Changes in telomere length 3-5 years after gastric bypass surgery.

Increased inflammation and oxidative stress associated with obesity can accelerate aging. Telomere length (TL) has the capacity to serve as an aging indicator at the cellular level. Obesity has a known association with shorter TL. This study evaluated TL of immune cells in a population of obese individuals who underwent gastric bypass surgery. Pre- and post-operative DNA samples were available for 50 subjects who had gastric bypass surgery. DNA was analyzed via quantitative polymerase chain reaction to determine TL. Changes in TL were evaluated by comparing TL at baseline to TL at 3-5 years post gastric bypass surgery. Sixty percent of the individuals in the study observed an increase in TL. Significant lengthening was observed for those with the shortest baseline TL (P=0.0011), but not for those with intermediate baseline TL (P=0.411) or longest baseline TL (P=0.207). Change in TL was negatively correlated with age and triglycerides but not correlated with weight loss induced by bariatric surgery. This study confirms that TL lengthening is observed post bariatric surgery and is the first to detect TL lengthening 3-5 years after surgery.

Gene expression profiling in subcutaneous, visceral and epigastric adipose tissues of patients with extreme obesity.

OBJECTIVE: The goal of the present study was to identify differences in gene expression between SAT, VAT and EAT depots in Class III severely obese individuals. DESIGN: Human subcutaneous (SAT) and visceral (VAT) adipose tissues exhibit differential gene expression profiles. There is little information, however, about the other proximal white adipose tissue, epigastric (EAT), in terms of its function and contribution to metabolism. SUBJECTS AND METHODS: Using RNA from adipose biospecimens obtained from Class III severely obese patients undergoing open Roux-en-Y gastric bypass surgery, we compared gene expression profiles between SAT, VAT and EAT, using microarrays validated by real-time quantitative PCR. RESULTS: The three depots were found to share 1907 genes. VAT had the greatest number of genes (66) expressed exclusively in this depot, followed by SAT (23), and then EAT (14). Moreover, VAT shared more genes with EAT (65) than with SAT (38). Further analyses using ratios of SAT/EAT, VAT/EAT and SAT/VAT identified specific as well as overlapping networks and pathways of genes representing dermatological diseases, inflammation, cell cycle and growth, cancer and development. Targeted analysis of genes, having a role in adipose tissue development and function, revealed that Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha (PGC1-α) that regulates the precursor of the hormone Irisin (FNCD5) were abundantly expressed in all three fat depots, along with fibroblast growth factors (FGF) FGF1, FGF7 and FGF10, whereas, FGF19 and FGF21 were undetectable. CONCLUSIONS: These data indicate that EAT has more in common with VAT, suggesting similar metabolic potential. The human epigastric adipose depot could have a significant functional role in metabolic diseases and should be further investigated.

Thermophilic amylase-digested rice-electrolyte solution in the treatment of acute diarrhea in children.

OBJECTIVE: To compare the efficacy of an oral rehydration solution (ORS) containing short polymers of glucose derived from rice (Amylyte-ORS) and five times the caloric density of current ORS to the standard glucose-ORS (World Health Organization [WHO] = ORS) in the treatment of acute diarrhea in children. METHODS: The rice ORS (Amylyte-ORS) was obtained by adding thermophilic amylase (252,500 MW units) and salts (1.5 g NaCl, 600 mg KCl, and 150 mg CaCl2) to 100 g rice and boiling for 10 minutes in 500 mL water. This yields 250 mL Amylyte-ORS, which contains 92% to 96% short-chain glucose polymers, three to nine molecules in length, and provides 425 kcal/L, compared to 80 kcal/L for the WHO-ORS. One hundred forty-four male children, 4 months to 3 years of age, presenting with acute diarrhea and mild, moderate, or severe dehydration, were assigned by random allocation to receive either WHO-ORS or Amylyte-ORS. Data from 127 children were analyzed (57 received the WHO-ORS and 70 the Amylyte-ORS). Two children given Amylyte-ORS and 15 given the WHO-ORS were not included in the analysis because of improperly collected data or lost urine or fecal specimens. None were given antibiotics during the study. Free water and feeding were allowed after the children were rehydrated. RESULTS: The clinical characteristics of the children in the two treatment groups were comparable. Five children who received the WHO-ORS and three children given Amylyte-ORS were treatment failures. Amylyte-ORS reduced diarrhea duration by 15% (41.4 +/- 2.5 vs 34.7 +/- 1.8 hours; P < .03) compared to the WHO-ORS, regardless of the severity of dehydration. In the Amylyte-treated group, ORS requirements were significantly less (234 +/- 15.2 vs 295 +/- 17.6 mL/kg; P < .01) and weight gain was significantly more (367.7 +/- 45.1 vs 199.2 +/- 38.2 g; P < .01) than in those given the WHO-ORS. The net intestinal fluid balance and total body fluid balance were similar in the two groups. CONCLUSIONS: Amylyte-ORS effectively rehydrates children with acute diarrhea, reduces diarrhea duration, decreases ORS requirements, and improves weight gain compared to the WHO-ORS.

Enzyme therapy for pancreatic insufficiency: present status and future needs.

Pancreatic enzyme extracts have been used for several decades to decrease maldigestion of macro- and micronutrients due to pancreatic insufficiency and to alleviate various abdominal symptoms, including the pain of alcohol-induced chronic pancreatitis and distal intestinal obstruction. Decreasing nutrient maldigestion and malabsorption in pancreatic insufficiency is of additional critical importance because improvement in nutritional status reduces morbidity and mortality. For example, pancreatic sufficient patients with cystic fibrosis (CF) demonstrate a slower decline in pulmonary function. In spite of the recognized importance of pancreatic enzymes, several problems exist with current preparations, and as newer enzyme preparations are marketed, proper evaluation becomes critical. There is a clear need to optimize the constituents of enzyme preparations, improve manufacturing processes, and find better sources of enzymes. Other issues that need addressing include standardization of the ratios of enzymes (lipase, amylase, protease) in these products; the stability of the enzymes at room temperature; the shelf life of the finished product; whether there are significant batch-to-batch differences; and the need for a USP reference standard.

Food-based solutions are a viable alternative to glucose-electrolyte solutions for oral hydration in acute diarrhoea--studies in a rat model of secretory diarrhoea.

A survey of acute diarrhoea and its treatment, in 3 groups of villages in south India, revealed that use of the World Health Organization oral rehydration solution (WHO-ORS) was poor or virtually non-existent and that several liquid foods were given to children during acute diarrhoea. The effects of the most commonly used, boiled and cooled supernatants of these liquid foods [rice (Oryza sativa)-water, ragi (Eleusine coracana)-water, arrowroot (Maranta arundinacea)-water], and tender coconut-water, and of the bicarbonate- and citrate-WHO-ORS on intestinal water transport were evaluated using a rat model of secretory diarrhoea. All solutions either decreased cholera toxin-induced net water secretion (arrowroot-water) or reversed it to net absorption. Ragi-water produced maximum net water absorption, significantly greater than the WHO oral rehydration solutions. WHO-ORS utilization is poor in some developing countries, and locally used food-based solutions could be used for maintaining hydration or correcting the dehydration due to acute diarrhoea once their effectiveness has been proved by clinical trials.

The relative merits of faecal and duodenal juice microscopy in the diagnosis of giardiasis.

We compared the diagnostic accuracy of microscopical examination of multiple faecal specimens with duodenal juice examination in the diagnosis of giardiasis. Of 292 patients who had stool microscopy and duodenal aspirate, Giardia were identified in either stools or duodenal fluid from 73 patients (25%). Giardiasis was diagnosed in 62 (73%) with the first faecal specimen, but examination of 3 specimens increased the diagnostic yield to 85%. Giardia, however, were found in only 32 of 73 duodenal aspirates examined (44%). This finding is contrary to the widely held belief that duodenal fluid examination is superior to stool microscopy for the diagnosis of giardiasis. The 2 approaches are complementary, however, since Giardia was found in duodenal fluid, only, from 15% of patients.

Diagnosis of Strongyloides and hookworm infections: comparison of faecal and duodenal fluid microscopy.

Faecal microscopical diagnosis of Strongyloides and hookworm infections is insensitive. We have therefore compared duodenal fluid and faecal microscopy for detection of these parasites in a group of 292 patients being investigated for gastrointestinal symptoms who were examined by both techniques. Thirty-three of these patients (8%) were infected with Strongyloides stercoralis and 88 (30%) had hookworm infections. Microscopical examination of up to 3 faecal specimens detected only 33% and 65% of patients with Strongyloides and hookworm infections, respectively. Microscopical examination of a single specimen of duodenal fluid was more sensitive for detection of strongyloidiasis, identifying 76% of patients; the parasite was found exclusively in duodenal fluid (and not in faeces) in 67% of patients. For hookworm, the diagnostic sensitivity was similar with both techniques but duodenal fluid microscopy detected some patients (35%) who had not been identified by faecal microscopy. This study confirms previous work indicating the insensitivity of faecal microscopy in these infections and emphasizes the need to consider routine examination of duodenal fluid to exclude chronic strongyloidiasis. This may have particular relevance for south-east Asian war veterans and immunocompromised patients.

Separation of hydrophobic and hydrophilic forms of gamma-glutamyltransferase from human serum by hydrophobic chromatography on phenyl-Sepharose CL-4B: studies on normal sera and sera of patients with liver disease.

A new method is described for the separation of hydrophobic and hydrophilic forms of gamma-glutamyltransferase (GGT) present in human serum using hydrophobic chromatography on phenyl-Sepharose CL-4B columns. The analysis of sera of 30 normal healthy people showed that 71.49 +/- 8.73% (mean +/- SD) of the GGT was in the hydrophilic form. In sera from 52 patients with various liver diseases the major part of the total enzyme was hydrophobic GGT, contributing 67.38 +/- 13.8% of the total GGT activity. Elevated total serum GGT and a hydrophobic to hydrophilic ratio of more than one helped in diagnosing hepatobiliary disease in 51 of 52 patients. Papain digestion of serum converted hydrophobic to hydrophilic GGT, which was similar to soluble form of liver GGT. The results are discussed in relation to the proposed mechanisms of release of GGT from the liver to the circulation.

Arterial occlusions as a presenting feature of acute promyelocytic leukemia.

Arterial thrombosis as a presentation of acute promyelocytic leukemia is uncommon. The authors report a patient who presented with a clot in the left external iliac artery and pulmonary emboli. The literature is reviewed.

Measurement of glucose and water transport in the human duodenum in vivo using a dialysis bag.

BACKGROUND/AIMS: Only a few studies have evaluated duodenal absorptive or secretory function in humans. In the present study we determined duodenal glucose and water transport in humans in vivo. MATERIAL AND METHODS: Duodenal glucose and water transport were studied in 27 healthy volunteers using a modification of the dialysis bag technique for measuring rectal water and sodium transport. RESULTS: Net glucose absorption increased progressively over the range of glucose concentrations studied (10 mM to 100 mM) from 0.21 +/- 0.19 to 1.76 +/- 0.15 mM/cm2/90 min. Maximum water absorption occurred from the 10 mM glucose solution (35.87 +/- 7.5 microliters/cm2/90 min) and at a significantly greater rate than from the 80 mM glucose (11.60 +/- 4.0 microliters/cm2/90 min) and the 100 mM glucose (14.90 +/- 1.7 microliters/cm2/90 min solution. CONCLUSION: This study demonstrates that glucose and water are absorbed by the human duodenum in vivo and that the dialysis bag technique can be adapted to measure transport processes in areas of the intestine other than the rectum.

Xylose transport in the human jejunum.

D-Xylose transport in the human jejunum was studied in vivo using a standard intestinal perfusion technique, and also in vitro in human jejunal brush border membrane vesicles. Initial D-xylose concentrations were linearly related to D-xylose absorption rates, a finding consistent with passive diffusion. Perfusion of D-xylose with varying D-glucose concentrations were aimed at examining D-xylose-D-glucose jejunal cotransport. D-Xylose absorption rates from a 30 mM D-xylose perfusate did not change significantly when 10, 30, or 60 mM glucose were added (-3.0 +/- 0.62 vs -3.34 +/- 0.71, -3.82 +/- 0.81, and -4.56 +/- 0.72 mM/30 cm/hr, respectively; minus indicates net absorption) suggesting an absence of a cotransport system. In brush border membrane vesicles, xylose uptake was partially inhibited by D-glucose and phlorizin. These data suggest that jejunal D-xylose absorption, at concentrations used clinically, is by passive diffusion, which process completely overrides a minor D-glucose cotransport component. The D-xylose tolerance test, therefore, reflects jejunal mucosal surface area and mucosal permeability to D-xylose and not nutrient carbohydrate absorption.

Effect of base precursors on water and electrolyte transport during oral hydration solution perfusion in secreting rat intestine.

In situ steady-state, single-pass small intestine perfusions in rats were carried out to compare the effect of the bicarbonate and citrate World Health Organization oral rehydration solutions and a base precursor-free solution on intestinal water and electrolyte transport after inducing intestinal secretion with purified heat-stable Escherichia coli enterotoxin. When toxin was not perfused, the rates of water, sodium, and bicarbonate absorption were significantly greater from the bicarbonate-containing solution than from the citrate or base precursor-free solutions. Chloride absorption was greater from the base precursor-free solution, but this might reflect the higher chloride concentration of the perfusate. When toxin was perfused, there was no significant difference among the solutions in the rates of water, potassium, or chloride absorption. Sodium absorption occurred at significantly greater rates from both the bicarbonate and the base precursor-free solutions than from the citrate solution. Base precursor-containing solutions may not provide any advantage over a base precursor-free solution in stimulating water and sodium absorption in 5'-cyclic guanosine monophosphate mediated acute diarrhea.

Jejunal and ileal glucose-stimulated water and sodium absorption in tropical enteropathy: implications for oral rehydration therapy.

Intestinal glucose and water absorption in response to glucose has been studied in tropical enteropathy with a view to determine the optimum glucose concentration in oral rehydration solutions for use in the tropics. Maximum jejunal water and sodium absorption occurred from an 80-mM glucose-sodium chloride solution (-285.7 +/- 46.0 ml/30 cm/h and -31.8 +/- 3.8 mM/30 cm/h, respectively) during in vivo steady-state jejunal perfusion. At perfusate glucose concentrations greater than 250 mM, however, jejunal water and sodium secretion occurred. In the ileum, maximum glucose-stimulated water absorption (-91.1 +/- 27.1 ml/30 cm/h) was significantly less than in the jejunum. Glucose absorption demonstrated saturation kinetics in both the jejunum and ileum. The half-saturation concentration was higher in the jejunum (167 mM) compared to the ileum (28 mM). This study suggests that the optimal glucose concentration for oral rehydration solutions used in the tropics should be 80 mM, as lower and higher concentrations result in diminished jejunal water absorption.

Effect of a maltodextrin-electrolyte, a maltodextrin-nutrient-electrolyte and a standard electrolyte solution on water and electrolyte fluxes in the secreting rat intestine.

The effects of a maltodextrin (dextrose equivalent 12)-electrolyte solution and a maltodextrin-electrolyte solution with added nutrients on net water and electrolyte transport in the secreting rat intestine was compared with the citrate-World Health Organization oral rehydration solution to determine the need for a clinical trial to evaluate the efficacy of these maltodextrin solutions in acute diarrhoea treatment. Cholera toxin consistently produced net water secretion (-36.5 +/- 9.9 mean +/- SEM microliter/min/g dry weight of intestine). All three solutions reversed the cholera toxin-induced net intestinal water secretion to net absorption. Significantly greater net water absorption occurred from the maltodextrin-electrolyte solution compared to the World Health Organization solution (P < 0.05) but not when compared to the maltodextrin-electrolyte-nutrient solution. Net sodium, potassium and chloride fluxes due to the World Health Organization-solution were not significantly different from the maltodextrin-electrolyte solution. These data provide a rationale for initiating a clinical trial.