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PubMed1991

Effect of protein and lactulose on the production of gamma-aminobutyric acid by faecal Escherichia coli.

The value of lactulose treatment in hepatic encephalopathy is widely recognised but its mode of action remains controversial. Much evidence supports a role for gamma-aminobutyric acid in hepatic encephalopathy, and lactulose could alter its bacterial production in the gut. Using the rat synaptic membrane assay and gas chromatography mass spectrometry, the production of gamma-aminobutyric acid by faecal Escherichia coli, with and without the addition of albumin, haemoglobin, whole blood, and lactulose under aerobic and anaerobic conditions was determined. Using an inorganic medium, maximal gamma-aminobutyric acid production occurred after a culture period of between 25 and 50 hours. The concentration after 30 hours of aerobic culture at 37 degrees C by a single strain was mean (SEM), 101 (5) mumol/l (99% confidence intervals 87-114 mumol/l; n = 8; interassay coefficient of variation 14.7%). gamma-aminobutyric acid production was significantly increased by the addition of albumin and haemoglobin. Under anerobic conditions, it was one fifth of that produced aerobically, but the addition of albumin and haemoglobin increased production by greater than 700%. Lactulose did not significantly attenuate gamma-aminobutyric acid production under aerobic or anaerobic conditions. gamma-aminobutyric acid determined by the rat synaptic membrane assay showed a highly significant correlation (r = 0.99) with that detected by gas chromatography mass spectrometry. These data confirm that gamma-aminobutyric acid is produced by faecal E coli and that protein enhances its production considerably, and suggest that lactulose does not exert its therapeutic effect by attenuating gamma-aminobutyric acid production.

Aerobiosis↗
PubMed1999

Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation.

BACKGROUND: Polyethylene glycol (PEG) 3350 is a non-absorbable, non-metabolised osmotic agent used in lavage solutions for gut cleansing. AIMS: To compare the efficacy of PEG and lactulose in chronic constipation. METHODS: A total of 115 patients with chronic constipation entered a multicentre, randomised, comparative trial. They initially received two sachets containing either PEG (13 g/sachet) or lactulose (10 g/sachet) and were given an option to change the dose to one or three sachets/day, depending on response. RESULTS: Ninety nine patients completed the trial. After four weeks, patients in the PEG group (n=50) had a higher number of stools and a lower median daily score for straining at stool than patients in the lactulose group (n=49). Overall improvement was greater in the PEG group. Clinical tolerance was similar in the two groups, but flatus was less frequently reported in the PEG group. The mean number of liquid stools was higher in the PEG group but the difference was significant only for the first two weeks. There were no serious adverse events and no significant change in laboratory tests in either group. At the end of the study, the number of sachets used by the patients was 1.6 (0.7)/day in the PEG group and 2.1 (0.7)/day in the lactulose group. Sixty one patients completed a further two months open study of one to three sachets PEG daily; there was no loss of efficacy and no serious toxicity. CONCLUSION: Low dose PEG 3350 was more effective than lactulose and better tolerated.

Adult↗
PubMedDate not supplied

Effects of prefeeding a prebiotic on diarrhea and colonic cell proliferation in piglets fed lactulose.

OBJECTIVES: Severe lactulose malabsorption causes osmotic diarrhea and decreased cecal cell proliferation. We tested the hypothesis that prefeeding with inulin, a prebiotic, would attenuate these effects. METHODS: Piglets aged 10 days were randomized to 3 feeding groups (n = 6 each group): Control (CON), fed sow-milk replacement formula (SMR; lactose, 60 g/L) for 14 days; a lactulose-challenged group (LAC) that was fed SMR for 7 days and then a formula containing lactose (30 g/L) and lactulose (60 g/L) for 7 days; and a group prefed SMR containing inulin (3 g/L) for 7 days and then fed the lactulose-supplemented formula (INULIN). Groups CON and INULIN were pair-fed to LAC. Then, cecal tissue was collected for histology, determination of crypt cell proliferation index, apoptosis, and Western blot determination of expression of Bax, a pro-apoptotic protein. RESULTS: The fraction of days when diarrhea was present (mean +/- SD) was greater for LAC (0.87 +/- 0.14; p = .004) than CON (0.28 +/- 0.22; INULIN: 0.52 +/- 0.44; p = .058 vs LAC). Cell proliferation index for the total crypt was less for LAC (0.12 +/- 0.04; p = .016) compared with CON (0.20 +/- 0.04; INULIN: 0.15 +/- 0.04; p = .06 vs LAC). BAX protein expression and apoptosis were similar in the 3 groups. CONCLUSIONS: We observed trends consistent with the hypothesis that prefeeding inulin attenuates diarrhea and the reduction in cell proliferation caused by lactulose.

Animals↗
PubMedDate not supplied

Experimental assessment of chemotherapy-induced early intestinal damage in colon cancer the lactulose-mannitol permeability test.

AIMS AND BACKGROUND: Although chemotherapy plays an important role in the management and cure of cancer, it has undesiderable side effects mostly affecting the bone marrow and gastrointestinal tract, which greatly limit patient compliance and treatment efficacy. METHODS: The lactulose-mannitol test was used to assess intestinal mucosa damage 48 hours after the end of the first adjuvant chemotherapy cycle with 5-fluorouracil (5-FU) and levamisole in 12 patients with colon cancer. Fifteen age- and sex-matched subjects were studied as controls. The excreted amount of lactulose and mannitol was expressed as the percentage of the administered doses recovered in the urine as well as their ratio. RESULTS: The percent urinary recovery of lactulose was significantly (P < 0.001) higher in colon cancer patients (1.1 +/- 0.5%) than in the control group (0.3 +/- 0.03%), whereas the mannitol recovery was only slightly reduced in the former. As a result, the lactulose/mannitol excretion ratio was significantly (P < 0.001) higher in colon cancer patients (0.07 +/- 0.03) than in the control group (0.01 +/- 0.01). CONCLUSIONS: As assessed by the lactulose-mannitol test, the combined chemotherapy regimen with 5-FU and levamisole affects mainly the barrier function of the intestinal mucosa rather than its absorption capacity. The toxic effect seems to be attributable to the 5-FU molecule rather than to levamisole. The lactulose-mannitol test is a simple, safe and reliable tool to evaluate chemotherapy-induced early damage to the intestinal epithelium, in particular when new kinds of substances are being administered. Its use in clinical practice seems appropriate to establish the correct timing of drug administration, thereby enhancing treatment efficacy and improving patient compliance.

Administration, Oral↗
PubMed1992

Lactulose in the management of constipation: a current review.

OBJECTIVE: To review the current published clinical studies evaluating the clinical efficacy and safety of lactulose compared with other laxatives or placebo. Adverse effects associated with lactulose are also reported. DATA SOURCES: Information was retrieved by searching the MEDLINE and EMBASE databases for clinical trials, abstracts, conference proceedings, and review articles dealing with lactulose. STUDY SELECTION: Emphasis was placed on clinical trials where lactulose was compared with other laxatives or placebo in patient populations where the diagnosis of constipation was reasonably established. DATA EXTRACTION: The methodology and results from clinical studies were evaluated. Assessment of the studies was made based on diagnosis of constipation, prior management of patients, follow-up of patients, dosage, and adverse effects. DATA SYNTHESIS: Clinical trials in geriatric patients, terminally ill patients, children, and normal and constipated subjects were reviewed. In most instances, lactulose was compared with a placebo, without incorporating the current education on dietary techniques for improving defecation. CONCLUSIONS: Generally, clinical trials have demonstrated a beneficial response compared with placebo, although sometimes that response has been only marginally better, from a clinical point of view.

Adolescent↗
PubMed1979

The lactulose hydrogen breath test as a diagnostic test for small-bowel bacterial overgrowth.

The lactulose hydrogen breath test has been evaluated as a diagnostic test for small-bowel bacterial overgrowth using the 14C-glycocholate breath test for comparison. Twenty-seven patients with suspected bacterial overgrowth and 37 control patients were studied. The lactulose test was positive in 8 out of 9 patients with Subsequently proven bacterial overgrowth, all of whom had positive 14C-glycocholate tests. However, 6 patients with ileal disease or resection had positive 14C-glycocholate tests but negative lactulose tests. subsequent bacteriological study of duodenal juice from these patients was negative. Negative results were obtained by both tests in the remaining 12 patients, none of whom were subsequently shown to have bacterial overgrowth. All 37 control subjects had negative lactulose tests. The lactulose breath test is a simple and promising diagnostic test for the detection of small-bowel bacterial overgrowth and, unlike the 14C-glycocholate test, has the advantage of being able to distinguish bacterial overgrowth from ileal disease.

Breath Tests↗
PubMed2003

C-reactive protein and antibacterial activity in blood plasma of colostrum-fed calves and the effect of lactulose.

Several milk proteins are very important for immunological defense and can be absorbed in the intestine of calves in the first hours after birth. The influence of colostrum intake and the effect of additional lactulose application on the concentration of C-reactive protein (CRP) in blood were investigated. The CRP is known as a mediator of innate immunity. Results were compared to the bovine acute phase protein haptoglobin, and to lactalbumin, lactoferrin, and immunoglobulins in plasma from calves. After colostrum intake, the concentration of most proteins were strongly increased. The data show, for the first time, a significant increase of CRP in the blood of calves 1 d after colostrum intake (nonlactulose group, n = 10), and an even more significant increase in CRP concentration (1 d postpartum) was measured in the group of animals with additional application of lactulose (lactulose group, n = 10) when compared to the nonlactulose group. In an in vitro assay with the plasma of these animals, an increased bactericidal activity was detected against Morganella morganii (1 d postpartum) in both groups, but again a higher activity occurred in the lactulose group. The results of these investigations emphasize the importance of colostrum intake during the first hours after birth for the defense potential of newborn calves. In addition, lactulose may have a positive effect in the period of passive transfer of colostrum proteins and in the immune defense.

Animal Nutritional Physiological Phenomena↗
PubMed1999

Assessment of protein quality of infant milk food formula supplemented with lactulose.

To examine the protein quality of infant food formula supplemented with lactulose (bifidogenic factor), groups of 21 day male weanling rats were fed diet containing lactulose at 0.5% for 4 weeks. The gain in body weight of rats fed lactulose supplemented diet were similar to that of rats fed lactulose free and skim milk powder fed diet as controls. No difference in overall acceptability pattern was also observed in studies conducted with human subjects for organoleptic evaluation. The results suggest that supplementation of lactulose in infant food formula does not affect either the protein quality as indicated by protein efficiency ratio in rats as compared to control formulae or overall acceptability by human subjects.

Animals↗
PubMed2001

Sub chronic toxicity studies of lactulose in rats.

Lactulose has profound health benefits by way of increasing bifidobacterial flora in the intestine of infants thereby protecting them against enteric infection, constipation and systemic encephalopathy. In the present study to assess the sub chronic toxicity of lactulose syrup, the rats were fed on a basal feed supplemented with lactulose syrup at 0.5, 1.0, 2.0 and 5.0% for a period of 21 weeks. Monitoring of food consumption, gain in body weight and physical observations did not reveal any treatment-related toxicity in any of the group of rats. Terminal autopsy also did not reveal any signs of toxicity. Further, no significant alterations in relative organ weight, serum biochemistry and urinalysis were observed up to 1% lactulose supplementation level. The results suggest that supplementation of lactulose in the diet does not produce any toxicity at the doses tested.

Administration, Oral↗
PubMed1991

Breath hydrogen excretion or plasma acetate levels during the lactulose tolerance test?

Since both acetate and hydrogen are produced by colonic bacterial fermentation, the clinical utility of the measurement of either parameter in nine subjects for the lactulose tolerance test was tested. The fasting plasma acetate concentration (mean +/- s.d., mmol/l) of 0.11 +/- 0.06 increased to peak levels between 150 min (0.23 +/- 0.12) and 180 min (0.23 +/- 0.09), both P less than 0.01, after ingesting 20 g lactulose. In one subject with previous gastrectomy and intestinal hurry, the peak was at 30 min. Mean post-lactulose acetate levels (0.21 +/- 0.09) were higher than fasting levels (P less than 0.03). Breath hydrogen excretion exhibited a similar trend. Indeed, a significant correlation (rs 0.39, P less than 0.01) was demonstrated between the acetate and hydrogen values. It is therefore concluded that patients for the lactulose breath test show fairly similar changes in plasma acetate and breath hydrogen excretion after lactulose ingestion. Either measurement could thus be used in assessing colonic fermentation in humans.

Acetates↗
PubMed1988

Lactulose interferes in the alkaline picrate assay for creatinine.

Errors of more than 10 mg/L in measured serum creatinine concentrations were encountered for an azotemic patient who was given lactulose orally. The magnitude of the apparent error fluctuated with the dose of lactulose. Additions of lactulose to serum produced a linear increase in the creatinine measured by each of two automated methods that involve use of the alkaline picrate (Jaffé) reaction. A lactulose concentration of 100 g/L produced positive interferences of 30 and 65 mg/L in kinetic (Beckman Astra) and continuous-flow (Technicon SMAC) assays, respectively, but caused no problem in an enzymatic assay for creatinine. The results of creatinine assays must be interpreted with caution in patients treated with lactulose.

Creatinine↗
PubMed1984

The effect of lactulose on psychomotor performance tests in alcoholic cirrhotics without overt hepatic encephalopathy.

Thirty-two alcoholic cirrhotics without clinical evidence of encephalopathy were randomized to lactulose or sucrose treatment in order to evaluate the effects of chronic lactulose therapy on five psychomotor performance tests. Statistically significant improvement was seen in three of the five tests in the lactulose-treated group, while no significant improvement in any test was noted in the sucrose group. However, because of the limited extent of improvement in the lactulose treated group, problems with medication intolerance, and lack of improvement in complex psychosocial behavior, the impact of chronic lactulose therapy on mental function in cirrhotics without overt encephalopathy appears to be limited.

Adult↗
PubMed1983

Hypernatremia and lactulose therapy.

Lactulose is used in the treatment of portal-systemic encephalopathy. Although it is usually safe, a case of hypernatremia has been reported. To evaluate further the association of lactulose therapy and hypernatremia, records of patients with hepatic failure treated with lactulose for encephalopathy were analyzed. In 20 of 75 courses of lactulose treatment, serum sodium level exceeded 145 mEq/L. Mortality was 41% in patients in whom hypernatremia developed as compared with 14% in those who remained normonatremic. In persons who died, hypernatremia persisted; in patients who eventually recovered, the serum sodium level returned to normal. The precise mechanism of hypernatremia in these cases is not clearly defined. As an osmotic cathartic, however, lactulose may cause fecal water loss in excess of sodium, resulting in contraction of extracellular fluid volume and, therefore, hypernatremia.

Creatinine↗
PubMed1980

Lactulose--a drug with antiendotoxin effect.

Lactulose (beta-galactosido-fructose) was found to have anti-endotoxin properties: 670 mg lactulose abolished the gelating activity of mg E. coli endotoxin on Limulus lysate in vitro. When lactulose was fed to rats (6.3 +/- 1.1 g/kg/day) over a period of 4 or 8 days before i.v. administration of 0.5 g/kg galactosamine, the liver damage that normally develops was prevented. Since galactosamine-induced necrosis of hepatocytes and inflammatory reaction of the liver are mediated by systemic endotoxemia of intestinal origin, an anti-endotoxin effect of lactulose was demonstrated in vivo. We suggest that lactulose might offer a therapeutic basis in clinical situations in which endotoxemia is of pathogenetic significance, such as certain gastrointestinal and liver diseases, shock states and gram-negative sepsis.

Animals↗
PubMed1995

Rapid gas-chromatographic assay of lactulose and mannitol for estimating intestinal permeability.

We developed a gas-chromatographic method to determine urinary mannitol and lactulose. The procedure for purification of urine by a resin was optimized for purification of analytes and high recovery; the aliquot of resin chosen (500 mg) was kept in contact with the urine for 1 min. The recoveries of mannitol and lactulose were > 85% at concentrations that include both normal and pathological values. Sugars were converted to oximes before the silylation step to avoid multiple peaks for the anomeric forms. The calibration was linear over the range 0.1-1 microgram of sugar injected. Analytical recovery of the sugars ranged from 90% to 95.3% for mannitol and from 90.4% to 95.8% for lactulose. The mean within-day imprecision (CV) was 6.2% for mannitol and 4.7% for lactulose; the between-day CV was 6.7% for mannitol and 5.1% for lactulose. A lactulose/mannitol ratio of 0.035 completely differentiated 28 normal children and 28 children with active gluten-sensitive enteropathy, whose mean ratios were 0.022 (SD 0.007) and 0.084 (SD 0.054), respectively.

Adolescent↗
PubMed1994

Lactulose or paromomycin do not affect ammonia generation in the isolated perfused rat small intestine.

It has been hypothesized that the beneficial effect on hepatic encephalopathy of lactulose or neomycin might be exerted by their effect on intermediary glutamine metabolism and ammonia generation within enterocytes. We examined glutamine consumption and the production of alanine and ammonia (net substrate exchange in nmol min-1 g-1) in isolated vascularly and luminally perfused small intestine from rats with and without pretreatment with lactulose (2.0 g/kg) or paromomycin (60 mg/kg). Without pretreatment, 50 mM lactulose or 1 mM paromomycin were equally ineffective to significantly reduce the consumption of arterial glutamine (-92 +/- 5 vs. -80 +/- 6 vs. -71 +/- 6 for controls, lactulose, or paromomycin; mean +/- SEM, n = 6 each, n.s. by analysis of variance), and the production of alanine (41 +/- 3 vs. 44 +/- 3 vs. 61 +/- 7, n.s.) or ammonia (42 +/- 6 vs. 42 +/- 6 vs. 38 +/- 6, n.s.). Similarly, glutamine utilisation, and the release of alanine and ammonia were not different after pretreatment for 10 days. Also, both agents did not reduce glutamine absorption from the lumen (-170 +/- 9 vs. -171 +/- 6 vs. -219 +/- 25, n = 5 each) or the concomitant vascular release of metabolic products alanine (92 +/- 7 vs. 78 +/- 10 vs. 77 +/- 10 vs. 77 +/- 7, n.s.) and ammonia (73 +/- 6 vs. 69 +/- 7 vs. 65 +/- 8, n.s.). Our results do not support the hypothesis, that lactulose or paromomycin reduce ammonia generation by small intestinal mucosa through a specific effect on intermediary glutamine metabolism.

Amino Acids↗
PubMed1997

Effect of lactulose on bacterial translocation.

OBJECTIVE: To find out if lactulose can prevent the bacterial translocation that is induced by obstructive jaundice in rats. DESIGN: Laboratory experiment. SETTING: Teaching hospital, Turkey. MATERIAL: 50 male Wistar-albino rats. INTERVENTIONS: 10 rats were not operated on and used as controls; 20 rats underwent laparotomy and sham ligation of the common bile duct (CBD); 20 had the CBD ligated alone; and 20 had the CBD ligated and were given oral lactulose 2 ml/day until death. All rats were killed after 14 days. MAIN OUTCOME MEASURES: Presence of Escherichia coli in mesenteric lymph nodes (MLN), and bacterial overgrowth as indicated by counts of E coli in the caecum. RESULTS: There was significantly less bacterial translocation to MLN in the group that had been given lactulose compared with CBD-ligated and lactulose not given (2/20 compared with 8/20, p = 0.06). There was also a significant reduction in the number of Gram negative bacteria in that group (p = < 0.01). CONCLUSION: Lactulose seems to reduce the incidence of translocation from the gut to MLN in rats with obstructive jaundice.

Animals↗
PubMed1998

Simultaneous HPLC determination with light-scattering detection of lactulose and mannitol in studies of intestinal permeability in pediatrics.

We describe a new HPLC method for the simultaneous determination of lactulose and mannitol in urine, in which cation-exchange chromatography and evaporative light-scattering detection are used. The two sugars are orally administered for the estimation of intestinal permeability in children. Samples were purified by solid phase extraction on a C18 cartridge and subsequent addition of anion-exchange resin. Cellobiose may be used as an internal standard. The chromatographic separation was carried out in 16 min at a flow rate of 0.5 mL/min, using deionized water as the mobile phase. Within-run precision (CV) measured at three concentrations was 1.6-2.3% for lactulose and 1.0-1.9% for mannitol. Between-run CVs were 2.1-4.1% and 1.3-2.7% for lactulose and mannitol, respectively. Analytical recovery of both sugar probes was 97-101%. The detection limits (signal-to-noise ratio = 3) were 0.82 mg/L for lactulose and 0.65 mg/L for mannitol. The lactulose/ mannitol ratio in control subjects was 0.024 +/- 0.006; in patients with Crohn's and coeliac diseases in active phase, the ratios were 0.200 +/- 0.082 and 0.072 +/- 0.025, respectively. The method is rapid, simple, and sensitive, and suitable for determination of intestinal permeability in children.

Administration, Oral↗