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Biomedical subjects

G Mazzacca

Publications and source records attributed to G Mazzacca.

At least 55 records · Page 3Linked to original sources

Effects of dietary treatment on bone mineral density in adults with celiac disease: factors predicting response.

OBJECTIVE: Conflicting evidence is reported about the effect of treatment on bone mineral density (BMD) in adults with celiac disease (CD). This study analyzed the effects on BMD induced by treatment with a calcium-rich, gluten-free diet in adults with nonsilent CD. METHODS: In 30 women and 11 men with newly diagnosed CD, BMD was measured at the right femur (femoral neck and right Ward's triangle) and the lumbar spine by dual-energy x-ray absorptiometry under untreated conditions (pretreatment) and after 1-yr treatment with a calcium-rich, gluten-free diet. RESULTS: On average, posttreatment BMD was greater than pretreatment BMD at the lumbar spine (mean +/- SE: 0.907 +/- 0.028 and 0.795 +/- 0.028 g/cm2, respectively; p < 0.001), the femoral neck (0.818 +/- 0.023 and 0.741 +/- 0.030 g/cm2, respectively; p = 0.002), and the Ward's triangle (0.703 +/- 0.025 and 0.654 +/- 0.025 g/cm2, respectively; p < 0.001). The greatest BMD change (percent of baseline) was observed at the lumbar spine (+14.1%), the smallest at the Ward's triangle (+7.5%). In the absence of appropriate controls, the BMD change expected in the patients under untreated conditions was estimated by regressing pretreatment BMD over duration of CD with control for gender and age at which CD became clinically evident. The regression coefficient of this analysis indicated that 1 yr of untreated CD was associated with a BMD decrease at the lumbar spine by 0.00570 g/cm2 (95% confidence interval -0.0103 to -0.0011 g/cm2). The 95% confidence interval of the treatment-induced change in BMD at the lumbar spine (+0.060 to +0.160 g/cm2) did not overlap the 95% confidence interval of the BMD change expected under untreated conditions. A large interindividual variability was observed in the BMD response to the treatment: in univariate and multivariate analyses, the treatment-induced change in BMD was significantly related to gender (greater in women than in men) and to pretreatment age and BMD. CONCLUSIONS: The data show that BMD is increased by dietary treatment of CD in most but not all adult patients; pretreatment BMD, gender, and pretreatment age predict the bone response after a 1-yr treatment.

Absorptiometry, Photon↗

Salt intake, urinary sodium, and hypercalciuria.

Several studies have reported that high sodium (Na) intake increases not only urinary Na but also urinary calcium (Ca), suggesting that high Na intake could be involved in the pathogenesis of hypercalciuria. No research data are available on the relationship of Na intake to the prevalence of hypercalciuria within the general population. Moreover, it is not clear if Na intake relates only to urinary Ca or also to other indices of Ca homeostasis, including intestinal Ca absorption. In the present paper, two distinct studies addressed these points using 24-hour urinary Na as an index of salt intake in individuals on their habitual unrestricted free diet. Study 1 analyzed the relationship between 24-hour urinary Na and hypercalciuria (24-hour urinary Ca > or = 7.5 mmol in men, > or = 6.25 mmol in women) in a population sample of 203 men and women, aged 20-59 years. Study 2 analyzed the relationship between 24-hour urinary Na and intestinal strontium (Sr) absorption, used as an index of intestinal Ca absorption, urinary (24-hour and fasting) and plasma Ca, and plasma parathyroid hormone in 36 healthy men and women, aged 18-65 years. Within the population sample (study 1), 24-hour urinary Na was directly and significantly correlated with prevalence of hypercalciuria when controlling for gender, age, weight, and urinary creatinine: the relationship was continuous and linear for urinary Na ranging between 40 and 200 mmol/24 h. In the 36 volunteers (study 2), 24-hour urinary Na was related to 24-hour and fasting urinary Ca (p < 0.001) but not to intestinal Sr absorption: the relationship between 24-hour urinary Na and urinary Ca (both 24 h and fasting) was also significant, controlling for other variables. The results indicate that in adults on their habitual diet, urinary Na, which reflects dietary salt intake, correlates with the prevalence of hypercalciuria independently of intestinal Ca absorption and mainly via renal mechanisms.

Adolescent↗

Small volume isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in treatment of chronic nonorganic constipation.

The present multicenter double-blind placebo-controlled trial evaluates the therapeutic effectiveness of small-volume daily doses of an isosmotic polyethylene glycol (PEG) electrolyte solution in the treatment of chronic nonorganic constipation. After a complete diagnostic investigation, patients still constipated at the end of a four-week placebo-treatment run-in period were enrolled and randomized to receive either placebo or PEG solution 250 ml twice a day for the following eight weeks. Patients were assessed at four and eight weeks of treatment, and they reported frequency and modality of evacuation, use of laxatives, and relevant symptoms daily on a diary card. Oroanal and segmental large-bowel transit times were assessed with radiopaque markers during the fourth week of the run-in period and the last week of the treatment period. During the study period, dietary fiber and liquids were standardized and laxatives were allowed only after five consecutive days without a bowel movement. Of the 55 patients enrolled, five dropped out, three because of adverse events and two for reasons unrelated to therapy; another two were excluded from the efficacy analysis because of protocol violation. Of the remaining 48 patients (37 women, age 42 +/- 15 years, mean +/- SD), 23 were assigned to placebo and 25 to PEG treatment. In comparison to placebo, PEG solution induced a statistically significant increase in weekly bowel frequency at four weeks and at the end of the study (PEG: 4.8 +/- 2.3 vs placebo: 2.8 +/- 1.6; P < 0.002) and a significant decrease in straining at defecation (P < 0.01), stool consistency (P < 0.02), and use of laxatives (P < 0.03). Oroanal, left colon, and rectal transit times were significantly shortened by PEG treatment. There was no difference between controls and PEG-treated patients as far as abdominal symptoms and side effects were concerned. In conclusion, PEG solution at 250 ml twice a day is effective in increasing bowel frequency, accelerating colorectal transit times, and improving difficult evacuation in patients with chronic nonorganic constipation and is devoid of significant side effects.

Adolescent↗

Direct evidence of oxidative damage in acute and chronic phases of experimental colitis in rats.

During inflammatory colitis in man and experimental animals, the production of free radicals increases. This study evaluated the histological pattern and biochemical parameters of oxidative damage during acute and chronic colitis induced by 2,4,-trinitrobenzenesulfonic acid + ethanol in rats. On the samples of scraped mucosa of six groups of rats, one not treated, one killed after 1 hr, and those killed one, two, four, and eight weeks after the induced-damage, we determined the histological and superoxide dismutase activity and the concentration of lipoperoxides, malonyldialdheyde, and reduced glutathione. After 1 hr, the mucosal damage and superoxide dismutase activity were slight; glutathione, lipoperoxides, and malonyldialdheyde were significantly increased. At one week, the histological damage was severe, decreasing progressively, and significantly correlated to superoxide dismutase activity. Lipoperoxides and malonyldialdheyde were high throughout the study. Glutathione was significantly increased at one and two weeks and dramatically decreased thereafter. Therefore, in experimental colitis the cascade of free-radical production induces a constant self-maintaining lipoperoxidation and consumes the cellular antioxidant capability.

Acute Disease↗

Histamine H2-receptor antagonists stimulate proliferation but not migration of human gastric mucosal cells in vitro.

Gastric mucosal cell migration and proliferation are crucial events in the repair of gastric mucosal erosions. This study was designed to test the hypothesis that the H2 blockers roxatidine and ranitidine might stimulate migration and proliferation of gastric mucous cells derived from a human well-differentiated gastric adenocarcinoma cell line (MKN 28 cells) in vitro, in conditions independent of systemic factors and of acid inhibition. Confluent monolayers of MKN 28 cells were wounded with a razor blade and were then incubated with roxatidine or ranitidine. The number of cells migrating to the damaged area was determined 24 hr later. Cell proliferation was assessed by means of [3H] thymidine uptake and cell counts after incubation with roxatidine or ranitidine. Neither H2 antagonist significantly stimulated cell migration. On the other hand, cell proliferation was dose-dependently and significantly enhanced by incubation with roxatidine and ranitidine. Exogenous administration of TGF-alpha significantly stimulated MKN 28 cell division. However, incubation with roxatidine or ranitidine did not increase the steady-state mRNA expression of TGF-alpha or EGFR as assessed by northern blot analysis. Based on these in vitro findings, we postulate that the ulcer healing effect of these H2 antagonists in vivo might be due in part to stimulation of gastric mucosal cell proliferation.

Adenocarcinoma↗

Butyrate enemas in experimental colitis and protection against large bowel cancer in a rat model.

BACKGROUND & AIMS: Butyrate is effective in experimental colitis by increasing transglutaminase activity. Because ulcerative colitis increases the risk of colonic neoplasia, the aim of this study was to investigate whether butyrate treatment reduces mucosal sensitivity to colon cancer development in rats with experimental colitis. METHODS: Colon cancer was induced by azoxymethane injections in 10 rats with trinitrobenzensulfonic acid-induced colitis and 10 rats without colitis. Three additional groups of rats with colitis were treated with butyrate, mesalamine, and saline enemas, respectively, twice daily for 8 weeks; 1 week after colitis induction, tumors were induced. Biopsy specimens for assessment of proliferation pattern and transglutaminase activity were obtained during the latent period of cancer development. Characteristics of tumors were recorded 27 weeks after the first exposure to azoxymethane. RESULTS: Experimental colitis enhanced carcinogenesis; butyrate therapy reduced both incidence and size of tumors and also affected colonic proliferation pattern. Transglutaminase levels were restored by butyrate treatment in rats with colitis. CONCLUSIONS: The protective effect of butyrate against large bowel cancer in experimental colitis suggests its usefulness in long-term therapy to decrease disease relapses and to reduce colon cancer risk in ulcerative colitis.

Animals↗

The arthritis of coeliac disease: prevalence and pattern in 200 adult patients.

Arthritis has often been alluded to as an extra-intestinal clinical manifestation of coeliac disease, but definitive data regarding its prevalence are still lacking. We therefore evaluated the overall prevalence of articular involvement in 200 consecutive adult coeliac patients attending routine gastroenterology follow-up and in 40 controls, and determined whether the prevalence and pattern of articular involvement varied according to the dietary status. An arthritis was present in 26% of patients and in 7.5% of controls, prevalences ranging from 41% in patients on a regular diet to 21.6% in patients on a gluten-free diet (P < 0.005). Arthritis was peripheral in 19 patients, axial in 15 and an overlap of both in 18 subjects. These data suggest that arthritis is much more common than previous reports have indicated, particularly in patients receiving an appropriate dietary regimen, and support the need for combined gastrointestinal and rheumatological follow-up in coeliac patients.

Adolescent↗

Celiac disease and pregnancy outcome.

OBJECTIVES: This study investigated the effect of gluten-free diet on pregnancy outcome and lactation in 125 women affected with celiac disease. METHODS: The study has been designed as a case-control study and a before-after study. RESULTS: In the case-control study, comparison of 94 untreated with 31 treated celiac women indicated that the relative risk of abortion was 8.90 times higher (95% confidence limits: 1.19/66.3), the relative risk of low birth weight baby was 5.84 times higher (90% confidence limits: 1.07/31.9), and duration of breast feeding was 2.54 times shorter (p < 0.001) in untreated mothers. Abortion, low birth weight of baby, and duration of breast feeding did not significantly relate to the severity of celiac disease among untreated women. In the before-after study, 12 pregnant celiac women in either treated or untreated condition were compared. Results indicated that the gluten-free diet reduced the relative risk of abortion by 9.18 times (95% confidence limits: 1.05/79.9), reduced the number of low birth weight babies from 29.4% down to zero (p < 0.05), and increased duration of breast feeding 2.38 times (p < 0.10). Both case-control and before-after studies indicated that threatened abortion and premature delivery did not significantly relate to treatment of celiac disease. CONCLUSIONS: The high incidence of abortion, of low birth weight babies, and of short breast-feeding periods is effectively corrected by gluten-free diet in women with celiac disease.

Abortion, Spontaneous↗

Effect of pregnancy on the clinical course of a cohort of women with inflammatory bowel disease.

The incidence of relapses of inflammatory bowel disease in pregnancy ranges from 20 to 35%. The effect of pregnancy on Crohn's disease and ulcerative colitis after pregnancy has been investigated here. During the survey period, 29 pregnancies occurred in 18 Crohn's patients, and 25 in 19 ulcerative colitis patients. Incidence of relapses during pregnancy and post-partum was 14 and 17% in Crohn's, and 36 and 12% in ulcerative colitis. Fourteen Crohn's patients (17 pregnancies) and 17 ulcerative colitis patients (19 pregnancies) were followed for 3 years before pregnancy and for 4 years after delivery. During the 3 years after pregnancy, the number of relapses/year was significantly lower compared to the 3 years before pregnancy and to the incidence in controls, both in Crohn's (p < 0.05) and ulcerative colitis (p < 0.005). Changes in nutritional status were recorded in 41% of Crohn's, but in none of the ulcerative colitis patients. The reduced incidence of relapses following delivery in Crohn's patients was more marked in the 10 with normal nutritional status at the time of conception (70% reduction in number of relapses, p < 0.05), while in the 7 significantly underweight patients, the reduction was slight (27% reduction in number of relapses, p = NS). In conclusion, the incidence of relapses in the first 3 years after pregnancy is lower than in the pre-pregnancy period. In Crohn's disease, the effect is more evident in patients with normal nutritional status at the time of conception than in malnourished patients.

Abortion, Spontaneous↗

Hypergastrinemia in rats with azoxymethane-induced colon cancers.

Gastrin has been suggested to be involved in the promotion and progression of colon cancer. Mice colon cancers and colon-carcinoma cell lines are stimulated to grow by gastrin, and gastrin receptors have been found in the majority of human colon-tumor specimens. High serum gastrin levels have been reported in patients with colon polyps and cancers, together with increased ornithine decarboxylase (ODC) activity. Since gastrin stimulates ornithine decarboxylase in colon cancer cells in vitro it has been suggested that increased synthesis of intracellular polyamines is one of the mechanisms activated by the hormone. In order to confirm the presence of hypergastrinemia in colon cancer and to investigate the relationship between plasma gastrin and tumor growth, we used an animal model of colon carcinogenesis that minimizes the possible bias of human studies, related to varying diet, age and environmental factors. We evaluated blood gastrin levels in 35 rats with colon cancer induced by the carcinogen azoxymethane (AOM), and we correlated gastrinemia with tumor proliferation, assessed by thymidine-labeling index (TLI) and ODC activity; 6 animals constituted the control group. Gastrin levels in rats with AOM-induced tumors were significantly higher than in controls. Significantly higher TLI and ODC activity were found in the tumors of hypergastrinemic rats than in neoplasms of animals with normal gastrin levels. Our data provide additional evidence of a role for gastrin as trophic hormone for colon neoplastic cells.

Animals↗

Transglutaminase in azoxymethane-induced colon cancer in the rat.

A widespread from of transglutaminase, tissue transglutaminase, has been identified in a number of mammalian cell types, both normal and transformed cells; its biological role is not well understood. We investigated the effect of experimentally induced colon cancer on transglutaminase activity in the rat. Azoxymethane (15 mg/kg for six weeks), given by a course of weekly intraperitoneal injections, produces tumors almost exclusively confined to the intestinal tract. Transglutaminase activity was assayed on tissue homogenates both during the period of treatment and, when the cancer had developed, on tumor tissue and on microscopically uninjured adjacent tissue. A transient proliferative phase was present in the intestine during azoxymethane treatment: in this phase we found a coincidentally increased transglutaminase levels. Transglutaminase activity in tumors of both small and large intestine was significantly higher than in adjacent tissue. Immunohistochemistry revealed higher levels of transglutaminase in tumors, mainly localized in the extracellular matrix, than in adjacent tissues, where it was widely distributed. The present study shows that transglutaminase, besides its potential role in intracellular process during early proliferative phase of carcinogenesis, may also play an important role in matrix processing during tumor growth and differentiation.

Adenocarcinoma↗

Transglutaminases in Crohn's disease.

Transglutaminases are a family of Ca-dependent enzymes involved in various biological events. Circulating transglutaminase (factor XIIIa) is decreased in blood of patients with inflammatory bowel diseases. There is evidence that factor XIIIa and tissue type transglutaminase, present in cell cytosol, bind to various proteins of the extracellular matrix. This study examined the value of serum transglutaminase assay in the treatment and follow up of Crohn's disease and then investigated the intestinal location of both forms of transglutaminases by immunohistochemistry in normal and abnormal tissues. Serum transglutaminase activity was assayed in 36 patients with active Crohn's disease (CDAI > 150). Eighteen patients were studied prospectively from relapse into remission. A significant inverse correlation (p < 0.001) was found between circulating transglutaminase and Crohn's disease activity index; a correlation was also found between serum transglutaminase and serum orosomucoid (p < 0.01) and C reactive protein (p < 0.01). Patients were prospectively studied until clinical remission showed improvement in both their CDAI score mean (SD) (230 (46) to 72 (34), p < 0.01) and transglutaminase activity mean (SD) (0.61 (0.12) to 0.93 (0.13) mU/ml, p < 0.01). The immunohistochemistry assessment showed a colocalisation of factor XIIIa and tissue transglutaminase to the extracellular matrix of damaged tissues. In conclusion, these data confirm the value of serum transglutaminase assay as marker of Crohn's disease activity, extend the utility of serum transglutaminase assay to follow up of the disease, and emphasised the role of different types of transglutaminases in extracellular matrix assembly in the damaged tissues.

Adult↗

Gender and clinical presentation in adult celiac disease.

BACKGROUND: Celiac disease may present in various forms. This study aimed to investigate whether gender affects the clinical presentation of the disease in adult celiac patients from the Mediterranean area. METHODS: This study retrospectively analyzes data collected in all adult patients with celiac disease (n = 195) seen during the past 13 years at the Gastrointestinal Unit of the Federico II University of Naples, Italy. RESULTS: In these series of patients the ratio of women to men was 3.33. Age at diagnosis was lower in women that in men (p < 0.05). Except for asthenia, all signs and symptoms were more frequent in women than in men. Hypochromic anemia was the most commonest finding in women and was 40% more frequent in women than in men (p < 0.001). Dyspepsia was twice as frequent in women as in men (p < 0.05); genital disorders were reported by 44% of women and by no men. Recent weight loss or low body mass index was the commonest finding in men. About 60% of men and women reported diarrhea; among patients without diarrhea, the prevalence of hypochromic anemia differed between sexes (p < 0.05), occurring in about 80% of women. CONCLUSION: This study shows that the clinical presentation of celiac disease is not the same in men and women. The disease is not only more frequent in women than in men but is also more severe and more rapid. The data also suggest the need to look for celiac disease in patients with unexplained hypochromic anemia.

Adult↗

Hypocalciuria in overt and subclinical celiac disease.

OBJECTIVE: To investigate indices of calcium (Ca) homeostasis in celiac disease (CD). METHODS: Urinary Ca excretion rate, intestinal absorption of strontium (Sr) (used as index of intestinal Ca absorption), and other variables related to these end points were measured in newly diagnosed, untreated adult patients (n = 32) with overt and subclinical CD and compared with those of healthy controls (n = 27). Subclinical CD was defined by the absence of diarrhea (> or = 3 bowel movements/24 h), steatorrhea (fecal fat excretion > 6 g/24 h), and low body mass index (weight/height, kg/m2 < 21). RESULTS: Compared with controls, untreated celiac patients had 2 x lower Ca excretion (p < 0.0001) in 24-h and overnight urine (fed condition) but normal Ca excretion in urine samples collected under fasting (2-h) condition; the increase in urinary Ca excretion from fast to fed condition was 4 x lower in untreated celiac patients (p < 0.0001). Patients with overt and subclinical CD did not have significantly different urinary Ca excretion rates. Sr absorption rate was 45% lower in untreated patients than controls (p < 0.0001). Patients with overt and subclinical CD did not have significantly different Sr absorption rates. Sr absorption rate (r = 0.576, p < 0.0001) related to the increase in urinary Ca excretion from fast to fed condition. In celiac patients, 24-h urinary Ca excretion increased by 52% (p < 0.0001) over baseline after 6 months of gluten-free diet, and urinary Ca excretion under fasting condition did not significantly change. CONCLUSIONS: Overt and subclinical CD is associated with low urinary Ca excretion under fed condition, which relates to low intestinal absorption.

Adult↗

Butyrate, mesalamine, and factor XIII in experimental colitis in the rat: effects on transglutaminase activity.

BACKGROUND/AIMS: Butyrate and factor XIII may improve ulcerative colitis; they also affect tissue and serum transglutaminase levels. We investigated the therapeutic potential of sodium butyrate and factor XIII and the role of transglutaminase during mucosal repair in experimental colitis. METHODS: Rats with induced colitis were treated with sodium butyrate, mesalamine, sodium butyrate plus mesalamine, or saline enemas. Thromboxane B2 was monitored as index of inflammation. In a fifth group, the effectiveness of intravenous Factor XIII was assessed. RESULTS: Sodium butyrate, alone or plus mesalamine, reduced histological activity from 13.7 +/- 1.7 (saline) to 2.5 +/- 1.3 and 2.3 +/- 1.1 (P < 0.01), respectively. Transglutaminase, reduced in the colons of the saline group (783 +/- 157 vs. normal 1800 +/- 192 mU/g; P < 0.01), returned toward normal values in the sodium butyrate or sodium butyrate plus mesalamine groups (1390 +/- 228 and 1226 +/- 172 mU/g, respectively; P < 0.01 vs. saline). Furthermore, sodium butyrate plus mesalamine reduced thromboxane B2 levels by day 5 (0.92 +/- 0.16 vs. saline 1.85 +/- 0.34 ng/mL; P < 0.05). Factor XIII therapy improved the histological picture (2.7 +/- 2.1 vs. saline 13.8 +/- 1.7; P < 0.01) and increased transglutaminase levels both in serum (2.81 +/- 0.11 vs. saline 1.45 +/- 0.09 mU/mL; P < 0.01) and in colon (1503 +/- 127 vs. saline 747 +/- 103). CONCLUSIONS: Sodium butyrate and factor XIII improve colitis, sodium butyrate plus mesalamine reduce early thromboxane B2 synthesis, and transglutaminase(s) plays a role in ulcer healing.

Aminosalicylic Acids↗

Cell kinetics and polyamine enzymes in the intestinal mucosa of rats with azoxymethane induced tumours.

We studied the proliferative activity and the modifications in ornithine decarboxylase (ODC) and diamine oxidase (DAO), enzymes involved in polyamine metabolism, in the apparently normal intestinal mucosae of rats with azoxymethane induced tumours. Fifty rats were treated with six weekly injections of 15 mg/kg body weight azoxymethane (AOM). Six rats died during the treatment. All the surviving rats developed intestinal tumours; tumour incidence was 93.1% (41/44) in the left colon, 40.9% (18/44) in the right colon and 45.4% (20/44) in the small bowel. In the normal-appearing mucosa close to intestinal tumours we found an extension of the normal proliferative compartment to the upper third of the crypts (stage I abnormality) and a shift of most of the DNA synthesizing cells from the basal region to the middle and upper third (stage II abnormality). Furthermore, the intestinal mucosa characterized by proliferative abnormalities showed an ODC activity significantly higher than the normal mucosa of control rats (small bowel: 1.01 +/- 0.26 vs 0.42 +/- 0.15, P < 0.01; right colon: 1.32 +/- 0.34 vs 0.25 +/- 0.02, P < 0.001; left colon: 1.93 +/- 0.35 vs 0.22 +/- 0.01, P < 0.01). We also detected a significant decrease of DAO activity in the mucosa of the small bowel and right colon of treated rats compared to controls (0.86 +/- 0.09 vs 4.39 +/- 0.85, P < 0.01; 1.04 +/- 0.43 vs 3.80 +/- 0.91, P < 0.01, respectively), while DAO activity in the left colon was unchanged. The lower incidence of tumours in the small bowel and right colon suggests the presence of factors protecting these segments from carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amine Oxidase (Copper-Containing)↗