Prevalence of Candida albicans in patients receiving total parenteral nutrition

The prevalence of Candida albicans was quantitatively compared in 74 surgical patients during and after total parenteral nutrition (TPN). Suppression of oral food intake is probably responsible for the decrease of the C. albicans population in the mouth. On the contrary anal swabs were more often positive for C. albicans during TPN. This may be due to local conditions as was observed in a group of patients who were not given TPN but were also immobilized for a long period.     

The effect of total parenteral nutrition (TPN) on gastrin release in the rat

The effect of short-term (7 days) total parenteral nutrition (TPN) on gastrin release was studied in vivo and in the isolated vascularly perfused rat stomach. The daily plasma gastrin concentration of parenterally fed rats was significantly lower than in ad lib fed control animals (53 +/- 17 pg/ml vs 159 +/- 32 pg/ml, P less than 0.05) as early as day 2 and a similar pattern was observed on days 4 and 6. The fasting plasma gastrin concentration of control animals was 2-fold greater than of the parenterally fed group (P less than 0.05). Following oral peptone, the gastrin response of TPN and control animals doubled although peak gastrin levels were greatly reduced in TPN rats. Basal gastrin release from the perfused stomachs of control rats was 2-fold greater than from TPN rats (P less than 0.05). Electrical stimulation of the vagal trunks resulted in a significantly greater elevation in gastrin secretion from control stomachs compared to TPN animals (4-fold vs. 2.4-fold increase, P less than 0.05). Quantification of the antral G-cell population revealed a significant reduction in the number of G-cell of TPN rats compared to controls (97 +/- 8 cells/mm vs 76 +/- 6 cells/mm, P less than 0.05). These results indicate that luminal nutrient stimulation is necessary for the maintenance of normal G-cell secretory activity in vivo and from the in vitro stomach. G-cell hypoplasia appears to be partially responsible for reduced gastrin output to basal and stimulated conditions after TPN.     

Selenium and zinc levels in surgical patients receiving total parenteral nutrition

The zinc and selenium levels of 40 surgical patients were monitored pre-and post-TPN. The initial selenium level was low normal, and the initial zinc level was also low. Both selenium and zinc are potent antioxidants involved in cellular defense against free radicals. Surgical patients are at risk for selenium and zinc deficiencies secondary to both increased needs and losses. TPN blood work protocols should include monitoring of selenium and zinc with supplementation of the nutrient solutions, as required.     

The effect of total parenteral nutrition (TPN) on the enteroinsular axis in the rat

The effect of 6 days of total parenteral nutrition (TPN) on the enteroinsular axis was studied in vivo and in vitro in the rat. During the TPN period, blood samples were taken from control and TPN animals to determine the comparative pattern of GIP release. Glucose, insulin and GIP responses to oral glucose (OGTT) were compared in TPN and control rats. The effect of glucose and GIP on insulin release from the isolated perfused pancreas of the same animals was investigated to determine if TPN altered the sensitivity of the beta cell. In conjunction with these studies the number and distribution of GIP-containing cells were compared in control and TPN animals. TPN resulted in no change in basal levels of glucose, insulin and IR-GIP. An exaggerated insulin response to OGTT occurred after TPN whereas the glucose response was reduced. The IR-GIP response to glucose was normal following TPN. The isolated perfused pancreas showed a 30% increase in insulin release in response to GIP after TPN. The insulin response to glucose appeared normal as did the number and distribution of GIP cells. Fluctuations in GIP and insulin levels in control animals were diurnal in nature, whereas IR-GIP levels in TPN animals remained near fasting levels. It was hypothesized that the increase in beta cell sensitivity to GIP may be causally connected to the exposure of the pancreas to chronically low levels of GIP during TPN.     

Free oxygen radical-induced lipid peroxidation and antioxidant in infants receiving total parenteral nutrition

OBJECTIVE: Increased oxygen-derived free radical activity has been reported during total parenteral nutrition (TPN) in infants particularly linked to the fat infusion. It is possible that partial enteral feeding can ameliorate some of the complications of TPN. By this study we aimed to investigate free radical formation and antioxidant activity in term and preterm infants during TPN and/or enteral feeding. STUDY DESIGN: We had 6 groups of term and preterm infants made up of 10 patients each. Group I had only enteral feeding, Group II enteral plus parenteral feeding, Group III only parenteral feeding. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), vitamin E and vitamin C levels were measured in all infants. Blood samples of infants receiving only TPN and TPN plus enteral feeding were measured on the 1st and 5th days, and 3h after the end of lipid infusion. RESULTS: There was no difference between the term and preterm infants in terms of MDA, SOD, vitamin C and E levels taken baseline and after parenteral, and enteral plus parenteral feeding on the 1st and 5th days. When 3 groups of both term and preterm infants were compared with each other none of the parameters showed a statistically significant difference. In addition, we compared baseline and 1st and 5th days of TPN therapy in both term and preterm infants fed only parenterally and enteral plus parenteral feedings. In term infants fed both parenterally and parenteral plus enterally, the MDA levels before TPN were significantly higher than that of the levels of patients on parenteral nutrition on the 5th day. On the 1st and 5th days of TPN therapy, the levels of vitamin C was significantly decreased, in term and preterm infants fed only parenterally, levels of vitamin E was increased, in term and preterm infants fed both parenterally and parenteral plus enterally. Also, when compared to their base line the SOD levels of the term infants detected on the 1st and 5th days were significantly high. CONCLUSION: Free radical production is increased by the administration of TPN and may be linked to its adverse effects. It may be assumed that long-term complications of preterm infants receiving TPN may be reduced by further strengthening the antioxidant capacities of the TPN solutions.     

Megaloblastic anemia in patients receiving total parenteral nutrition without folic acid or vitamin B12 supplementation.

Pancytopenia developed in four patients receiving postoperatively total parenteral nutrition (TPN). Symptoms and signs were related mainly to underlying bowel disease. Hematologic abnormalities, first noted from 4 to 7 weeks following institution of TPN, consisted of normocytic anemia (mean decrease in hemoglobin value, 2.2 g/dL), occasional macrocytes being noted, leukopenia (range of leukocyte counts, 1.2 to 3.6 X 10(9) L), some hypersegmented neutrophils being detected, and clinically significant thrombocytopenia (range of platelet counts, 25 to 52 X 10(9)/L). In all patients the bone marrow showed megaloblastic changes, with ring sideroblasts, although pyridoxine was included in the TPN regimens. Serum vitamin B12 values were normal in one patient and at the lower limit of normal in the other two patients in whom it was measured, while serum or erythrocyte folate values, or both, were reduced in three patients. Full hematologic response was observed in the four patients after folic acid replacement therapy; leukocytosis and thrombocytosis were noted in three. Thus, folic acid and possibly vitamin B12 should be added routinely to TPN regimens to prevent deficiency of either substance.     

Blood glucose control in healthy subject and patients receiving intravenous glucose infusion or total parenteral nutrition using glucagon-like peptide 1

AIMS: It was the aim of the study to examine whether the insulinotropic gut hormone GLP-1 is able to control or even normalise glycaemia in healthy subjects receiving intravenous glucose infusions and in severely ill patients hyperglycaemic during total parenteral nutrition. PATIENTS AND METHODS: Eight healthy subjects and nine patients were examined. The volunteers received, in six separate experiments in randomised order, intravenous glucose at doses of 0, 2 and 5mg kg(-1) min(-1), each with intravenous GLP-1 or placebo for 6 h. Patients were selected on the basis of hyperglycaemia (>150 mg/dl) during complete parenteral nutrition with glucose (3.2+/-1.4 mg kg(-1) min(-1)), amino acids (n=8; 0.9+/-0.2 mg kg(-1) min(-1)), with or without lipid emulsions. Four hours (8 a.m. to 12 a.m. on parenteral nutrition plus NaCl as placebo) were compared to 4 h (12 a.m. to 4 p.m.) with additional GLP-1 administered intravenously. The dose of GLP-1 was 1.2 pmol kg(-1) min(-1). Blood was drawn for the determination of glucose, insulin, C-peptide, GLP-1, glucagon, and free fatty acids. RESULTS: Glycaemia was raised dose-dependently by glucose infusions in healthy volunteers (p<0.0001). GLP-1 ( approximately 100-150 pmol/l) stimulated insulin and reduced glucagon secretion and reduced glucose concentrations into the normoglycaemic fasting range (all p<0.05). In hyperglycaemic patients, glucose concentrations during the placebo period averaged 211+/-24 mg/dl. This level was reduced to 159+/-25 mg/dl with GLP-1 (p<0.0001), accompanied by a rise in insulin (p=0.0002) and C-peptide (p<0.0001), and by trend towards a reduction in glucagon (p=0.08) and free fatty acids (p=0.02). GLP-1 was well tolerated. CONCLUSIONS: Hyperglycaemia during parenteral nutrition can be controlled by exogenous GLP-1, e.g. the natural peptide (available today), whereas the chronic therapy of Type 2 diabetes requires GLP-1 derivatives with longer duration of action.     

Circadian rhythms of urinary electrolyte excretion in freely moving rats

In 8 freely moving rats the circadian variation in the eletrolyte excretion was studied. Food was available during either the dark or the light period. The lights were on from 0800–2000 hr. Potassium, phosphate and magnesium showed peak excretion values during the dark period under both feeding conditions, although the maxima occurred 2.5 hr earlier when the rats were fed during the light period; minimum excretion was recorded just prior to feeding. Sodium excretion followed a different pattern; for animals fed during the night, maximum excretion occurred almost at the end of the dark period and minimum excretion at the start of the feeding period. For day-fed animals these values were recorded 5 and 4 hours earlier, respectively. Calcium excretion reached a maximum after the feeding period and a minimum shortly after the onset of feeding. From this study it can be concluded that the peak excretions of potassium, phosphate and magnesium are only slightly influenced by the feeding regimen, indicating that they depend mainly on an endogenous rhythm. In contrast, the minimum excretion of these ions is determined by feeding. For calcium maximum as well as minimum excretion is correlated with the feeding regimen. The excretion pattern of sodium differs from that of calcium, as well as potassium, phosphate and magnesium, indicating that it is controlled by a different mechanism.     

Long-term infusion of nutrients (total parenteral nutrition) suppresses circulating ghrelin in food-deprived rats

BACKGROUND: Ghrelin derives from endocrine cells (A-like cells) in the stomach (mainly the oxyntic mucosa). Its concentration in the circulation increases during fasting and decreases upon re-feeding. This has fostered the notion that the absence of food in the upper gastrointestinal (GI) tract stimulates the secretion of ghrelin. The purpose of the present study was to determine the concentration of ghrelin in serum and oxyntic mucosa after replacing food with intravenous (iv) infusion of nutrients for 8 days using the technique known as total parenteral nutrition (TPN) MATERIALS AND METHODS: Male Sprague-Dawley rats (200-250 g) were given nutrients (lipids, glucose, amino acids, minerals and vitamins) by iv infusion for 8 days during which time they were deprived of food and water; another group was deprived of food for 24-48 h (fasted controls), while fed controls had free access to food and water. Serum ghrelin, gastrin and pancreastatin concentrations were measured together with the ghrelin content of the oxyntic mucosa. Plasma insulin and glucose as well as serum lipid concentrations were also determined. RESULTS: Fasted rats had higher serum ghrelin than TPN rats and fed controls. The oxyntic mucosal ghrelin concentration (and content) was lower in TPN rats than in fasted rats or fed controls. The serum gastrin and pancreastatin concentrations were lower in TPN rats and fasted rats than in fed controls. The plasma insulin concentration was 87 pmol/l+/-8 (SEM) in TPN rats compared to 101+/-16 pmol/l in fed controls; it was 26+/-14 pmol/l in fasted rats. The basal plasma glucose level was 11+/-0.6 mmol/l in TPN rats and 12+/-0.8 mmol/l in fed controls; it was 7+/-0.3 mmol/l in fasted rats. In TPN rats, the serum concentrations of free fatty acids, triglycerides and cholesterol were increased by 100%, 50% and 25%, respectively, compared to fed controls. Fasted rats had higher circulating concentrations of free fatty acids (20%) and lower concentrations of triglycerides (-40%) than fed controls; fasted rats did not differ from fed controls with respect to serum cholesterol. CONCLUSION: The circulating ghrelin concentration is high in situations of nutritional deficiency (starvation) and low in situations of nutritional plenty (free access to food or TPN). The actual presence or absence of food in the GI tract seems irrelevant. Circulating insulin and glucose concentrations did not differ much between TPN rats and fed controls; serum lipids, however, were elevated in the TPN rats. We suggest that elevated blood lipid levels contribute to the suppression of circulating ghrelin in rats subjected to TPN for 8 days.     

Bacterial and fungal growth in total parenteral nutrition solutions

The most serious complication of prolonged intravenous infusion of hypertonic dextrose and amino acids is infection. Frequently, the etiology is fungal rather than bacterial. Previous authors have suggested that bacterial survival and growth in the solutions is suppressed by (a) high dextrose concentration, (b) high osmolality, or (c) low pH. This paper presents evidence that proposals (a) and (b) are untenable and (c) is only partly responsible. We call attention to the presence of a factor that is antibacterial but not antifungal; namely, a high concentration of glycine.     

Bacterial and fungal growth in total parenteral nutrition solutions,.

The most serious complication of prolonged intravenous infusion of hypertonic dextrose and amino acids is infection. Frequently, the etiology is fungal rather than bacterial. Previous authors have suggested that bacterial survival and growth in the solutions is suppressed by (a) high dextrose concentration, (b) high osmolality, or (c) low pH. This paper presents evidence that proposals (a) and (b) are untenable and (c) is only partly responsible. We call attention to the presence of a factor that is antibacterial but not antifungal; namely, a high concentration of glycine.     

Circadian rhythmus of the excretion of electrolytes and urinary proteins in rats]

Circadian rhythms in urinary water, sodium, potassium and proteins excretion are studied in 45 rats living alone in metabolism cages. Urines are collected during 4 consecutive 6 hours long periods during 2 consecutive days. Large circadian variations of these parameters (especially water and proteins excretion and urinary protein concentration) are described. The influence of feeding rhythms on the circadian urinary excretion rhythms is discussed. It is proposed that nightly renal hemodynamic changes (during meal digestion or with high renin plasma levels) can induce modifications in glomerular filtration rate and electrolytes and macromolecules transglomerular flow.     

Circadian activity rhythms in the crayfish Paranephrops zealandicus (Crustacea)

The diel activity rhythm shown by Paranephrops is usually unimodal with most activity occurring at night. In constant darkness, locomotor activity is expressed for up to 60 days as a free-running circadian rhythm. The period varies from 18 to 38 hours following a seasonal cycle (summer mean period 24 hours, winter mean 30 hours). No adaptive significance can be attached to either seasonal or individual variations in period and it is suggested that such variations are a consequence of the way in which the clock mechanism operates, the period being linked to the overall activity level following Aschoff's ( 1960 ) Circadian Rule. Activity levels will inevitably vary individually and seasonally.     

Circadian rhythms of self-feeding and locomotor activity in zebrafish (Danio Rerio)

To investigate daily feeding rhythms in zebrafish, the authors have developed a new self-feeding system with an infrared photocell acting as a food-demand sensor, which lets small-size fish such as zebrafish trigger a self-feeder. In this paper, the authors used eight groups of 20 fish. Locomotor activity rhythms were also investigated by means of infrared sensors. Under a 12?h:12?h light (L)-dark (D) cycle, zebrafish showed a clear nocturnal feeding pattern (88.0% of the total daily food-demands occurring in the dark phase), concentrated during the last 4?h of the dark phase. In contrast, locomotor activity was mostly diurnal (88.2% of total daily activity occurring in the light phase). Moreover, both feeding and locomotor rhythms were endogenously driven, as they persisted under free-running conditions. The average period length (τ) of the locomotor and feeding rhythms was shorter (τ?=?22.9?h) and longer (τ?=?24.6?h) than 24?h, respectively. During the time that food availability was restricted, fish could only feed during ZT0-ZT12 or ZT12-ZT16. This resulted in feeding activity being significantly modified according to feeding time, whereas the locomotor activity pattern remained synchronized to the LD cycle and did not change during this trial. These findings revealed an independent phasing between locomotor and feeding activities (which were mostly nocturnal or diurnal, respectively), thus supporting the concept of multioscillatory control of circadian rhythmicity in zebrafish.     

Elevated serum chromium in patients on total parenteral nutrition and the ionic species of contaminant chromium

Chromium (Cr), an essential micronutrient required for glucose metabolism, was found in high concentrations in up to 94% of the patients on short-term total parenteral nutrition. Approximately 50% had serum levels >10-fold of normal (upper reference value of 3.8 nmol/L), about 18% were >20-fold, and about 2% were 40-fold higher. The major Cr contaminant was detected in the amino acid constituents, and was found to have the trivalent ionic form. Although trivalent Cr is reported to be less genotoxic, further study is required to determine the effects on cells exposed to high concentrations of this element during parenteral nutrition over an extended period of time.     

Circadian rhythms of agitation in institutionalized patients with Alzheimer's disease

Agitation is a common problem in institutionalized patients with Alzheimer's disease (AD). “Sundowning,” or agitation that occurs primarily in the evening, is estimated to occur in 10—25% of nursing home patients. The current study examined circadian patterns of agitation in 85 patients with AD living in nursing homes in the San Diego, California, area. Agitation was assessed using behavioral ratings collected every 15 minutes over 3 days, and activity and light exposure data were collected continuously using Actillume recorders. A five-parameter extension of the traditional cosine function was used to describe the circadian rhythms. The mean acrophase for agitation was 14:38, although there was considerable variability in the agitation rhythms displayed by the patients. Agitation rhythms were more robust than activity rhythms. Surprisingly, only 2 patients (2.4%) were“sundowners.”In general, patients were exposed to very low levels of illumination, with higher illumination during the night being associated with less robust agitation rhythms with higher rhythm minima (i.e., some agitation present throughout the day and night). Seasonality was examined; however, there were no consistent seasonal patterns found. This is the largest study to date to examine agitation rhythms using behavioral observations over multiple 24h periods. The results suggest that, although sundowning is uncommon, agitation appears to have a strong circadian component in most patients that is related to light exposure, sleep, and medication use. Further research into the understanding of agitation rhythms is needed to examine the potential effects of interventions targeting sleep and circadian rhythms. (Chronobiology International, 17(3), 405-418, 2000)