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Biomedical subjects

M Di Stefano

Publications and source records attributed to M Di Stefano.

At least 19 recordsLinked to original sources

Small intestine bacterial overgrowth and metabolic bone disease.

Small intestine bacterial overgrowth is a malabsorption syndrome and, therefore, it may contribute to the occurrence of metabolic bone disease. However, studies that evaluate the magnitude of this problem and the potential underlying mechanisms are still needed. Fourteen patients with bacterial overgrowth and 22 comparable healthy volunteers took part in this study. All patients were affected by conditions known to predispose to bacterial overgrowth. Diagnosis was based on the following criteria: increased breath hydrogen levels in the fasting state and/or increased breath hydrogen excretion after the ingestion of 50 g of glucose solution, improvement after a 10-day course of antibiotic therapy of severity of symptoms and of H2 excretion parameters. Measurement of bone mineral density by dual-energy x-ray absorptiometry at lumbar spine and femoral level and evaluation of nutritional status were performed. Physical activity, sunlight exposure, and cigarette smoking were also evaluated. Patients showed lumbar and femoral bone mineral density values significantly lower than control group; also the prevalence of bone loss at both lumbar and femoral levels was higher in patient group than in healthy volunteers. Body mass index was significantly lower in patients than in healthy volunteers. Lumbar and femoral bone mineral density were significantly correlated and both correlated with body mass index and with duration of symptoms. No correlation between BMD values and physical activity, sunlight exposure, and cigarette smoking was evident. Our results show that small intestine bacterial overgrowth is an important cofactor in the development of metabolic bone disease. The severity of bone loss is related to poor nutritional status and duration of malabsorption symptoms.

Absorptiometry, Photon↗

"In vitro" spontaneous production of B-chemokines by endocervical and endometrial short-term bioptic cultures.

Several studies indicate that HIV-1 is present in the cervico-vaginal tissues and secretions of infected women representing an important determinant of both sexual and mother-to-child transmission. HIV-1 genital shedding is influenced by various factors; among these, proinflammatory cytokines, in particular the beta/C-C chemokine group (RANTES, MIP-1alpha and MIP-1beta), are known to suppress HIV-1 replication and thus might affect both sexual and vertical transmission. This study aimed to standardize a procedure to measure "in vitro" uterine spontaneous chemokine production by means of short-term cultures of endocervical and endometrial bioptic fragments. In most cases, "in vitro" chemokine production was observed in both fragment cultures. These results further confirm that beta/C-C chemokines exist in the female genital tract and that uterine mucosa actively produces basal levels of these immuno-active substances. This method constitutes a useful approach to evaluate cytokine production and expression in the female genital tract, their influence on HIV-1 expression and infectivity in this site, and their possible role in viral transmission.

Adult↗

Ossification centers of human femur.

The purpose of the present work was to investigate the appearance of ossification centers in human femur by Dual-energy X-ray Absorptiometry (DXA), comparing densitometric data with morphogenetic events. Posteroanterior scans were performed on 31 dried femora (from 11.5 weeks of conceptual age to 1 year of postnatal life) by a Hologic QDR 1000 X-ray densitometer with Ultra-Hi-Resolution software. The results were expressed as bone mineral content (BMC, g) and bone mineral density (BMD, g/cm2). The analyses were performed on a rectangular area corresponding to the minimum width and total length of the shaft. The rectangular area was divided into five equal sections along its longitudinal axis, and BMC was calculated on each section. To distinguish the ossification area of the lesser trochanter with respect to the area of the greater trochanter, the proximal femoral end was divided into two portions, medial and lateral, respectively; BMC and BMD were calculated on each portion. Our data show that the ossification center of the femoral shaft extends prevalently in the proximal direction. A denser area was recognizable on the densitometric images at the level of the lesser trochanter from the 19th week of prenatal life and at the level of the greater trochanter at term. During development, the trends of BMC and BMD are similar in both trochanteric areas, but these parameters are fairly constantly higher at the level of the lesser trochanter. Our findings disagree with the data of the current literature on the postnatal appearance of the trochanteric ossification centers and suggest a different biomechanical interpretation of the secondary ossification of the femur.

Absorptiometry, Photon↗

Increased red cell distribution width and coeliac disease.

BACKGROUND/AIMS: Despite availability of sensitive screening tests, coeliac disease is still underdiagnosed. To determine which haematochemical abnormalities might be more predictive of this condition, we reviewed the clinical records of our series of adult patients affected by coeliac disease. METHODS: Six haematochemical parameters (haemoglobin, red cell distribution width, serum levels of iron, albumin, calcium and potassium) were evaluated in 126 consecutive adult untreated coeliac patients diagnosed since 1990. RESULTS: Elevated red cell distribution width was the most frequent haematochemical abnormality, being present in 57.9% of our patients (Chi square analysis, p<0.01 versus other laboratory changes). CONCLUSION: The increase of red cell distribution width was more common than iron-deficiency anaemia, a well-known indicator of coeliac disease. Elevated red cell distribution width can thus be considered a new predictor of coeliac disease and in the presence of this a search should be made for antiendomysial antibodies.

Adolescent↗

Early increase of bone resorption in patients with liver cirrhosis secondary to viral hepatitis.

Bone loss is an established complication of cholestatic liver cirrhosis, while little is known about bone mass and metabolism in noncholestatic liver cirrhosis. The aim of the present study is, therefore, to evaluate bone mass and mineral metabolism in patients with liver cirrhosis secondary to viral hepatitis. Bone mineral density measurement at lumbar and femoral levels and the evaluation of bone and mineral metabolism and gonadal function were performed in 31 patients with liver cirrhosis and 37 healthy volunteers. Lumbar and femoral bone mineral density values were significantly lower in patients than in healthy volunteers. Prevalence and severity of bone loss increased according to the severity of liver disease. All serum indices of bone and mineral metabolism and of gonadal function showed a similar behavior, but a significant increase of bone resorption was present in all Child-Pugh classes. In particular, class A patients showed normal mean bone mineral density values but increased serum levels of the telopeptide of type I collagen. Liver cirrhosis predisposes to bone loss regardless of the presence of cholestasis. The severity of metabolic osteopathy worsens as liver function does. The underlying mechanism is represented by an increased bone resorption.

Adult↗

The effects of 1-year gluten withdrawal on bone mass, bone metabolism and nutritional status in newly-diagnosed adult coeliac disease patients.

OBJECTIVES: To evaluate the impact of a 1-year gluten-free diet on bone metabolism and nutritional status in coeliac disease. METHODS: Bone mineral density, serum indices of bone remodelling, clinical and biochemical nutritional assessment were evaluated in 86 consecutive newly-diagnosed, biopsy proven, coeliac disease patients (untreated). A complete reevaluation, including intestinal biopsy, was repeated within 1 year of dietary treatment (treated). RESULTS: Untreated: according to WHO criteria, 34% of patients had a normal bone mineral density, 40% had osteopenia and 26% osteoporosis. Between males and females there were no statistical differences in bone metabolism or in most of the nutritional indices, while, between fertile and postmenopausal women, bone mineral density and several bone metabolism markers were significantly different. Compared to subjects with a normal bone mineral density, osteopenics had higher bone specific alkaline phosphatase (BAP) and Bone-Gla-protein (BGP) values. In patients with a concomitant BAP increase and 25OH vitamin D serum level reduction, bone mineral density and several bone turnover markers were statistically different compared to patients without such a serological pattern. Treated: notwithstanding intestinal biopsy which showed a mucosal recovery in only 57%, gluten-free diet led, even in postmenopausal women, to a significant improvement in bone mineral density, bone metabolism and nutrition, except for folic acid, albumin and pre-albumin serum levels which persisted as abnormal in patients with obdurate mucosal impairment. CONCLUSIONS: Coeliac disease patients are at high risk for developing a low bone mineral density and bone turnover impairment. A gluten-free diet can improve this situation even in postmenopausal women and in patients with incomplete mucosal recovery.

Adult↗

Rifaximin versus chlortetracycline in the short-term treatment of small intestinal bacterial overgrowth.

BACKGROUND: Bacterial overgrowth of the small intestine is a condition characterized by nutrient malabsorption due to an excessive number of bacteria in the lumen of the small intestine. Current treatment is based on empirical courses of broad spectrum antibiotics; few controlled data, with respect to the duration and choice of antibiotic drug, exist at present. The recent availability of rifaximin, a non-absorbable rifamycin derivative, highly effective against anaerobic bacteria, prompted us to carry out a randomized, double-blind controlled trial in order to compare its efficacy and tolerability to those of tetracycline, currently considered the first-choice drug. METHODS: In 21 patients affected by small intestinal bacterial overgrowth, fasting, peak and total H2 excretion after ingestion of 50 g glucose and severity of symptoms were evaluated before and after a 7-day course of rifaximin, 1200 mg/day (400 mg t.d.s.), or chlortetracycline, 1 g/day (333 mg t.d.s. ). RESULTS: Fasting, peak and total H2 excretion decreased significantly in the group of patients treated with rifaximin whereas chlortetracycline did not modify these parameters. The H2 breath test normalized in 70% of patients after rifaximin and in 27% of patients after chlortetracycline. The improvement in symptoms was significantly higher in patients treated with rifaximin. CONCLUSIONS: Rifaximin is a promising, easily-handled and safe drug for the short-term treatment of small intestinal bacterial overgrowth.

Adult↗

Non-absorbable antibiotics for managing intestinal gas production and gas-related symptoms.

BACKGROUND: Simethicone, activated charcoal and antimicrobial drugs have been used to treat gas-related symptoms with conflicting results. AIM: To study the relationship between gaseous symptoms and colonic gas production and to test the efficacy of rifaximin, a new non-absorbable antimicrobial agent, on these symptoms. METHODS: Intestinal gas production was measured by hydrogen (H2) and methane (CH4) breath testing after lactulose in 21 healthy volunteers and 34 functional patients. Only the 34 functional patients took part in a double-blind, double-dummy controlled trial, receiving, at random, rifaximin (400 mg b.d per 7 days), or activated charcoal (400 mg b.d per 7 days). The following parameters were evaluated at the start of the study and 1 and 10 days after therapy: bloating, abdominal pain, number of flatus episodes, abdominal girth, and cumulative breath H2 excretion. RESULTS: Hydrogen excretion was greater in functional patients than in healthy volunteers. Rifaximin, but not activated charcoal, led to a significant reduction in H2 excretion and overall severity of symptoms. In particular, in patients treated with rifaximin, a significant reduction in the mean number of flatus episodes and of mean abdominal girth was evident. CONCLUSIONS: In patients with gas-related symptoms the colonic production of H2 is increased. Rifaximin significantly reduces this production and the excessive number of flatus episodes.

Absorption↗

Role of lifestyle factors in the pathogenesis of osteopenia in adult coeliac disease: a multivariate analysis.

OBJECTIVES: Coeliac disease is frequently complicated by alterations of bone mass and mineral metabolism. In this condition the degree of malabsorption is a major determinant of bone loss. However, the role of lifestyle factors such as exposure to sunlight, physical activity and cigarette smoking, which have been demonstrated to influence bone mass and mineral metabolism in other conditions, has never been investigated in coeliac disease. DESIGN: We evaluated the impact of potential co-factors on bone homeostasis in coeliac disease by means of a multivariate analysis model. METHODS: Thirty-nine adult patients with untreated coeliac disease (18 symptomatic, 21 subclinical/silent) were studied. Bone mineral density was measured by dual-energy X-ray absorptiometry at lumbar spine and femoral neck levels. Age at diagnosis, gender, duration of symptoms and severity of symptoms were recorded. Nutritional status, cigarette smoking habit, exposure to sunlight, and physical activity were evaluated. The impact of each independent variable on lumbar and femoral bone mineral density was evaluated by means of a multivariate analysis model. RESULTS: The severity of symptoms and nutritional status were significant sources of variability of both lumbar and femoral bone mineral density. Physical activity was a significant source of variability at femoral level, while gender was at lumbar level. Cigarette smoking habit and exposure to sunlight showed no significant effect on bone mineral density. CONCLUSIONS: Gender, malnutrition, global severity of the disease and physical activity are important co-factors in the pathogenesis of bone loss in coeliac disease.

Absorptiometry, Photon↗

Frequent detection of HIV-1 RNA but low rates of HIV-1 isolation in cervicovaginal secretions from infected women.

Information regarding the presence of HIV-1 in the female genital tract is necessary to gain insight into the mechanism of HIV-1 heterosexual transmission. Herein, we present the results of a study on virus isolation and HIV-1 RNA detection from cervicovaginal lavage (CVL) samples from 25 HIV-1 seropositive women. Despite detectable levels of HIV-1 RNA in 88% of CVL samples, HIV-1 was isolated in only four (19%) samples. Although HIV-1 shedding in cervicovaginal secretions is a common event at all disease stages, the recovery of infectious virus in cell cultures appears to be rare; this renders viral isolation in studies aimed to evaluate the infectivity of cervicovaginal secretions relatively useless.

Cervix Uteri↗

Limited secretory-IgA response in cervicovaginal secretions from HIV-1 infected, but not high risk seronegative women: lack of correlation to genital viral shedding.

The presence and antigen specificity of IgG and secretory-IgA (s-IgA) to HIV-1 were evaluated in cervicovaginal lavages (CVL) from 26 infected and 10 high-risk seronegative women. All the seropositive women had detectable IgG recognizing several viral antigens, while a smaller percentage of women demonstrated s-IgA to the virus. In addition, s-IgA were of limited specificity and provided weak reactivities on Immunoblot bands; an almost constant absence of s-IgA to gp120 was also observed. Neither the presence nor the specificity of either IgG or s-IgA to the virus in CVL prevented the shedding of HIV-1 in this body fluid; in fact, viral RNA was detected in all the women studied and the amounts of viral shedding was unrelated to the genital antibody response. On the other hand, none of the high-risk seronegative women had detectable antibodies to HIV-1 in CVL of either the IgG or s-IgA isotype. Our results a) confirm an impairment of mucosal antibody response during HIV-1 infection and suggest that mucosal immunity is not able to prevent viral shedding in the female genital tract and thus cannot modulate the infectivity of genital secretions; aa) do not provide evidence for a mucosal "memory/protective" antibody response in the genital tract of high-risk seronegative women.

Cervix Uteri↗

An animal model based on the Sprague Dawley rat for the evaluation of ototoxicity.

Various methodological approaches that can be used to detect ototoxic effects caused by the administration of various substances are presented, using the Sprague-Dawley rat as an animal model. Electrophysiological data are also presented to show how the model behaves with potentially ototoxic (hyaluronic acid) and initially inert (hydroxy-propyl-methyl-cellulose) substances.

Acoustic Stimulation↗

Evaluation of cisplatin ototoxicity in a rat animal model.

The ototoxic effects of cisplatin were evaluated by otoacoustic emissions and evoked auditory responses. A transient otoacoustic emissions protocol indicated no significant ototoxic effects in rats treated intravenously with 7.5 mg/kg/week for 2-weeks. A chronic 6-week treatment (2.5 mg/kg/week) monitored by 2F1-F2 distortion product emissions presented significant SNR alterations in a narrow range of frequencies (5.04-5.66 kHz). An acute treatment of 15 mg/kg, using slow 30-min intraperitoneal infusion, presented the highest DP and ABR alterations. The SNR at the 2F1-F2 frequencies 6.34, 7.13, and 7.56 kHz was found significantly decreased, and ABR latency measurements from 8-kHz burst stimuli verified these alterations.

Animals↗

Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: independence from CD4 and major chemokine receptors.

Human immunodeficiency virus type 1 (HIV-1) infection of the brain is associated with neurological manifestations both in adults and in children. The primary target for HIV-1 infection in the brain is the microglia, but astrocytes can also be infected. We tested 26 primary HIV-1 isolates for their capacity to infect human fetal astrocytes in culture. Eight of these isolates, independent of their biological phenotype and chemokine receptor usage, were able to infect astrocytes. Although no sustained viral replication could be demonstrated, the virus was recovered by coculture with receptive cells such as macrophages or on stimulation with interleukin-1beta. To gain knowledge into the molecular events that regulate attachment and penetration of HIV-1 in astrocytes, we investigated the expression of several chemokine receptors. Fluorocytometry and calcium-mobilization assay did not provide evidence of expression of any of the major HIV-1 coreceptors, including CXCR4, CCR5, CCR3, and CCR2b, as well as the CD4 molecule on the cell surface of human fetal astrocytes. However, mRNA transcripts for CXCR4, CCR5, Bonzo/STRL33/TYMSTR, and APJ were detected by RT-PCR. Furthermore, infection of astrocytes by HIV-1 isolates with different chemokine receptor usage was not inhibited by the chemokines SDF-1beta, RANTES, MIP-1beta, or MCP-1 or by antibodies directed against the third variable region or the CD4 binding site of gp120. These data show that astrocytes can be infected by primary HIV-1 isolates via a mechanism independent of CD4 or major chemokine receptors. Furthermore, astrocytes are potential carriers of latent HIV-1 and on activation may be implicated in spreading the infection to other neighbouring cells, such as microglia or macrophages.

Adult↗