Lactulose Treatment Research Articles

Lactulose for minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction

Background/Aims:Minimal hepatic encephalopathy (MHE) is common in patients with extrahepatic portal vein obstruction (EHPVO). There is no study on the treatment of MHE using lactulose in patients with EHPVO.Patients and Methods:Consecutive EHPVO patients were assessed by psychometric (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), and critical flicker frequency (CFF) at inclusion. Patients diagnosed as MHE were treated with lactulose and psychometric tests, CFF, and were reassessed after 3 months.Results:Of the 70 patients screened, the prevalence of abnormal psychometric test was as follows: NCT-A (41%), NCT-B (53%), DST (38%), SDT (40%), and LTT (44%). Thirty patients (43%) had two or more than two abnormal (>2 SD) psychometry tests. Lactulose improved MHE in 16/30 (53%) of patients after 3 months of treatment. Arterial ammonia decreased after lactulose treatment compared to baseline (83.7±19.1 vs. 65.1±19.3 μmol/l, P=0.001). A total of 9 (75%) of 12 patients with large spontaneous shunt and 7 (39%) of 18 patients without spontaneous shunt improved with lactulose (P=0.07). CFF in patients with MHE (n=30) was significantly lower than those without MHE (n=40) (38.1±2.4 vs. 41.5±3.1 Hz, P=0.01). CFF was less than 38 Hz in 21 (70%) of 30 patients before treatment and in 10 (33%) patients after lactulose therapy in MHE patients. All patients could tolerate lactulose without any significant side effects. Four patients (13%) developed transient diarrhea in whom dose needed reduction, 3 (10%) did not like its taste but have continued, and 2 (6%) developed abdominal bloating sensation.Conclusions:Lactulose is effective in the treatment of MHE in patients with EHPVO.

Can partially hydrolyzed guar gum be an alternative to lactulose in treatment of childhood constipation?

In the present study, we aimed to investigate if partially hydrolyzed guar gum (PHGG) can be used safely as a fiber source for treatment of constipation in children and to compare its success with the most commonly used osmotic laxative, lactulose. A randomized prospective controlled study on 61 patients (partially hydrolyzed guar gum group, n: 31; lactulose group, n: 30) was performed. Patients were given lactulose or partially hydrolyzed guar gum for four weeks. Using a standardized bowel diary, defecation frequency, stool consistency, and presence of flatulence and abdominal pain were recorded. Family questionnaires about the success, safety and side effect profile of both treatment arms were also obtained. No significant differences were found in the baseline daily fiber (fruits and vegetables) intake between the two groups. Bowel movement frequency per week and stool consistency improved significantly in both treatment groups (p<0.05). The percent of children with abdominal pain and stool withholding also decreased eminently in both groups (p<0.05). Weekly defecation frequency increased from 4±0.7 to 6±1.06 and from 4±0.7 to 5±1.7 in the lactulose and partially hydrolyzed guar gum treated groups, respectively (p<0.05). According to the family questionnaire, the parents complained of bad taste, flatulence and necessity to ingest a high amount of drug in the lactulose treatment group. In the partially hydrolyzed guar gum treatment group, parents were satisfied with the defecation frequency of their children. Treatment with partially hydrolyzed guar gum is as effective as lactulose treatment in relieving stool withholding and constipation-associated abdominal pain, and its use improves stool consistency. Lactulose seemed to have more side effects, including flatulence and sensation of bad taste.

Effects of intestinal intervention on bacterial translocation in a rat model of acute liver failure in vivo

The study aimed to confirm bacterial translocation (BT) in rats with acute liver failure (ALF), to explore the correlation between the concentration of lipopolysaccharides and Toll-like receptor 4 (TLR4) expression, and further, to evaluate the curative effects of lactulose and montmorillonite (smecta) in this setting. D-Galactosamine was injected into the abdominal cavity of rats to induce ALF. Escherichia coli JM109 labeled with enhanced green fluorescent protein was administered to track BT. Simultaneously, the rats were given lactulose or smecta. Blood samples were collected for measuring liver function, cytokines, endotoxins, and TLR4 expression. Representative tissue specimens from the liver, spleen, and mesenteric lymph nodes were aseptically harvested for bacterial identification by agarose gel electrophoresis, laser scanning confocal microscopy, and flow cytometry. BT occurred in ALF, accompanied by impaired liver function with increased cytokines, endotoxins, and TLR4 expression. After the treatment with lactulose or smecta, all these parameters decreased, including the relative quantity of translocated bacteria while albumin increased. Furthermore, compared with the lactulose treatment group, the parameters in the smecta treatment group improved. Moreover, in the group in which smecta was given for prophylaxis, there was greater improvement than with treatment. Intestinal intervention with lactulose or smecta can ameliorate BT; moreover, smecta has a better effect than lactulose, and its preventive effect was also better than its therapeutic effect.

Effects of caffeic acid phenethyl ester on thioacetamide-induced hepatic encephalopathy in rats

Hepatic encephalopathy (HE) is a major neurological complication secondary to severe liver failure. The aim of the present study was to examine the possible neuroprotective effects of caffeic acid phenethyl ester (CAPE) with or without laxative treatment against thioacetamide-induced HE by investigating behavioral and motor activities in rats as well as blood ammonia level and oxidant–antioxidant parameters of cortex, brain stem and cerebellum. After induction of HE by thioacetamide, the rats were treated with lactulose, CAPE (CAPE treatment was started one day before the first dose of thioacetamide) or CAPE plus lactulose. The behavioral and motor scales were measured at the 54th hour after the first thioacetamide injection, the blood samples and brains were taken under anesthesia at the 60th hour for biochemical analysis. The survival rates were 37.5% in HE group, 70% in HE + lactulose group, 80% in HE + CAPE group, and 100% in HE + CAPE + lactulose group. Increased ammonia, ALT and AST levels in blood along with impaired sensory-motor behavior tests were reversed to proximate control values in CAPE + lactulose treated group. There were increased lipid peroxidation and protein oxidation and decreased antioxidant enzyme activities in almost all brain parts of HE group. CAPE or lactulose treatment alone ameliorated those oxidant and antioxidant parameters; however, CAPE treatment together with lactulose reversed them to almost control level. In conclusion, thioacetamide-induced HE injury in rats was reversed almost fully by CAPE and laxative combination. There was no death in CAPE and laxative treated group animals and it may be due to the direct neuroprotective effect of CAPE together with the prevention of the body from ammonia production.

Unilateral pleural effusion—but where from?

In December, 2007, a 63-year-old woman presented with a week’s history of shortness of breath, 4 months of ankle swelling, and weight gain. She had no chest pain, palpitations, cough, or fever. She had been diagnosed with non-A, non-B hepatitis in 1980. There was a large right-sided pleural eff usion on chest radiograph, shown to be loculated by CT. Thoracentesis yielded 1·5 L of clear, yellow transudate. CT of the abdomen showed a shrunken liver consistent with cirrhosis without ascites. No abnormalities were found in full blood count, renal function, liver function, concentrations of thyroid hormones, pancreatic enzymes, and brain natriuretic peptide, electrocardiogram, tuberculin test, pelvic ultrasonography, echocardiogram, or urine analysis. Hepatitis B and C, Wilson’s disease, haemochromatosis, α-1 antitrypsin defi ciency, and autoimmune hepatitis were excluded. A liver biopsy sample showed regenerative nodule formation consistent with cirrhosis of unknown cause. Doppler ultrasonography of the portal vein was normal, whereas oesophagogastroduodenoscopy showed mosaic patterning of the stomach consistent with portal hypertensive gastropathy. Repeat thoracentesis on day 4 drained 1·5 L of fl uid. Treatment with fl uid restriction, low salt diet, furosemide, and spironolactone was started, but fl uid reaccumulated within 3 days. On day 8, talc pleurodesis was done and she was discharged. 2 weeks later she was readmitted with recurrent pleural eff usion. Hepatic hydrothorax was considered a possible diagnosis. Hepatic vein catheterisation (fi gure) revealed a hepatic vein pressure gradient (HVPG) of 21 mm Hg (normal value: 1-5 mm Hg). Transjugular intrahepatic portosystemic shunt (TIPS) was undertaken, after which the HVPG was 4 mm Hg and no reaccumulation of pleural fl uid occurred. 4 days later, the patient became encephalopathic with a rise in concentrations of bilirubin (68 μmol/L) and aminotransferases (aspartate amino transferase 750 U/L, alanine aminotransferase 291 U/L). Intracranial processes were ruled out as a potential cause of altered mental status. Lactulose treatment was initiated and a reduction in TIPS size was considered but she developed aspiration pneumonia necessitating intubation and died within 4 days. The family declined autopsy. Hepatic hydrothorax is a signifi cant pleural eff usion in a cirrhotic patient in the absence of a primary cardiopulmonary cause; it is a complication of portal hypertension, with a prevalence of 5–12%. Although usually right-sided, it can be left-sided or bilateral. The cause is thought to be leakage of ascitic fl uid via a diaphragmatic defect. Diagnosis of hepatic hydrothorax without ascites and obvious signs of portal hypertension is challenging. Doppler ultrasonography of the portal vein can show portal hypertension, but HVPG is the gold standard. Scintigraphic demonstration of a diaphragmatic defect by use of radiolabelled human serum albumin is helpful, and in retrospect might have been useful in our patient. Treatment of hepatic hydrothorax is challenging, with liver transplant the ultimate goal. Diuretics, fl uid restriction, and repetitive thoracenteses are used to prevent pulmonary complications. Diaphragmatic repair, pleurodesis, and TIPS are reserved for refractory cases. Rapid migration of fl uid from peritoneum to the pleural space means pleurodesis is often unsuccessful. 30-day mortality with TIPS ranges from 19% to 68%; complications include hepatic encephalopathy, stent occlusion, infection, bleeding, acute renal failure, and acute respiratory distress syndrome. Rapid onset of encephalopathy after TIPS can be due to infection or to insuffi cient arterial liver perfusion as a result of arterial-stent fi stula, arterial-biliary fi stula, or stent-related stenosis of the artery causing liver infarction. In patients with unilateral pleural eff usion, after exclusion of cardiac and pulmonary causes, a hepatic cause should be considered. Defects should be demonstrated by scintigraphy if the diagnosis is in doubt before extensive work-up. TIPS is an eff ective treatment, but serious side-eff ects can occur even in patients with well-compensated liver disease.

M1266 The Impact of Age on Risks of Venous Thromboembolism in Hospitalized Patients With Liver Cirrhosis: A Nationwide U.S. Study

Even after the precipitant of a hepatic encephalopathy (HE) episode is treated,lactulose is often continued indefinitely. Clinical tools to predict relapse off of lactulose and guide the safe withdrawal of Rx have not been studied. Aim: Evaluate change in psychometric & MR spectroscopic(MRS)after lactulose withdrawal. Methods: Cirrhotics with prior HE underwent number connection (NCT-A/B),Block design(BDT),Digit symbol(DST)& Inhibitory control tests(ICT;lures are the outcomes) & MRS while on lactulose. Lactulose was then withdrawn. Psychometric tests were repeated 2,14& 30 days post-withdrawal. MRS was repeated 14 days post-withdrawal. Occipital gray(GM) & right parietal white matter(WM) regions were studied for glutamine(Gln), myoinositol & choline. Worsening HE leads to increase in Gln. Repeated measures analyses were used to model tests over time & determine relapse predictors. Results: 7 cirrhotics (age 53±7yrs,5 HCV,2 alcohol) on lactulose for 6±5 mths for precipitated HE(5 GI bleed, 2 infections) were included.3 patients clinically relapsed 38±6 days post-withdrawal; all 3 had >15 ICT lures while on lactulose. None of those who scored 15 ICT lures on lactulose relapsed. Gln levels in gray/white matter increased after lactulose withdrawal. Psychometric performance on therapy can predict the risk of relapse off of lactulose treatment.

M1265 Controlled Lactulose Withdrawal in Hepatic Encephalopathy: Can We Predict the Risk of Relapse Using Psychometric Tests and MR Spectroscopy?

Even after the precipitant of a hepatic encephalopathy (HE) episode is treated,lactulose is often continued indefinitely. Clinical tools to predict relapse off of lactulose and guide the safe withdrawal of Rx have not been studied. Aim: Evaluate change in psychometric & MR spectroscopic(MRS)after lactulose withdrawal. Methods: Cirrhotics with prior HE underwent number connection (NCT-A/B),Block design(BDT),Digit symbol(DST)& Inhibitory control tests(ICT;lures are the outcomes) & MRS while on lactulose. Lactulose was then withdrawn. Psychometric tests were repeated 2,14& 30 days post-withdrawal. MRS was repeated 14 days post-withdrawal. Occipital gray(GM) & right parietal white matter(WM) regions were studied for glutamine(Gln), myoinositol & choline. Worsening HE leads to increase in Gln. Repeated measures analyses were used to model tests over time & determine relapse predictors. Results: 7 cirrhotics (age 53±7yrs,5 HCV,2 alcohol) on lactulose for 6±5 mths for precipitated HE(5 GI bleed, 2 infections) were included.3 patients clinically relapsed 38±6 days post-withdrawal; all 3 had >15 ICT lures while on lactulose. None of those who scored 15 ICT lures on lactulose relapsed. Gln levels in gray/white matter increased after lactulose withdrawal. Psychometric performance on therapy can predict the risk of relapse off of lactulose treatment.

Triptorelin improves intestinal symptoms among patients with colorectal endometriosis

⁎ Corresponding author. Department of Obstetrics and Gynecology, San Martino Hospital, Largo R. Benzi 1, 16132 Genoa, Italy. Tel./fax: +39 10 511 525. E-mail address: dr@simoneferrero.com (S. Ferrero). Little attention has been given to the role of hormonal therapies in treating symptoms caused by bowel endometriosis [1]. The aim of the present open-label prospective study was to evaluate the effects of GnRH analogues (GnRH-a) on pain and intestinal symptoms among patients with colorectal endometriosis. Multidetector computerized tomographyenteroclysis (MDCT-e)was used to determine the presence and severity of colorectal endometriosis [2]. Inclusion criteria for the study were reproductive age, pain and gastrointestinal symptoms suggestive of bowel endometriosis (persisting for at least 12 months), and colorectal nodules infiltrating at least the muscularis propria of the bowel. Exclusion criteria were stenosis of the bowel lumen greater than 60% and presence of endometriotic nodules located on the cecum or the ileum. Study participants received depot intramuscular injections of the 3-month formulation of triptorelin (11.25 mg; Decapeptyl, Ipsen Pharma, Milan, Italy) and oral tibolone (2.5 mg daily; Livial, Organon, Rome, Italy) for 12 months. Patients were allowed to take nonsteroidal anti-inflammatory drugs for the treatment of pain (550 mg naproxen sodium tablet; Synflex Forte 550, Recordati Industria Chimica e Farmaceutica, Milan, Italy) and lactulose (dose of 10 g per 15 mL; Laevolac, Roche, Milan, Italy) for the treatment of constipation. Presence and intensity of symptoms were evaluated before starting the treatment andafter 6 and12 months of treatment. At completion, the overall degree of patient satisfactionwith the treatmentwas determined by responses given to the following question: “Taking into consideration the variations in pain symptoms, overall well-being, and quality of life, as well as any adverse effects experienced, howwould you define the level of satisfaction with your treatment?” [3]. Patients were also asked whether their intestinal symptoms changed during treatment. The local Institutional Review Board approved the study protocol. Patients were informed that surgery is the standard treatment for symptomatic bowel endometriosis [1,4] and the potential benefits and complications of surgery were explained in detail. All study subjects wished to avoid or postpone surgery and requested amedical therapy. Patients were also told that hormonal therapies are not expected to be definitely curative of endometriosis [5]. Study participants provided written informed consent. Variations in grading of symptoms between baseline and follow-up were compared using the paired t test and the signed rank test according to data distribution. Eighteen women were included in the study, with a mean age of 36.1±4.7 years. The larger endometriotic bowel nodule was located on the sigmoid in9women,on the rectosigmoid junction in5women, and on the rectum in 4 women. The mean estimated size of the larger colorectal nodulewas2.2±0.6 cmand themeanestimatedstenosisof the bowel lumenwas42.0%±9.7%.At the 12-monthassessment of the effects of therapy on the symptoms, 13 (72.2%) women were very satisfied or satisfied, 2 (11.1%) were uncertain, and 3 (16.7%) were dissatisfied. Intestinal symptomswere unchanged during treatment in 7 (38.9%) women, while 11 patients (61.1%) reported some improvements in intestinal function. Table 1 shows that patients with symptoms mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) reported improvements in intestinal symptoms significantly more frequently than those with symptoms mimicking constipationpredominant irritable bowel syndrome (IBS-C; 100.0% vs 14.3,P=0.003). The severity of dysmenorrhea, nonmenstrual pelvic pain, deep dyspareunia, anddyscheziawasmeasuredusing a 10-cmvisual analogue scale (VAS). The treatment significantly decreased the intensity of pain symptoms (Table 2). The severity of the intestinal symptoms was measured using a symptom analogue scale questionnaire (1 indicated the absence of the symptom; 10 indicated the highest severity of the symptom). IBS-D, intestinal cramping, abdominal bloating, and passage of mucus improved during treatment; no significant change was observed in IBS-C and feeling of incomplete evacuation (Table 2). The number of naproxen sodium tablets used by patients decreased during treatment; the number of lactulose doses used by patients did not change during treatment (Table 2). Fifteen women (83.3%) reported at least 1 adverse effect (hot flushes, n=6; vaginal bleeding, n=6; sweating episodes, n=3; vaginal dryness and superficial dyspareunia, n=2; nervousness and irritability, n=2; loss of libido, n=2; weight gain, n=2; sleeplessness, n=1; difficulty in concentrating, n=1; fatigue, n=1). At the completion of the study, 7 patients (38.9%) continued the treatment with triptorelin and tibolone; 50.0% of the patients with IBS-D continued the treatment with triptorelin versus 14.3% of the patients with IBS-C (P=0.282).

Effects of Lactulose Treatment in Patients with Minimal Hepatic Encephalopathy: A Meta-Analysis of Randomized Controlled Trials

Effects of Lactulose Treatment in Patients with Minimal Hepatic Encephalopathy: A Meta-Analysis of Randomized Controlled Trials

The immunomodulatory effect of lactulose on Enterococcus faecium fed preruminant calves1

Prebiotics and probiotics could represent an effective alternative to the use of synthetic antibiotics in nutrition. The mechanisms by which prebiotics affect the immune system have not yet been investigated in detail. Most effects have been attributed to increases in the innate and acquired immune responses. This study was conducted to elucidate the long-term effects of orally administered lactulose on the immune response in the intestinal tract of probiotic-fed calves. Preruminant calves were randomized to 3 feeding groups: milk replacer containing 1) no lactulose, 2) 1% lactulose, or 3) 3% lactulose. All 3 milk replacers contained 10(9) cfu Enterococcus faecium/kg. Messenger RNA expression of different cell activation markers, pro- and antiinflammatory cytokines, and IgA Fc receptor was investigated in the ileum, mesenterial lymph node, spleen, and white blood cells. A significantly greater number of blood lymphocytes were detected in the 3% lactulose group (P = 0.02) than in the control group. The expression results in male calves indicated that the transcription of IgA Fc receptor in the ileal mucosa of the 1% lactulose treatment group increased significantly (P = 0.04) and also tended to increase in the 3% lactulose group (P = 0.07). Furthermore, decreases in IL-10 and interferon-gamma mRNA expression were observed in the ileum (P = 0.04). The CD4-presenting lymphocytes were decreased significantly in the ileum (P = 0.04) and mesenteric lymph node (P = 0.01), whereas CD8-presenting lymphocytes were increased in the blood (P = 0.03) of females. Other proinflammatory cytokines (IL-1beta, IL-8, and tumor necrosis factor-alpha) and antiinflammatory cytokines (transforming growth factor-beta1) did not show significant differences in mRNA expression among treatment groups. The results indicate that additional lactulose feeding had an immunomodulatory effect on the composition of T-cell subsets in different immune compartments and had minor effects on pro- and antiinflammatory cytokine mRNA expression.

Hospitalizations During the Use of Rifaximin Versus Lactulose for the Treatment of Hepatic Encephalopathy

We sought to compare frequency and duration of hepatic encephalopathy-related hospitalizations during rifaximin versus lactulose treatment. Hospitalizations, clinical efficacy data, and adverse events obtained from charts of 145 patients with hepatic encephalopathy who received lactulose (30 cc twice daily) for > or = 6 months and then rifaximin (400 mg 3 times a day) for > or = 6 months compared last 6 months on lactulose (lactulose period) to first 6 months on rifaximin (rifaximin period). Fewer hospitalizations (0.5 versus 1.6; P < .001), fewer days hospitalized (2.5 versus 7.3; P < .001), fewer total weeks hospitalized (0.4 versus 1.8; P < .001), and lower hospitalization charges per patient ($14,222 versus $56,635) were reported during the rifaximin period. More patients had asterixis, diarrhea, flatulence, and abdominal pain during the lactulose period (P < .001). Treatment of hepatic encephalopathy with rifaximin was associated with lower hospitalization frequency and duration, lower hospital charges, better clinical status, and fewer adverse events.

Can we ignore minimal hepatic encephalopathy any longer?

Can we ignore minimal hepatic encephalopathy any longer?

Effect of lactulose on growth performance and intestinal morphology of pre-ruminant calves using a milk replacer containing Enterococcus faecium

The synthetic disaccharide lactulose is known to improve the intestinal microflora by stimulating the growth of selected probiotic bacteria in the gut. In our experiment the effects of lactulose in combination with the probiotic bacteria Enterococcus faecium on growth performance and morphology of the bovine intestine were examined. Calves aged 39 ± 2 days were randomised to three feeding groups (no. = 14 each group): control (L0), fed milk replacer (MR) containing E. faecium; a lactulose group (L1) containing additional 1% lactulose and a second lactulose group (L3) containing 3% lactulose dry matter. The calves were weighed weekly. After 19 weeks the calves were slaughtered and tissues were collected for histological studies. The average daily live weight gain tended to be higher (P < 0.1) for L3 (1350 g/day) than L0 (1288 g/day). Compared with L0, a reduction (P < 0.001) of ileal villus height due to lactulose treatment of approximately 14% in group L1 and 20% in L3 was determined. A significant decrease in the depth of the crypts about 12% in L1 and 8% in L3 was detected in the caecum. The surface area of lymph follicles from Peyer's patches was decreased by lactulose treatment. Results show that lactulose has an effect on the morphology of intestine. A significant effect on growth performance can not be confirmed. However, results permit the conclusion that lactulose feeding has the tendency to increase growth performance.

Lactulose treatment for hepatic encephalopathy, gastrointestinal symptoms, and health-related quality of life

Lactulose treatment for hepatic encephalopathy, gastrointestinal symptoms, and health-related quality of life

Effect of antitumour necrosis factor treatment on circulating tumour necrosis factor levels and mortality after surgery in jaundiced mice.

Tumour necrosis factor (TNF) may play an important role in the increased incidence of complications after surgery in patients with obstructive jaundice. This study evaluated the effect of three different anti-TNF treatments, a monoclonal anti-TNF antibody (TN3), pentoxifylline and lactulose, on outcome after severe surgical trauma in mice with experimental biliary obstruction. Circulating serum TNF levels and mortality rate were monitored. Severe surgical trauma, such as renal ischaemia, in jaundiced mice resulted in increased levels of circulating TNF (3.5 ng/ml) and a high mortality rate (54 per cent). The three different anti-TNF treatments caused a significant reduction in postoperative levels of circulating TNF (TN3, P < 0.001; pentoxifylline, P < 0.01; lactulose, P < 0.05). Treatment with TN3 and pentoxifylline did not lead to a significantly reduced mortality rate (36 and 44 per cent respectively). Only lactulose treatment produced a significantly reduced mortality rate (7 per cent, P < 0.01). TNF is therefore not the only mediator responsible for death after surgery in jaundiced mice. Other mechanisms affected by lactulose are also involved.

Colonic fermentation from lactulose inhibits lipolysis in overweight subjects

One of the strategies to prevent insulin resistance is to reduce circulating free fatty acids (FFA). The aim of this study is to assess the effect of an oral lactulose load on fatty acid metabolism in overweight subjects. Eight overweight subjects received a primed constant intravenous infusion of [1-(13)C]acetate and of [1,1,2,3,3-(2)H(5)]glycerol for 9 h. After 3 h of tracer infusion, patients ingested 30 g lactulose, or saline solution. Arterialized blood samples were collected every 20 min. Basal plasma concentrations of acetate were similar before and between oral treatments as well as glycerol and FFA concentrations. Plasma acetate turnover was 11.4 +/- 2.4 vs. 10.7 +/- 1.4 micromol.kg(-1).min(-1) [not significant (NS)], and plasma glycerol turnover was 3.8 +/- 0.4 vs. 4.8 +/- 1.9 micromol.kg(-1).min(-1) (NS). After lactulose ingestion, acetate concentration increased twofold and then decreased to baseline. Acetate turnover rate increased to 15.5 +/- 2.2 micromol.kg(-1).min(-1) after lactulose treatment, whereas it was unchanged after saline treatment (10.3 +/- 2.2 micromol.kg(-1).min(-1), P < or = 0.0001). In contrast, FFA concentrations decreased significantly after lactulose ingestion and then increased slowly. Glycerol turnover decreased after lactulose ingestion compared with saline, 2.8 +/- 0.4 vs. 3.5 +/- 0.3 micromol.kg(-1).min(-1) (P < or = 0.05). A significant negative correlation was found between glycerol and acetate turnover after lactulose treatments (r = -0.78, P < or = 0.02). These results showed in overweight subjects a short-term decrease in FFA level and glycerol turnover after lactulose ingestion related to a decrease of lipolysis in close relationship with an increase of acetate production.

Protective Effect of Lactulose on Dextran Sulfate Sodium-Induced Colonic Inflammation in Rats

Promising results have recently been obtained with pre- and probiotic therapy in ulcerative colitis (UC). The prebiotic potential of lactulose is well established, but it has not yet been investigated in experimental colitis models. The purpose of the study was to examine the effect of lactulose on an UC model induced by 3% dextran sulfate sodium (DSS) solution added to drinking water for 7 days in male Wistar rats. Lactulose (300-1000 mg/kg) or 5-aminosalicylic acid (5-ASA; 150 mg/kg) was administered orally twice daily for 6 days. Colonic ulceration area, colon length, body weight changes, diarrhea/bloody feces, colonic mucosal myeloperoxidase activity (MPO), thiobarbituric acid reactive substances (TBARS), and histology were examined. Treatment of animals with DSS for 7 days resulted in severe colonic lesions accompanied by diarrhea, bloody feces, a decrese in body weight, shortening of the colon length, and an increase in MPO activity as well as TBARS, compared to normal rats. Lactulose treatment ameliorated DSS-induced colitis in a dose-dependent manner, and at 1000 mg/kg all of the parameters examined, except TBARS, were shown to improve significantly as compared to controls. Daily administration of 5-ASA also significantly reduced the severity of colonic lesions following DSS treatment. These results demonstrated the protective effect of lactulose in this rat colitis model and suggested that the background of this lactulose effect may be due to alterations of colonic microflora.

Clinical effects of rifaximin in patientswith hepatic encephalopathy intolerant or nonresponsive to previous lactulose treatment: An open-label, pilot study

Background: Hepatic encephalopathy (HE) is a metabolic-neurophysiologicsyndrome that occurs in patients with advanced hepatic disease. One of the main pathogenic mechanisms is represented by circulating toxins produced by the intestinal metabolism of nitrogenous compounds. The therapeutic approach to HE is mainly based on drugs that eliminate ammonia-producing bacteria. Objectives: The aim of this study was to evaluate the effects of the nonabsorbable antibiotic rifaximin in patients with HE who were intolerant or nonresponsive to treatment with an oral, nonabsorbable disaccharide (lactulose). Methods: This uncontrolled, open-label, pilot study was conducted at the University of Bologna, Bologna, Italy. Patients aged ≥ 18 years with histologically proven liver cirrhosis and HE were studied. All patients were intolerant or nonresponsive to previous treatment with lactulose. Rifaximin tablets were administered to patients at a dosage of 400 mg TID for 10 days. The portal systemic encephalopathy (PSE) index was evaluated at enrollment and at the end of the treatment period. Tolerability was assessed using hematology, biochemistry, and urinalysis and by recording adverse effects (AEs). Results: Twenty-six patients (18 men, 8 women; mean [SD] age, 55.8 [8.0] years) were enrolled (intolerants, n = 17; nonresponders, n = 9). All patients completed the study. Significant improvement was shown in most of the 5 components of the PSE index after rifaximin administration in both intolerants and nonresponders. At the end of the 10-day treatment period, the PSE index was significantly reduced in both intolerants and nonresponders. Rifaximin was well tolerated; no clinically relevant AEs were observed during the treatment period. Conclusions: This pilot study of patients with liver cirrhosis and HE who were intolerant or nonresponsive to previous treatment with an oral, nonabsorbable disaccharide suggests that treatment with rifaximin may be considered as an adjuvant or an alternative treatment in reducing HE.

Lactulose Reduces Intracolonic Acetaldehyde Concentration and Ethanol Elimination Rate in Rats

Normal colonic bacteria possessing alcohol dehydrogenase activity can oxidize ethanol to acetaldehyde. Acetaldehyde recently has been shown to be a local carcinogen in humans. The aim of the study was to examine the effect of lactulose feeding on fecal and cecal pH, intracolonic acetaldehyde concentration, and total ethanol elimination rate in rats. Sixty Wistar rats were divided into four groups. Groups 2 and 4 received lactulose daily (11 g/kg body weight for 14 days). On days 7 and 14, groups 1 and 2 received ethanol (1.5 g/kg body weight) intraperitoneally, whereas groups 3 and 4 received saline. Fecal and cecal pH values decreased significantly after lactulose treatment compared with the controls. Lactulose feeding reduced the total ethanol elimination rate by 13.8% (257 +/- 0.008 mg/kg/hr vs. 298 +/- 0.003 mg/kg/hr, p < 0.001) and the intracecal acetaldehyde concentration by 66.2% after ethanol (49 +/- 29 microM vs. 145 +/- 47 microM, p = 0.03) compared with the controls. Lactulose feeding to rats significantly reduces ethanol elimination rate and intraluminal acetaldehyde concentration in the colon after ethanol administration. This prebiotic thus could be used as an effective agent to block the microbial production of carcinogenic acetaldehyde in the large intestine.

Molecular Analysis of Intestinal Microbiota Composition to Evaluate the Effect of PEG and Lactulose Laxatives in Humans

Methods using bacteriological cultures allow only 30–50% of colonic bacterial populations to be detected. Our aim was to assess the effect of osmotic laxative administration on fecal bacteria during chronic idiopathic constipation, by a culture-independent molecular method. Forty-eight constipated patients were included in a randomized blinded trial and received either polyethylene glycol (PEG, n =23) or lactulose ( n= 25) for 28 days. Non-fermentable laxative (PEG) should not affect the bacterial groups, whereas fermentable (lactulose) could modulate them. The treatment dosage was 20 g per day for a 7-day period, then adjusted according to ef? cacy for 7 days and constant from 10 to 30 g per day for 14 days. Stools were collected at d0, d21 and d28, and analyzed by quantitative dot-blot hybridization using 16S ribosomal RNA-targeted oligonucleotide probes. We used a new Bifidobacterium group specific probe and five other probes to monitor the dominant groups of the intestinal bacteria: Bacteroides -Prevotella-Porphyromonas , Lactobacillus -Enterococcus- Streptococcus , enterobacteria: Clostridium coccoides and Clostridium leptum . Lactulose and PEG administration were associated with an increase of bifidobacterial rRNA index in 72% (18/25) and 17% (4/23) of cases, respectively. In the lactulose group, bifidobacterial rRNA index increased from [mean (SEM)] 1.1% (0.2%) at d0 (a), to 4.3% (1.2%) at d21 (b) and 4.5% (1.1%) at d28 (b), (a ≠ b, p=0.011). Lactulose treatment when administered at doses usually prescribed for constipation selectively stimulated bifidobacteria within the intestinal microbiota. The quantitative rRNA dot-blot hybridization method is an efficient tool to quantify intestinal bacteria, without the limitations of classical culture methods. Keywords: constipation, lactulose, quantitative dot-blot hybridization, Bifidobacterium probe, 16S rRNA.