalance of Interleukin-18 and Interleukin-18 Binding Protein in Children with Henoch-Schönlein Purpura

The balance between interleukin-18 (IL-18) and its endogenous antagonist, IL-18 binding protein (IL-18BP), was evaluated in children with Henoch-Schönlein purpura (HSP). Plasma IL-18 and IL-18BP levels and peripheral blood mononuclear cell IL-18 mRNA expression were significantly higher in patients with active HSP (n = 30) than in healthy controls (n = 20); IL-18BP mRNA expression was similar in active HSP and controls. Plasma levels and mRNA expression of IL-18 and IL-18BP in patients in remission (n = 19) were similar to those in controls. The ratios of IL-18 / IL-18BP plasma levels and IL-18 / IL-18BP mRNA levels in active HSP were significantly higher than in patients in remission and healthy controls. Thus, adequate IL-18BP to block the proinflammatory activity of IL-18 may not be present in active HSP and regulation of the IL-18 / IL-18BP balance might provide a potential therapeutic strategy.

Advances in the pathogenesis of primary intrahepatic cholelithiasis

Primary intrahepatic stone is a common disease in China. It is difficult to treat this benign biliary tract disease because it has many complications and the surgery is difficult. Understanding the cause of this disease has important implications in prevention and treatment. This article reviewed the cause of primary intrahepatic stone from four aspects: imbalance of bile components, infection, bile protein, and macromolecular and metabolism of the cells. Key words: Primary intrahepatic stone

Blood biochemical parameters of simmental cows in different phases of reproductive cycle

This paper presents the values of blood biochemical parameters of Simmental cows (n = 60), divided into five groups (dry cows, early puerperium, late puerperium, the fifth month of lactation, and cows with an extended service period). The ration for lactating cows contained an insufficient amount of dry matter, a third less than the lower limit of their requirements. In all examined groups of cows, a strong protein deficiency and excess calcium was found in the diet. Total protein concentration in all groups of cows were on the upper physiological limit, and the concentrations of bilirubin, carotene, vitamin A and total lipids were within the normal range. Low concentrations of urea in the third, fourth and fifth group of cows (3.1?0.39 mmol/l, 2.9?0.38 mmol/l and 3.3?0.43 mmol/l, respectively) indicate the imbalance of protein and energy in the diet. The presence of an energy deficit is also indicated by the low blood glucose in all groups of cows, especially the second and fifth groups of cows (2.2?0.04 mmol/l and 2.3?0.07 mmol/l, respectively). The unfavorable ratio of calcium and phosphorus in the diet resulted in the narrowing of the calcium:phosporus ratio in blood serum, which is particularly evident in cows with an extended service period (2.1?0.07 mmol/l compared to 1.9? 0.11 mmol/l). Based on these results,we conclude that the tested herd exhibits subclinical health disorders, caused by an inadequate diet and with adverse effects on the productive and reproductive parameters.

Análisis del catabolismo muscular en la enfermedad pulmonar obstructiva crónica

IntroductionChronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the world, appreciating muscle involvement, asymptomatic in early stages, which is due to a protein imbalance that has been measured in other processes by the urinary excretion of pseudouridine. ObjectivesTo research, using urinary excretion of pseudouridine, if muscle catabolism in COPD is high and until what extent is related to age and gender. Material and methodsThe study is based on an analysis of a prospective randomized control group and one with COPD. Simultaneous determination of pseudouridine and creatinine in urine was performed by high-performance liquid chromatography (HPLC). We performed a descriptive statistical study of the variables age, gender, excretion of pseudouridine, and a ROC curve of the variable pseudouridine excretion, determines the cut point with higher sensitivity and specificity between the two populations. ResultsNo statistically significant differences were found in the pseudouridine excreted, with respect to age or gender, in the groups studied. Pseudouridine excretion was significantly higher in patients with COPD, 94.40 (87.64)μmol/mmol, with respect to the control group, 19.90 (6.6)μmol/mmol Md (IQR) (p<0.001). In the ROC curves analysis, pseudouridine excretion had area under the curve 0.972 and the optime cut point for pseudouridine excretion in our trial was 29.39 μmol/mmol (Sensibility 93.1% and Specificity 100%) and can be used to distinguish people with altered muscle catabolism. ConclusionsThe measure of pseudouridine excreted in urine, performed by this method, can be used as a control of muscle breakdown. In our study, the cut point was 29.39μmol/mmol which means, that people with a pseudouridine excretion 29.39μmol/mmol, shall be individuals with an increased catabolism due to COPD.

Mundane, yet challenging: The assessment of malnutrition in inflammatory bowel disease

Protein-energy malnutrition (PEM) is defined as a "state of nutrition in which a deficiency or excess (or imbalance) of energy, protein, and other nutrients causes measurable adverse effects on tissue/body form (body shape, size and composition) and function, and clinical outcome". Although this definition resulted from a long discussion among experts, it lacks concise assessment criteria. Essential to an effective practice of nutrition support, however, is the ability to identify who actually needs medical nutrition therapy. Patients with active inflammatory bowel disease (IBD) are a high risk group for protein-energy malnutrition, with a prevalence ranging up to 75%.

Lifelong Calorie Restriction Alleviates Age-Related Oxidative Damage in Peripheral Nerves

Aging is associated with protein damage and imbalance in redox status in a variety of cells and tissues, yet little is known about the extent of age-related oxidative stress in the peripheral nervous system. Previously, we showed a drastic decline in the expression of glial and neuronal proteins in myelinated peripheral nerves with age, which is significantly ameliorated by lifelong calorie restriction. The age-related decline in functional molecules is associated with alterations in cellular protein homeostatic mechanisms, which could lead to a buildup of damaged, aggregated proteins. To determine the extent of oxidative damage within myelinated peripheral nerves, we studied sciatic nerves from rats of four different ages (8, 18, 29, and 38 months) maintained on an ad libitum or a 40% calorie-restricted diet. We found a prominent accumulation of polyubiquitinated substrates with age, which are associated with the conglomeration of distended lysosomes and lipofuscin adducts. The occurrence of these structures is notably less frequent within nerves of age-matched rodents kept on a lifelong reduced calorie diet. Markers for lipid peroxidation, inflammation, and immune cell infiltration are all elevated in nerves of ad libitum-fed rats, whereas food restriction is able to attenuate such deleterious processes with age. Together these results show that dietary restriction is an efficient means of defying age-related oxidative damage and maintaining a younger state in peripheral nerves.

Electrolyte and protein imbalance following anti-EGFR therapy in cancer patients: A comparative study

Electrolytic changes in blood have been associated with the use of anti-epidermal growth factor receptor (EGFR) antibodies. The objective of this retrospective study was to compare the rate of incidence and the severity of blood electrolyte and protein imbalances occurring in patients receiving cetuximab or panitumumab with or without concurrent chemotherapy. Treatment data of 58 patients who received cetuximab and 21 patients who received panitumumab were analyzed. Cetuximab caused hypomagnesemia in more than half of the patients, among whom 4 had severity up to grade 2/3 level, whereas panitumumab induced hypomagnesemia in 90% of the patients with severity up to grade 2 level occurring in 38% of the patients. Intravenous magnesium supplementation on the day of anti-EGFR treatment did not always adequately control the magnesium wasting in these patients. Often treatments with these agents had to be interrupted or terminated as a result of severe electrolyte depletion despite supplementation. Taking into consideration the mechanism of magnesium wasting from the kidney and the magnesium transport process in the gut, intravenous magnesium infusion coupled with oral supplementation with more tolerant oral magnesium products may help improve the treatment outcome in these patients. Surprisingly, more than half of these patients showed significant decreases in their albumin levels, which were correlated with the initiation or discontinuation of anti-EGFR therapy. The underlying mechanism of this decrease in albumin level is not known. The increased likelihood of poor outcomes such as mortality, morbidity and prolonged hospital stay in acutely ill patients with hypoalbuminemia is well recognized. Moreover, the maintenance of adequate serum albumin levels in these patients receiving anti-EGFR therapy may play an important role in containing some of the adverse effects of concurrently administered chemotherapeutic agents.

Evidence based practice guidelines for the nutritional management of malnutrition in adult patients across the continuum of care

Evidence based practice guidelines for the nutritional management of malnutrition in adult patients across the continuum of care

Athletes' dietary intake was closer to French RDA's than those of young sedentary counterparts

It has been demonstrated that athletes' dietary intake was relatively well-balanced according to the recommended dietary allowances (RDAs). In contrast, other studies have shown that athletes may have low energy intake or imbalance of protein and fat and insufficient minerals and vitamins. Nonetheless, we hypothesized that practicing a sport may allow young adults to have a nutritional status closer to recommended values. The purpose of this experiment was to study the nutritional status of young French adults, particularly to compare the nutritional status of trained young male and female athletes to those of young sedentary control subjects, and to national RDAs. A total of 85 young adults were recruited and filled a 4-day food and physical activity record. Dietary intake, energy expenditure, energy balance, carbohydrate, protein, fat, water, vitamins, and minerals were recorded. Data were analyzed with a software Nutrilog and statistics with Sigma Stat. Energy intake values were 9874 +/- 3050 kJ for the athletes and 7506 +/- 1845 kJ for control subjects. Athletes' nutritional status was closer to French RDAs than those of sedentary subjects who present a lower energy intake, a greater percentage of the energy intake from fat and lower values for minerals and vitamins. In conclusion, practicing a sport may allow athletes to balance their energy intake and expenditure and could be a good way to have a nutritional status closer to RDAs. Educational programs for students on proper food selection, eating habits and physical activity are needed to improve the nutritional status of these young French adults, particularly in sedentary students.

Proteomic analysis of 'hybrid necrosis' in wheat (Triticum aestivum) leaves.

Wheat hybrid necrosis has been genetically characterised for many years, but the specific gene(s) and the protein products involved in the processes remains unknown. In this study, protein expression in the base (B), mid (M) and tip (T) segments of the FL-2 leaves of a necrotic hybrid, PZF1 and its parents, Pan555 and Zheng891, was analysed and compared using a high throughput proteomic approach. Twenty-three protein spots, with significant variations in intensity across the necrotic leaf segments, were analysed by MALDI-TOF-MS, of which, 18 were matched to protein accessions in the NCBI database. Several of these proteins are enzymes involved in the methylation cycle, including AdoHcy hydrolase, AdoMet synthase 3 and methionine synthase 1; AdoHcy hydrolase was downregulated sharply in M and T, and AdoMet synthase 3 and methionine synthase 1 were upregulated gradually from M to T. This result suggests that methylation-associated processes, including epigenetic mechanisms, may play a role in the initiation and development of hybrid necrosis. Several energy cycle-associated proteins and cytoprotective proteins were also differentially expressed across the leaf segments, suggesting their direct association with or possible involvement in the necrotic processes. The significant imbalance of a heat-shock protein, a transposon protein and a RNA- and ssDNA-binding protein also makes these proteins potential molecular components in the necrotic processes.

ORIGINAL ARTICLE: Bcl‐2 and Bax Expressions in Pre‐Term, Term and Post‐Term Placentas

Problem Placental apoptosis‐associated protein imbalance might contribute to the pathogenesis of pre‐ and post‐term birth. Therefore, we evaluated the expression and distribution of pro‐apoptotic (Bax) and anti‐apoptotic (Bcl‐2) molecules in term, pre‐term and post‐term placentas.Method of study Placental samples were collected from women with term (n = 25), pre‐term (n = 7) and post‐term (n = 10) deliveries. The expression of Bcl‐2 and Bax was assessed by immunochemistry on paraffin‐embedded placental specimens.Results The pattern of immunostaining for Bcl‐2 and Bax was the same in all samples, but not the intensity. The Bax/Bcl‐2 ratio was higher in both pre‐term and post‐term placental samples compared with term placentas as a result of intense reactivity for the pro‐apoptotic factor, Bax in pre‐term and post‐term placentas and, for Bcl‐2 decrease in pre‐term placentas.Conclusion These findings suggest that different unbalance mechanisms in placental apoptotic‐associated protein expressions may be involved in the physiopathology of pre‐term and post‐term births.

Loss-of-function genetic screening identifies a cluster of ribosomal proteins regulating p53 function

Introduction of conditional murine p53 (p53val135) and oncogenic ras into double p53/p21-null mouse embryonic fibroblasts (MEFs) showed that p21waf1 was not required for combined ras/p53-induced senescent-like growth arrest. We used this cellular system to identify key players in the ras-p53-induced senescence in the absence of p21. Applying a retroviral-based genetic screen, we obtained mRNA antisense fragments against a cluster of 14 different ribosomal proteins which loss of function bypasses p53-induced growth arrest. The expression of the ribosomal protein antisense fragments reduced the transcriptional activity of p53. Experiments with eGFP-p53 chimeras suggest that the effect is mediated by a reduction of p53. To study whether p53 was downregulated by MDM2-dependent degradation, we tested the effect of the RP antisenses in double p53/MDM2-null MEFs and observed that in the absence of MDM2, reduction of the RP levels also decreases p53 levels. Therefore, although we cannot discard other unknown mechanism, we suggest that the decrease in the levels of ribosomal proteins might inhibit p53-specific translation. Finally, quantitative analysis comparing levels of mRNA in tumours versus mRNA in normal tissue of the same organ and patient showed that a variable percentage of lung, prostate or colon tumours have reduced levels of the RPs tested. Interestingly, in most cases, the reduction of ribosomal protein mRNAs occurs only to 50%. Our data suggest that ribosomal protein imbalance might contribute to p53 regulation through the ribosomal biogenesis checkpoint.

The lymphatics in the pathophysiology of thoracic and abdominal surgical pathology: Immunological consequences and the unexpected role of microsurgery

The authors report their experience in the diagnosis and treatment of lymphatic and chylous disorders in the thoracic and abdominal areas. Sixteen patients (10 adults, 6 children) affected by primary chylous ascites with associated syndromes and consequent immunological incompetence were studied. Diagnostic investigations included abdominal sonography scans, lymphoscintigraphy, and lymphography combined with computed tomography and laparoscopy. Surgical treatment included laparoscopy, drainage of ascites and/or the chylothorax, treatment of abdominal and retroperitoneal chylous leaks, exeresis of lymphodysplastic tissues, ligation of incompetent lymph vessels also by CO(2) LASER, and chylo-venous and lympho-venous microsurgical shunts. Eleven patients did not have a relapse of the ascites and four patients had a persistence of a small quantity of ascites with no protein imbalance. All patients had an improvement of their immunocompetence. Median follow-up was 5 years. We demonstrated that the use of microsurgery is remarkably advantageous for performing a causal treatment of the dysfunction.

Hypercoagulability Risks Among Adult Living Liver Donors

Background Review of the literature is limited with respect to thrombotic risk in the living liver donor. This study examines inherent coagulable changes that occur as a result of the surgery. Materials and Methods At our center, we have performed 353 orthotopic adult liver transplants in the past 4 years. Of these, 20 were adult-adult right lobe living donor transplants. All living donors are alive and doing well. Of these, eight living donors were followed preoperatively and postoperatively monitoring protein C, protein S, antithrombin III, and factor VIII levels. Levels were checked at 48 hours postoperatively, as well as at 2, 4, and 6 weeks. Results All eight patients had normal levels preoperatively, although significantly low levels were identified postoperatively of these coagulation markers: protein C decreased to as low as 0%, (range 0–29; normal 50–150) within 48 hours postoperatively; protein S decreased to 3% to 40% during the same time frame (normal 50–150), and antithrombin III levels decreased to 47% to 55% (normal range 50–150%). Factor VIII levels significantly increased to >200% (normal 50– 150). All coagulation levels returned to the normal range within 4 to 6 weeks. None of the patients developed a thromboembolic event. Conclusions We observed an imbalance of low protein C, S, and antithrombin III and elevated factor VIII levels, which have been documented as thrombotic risks in adults. Our findings suggest that the imbalance in the coagulation profile after surgery may be an independent risk factor for thrombosis beyond the surgical event, a phenomenon that requires further exploration.

Edaravone protects PC12 cells from ischemic-like injury via attenuating the damage to mitochondria

Edaravone had been validated to effectively protect against ischemic injuries. In this study, we investigated the protective effect of edaravone by observing the effects on anti-apoptosis, regulation of Bcl-2/Bax protein expression and recovering from damage to mitochondria after OGD (oxygen-glucose deprivation)-reperfusion. Viability of PC12 cells which were injured at different time of OGD injury, was quantified by measuring MTT (2-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide) staining. In addition, PC12 cells' viability was also quantified after their preincubation in different concentration of edaravone for 30 min followed by (OGD). Furthermore, apoptotic population of PC12 cells that reinsulted from OGD-reperfusion with or without preincubation with edaravone was determined by flow cytometer analysis, electron microscope and Hoechst/PI staining. Finally, change of Bcl-2/Bax protein expression was detected by Western blot. (1) The viability of PC12 cells decreased with time (1 - 12 h) after OGD. We regarded the model of OGD 2 h, then replacing DMEM (Dulbecco's Modified Eagle's Medium) for another 24 h as an OGD-reperfusion in this research. Furthermore, most PC12 cells were in the state of apoptosis after OGD-reperfusion. (2) The viability of PC12 cells preincubated with edaravone at high concentrations (1, 0.1, 0.01 micromol/L) increased significantly with edaravone protecting PC12 cells from apoptosis after OGD-reperfusion injury. (3) Furthermore, edaravone attenuates the damage of OGD-reperfusion on mitochondria and regulated Bcl-2/Bax protein imbalance expression after OGD-reperfusion. Neuroprotective effects of edaravone on ischemic or other brain injuries may be partly mediated through inhibition of Bcl-2/Bax apoptotic pathways by recovering from the damage of mitochondria.

Diagnosis and management of primary chylous ascites

Chylous ascites is the accumulation of triglyceride-rich, free, milk-like peritoneal fluid caused by the presence of intestinal lymph in the abdominal cavity. Primary chylous ascites is uncommon. We present our experience in the diagnosis and treatment of this condition. Twelve patients (7 adults, 5 children) affected by primary chylous ascites were studied. Diagnostic investigations included abdominal sonography scans, lymphoscintigraphy, and lymphography combined with computed tomography (CT) with intravenous and intralymphatic lipid-soluble contrast, and laparoscopy. Magnetic resonance imaging was used when lymphography and lymphatic CT were not able to define the dysplasia well, or in the presence of lymphatic dilatation. Surgical treatment included laparoscopy (12/12), drainage of ascites (12/12), the search for and treatment of abdominal and retroperitoneal chylous leaks (12/12), exeresis of lymphodysplastic tissues (12/12), ligation of incompetent lymph vessels (9/12), carbon dioxide laser treatment (cut and welding effects) of the dilated lymph vessels using an operating microscope for magnification (9/12), and chylovenous and lymphovenous microsurgical shunts (7/12). Eight patients did not have a relapse of the ascites, and three patients had a persistence of a small quantity of ascites with no protein imbalance. Postoperative lymphoscintigraphy in seven patients confirmed better lymph flow and less lymph reflux. Median follow-up was 5 years (range, 3 to 7 years). We observed early relapse of chylous ascites in only one case that required a peritoneal-jugular shunt and led to good outcome. Primary chylous ascites is closely correlated to lymphatic-lymphonodal dysplasia that does not involve a single visceral district alone. Medical preoperative treatment played an essential role in the global management of this complex pathology. We demonstrated that the use of laparoscopy is remarkably advantageous for confirming diagnosis, for draining the ascites, and for evaluating the extension of the dysplasia. Our diagnostic work-up provided us with an exact diagnostic assessment and allowed us to plan a precise surgical approach.

Clinical trial to determine the productivity impact of milk urea nitrogen reports

A clinical trial was conducted to determine the perceived and actual utility of milk urea nitrogen (MUN) notification and interpretation as a tool for monitoring protein and energy imbalances in dairy cows. Based on MUN results during the summer of 2001, 50 farms with high MUN values and 30 with low values were randomly allocated to become either intervention or control farms. From January to November 2002 (the trial period), intervention included monthly notification of individual cow MUN results, interpretation of abnormal average MUN values in subgroups of cows based on parity and days-in-milk, and suggestion of possible nutritional reasons for the abnormal MUNs. Intervention farms responded to a survey regarding report utilization, subsequent feed changes and perceptions of MUN testing. Control farms received the individual cow MUN results, but no additional interpretation. No significant differences in average MUN or standardized milk production between intervention and control farms were seen during the last three months of the trial (the outcome period). However, in herds making a feed change in response to MUN notification and interpretation (71% of intervention herds), milk production increased 2.4 lb (1.1 kg)/cow per day in the month after the feed change when compared to randomly selected herds not making a feed change during the same time period. Most dairy producers receiving the MUN notification and interpretation reports felt they knew how to use MUN reports after the trial, and felt that MUN testing was at least somewhat useful as a nutritional tool.

Is Cronkhite???Canada Syndrome necessarily a late-onset disease?

Cronkhite-Canada Syndrome is a non-inherited, non-congenital disease characterized by juvenile hamartomatous gastrointestinal polyps with a typically late onset. In the case described herein the disease was diagnosed in a 17-year-old male with type I diabetes and thalassaemia minor, in coincidence with severe symptomatic intestinal candidiasis. Following the disappearance of the mycosis and correction of the protein and electrolyte imbalance, the ectodermal abnormalities returned to normal and the patient remained asymptomatic during a 7-year follow-up period, despite proteinuria resulting from membranous glomerulopathy. The concept that Cronkhite-Canada Syndrome is a late-onset disease should probably be reconsidered as it may remain asymptomatic, and thus not diagnosed, for a long a time.

Malnutrition screening in the elderly population

Malnutrition is a state in which a deficiency, excess or imbalance of energy, protein and other nutrients causes adverse effects on body form, function and clinical outcome.1 To justify screening for this state in the elderly, four criteria must be satisfied: malnutrition must be a frequent cause of ill-health in this population; it must have a negative effect on outcomes; a simple, reliable, valid and acceptable screening test must be available to detect those who are malnourished or at risk of malnutrition; and there must be benefit from nutritional intervention in those identified by screening. In this review we consider whether these conditions are satisfied by tests of various kinds.