Abstract: The aging process is paralleled by two- to fourfold increases in plasma/serum levels of inflammatory mediators, such as cytokines and acute-phase proteins. In this study we assessed the inflammatory profile and polymorphism of healthy elderly subjects and the influence of a nutraceutical supplement. Forty elderly, generally healthy subjects were recruited, divided into two matched groups, and given either a fermented papaya preparation 9 g/day by mouth or the same amount of placebo. Treatments were carried out in a cross-over manner with a 3-month supplementation period followed by a 6-week washout period between treatments. Ten healthy young subjects served as controls. Interleukin-6 (IL-6) promoter -174 G/C polymorphism genotype was determined together with blood levels for redox status, proinflammatory cytokines, high sensitivity C-reactive protein, and serum 70 kDa heat shock protein (Hsp70) concentrations. Tumor necrosis factor-alpha and IL-6 were higher in elderly subjects (P < 0.05 versus young controls). The concentration of Hsp70 inversely correlated with markers of inflammation in -174 G/C-negative subjects (r = 0.62, P < 0.05). Nutraceutical intervention normalized the inflammatory parameters (P < 0.05) with a rise of Hsp70 (P < 0.05). This suggests that healthy elderly individuals may have a proinflammatory profile playing as a downregulating factor for inducible Hsp70, particularly if -174 G/C-negative. A nutraceutical intervention seems able to beneficially modulate such a phenomenon.
Abstract: OBJECTIVE: To isolate, identify and determine the prevalence of yeasts in the oral cavity of individuals and to test the minimum inhibitory dilution (MID) of Kolorex against the yeasts isolated. METHODS: Twenty-nine individuals of both sexes aged on average 61.3 years were evaluated at the dental clinic in order to isolate and identify yeasts from their oral cavity, with and without lesions, and to determine the MID of the commercial phyto-product Kolorex against the strains isolated. The antifungal activity of the product tested was determined by the technique of dilution on a solid medium. Monocyte chemoattractant protein 1 (MCP-1) was measured by biotinylated antibody assay by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Yeasts of the genus Candida were detected in the saliva of 45.4% of the 11 individuals with a clinically healthy mouth and in 88.2% of 17 individuals with oral lesions. In the group with oral candidiasis we isolated in tongue and lesion, respectively, for each species: C. tropicalis (5.8% and 11.7%), C. glabrata (5.8% and 5.8%) and C. parapsilosis (0% and 5.8%), in addition to C. albicans as the only species or in association with others, respectively (64.7% and 70.5%). The total clonal formation unit (CFU) (counts/mL) in the saliva showed a higher mean value in the group with oral candidiasis (158.3x10(3)) than in the control group (64.6x10(3)). Most of the 70 test strains (95.7%) were sensitive to Kolorex by presenting a MID of 1:20. Sixty percent of strains from the 70 healthy sites showed results similar to those obtained with strains from oral lesions. Different results were mainly observed among different species. Patients with oral lesions showed a significant time-course increase of the level of monocyte chemoattractant protein 1 (MCP 1) as compared to those without lesions or to healthy people in whom Candida has not been detected (P<0.05). Co-culture with Kolorex using aliquots from the same patients with oral lesions inhibited such event (P<0.05). CONCLUSION: Although this study was focused on oral cavity candidiasis, the results indicate the possibility of a broader use of the antifungal Kolorex in the prevention and treatment of mucosal candidiasis located elsewhere.
Abstract: BACKGROUND AND AIM: Oxidative DNA damage occurs as an early event in hepatitis C virus (HCV) infection and is an indication of the potential for carcinogenesis. The aim of this study was to test a novel antioxidant/immunomodulator in patients with HCV-related cirrhosis. METHODS: The study group consisted of 50 patients with HCV-related cirrhosis with transaminase values less than twofold increased (alanine aminotransferase [ALT] < 80 IU/L). Patients underwent a standardized food-vitamin composition assessment and were assessed for dietary intake, nutritional status and iron level. Patients were randomly allocated into two groups and then given either alpha-tocopherol 900 IU/day or 9 g/day of a fermented papaya preparation (FPP, Immun-Age, Osato Research Institute, Gifu, Japan) at bedtime for 6 months. Ten healthy subjects served as controls. Patients were checked monthly for: routine tests, redox status (reduced glutathione, glutathione peroxidase, oxidized glutathione, malondialdehyde), plasma alpha-tocopherol, 8-hydroxy-deoxy-guanidine (8-OHdG) level in circulating leukocyte DNA and serum levels of cytokines. RESULTS: Patients with cirrhosis showed a significant imbalance of redox status (low antioxidants/high oxidative stress markers) (P < 0.005 vs controls). Neither treatment regimen affected transaminases as a whole. However, vitamin E supplementation almost normalized ALT only in the limited vitamin-E-deficient subgroup. A significant improvement of redox status was obtained by both regimens. However, only FPP significantly decreased 8-OHdG and the improvement of cytokine balance with FPP was significantly better than with vitamin E treatment (P < 0.05). CONCLUSIONS: Although the present data seem to suggest a potential supportive role of antioxidants/immunomodulators as FPP in HCV patients, more studies are needed to substantiate their effect on the natural history of the disease.
Abstract: OBJECTIVE: Acute radiation of the small intestine causes an immediate and potentially reversible effect on the sensitive regenerative epithelium of the intestinal mucosa while markedly altering the overall intestinal ecosystem. The aim of the present study was test a novel probiotic mixture formulation (Microflorana-F) in an experimental model of acute radiation enteritis with particular interest in endotoxinemia and bacterial translocation. MATERIALS AND METHODS: Male Wistar rats allocated to three groups were fed for 7 days with: (A) a standard balanced diet; (B) a standard diet with the addition of 1 mL t.i.d. of Microflorana-F and (C) the same probiotic but after heat inactivation. Under ketamine anesthesia, abdominal irradiation was performed at a single dose rate of 20 Gy. Sham-radiated healthy rats served as a control (D). Standard food and active/inactive probiotic supplementation schedule was maintained throughout the study period. When they were killed 14 days later a midline laparotomy and a medium sternotomy was carried out. The mesenteric lymph nodes, whole spleen and liver samples as well as blood, the portal vein and bile samples were cultured. Endotoxinemia was also measured. RESULTS: Early deaths (1 week) occurred mostly in rats fed standard food or inactivated probiotic. The endotoxin level significantly increased in irradiated rats fed standard food and inactivated probiotic while supplementation with the active form of the probiotic mixture significantly improved such parameters (P < 0.05). After radiation injury, mesenteric lymph nodes and portal blood were the samples most frequently yielding bacterial growth. Treatment with only the active form of probiotic significantly reduced the incidence of bacterial contamination in all samples. CONCLUSIONS: These data suggest that the manipulation of gut ecosystem by biologically effective probiotic preparations might be a worthwhile therapeutic and preventive tool in radiation-induced enteritis.
Abstract: HepG2 human hepatoma cells were incubated for 24 or 48 h with various concentrations of YHK solution. After 24 h incubation, cell proliferation and cytotoxicity were determined by 3-(4,5-dimethylthiazol-2- yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium (MTT) assay. Cytotoxicity or necrosis was expressed as lactate dehydrogenase (LDH) release. After exponential growth phase HepG2 cells were treated with different doses of YHK and apoptosis was assessed by using an Annexin V-FITC kit. Further, oxidative stress was measured by dichlorofluorescein-diacetate (DCFH-DA) assay. As compared to control, YHK-treated cultures showed a significant time-course decrease of the proliferation rate of HepG2 cell growth (p < 0.01). This is likely to be due to an enhanced cytotoxicity (MTT and LDH tests) (p < 0.001). On the other hand, YHK showed in vitro to significantly enhance the oxidative stress of HepG2 cell (p < 0.01) while also markedly increasing apoptosis at 72 h with cells G2/M phase arrest (p < 0.01). These data suggest that YHK seem to modulate the extrinsic and intrinsic regulators of apoptosis and sensitize tumour cells to apoptosis. These preliminary data are worth interest when considering that this nutraceutical has been shown in vitro and in vivo to exert protective anti-tumour effect by redox statusmodulating and immuno-regulatory actions. Given its lack of toxicity so far reported, such natural product might represent an effective nutritional supplement in a number of pathological conditions where a chemopreventive strategy is planned.
Abstract: Our study group consisted of 54 elderly patients without major invalidating diseases who were randomly divided into two fully matched groups. Group A was given a certified fermented papaya preparation 9 g/day by mouth, while group B received placebo. Treatment was carried out in a cross-over manner with a 3-month supplementation followed by a 6-week washout period. Blood samples were drawn at entry and on a monthly basis to check routine parameters, redox status, and 8-OHdG in circulating leukocyte DNA. Polymorphism analysis of GSTM1 was carried out as well. The glutathune-S transferase M1 (GSTM1) genotype was null (-) in 40% and 46% of groups A and B, respectively. GSTM1 (-) smokers had a significantly higher level of plasma DNA adducts and leukocytes level of 8-OHdG than their GSTM1 (+) counterparts (P < 0.01). There was a weak correlation between cigarettes smoked/day and DNA adduct (r: 0.61, P < 0.05), which also correlated with antioxidant concentrations, but only in GSTM1 (-) smokers (P < 0.01). The fermented papaya preparation (FPP)-supplemented group showed a significant enhancement of the antioxidant protection (P < 0.01 vs. A) within the subgroups with GSTM1 (-) and of plasma DNA adduct, irrespective of the GSTM1 genotype. Only the GSTM1 (-) subgroup was the one that, under FPP treatment, increased lymphocyte 8-OHdG (P < 0.01). Such preliminary data show that FPP is a promising nutraceutical for improving antioxidant-defense in elderly patients even without any overt antioxidant-deficiency state while helping explain some inconsistent results of prior interventional studies.
Abstract: Hepatocytes isolated from 20- and 4-month Wistar rats and cultured with or without alpha-linolenic acid (LNA) were then added with nutraceutical YHK or sylibin before the test with iron or copper. Overall, YHK proved to be more effective than sylibin in Fe/Cu-induced peroxidative damage on normal and LNA-loaded hepatocytes (p < 0.05). YHK exerted a significant protection against DPPH radical-scavenging activity in the "old" group (p versus sylibin) and against lipophilic generators in both age groups (p < 0.05 versus sylibin). Both compounds were ineffective on age-related increase of surface-charge density. These preliminary data suggest that age per se enhances the vulnerability of hepatocytes to xenobiotics, whereas some safe nutraceuticals seem to exert significant protective effects.
Abstract: OBJECTIVE: The aim of the present study was to test the hypothesis that protein-calorie malnutrition aggravates the gut translocation of Candida albicans triggered by mesenteric ischemia-reperfusion (IR) injury in an experimental model while testing a natural product containing the antifungal anethole/polygodial mixture (Kolorex). METHODS: MFI strain white mice (n = 90) were randomly allocated to a 4-week dietary regimen: (1) standard pellet diet containing 25% casein; (2) low-protein (2.5%) casein diet; (3) as group 2 plus oral supplementation with 20 microL of a 5% solution of Kolorex during the last 4 days. Twenty rats from each of these groups (termed 1a, 2a and 3a) were orally inoculated with Candida suspension 6 h prior to mesenteric IR injury. Animals of each group but without Candida inoculation (termed 1b, 2b and 3b) served as control. A colon permeability study was carried out as well. Rats were killed prior to the IR injury and 3 h afterwards. Control rats were killed at the same time. RESULTS: Over 60% of the mesenteric lymph nodes and 30% of kidney samples were positive for C. albicans in the low-protein-fed rats after IR injury. Kolorex significantly decreased that rate of positivity and also significantly reduced the concentration of C. albicans per gram of each positive tissue sample examined. Protein-calorie malnourished animals showed a statistically significant increase in colon permeability and this phenomenon further increased after IR injury. The groups of rats treated with Kolorex compound showed a partial, although significant, improvement of this parameter. CONCLUSIONS: These results suggest that Kolorex might exert a competitive effect against with C. albicans colonization. The present study represents the first experimental in vivo investigation of the anethole/polygodial-containing compound under the specific conditions of calorie-protein malnutrition and the results have potential clinical interest.
Abstract: T-maze test-selected prematurely senescent mice (PSM) were allocated into two groups: (A) those given DTS (150 mg/kg) orally for 30 days and (B) untreated PSM with age-matched fast T-maze performers as control. After sacrifice, the liver and kidney were analyzed for catalase (CAT) activity, glutathione peroxidase (GPx), superoxide dismutase (SOD), malondyaldehyde (MDA), and plasma thiols. Untreated PSM showed decreased plasma thiols and tissue level of CAT, SOD, GPx, with higher MDA (P < 0.01 vs. fast performers), while DTS (Denshichi-Tochiu-Sen) significantly improved glutathione and cysteine (P < 0.05) and tissue concentration of the above parameters (P < 0.05). Such preliminary data suggest that DTS mitigated oxidative damage in PSM, with likely action on the cytoplasm and mitochondrial matrix.
Abstract: Twelve (12) healthy elderly subjects were divided into two groups: (a) those given an antioxidant/NO-modulating fermented papaya preparation (FPP) 9 g/day for 4 weeks, and (b) a placebo group. No protein/lipid distribution in erythrocytes (RBC) membranes was noted among different ages and treatments. Higher RBC concentration of malondialdehyde and nitric oxide synthase were found in the elderly (p < 0.05 versus "young" controls), whereas superoxide dismutase was unaltered. Such abnormalities were prevented by FPP supplementation (p < 0.01). RBC and RBC ghosts showed an enhanced susceptibility to lipid peroxidation by using cumene hydroperoxide (p < 0.01 versus young) but FPP supplementation significantly protected intact RBC (p < 0.05). These preliminary data suggest that nutraceuticals with antioxidant/NO-regulating properties significantly protect from RBC oxidative damage, and are potential weapons for the aging process and chronic and degenerative diseases.
Abstract: Motility recording of small and large intestine was performed in old Wistar rats divided into three groups: (a) standard diet, (b) standard diet plus a symbiotic preparation, and (c) standard diet plus a heat-inactivated symbiotic preparation. SCM-III. significantly increased the myoelectric activity of small intestine and colon (p < 0.01 versus [a] and [c]) paralleling "young" values of 4-month-old rats and increased the spike burst frequency in the proximal-distal colon (p < 0.05). SCM-III significantly increased the frequency and duration of spike bursts in the jejunum, transverse-distal colon, and defecation frequency, while decreasing the intervals of migrating motor complex in the colon (p < 0.01) to "young" values with an increased mRNA expression of VIP (p < 0.05). Gut flora manipulation aimed to modulate myoelectric activity can tentatively help reversing age-related motility decay.
Abstract: Ovariectomized Wistar rats received orally 15 mg/kg of a phytoestrogen compound (genistein, daidzein, glycitein, black cohosh, angelica sin., licorice, vitex agnus) for 2 weeks to test its ability to modulate inflammatory microglia response. Microglial proliferation was tested by trypan blue and by absorbance. Serial supernatant sampling was performed for 24 h to check TNF-alpha, IL-beta, IL-6, and TGF-beta. LPS caused a time course increase of all cytokines, with IL-beta and TNF-alpha peaking at the 12th hour, whereas IL-6 and TGF-beta peaked at the 24 h observation. Rats fed with the phytoestrogen displayed a significantly lower level of proinflammatory cytokines and a higher level of TGF-beta, as shown also by Western blot analysis. This finding may offer promise in the field of nutraceutical intervention.
Abstract: Twenty-month-old Swiss mice were allocated into three groups: (A) control; (B) infected group; and (C) infected but treated with 5 mg of the phytocompound MMT. Mice were infected intranasally with 30 microL of 75 HA viral units. MMT markedly blunted the nasal signs of virus infection and the febrile response. Formazan-positive cells, lung and plasma lipoperoxides, and TNF-alpha in lung tissue increased during viral infection, but improvement was seen in the MMT-treated group (P < 0.05). MMT also normalized SOD, catalase activities, and ascorbic acid and determined a significant decrease of lung but not nasal viral titer, although nasal inflammatory infiltrate dropped significantly. MMT has potential clinical applications with and has an excellent safety profile even in old animals.
Abstract: The aim of this study was to investigate the effects of the herbal compound YHK on hepatocarcinogenesis induced by diethylntrosamine (DEN) in Sprague Dawley rats. Rats were randomly divided into 3 groups and followed up for 15 weeks. Groups 1 was given standard food and represented the healthy control. Liver preneoplastic foci were induced using the DEN method in groups 2 and 3 (20 rats each). However, group 3 was concomitantly given 50mg/kg/day of YHK. For quantitative assessment of liver preneoplastic foci, the placental form of glutathione-S-transferase (GST-P) positive foci were measured using immunohistochemical staining and image analysis. Treatment using DEN caused a significant decrease in body weight and increase in liver weight compared to the control group while concomitant supplementation with YHK prevented body weight loss and liver weight increase. As compared to DENonly treated rats, the group given YHK showed a significant decrease in the number, size and volume of GSTP- positive foci. Moreover, co-administration of YHK significantly reduced the incidence, number, size and volume of hepatocellular carcinoma. Anti-inflammatory, anti-fibrotic as well as antioxidative properties of this compound are mechanisms which are likely to be advocated for to explain its protective effect. It is concluded that herbal compound YHK by preventing hepatocarcinogenesis in DEN-induced liver preneoplastic lesions in rats has the potential to a large clinical application as a functional food.
Abstract: OBJECTIVE: The aim of the present study was to test a prebiotic-phytotherapic compound in an experimental model of oral allergenicity. METHODS: Antigen-specific immunoglobulin E (IgE) elevated mice were prepared by injecting them intraperitoneally with 10 microg of ovalbumin. Subsequently, the mice were exposed to ovalbumin solution intranasally and blood samples were obtained on weekly intervals for 4 weeks to measure serum-ovalbumin-specific IgE and total immunoglobulin G. Mice with high titers of ovalbumin-IgE were intragastrically administered with 0.3 mL of phosphate buffered solution containing either 20 mg of ovalbumin, the same solution with 5 mL of milk, or 20 mg milk added to prebiotic-phytocompound. RESULTS: Ovalbumin administration caused a significant increase of plasma ovalbumin concentration in sensitized mice while prebiotic-phytocompound-supplemented mice showed a significantly reduced peak value (P < 0.05). Prebiotic-phytocompound added to milk exerted a significant effect in lowering the ovalbumin-IgE level and the total immunoglobulin G level as compared to control plain milk (P < 0.01). CONCLUSION: This study provides a rationale basis for a feasible non-pharmacological therapeutic strategy in food allergen hypersensitivity syndromes.
Abstract: The cell is thermodynamically an open system and aging is characterized by an increasingly higher structural disorder (increase of entropy) and functional loss. If a variation of negative entropy is introduced by an external source, an anti-clockwise effect leading to regenerative processes and/or increase of the functional reserve supporting regenerative tissue changes is theoretically expected. The achievement of a negative variation of entropy is the main principle of a new technology which implies an exogenous delivery of energy with higher performance than the physiological production. Promising clinical experiences in liver cirrhosis and in long-standing scarring lesions seem to confirm the clinical applicability of the theoretical model.
Abstract: OBJECTIVE: Metals undergo redox cycling and there is increasing evidence of free radical generation and oxidative injury in the pathogenesis of liver injury and fibrosis in metal storage diseases. The aim of the present study was to test a natural hepatoprotective compound in metal-induced liver injury. METHODS: Hepatocytes were isolated from Wistar rats by collagenase perfusion method and cultured as such and also with alpha-linolenic acid (LNA)-bovine serum albumin (BSA). Hepatocytes were then cultured with a graded dilution of PN-M001 (100 microg/mL and 200 microg/mL), which is a curcuma/absinthium-containing compound, or sylibin (100 microg/mL) dissolved in dimethyl sulfoxide for 10 min before the addition of metallic salts (iron, copper and vanadium). Lysosomal fractions were prepared for lysosome fragility tests in which beta-galactosidase activity and lactate dehydrogenase (LDH) leakage were measured, as well as oxidative damage tests in the presence of hydrophilic and lipophilic free radical generators. Quenching activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH) was also assessed. RESULTS: Malonildialdehyde accumulation in the medium showed a direct time-course increase with incubation time. Both PN-M001 and sylibin showed a significant protective effect against all challenge metal ions, as expressed by the half inhibition concentration (IC(50)) against lipid peroxidation. However, on a molar ratio, sylibin seemed to be more effective than PN-M001 in Fe-induced peroxidative damage (P < 0.05). Both test compounds, irrespective of the concentration, significantly reduced the LDH and beta-galactosidase concentration in the lysosomal fractions. As compared with untreated lysosomal fractions challenged with the two peroxide radicals generators, either PN-M001 or sylibin exerted significant protection However, PN-M001 was significantly better than sylibin in suppressing acid phosphatase enzyme activity. Both compounds showed comparable and significant DPPH radical-scavenging activity. CONCLUSION: These data support the potential clinical application of curcumin-containing compounds.
Abstract: OBJECTIVE: In view of the raising concern for gut fungal infection, the aim of the present research was to carry out a systematic in vitro study testing the antifungal activity and possible toxicity of a polygodyal-anethole compound (Kolorex) in several strains of Candida albicans and in other fungal pathogens. METHODS: The in vitro susceptibility tests were carried out on 4 strains of C. albicans (C. krusei, C. lipolytica, C. tropicalis, C. utilis), Aspergillus flavus and A. fumigatus. Cultures were also analyzed by varying medium, pH and inoculum size, and a time-course killing test was carried out. RESULTS: In the present study the polygodyal-anethole compound showed remarkable in vitro activity against the most common fungi, which was significantly better than polygodyal alone. Moreover, such mixture compound was shown to exert its activity against a wide spectrum of fungi, including C. lipolytica and C. tropicalis, which required significantly higher MIC of polygodyal to be unfeasible in clinical application. The activity of the polygodyal-anethole compound was significantly better than polygodyal alone with high inoculum size and low pH. Moreover, it proved to exert a significantly faster biological activity against low inoculum. CONCLUSIONS: This study suggests that the mixture compound Kolorex has a very good profile of antifungal activity in terms of effectiveness and spectrum of action while being devoid of any significant toxicity.
Abstract: OBJECTIVE: The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion. METHODS: Sprague-Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full-blown, rats were fed an alcohol-rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis. RESULTS: Synbiotics but not metronidazole improved the acute pancreatitis-induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic-treated group, while metronidazole had a negative effect on liver damage. CONCLUSIONS: Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation.
Abstract: The aim of this study was to test the effect of antioxidant supplementation on enzymatic abnormalities and free radical-modified DNA adducts associated with premalignant changes in the gastric mucosa of elderly patients with HP-negative atrophic gastritis (CAG). Sixty patients with atrophic gastritis and intestinal metaplasia underwent a nutritional interview and a gastroscopy with multiple biopsy samples in the antrum that were processed for histology and for assaying: alpha-tocopherol, MDA, xanthine oxidase (XO), ornithine decarboxylase (ODC), and 8-OHdG. Patients were randomly allocated into three matched groups and supplemented for 6 months with (1) vitamin E, 300 mg/day; (2) multivitamin, two tablets t.i.d.; and (3) Immun-Age 6 g/day nocte (ORI, Gifu, Japan), a certified fermented papaya preparation with basic science-validated antioxidant/immunomodulant properties. Ten dyspeptic patients served as controls. Histology and biochemistry were blindly repeated at 3 and 6 months. CAG patients showed a significantly (P <.05) increased level of mucosal MDA and XO concentration that were reverted to normal by each supplementation (P <.05). All supplements caused a significant decrease of ODC (P <.01), but Immun-Age yielded the most effective (P < 0.05) and was the only one significantly decreasing 8-OhdG (P < 0.05). These data suggest that antioxidant supplementation, and, namely, Immun-Age, might be potential chemopreventive agents in HP-eradicated CAG patients and especially in the elderly population.
Abstract: Aim: The aim of the present investigation was to test study benzodiazepines (BZDs) profile in patients with viral cirrhosis under different combinations of rifaximine and of a novel symbiotic. Methods: Our study groups consisted of 30 patients with a confirmed diagnosis of HCV-related Child B liver cirrhosis. Patients were randomly allocated into three groups: rifaximine 400mg t.i.d. for 2 weeks; (B) SCM-III (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacteria in a ion- and vitamin-enriched medium, Named srl, Italy) 10ml t.i.d. for 2 weeks; (C) rifaximine 400mg t.i.d. for 1 week followed by SCM-III 10ml t.i.d. for 5 weeks. At weekly interval, blood samples were withdrawn to test BZD-like substances, ammonia and endotoxin. Results: Rifaximine treatment brought about a significant early drop of BZDs ( [Formula: see text] versus pre-treatment and versus control) till fourth week of observation when a gradual increase took place with return to pre-treatment values at the sixth week. Symbiotic treatment was comparably effective while given to patients but significantly elevated BZDs level were noted starting from the third week. Similar phenomena were noted for endotoxin and ammonia although symbiotic seemed more effective against endotoxin and rifaximine against ammonia increase. However, the sequential treatment rifaximine-symbiotic brought about a sustained normalization of BZDs, ammonia and endotoxin throughout the 6-week study. Conclusion: The present pilot study suggests that a rifaximine-symbiotic regimen could be an effective tool in compensated liver cirrhosis to limit some triggering factors of hepatic encephalopathy while being amenable to long-term use and devoid of significant side effects.
Abstract: To test new treatment modalities, a pilot study with a novel noninvasive biophysical methodology (Delta-S DVD) that can artificially exert a "decrease of entropy" through the patented electromagnetic-driven delivery of "energy clusters" was designed. This process has been modulated and integrated by the body as a "self" source to support the energy-dependent functional stores, thus modifying reparative into regenerative mechanisms of liver parenchyma. Seven long-standing hepatitis C virus-positive (Child A-B) cirrhosis patients with overt symptoms and portal hypertension and failure or side effects of antiviral drug treatment underwent 40-min sessions of Delta-S DVD daily for six months and were followed up monthly. At the end of the first month, rapid improvement of symptoms and a decrease of portal hypertension were noted. At the end of treatment, all patients showed either a complete (80%) or a partial (20%) regression of fatigue (FISK score), peripheral edema, pruritus, and palmar erythema. As observed, despite having stopped beta-blockers, F1 esophageal varices disappeared (60%), whereas F2 decreased to F1. The Doppler ultrasound aspect of partial (40%) or total (20%) atrophy was either reduced (60%) or reverted to normal (20%), and the respiratory dynamics of the portal vein improved (80%) or normalized (20%), whereas gross scarring nodules disappeared in 40% of cases. These promising data pave the way for an innovative physiopathological approach with extensive clinical applications.
Abstract: OBJECTIVE: Experimental and clinical studies have shown that a novel symbiotic (known as SCM-III) exerts a beneficial effect on gut translocation and local and systemic inflammatory and microbial metabolic parameters. The present investigation was a preliminary trial on the effectiveness of SCM-III for irritable bowel syndrome (IBS). METHODS: Sixty-eight consecutive adult patients with IBS who were free from lactose malabsorption, abdominal surgery, overt psychiatric disorders and ongoing psychotropic drug therapy or ethanol abuse were studied prospectively and divided into 2 groups that were comparable for age, gender, body size, education and pattern of presenting symptoms. The 2 groups were blindly given for 12 weeks either SCM-III 10 mL t.i.d or the same dosage of heat-inactivated symbiotic. RESULTS: Treatment with SCM-III was 'effective' or 'very effective' in more than 80% of the patients (P < 0.01 vs baseline values and control). Less than 5% reported 'not effective' as the final evaluation compared with over 40% of patients in the control group. After 6 weeks of treatment, a significant improvement of pain and bloating was reported in the treatment group compared with control and baseline values. There was also a benefit for bowel habits, mostly for patients with constipation or alternating bowel habits. No overt clinical or biochemical adverse side-effects were recorded. CONCLUSION: Compared with baseline values and the control group, SCM-III resulted in a significant increase in lactobacilla, eubacteria and bifidobacteria, which suggests that some selected IBS patients could benefit substantially from symbiotics, but the treatment may need to be given on a cyclic schedule because of the temporary modification of the fecal flora.
Abstract: BACKGROUND/AIMS: A number of studies have suggested a key role played by certain resident gut bacteria in the development of large bowel cancer. The aim of the present study was to test the effect of a novel symbiotic preparation, which has been recently shown to beneficially modify gut ecosystem and systemic immunity, on either preneoplastic and neoplastic changes in a colon carcinogenesis model. METHODOLOGY: Sprague-Dawley rats were fed a standard diet for 1 week and then were randomly assigned to three groups. The control diet was given to groups A and B, whereas in group C, the same diet plus 2 mL of a probiotic mixture was given throughout the experiment. Thirty rats (groups B, C) each received a weekly subcutaneous injection of azoxymethane at a dose of 15 mg/kg of body weight for 10 weeks. Group A served as a control group and received a subcutaneous injection of saline for 10 weeks. Forty-five rats were sacrificed at 3-week observation and 60 rats at 20-week observation for assessing metaphase index together with aberrant crypt foci and intestinal immune system markers from one hand and tumor occurrence from the other, respectively. RESULTS: Group A showed a significantly increased metaphase index either in aberrant crypt foci or in "normal appearing" crypts when compared to group A (p < 0.01). Group B rats caused a significant decrease at both sites (p < 0.05). The numbers of lymphocytes derived from the mesenteric lymph nodes in group B rats were significantly decreased (p < 0.01) as compared to either control and to group C. The percentage of CD8 lymphocytes in group C was significantly higher than that in group B. Group C showed a significantly reduced ratio of aberrant crypt foci/colon and of aberrant crypt per colon and per each single focus (p < 0.05). A total of 18 (90%) group B and 10 (50%) group C rats had colon tumors, this difference was significant. The mean number of colon tumors per rat was 2.2 and 1.0 in group B and C, respectively. CONCLUSIONS: Effective probiotics treatment, through mechanisms still to be fully elucidated (decreased fecal pH, specific reduction of carcinogenetic bacterial enzymes, modulation of gut-associated and systemic immune system etc.) has the potential to exert significant antimutagenic properties against colon cancer.
Abstract: BACKGROUND/AIMS: It has been shown that alcohol impairs erythrocyte (red blood cell) membrane fluidity and lipid composition. The aim of this study was to test the effect of a novel acid-resistant antioxidant on the hemorrheology in alcoholics. METHODOLOGY: Thirty alcoholics (25 males, 5 females; mean age: 42 years; range: 31-54; 150 g ethanol/day for 3-5 years) were enrolled into the study. Patients were randomly and double-blindly allocated into 2 groups which were given, for a 2 week period, 18 g/day of Bionormalizer (obtained from biofermentation of carica papaya, pennisetum purpureum, sechium edule, Osato Res. Foundation, Gifu, Japan) dissolved in 5 mL of water at bedtime and 3 hours prior to examination. Placebo consisted of flavored sugar. Healthy teetotalers served as control. On the examination day, blood samples were taken for testing: routine tests, plasma glutathione, ascorbic acid, selenium, plasma lipid hydroperoxides and alpha-tocopherol. Erythrocytes were separated and tested for red blood cell malonyldialdehyde and glutathione content. The hemorheological studies were as follows: blood and plasma viscosity, whole blood filterability, red blood cell membrane fluidity by electron spin resonance, red blood cell aggregation index by photometric rheoscopy and red blood cell deformability by ektacytometry. RESULTS: As compared to healthy controls, alcoholics on placebo treatment showed no change of plasma viscosity but a significantly higher red blood cell malonyldialdehyde, blood viscosity (P < 0.05) and lower plasma glutathione, whole blood filterability and red blood cell fluidity (P < 0.01). No relationship appeared between biochemical tests and red blood cell membrane fluidity. Bionormalizer group showed a significant recovery to control values of either blood viscosity and whole blood filterability (P < 0.01) and a partial, although significant, improvement of red blood cell membrane fluidity, red blood cell malonyldialdehyde and plasma glutathione (P < 0.05). As compared to healthy control, red blood cell aggregation decreased in alcoholics (P < 0.05) and was not affected by Bionormalizer. However, Bionormalizer significantly improved the reduced red blood cell deformability (P < 0.05 vs. alcoholics) and this parameter correlated with red blood cell malonyldialdehyde (r: 0.62. P < 0.05). CONCLUSIONS: These preliminary data suggest that an effective antioxidant supplementation is able to improve the hemorrheology in alcoholics either by directly affecting the ethanol-related lipoperoxidation and xanthine oxidase system activation and/or by modifying red blood cell membrane characteristics.
Abstract: BACKGROUND/AIMS: Thirty alcoholic patients and 24 teetotaler dyspeptic patients were considered and underwent baseline blood chemical evaluation and the Schilling test. METHODOLOGY: During gastroscopy, biopsy samples were taken to assay: routine histology, malonyldialdehyde, vitamin E and glutathione concentration and for testing vitamin B12-Intrinsic Factor binding. Examinations were repeated after 1-week supplementation with Bionormalizer. RESULTS: Plasma malonyldialdehyde level and lipid hydroperoxides concentration as well as either malonyldialdehyde and xanthine oxidase concentration in the gastric mucosa in alcoholics were significantly higher than in controls and despite unchanged alcohol consumption, significantly decreased after Bionormalizer supplementation. Gastric mucosal glutathione was markedly depressed in alcoholics and partly recovered after Bionormalizer supplementation. Although the alcoholics showed a normal intrinsic factor secretion in the gastric juice, they exhibited a markedly depressed intrinsic factor-cobalamin binding on the "ex vivo" study. Moreover, nearly 23% of them had an abnormal Schilling test. Both these impairments reverted to normal after Bio-normalizer supplementation. CONCLUSIONS: It can be postulated that the antioxidative action played by Bionormalizer, possibly due to its availability substrates for glutathione synthesis as well as to its effects on local oxidative burst from neutrophil, is able to recover a normal cobalamin absorption.
Abstract: Twenty-two healthy teetotal volunteers underwent gastroscopy during which biopsy samples from the antrum and body were taken for chemiluminescence assay, routine histology, and for malonyldialdehyde, xanthine oxidase and glutathione determination. Subjects were divided into 2 groups which, in a double-blind fashion, were randomly and orally given either (a) Bionormalizer 9 g at bedtime and 3 h prior examination, or (b) flavored sugar 9 g as placebo. During the second gastroscopy 40 ml of 80% ethanol were sprayed perendoscopically. Gastroscopy with biopsy was repeated 60 min later. As compared to the placebo group, subjects given Bionormalizer showed significantly reduced gastric mucosal damage at endoscopy and the histological level. When considering the placebo group, ethanol administration brought about a significant increase in the luminol-amplified chemiluminescence response in gastric mucosa as compared to the baseline value which was correlated with the histological score. The mean chemiluminescence value in the Bionormalizer group was significantly lower than in the placebo group. Ethanol ingestion brought about a significant increase in xanthine oxidase and malonyldialdehyde together with a decreased glutathione concentration. Bionormalizer significantly prevented such changes. The present data suggest that the natural antioxidant Bionormalizer when given orally promotes an effective protection against ethanol-induced gastric mucosal damage.
Abstract: BACKGROUND/AIMS: The aim of this investigation was to study the oxidative phenomena which take place in the early recovery phase after alcohol withdrawal. Furthermore, the effects of a novel natural antioxidant, Bionormalizer (BN), in such a clinical setting was studied. METHODOLOGY: Forty-six alcoholics with moderate drinking habits (daily ethanol intake: > 80g to < 120g) were enrolled in the study, divided into two groups and given either a placebo or 9g of BN by mouth every night for one week. The patients agreed to stop drinking alcohol, and daily blood sampling was obtained for routine tests and to check plasma and erythrocyte levels of MDA, SOD, GPX and the hydroperoxide level. The groups were comparable in terms of initial biochemical parameters. RESULTS: BN prevented the early increase of plasma TBARS observed in the placebo group, enabling a near-to-normal level of plasma and erythrocyte MDA by the fourth day. BN also prevented the significant drop of erythrocyte GPX and the transient decrease of plasma SOD observed in the placebo group. Despite alcohol withdrawal, plasma lipid hydroperoxide remained significantly elevated in the placebo group, but this phenomenon was rapidly improved by BN. CONCLUSIONS: To a significant extent, BN is able to prevent the free radical-mediated lipoperoxidative changes that occur soon after alcohol withdrawal, while fastening the recovery mechanisms.
Abstract: CONCLUSION: These data show that pure pancreatic juice of AICP patients has a markedly defective antibacterial activity. This finding might be of potential clinical interest in the understanding of the pathophysiology of the disease. BACKGROUND: The aim of the present study was to test the antibacterial activity of pure pancreatic juice in patients with chronic pancreatitis. METHODS: The study group consisted of ten patients with ethanol-induced chronic pancreatitis (AICP) and seven control patients free of pancreatic disease. All subjects had recently undergone a secretin-pancreozymin pancreatic function test. After an overnight fast, through a side-viewing endoscope, selective pancreatic duct cannulation was performed. After secretin stimulation, pure pancreatic juice was obtained. Three fractions of different molecular weights were separated. Samples were incubated with 1-mL suspension of 10(5) Escherichia coli ATCC 25,922, and log10 of colony-forming units were counted. Experiments were repeated by grading pancreatic juice concentration, pH of the medium, and inoculum size. RESULTS: No significant change of pH of pure pancreatic juice appeared between AICP and controls. Starting from 6-h observation, pure pancreatic juice of AICP patients showed a significant bacterial colonization vs controls (p < 0.01). A direct correlation appeared between bacterial colonization and either pH and dilution of pancreatic juice (p < 0.001). Antibacterial activity was independent of inoculum size, enzymatic activation or inhibition, and heat treatment. The fraction with 1000-10,000 molecular weight was the one endowed with antibacterial activity.
Abstract: Two-hundred Wistar rats were allocated to 4 groups. The groups, 3 representing our acute pancreatitis model induced by intrabiliary injection of a trypsin/enterokinase mixture, were studied as follows: (A) no treatment; (B) given a daily 30-ml enema with 20 mg/kg rifaximin; (C) given a daily 30-ml enema with 20 mg/kg rifaximin plus lactitol 0.5 g/kg, and (D) given a daily 30-ml enema with warm saline. A further group of healthy rats was given an intrabiliary injection of 0.15 ml saline. Sacrifices were made after 6, 12, 24, 48 and 72 h of observation. Serial blood samples were drawn to measure pancreatic enzymes and endotoxin. At sacrifice, ascites, lymph nodes, pancreas, spleen, portal vein blood, arterial blood and bile were obtained for bacteriological culture. Both enema treatments brought about a significant improvement in survival. Enema treatments did not affect the serum level of pancreatic enzymes. A time-course increase in endotoxin level was observed in untreated rats. However, significantly decreased levels were observed after both enema treatments. Overall, ascites was the sample most frequently infected. Lymph nodes contiguous to the gut were found to be infected more frequently than those close to major vessels. The histological pancreatic damage was of a significantly lesser degree in both enema treatment groups. Virtually all severe necrotico-hemorrhagic pancreatic lesions were associated with bacterial infection. These data suggest that bacterial translocation plays a relevant role in the outcome of experimental necrotizing pancreatitis. Intra-abdominal spread and lymphatics seem to be the pathways most likely involved in such processes. Colonic cleansing by non-absorbable antibiotics and lactitol seems to exert a beneficial effect on the supervening infection of experimental necrotizing pancreatitis.
Abstract: Marine lipids contain eicosapentaenoic acid (EPA) which has anti-inflammatory effects. The aim of this research was to study, using the dextran sulfate induced acute colitis (AC) model, the effect of an EPA-rich shark fin supplemented diet on the mucosal lipid composition. The histology score increased in AC (p < 0.05), but only slightly in the EPA group. Similarly, colonic permeability to a intraluminally instilled water-soluble contrast medium significantly increased in the AC group, but not in EPA group. As compared with controls, the AC group showed lower levels of phosphatidylethanolamine, phosphatidylinositol, free fatty acid C20:5, and PL-FA C18:1 and C18:2 and higher levels of sphingomyelin, lysophosphatidylcholine, and C18:1 and free fatty acid C20:4 (p < 0.01) after 2 and 7 days. In the EPA group sphinogmyelin and lysophosphatidylcholine slightly increased and free fatty acid C20:4 decreased (p < 0.05) after 7 days, and no PL-FA change occurred. This study confirms the protective properties of EPA-rich marine food. EPA-enriched diet is protecting the colonic mucosa from the early derangements of lipid components occurring in this experimental AC model. This effect is likely to contribute to maintain an effective mucosal lining barrier.
Abstract: Three hundred sixty Sprague-Dawley rats were allocated into four groups, according to different content of a 24-h i.v. infusion performed 1 h after intrabiliary injection of enterokinase/sodium taurocholate to induce acute pancreatitis (AP): (1) Saline; (2) 5 micrograms/kg/h nafamostat mesilate (FUT-175); (3) 10 micrograms/kg/h FUT-175; and (4) 25 micrograms/kg/h FUT-175. Peritoneal fluid was removed and exchanged with 1 mL 3.33 M fluorescein-isothiocyanate-conjugated (FITC) dextrans of 4000-40,000 Dalton. Serial blood samples were withdrawn and examined for FITC-dextrans, phospholipase A2 (PLA2), blood gases, amylase, and lipase. As compared to control (55%), FUT-175 brought about a lower (5 micrograms/kg/h: 25%) or no mortality (10 and 25 micrograms/kg/h), and a milder histological and biochemical evidence of AP. Untreated animals with PLA2 values over two times the standard deviation showed a respiratory distress. Further, unlike group 1, FUT-175 doses as low as 5 micrograms/kg prevented the increase in peritoneal permeability to small-size molecules (up to 20,000 Dalton). In a second experiment under the same drug protocol, 1000 U/mL of PLA2 and 2 mL of pancreatitis ascites were instilled ip. Peritoneal permeability to FITC-dextrans up to 30,000 Dalton and to PLA2 significantly increased in the saline group and in the 5 micrograms/kg FUT-175 group. However, 10 micrograms/kg and 25 micrograms/kg FUT-175 doses prevented such phenomenon. In conclusion, FUT-175 proves to be a potent antiprotease molecule with a biochemical activity also against PLA2 in vivo and prevents significant transperitoneal-blood access of pancreatic enzymes.
Abstract: In order to study the fat-soluble vitamin concentration of patients with chronic alcohol-induced pancreatitis (CAIP) we measured vitamins A and E, total lipids, and retinol-binding protein (RBP) in the plasma of 44 patients with CAIP and 83 controls (44 healthy controls; 39 Crohn's disease patients). Mean plasma vitamin E and vitamin E/total lipid ratio were significantly lower in CAIP when compared with either control or Crohn's disease groups. A low vitamin E/total lipid ratio was found in 75% of CAIP patients (91% with steatorrhea) and a ratio less than 1.0 was virtually 100% predictive of steatorrhea. The mean plasma vitamin A level for the CAIP group was significantly lower (overall 16%, 38% with steatorrhea) than in controls. Patients with CAIP show subnormal plasma levels vitamin E more often as compared to vitamin A. Further, the plasma vitamin E/total lipids ratio may be a sensitive and practical means in the detection and follow-up of steatorrhea in these patients.
Abstract: Three hepatitis C patients out of 15 who received recombinant interferon-alpha 2a (rIFN-alpha 2a) therapy developed high levels of neutralizing antibody coincident with clinical relapse. On analysis, antibodies in their sera were found to also produce some neutralization of lymphoblastoid IFN. Purified lymphoblastoid IFN was separated chromatographically into 10 fractions, each containing one or two IFN-alpha subtypes, and these were used individually to examine the subtype specificity of the neutralizing antibodies in the patients' sera. All three sera neutralized all the subtypes present in the 10 lymphoblastoid IFN fractions. These findings may explain why some patients who develop antibody-mediated resistance to treatment with rIFN-alpha 2 preparations are unable to respond again when treated instead with a human cell derived preparation containing many IFN-alpha subtypes.
Abstract: In the present study, the effect of graded intravenous infusions of human epidermal growth factor (hEGF) 0.005, 0.05 and 0.25 micrograms/ml, with or without 4 mg/kg i.p. indomethacin pretreatment, on rat duodenal bicarbonate secretion was investigated. Perfused duodenal loops were prepared in rats which were given intravenous infusions of hEGF with or without indomethacin. Duodenal pH and pCO2 were measured at 5-min intervals for 45 min, and bicarbonate secretion was calculated. Compared to control, each dose of hEGF caused a significant dose/response rise of duodenal bicarbonate secretion. Prostaglandin release was abolished by indomethacin pretreatment. Indomethacin-pretreated rats had a significant reduction of bicarbonate secretion which was still higher than in controls. These results provide evidence that duodenal bicarbonate secretion induced by hEGF is only partly accounted for by a prostaglandin-dependent mechanism.
Abstract: The aim of the present research was to provide further insight into the debated problem of the existence of modified LDL in vivo. For this purpose a novel model was devised for studying LDL injurious effect on endothelial cells (EC) by infusing native cholesterol rich LDL, diluted to physiological LDL cholesterol concentration. Normal rabbits were infused with LDL separated from rabbits previously fed either with standard food (I-LDL Group), 1% cholesterol (II-LDL Group) or 1% cholesterol plus probucol (IV-LDL Group). Cu++ modified II-LDL was infused as well (III-LDL Group). After dilution as above, lipid oxide (LP) significantly increased in III- and II-LDL media, as compared to I- and IV-LDL media. EC of III- and II-LDL Groups showed irregular shape and surface pattern. Further, they showed adhering clusters of monocytes, platelets and erythrocytes. Endocytic vesicles and ruthenium red-positive particles increased too. EC of IV-LDL Group were only slightly affected as compared to I-LDL Group. These data suggest that native LDL from hypercholesterolemic rabbits contain an oxidized form which is noxious to EC even when LDL is infused at physiological LDL-cholesterol concentration. This early injury is in part LP-associated and actively involves platelets and monocytes.
Abstract: The aim of this research was to perform an in vivo study on the relationships between lipid oxide (LP), platelet aggregation and PAF-acetylhydrolase in a model using perfusion of cholesterol-rich LDL media diluted to physiological LDL-cholesterol concentration. Normal rabbits were infused with LDL (d 1.025-1.063 g/ml) extracted from rabbits previously fed either with standard food (I-LDL group), 1% cholesterol food (II-LDL group) or 1% cholesterol plus probucol (IV-LDL group). CU2+ modified II-LDL was also infused (III-LDL group). After dilution as above, LP increased significantly in III- and II-LDL media. After perfusion, LP significantly increased in III- and II-LDL groups as compared to baseline values and to control. Compared to the I-LDL group, PAF-acetylhydrolase and platelet aggregation significantly increased in III- and II-LDL groups. These data indicate the property of cholesterol- rich LDL to activate PAF-acetylhydrolase and enhance platelet aggregation, even when perfused through a medium containing a physiological LDL-cholesterol concentration.
Abstract: A nine year retrospective survey was carried out at the National Cancer Center Hospital in order to define the diagnostic clues and most suitable diagnostic assessment in resectable pancreatic cancer patients. Forty six cases were detected (27 pancreatic head cancers, 19 pancreatic body and tail cancers). There were 8, 26, 3 and 9 cases of t1, t2, t3 and t4 tumour size cancers, respectively. Abdominal pain and/or discomfort and back pain were the most common initial symptoms and chief complaints. Jaundice was present only in pancreatic head cancer cases. Abnormal GTT and CA 19-9 were the biochemical tests most commonly found abnormal, irrespective of tumour size. ERCP followed by US and CT were the most accurate technical tests. The best care toward the awareness of the initial symptoms needs to be followed, as a first choice, by a proper biochemical (CA 19-9, GTT) and technical (US, ERCP, CT) assessment in the hope of identifying those patients whose prognosis might be improved by an early operation.
Abstract: Forty-nine liver disease patients (7 chronic persistent hepatitis, CPH; 10 chronic active hepatitis, CAH; 13 liver cirrhosis, LC; 9 primary hepatocellular carcinoma, PHC, without LC; and 10 PHC with associated LC) and 20 controls were assessed for their serum alpha-L-fucosidase (ALF) and alpha-fetoprotein (AFP) levels and several routine liver injury parameters. Tumor diameter in those with hepatic cancer was assessed by angio-CT. Only ALF and AFP were significantly greater in patients with PHC and PHC + LC patients as compared to patients with LC alone. At an accepted cutoff level of 500 ng/ml, the AFP level provided 43% false negative tests. On the other hand, an ALF level exceeding 740 mumol/hr/ml provided a sensitivity of 84% with a specificity of 94%. No relationship between the ALF level and Child's criteria or with any liver injury parameter was evident. Considering all individual values, the ALF, rather than the AFP, correlated with tumor size. This finding suggests the ALF level may be of value in the early detection of PHC as well as in the follow-up of patients treated for PHC.
Abstract: In the present study, the effect of graded intravenous bolus injections of urogastrone, 0.5, 5, 25 and 50 micrograms/kg, on rat duodenal bicarbonate secretion was investigated. Perfused duodenal loops were prepared in rats in a strictly controlled fashion. After full recovery, different groups of rats were injected with intravenous graded bolus doses of urogastrone. During the following 45-min study period, duodenal pH and pCO2 were measured at 5-min intervals and bicarbonate secretion was calculated accordingly. Compared to controls, each dose of urogastrone caused a significant dose-response increase in duodenal bicarbonate secretion, measured either at each 5-min reading or as total 45-min output. These results provide the evidence that urogastrone may play a role in the humoral control of duodenal alkaline secretion.
Abstract: In the present paper we have evaluated the accuracy of a fully automated liquid-chromatographic method to study the variations of serum bile acid concentration after oral administration of 500 mg of chenodeoxycholic as a bile acid tolerance test. The study population consisted of 11 subjects with liver cirrhosis (L.C.), 6 with chronic active hepatitis (C.A.H.) and of 15 healthy volunteers, as a control. A clear linear correlation was observed between the integrated peak area and the concentration of each bile acid. Bile acids were detected at a minimum concentration of 5 ng. Intra-assay variation, based on 10 consecutive determinations, was limited to a range of 0.42% and 3.23%. Compared to control group, L.C. and C.A.H. patients showed significantly higher levels of total bile acids and of CDCA. Significative was also the increase of glycine- and taurine-conjugates as well as the decrease of the ratio between the two. The present method, fully automated and using a low cost enzymatic reagent, has yielded an accurate analysis of bile acid fractions on a minute volume of serum in a short examination time.
Abstract: The aim of our study was to investigate the relationship between gastrin producing cell density with antral mucosa, luminal and serum gastrin concentration in antral atrophic gastritis. Our study group consisted of 17 patients: six with mild atrophic gastritis, seven with moderate atrophic gastritis and four with severe atrophic gastritis. None of the patients had type-A atrophic gastritis but the body mucosa was affected by superficial gastritis at various extent in some. A group of 15 healthy subjects served as control. All subjects underwent gastroscopic examination with multiple bioptic sampling. Radioimmunoassay was used for gastrin determination and photomicroscopy for gastrin producing cell density assessment. Electron microscopy was used to assess the gastrin producing granule density index. Patients with moderate and severe atrophic gastritis showed a lower gastric acidity and acid output as compared to control. Serum gastrin did not show significant differences among the groups. In moderate and severe atrophic gastritis, gastrin producing cell granule density index, gastrin producing cell density and antral mucosa gastrin concentration were significantly lower when compared with control and decreased with advancing of the severity of atrophic gastritis. In atrophic gastritis, however, the latter two measurements were not correlated. In moderate and severe atrophic gastritis luminal gastrin concentration significantly increased, compared with control, after the severity of atrophic gastritis. Gastrin producing cell granule density index and luminal gastrin concentration showed a significant correlation with gastric pH. These data suggest that in antral atrophic gastritis with reduced gastric acidity, the decrement of gastrin producing cells is followed by gastrin producing cell hyperfunction with increased luminal release of gastrin.
Abstract: Patients with chronic liver disease (CLD) may show an abnormal glucose tolerance test (GTT). On the other hand, it is debated whether diabetics may undergo abnormalities of liver function. The aim of our study was to see whether galactose tolerance test (GaTT) is a suitable complementary diagnostic tool in defining the glucose metabolism abnormalities characteristic of the two above mentioned clinical entities. Thirty-one patients with CLD, 16 adult diabetics and 12 healthy volunteers were considered. GTT with radioimmunoassay of plasmatic insulin (IRI) and oral GaTT were performed. CLD patients were divided into two groups: with IRI/glycemia greater than 0.4 or less than 0.4. On GaTT, galactosemia was significantly raised in CLD compared to diabetics and control. Further, a statistically significant difference was shown in the glycemic variations during GaTT between diabetics and both CLD groups. A significantly inverse ratio galactosemia/glycemia occurred during GaTT and showed a different pattern between diabetics and CLD patients with impaired insulin secretion. A careful study of galactosemia and glycemia variations during GaTT reliably defines the different patterns of glucose metabolism derangement in CLD with abnormal GTT and in diabetics.
Abstract: The relative efficacy of three commercial pancreatic enzyme supplements in improving fat absorption was studied using the [14C]triolein breath test in 12 patients with chronic pancreatitis. Two of the supplements were enteric coated. The one nonenteric coated product was studied twice: with and without ranitidine coadministration. Doses complied with the manufacturers recommendations. Baseline studies included pentagastrin-stimulated gastric acids, 72-hr fecal fat excretion, and [14C]triolein absorption while not on supplementation. Acid outputs were variable (BAO: 0.3-4.1 meq/hr; MAO: 3.5-34.6 meq/hr). Three patients had mild steatorrhea (i.e., less than 10 g/day) and the remaining severe fat malabsorption (56.9 +/- 41.5 g/day). Although fat absorption was significantly improved by all three supplements, the nonenteric coated preparation was most effective (P less than 0.001). However, laboratory analysis demonstrated that lipase content was four times greater, ie, 17,000 IU/4 tablets. Pretreatment with ranitidine failed to further improve the absorption in patients given nonenteric supplements but was effective in those found to have high or normal acid outputs (P less than 0.001). Our results suggest that the recommended dosage of enteric coated preparations is insufficient for adult patients with severe chronic pancreatitis. Secondly, the marked variability of acid secretion in such patients possibly accounts for the variability of results obtained by others on the usefulness of coadministration of antacids and H2 antagonists. Routine measurement of gastric acid secretion status may help optimize the choice and form of pancreatic enzyme supplementation.
Abstract: The aim of our investigation was to study the gastric mucosa DNA synthesis pattern in different experimental models of duodenal reflux. The following operations were performed on male Wistar rats: (A) sham-operation; (B) Roux-Y gastrectomy; (C) Billroth I; (D) Polya-type partial gastrectomy; (E) Billroth II; and (F) simple gastroenterostomy. Fifteen weeks later rats were sacrificed and histological and in vitro 3H thymidine autoradiographic studies were carried out. Gastric mucosal DNA synthesis rate was also estimated. Besides group A, all other groups showed variable degrees of gastritis mainly located at the anastomosis or at the gastrostomy suture line. Severe gastritis was not present in group B rats and most commonly occurred in group F rats. Group C, D, E and F showed an intense epithelial proliferation with a labeling index significantly higher than in the controls. However, mucosal DNA synthesis rate appeared to decrease with the progression of gastritis and in group F, the group more exposed to duodenal reflux, was significantly lower than in the controls. It is postulated that progressive exposure to duodenal reflux and secondary atrophic gastric changes following gastric surgery is accompanied by a reduction in the mucosal layer of the DNA synthesis rate, due to the loss of epithelial elements and the increase in connective and inflammatory elements, together with an enhanced turnover of the residual epithelial cells.
Abstract: One hundred seventeen patients with recently healed duodenal ulcers were entered into a one-year maintenance study. Patients were randomly assigned to treatment with sucralfate 2 g at night, cimetidine 400 mg, or placebo. The sucralfate versus placebo leg of the study was double-blind, whereas the cimetidine leg was single-blind. Endoscopy was repeated on clinical relapse and routinely at six and 12 months. Ninety-six of the 117 patients were followed up for one year or to an endoscopically proven recurrence. The remaining 21 patients were excluded from analysis because of default or protocol violation. The one-year analysis showed by endoscopy that ulcers had recurred in 17 of the 31 sucralfate-treated patients, 19 of the 32 cimetidine-treated patients, and in 28 of the 33 placebo-treated patients. These data included asymptomatic recurrences in four, four, and three patients, respectively. The relapse rate at 24 weeks was greater in patients healed initially with a histamine (H2)-blocker alone than in those healed initially with sucralfate alone, a combination of sucralfate with a H2-blocker or an antacid alone.
Abstract: Pneumonia and cardiac arrhythmias represent the most common life-threatening complications during delirium tremens. Electrolyte abnormalities are common underlying conditions in chronic alcoholics and they may further complicate the management of patients with alcohol-withdrawal syndrome or with delirium tremens. The authors present two cases in which the clinical picture of severe paralytic ileus complicating delirium tremens was closely associated with electrolyte status and postulate that the two were cause-effect related. A careful electrolyte supplement therapy guided by a strict monitoring of electrolyte balance and renal function proved to be particularly useful in successful management.
Abstract: The aim of our study was to assess the diagnostic accuracy yielded by endoscopic retrograde cholangio-pancreatography (ERCP) in a group of 41 patients presenting with persistent or recurrent abdominal pain and/or cholestasis following cholecystectomy. Each patient had previously undergone, without success, a different combination of non-invasive tests. Cannulation with adequate opacification of at least one duct was achieved in all patients. Aetiologically diagnostic findings obtained with ERCP were as follows: normal 36.8%, choledocholithiasis 34%, benign biliary stenosis 9.8%, chronic pancreatitis 4.9%, pancreatic carcinoma 2.4%, ampullary carcinoma 2.4%, cholangiocarcinoma 2.4%, miscellaneous 7.3%. ERCP gave a final diagnosis in 26 patients (63%) and in all the cases presenting with cholestasis. ERCP plays a first-line role in the diagnostic assessment of patients with the post-cholecystectomy syndrome. However, there is still a considerable part of this population in whom ERCP does not contribute to a diagnosis.
