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Biomedical subjects

S Milani

Publications and source records attributed to S Milani.

At least 109 records · Page 6Linked to original sources
PubMed1990

Bone histomorphometric reference values in 88 normal Italian subjects.

The study deals with bone histomorphometric results obtained from 88 normal subjects (38 women and 50 men; range: 20-89 years), in order to establish control values in an Italian population. Bone specimens were obtained at autopsy from a standardized area of the iliac crest. The following indicators were measured: bone volume (BV/TV), osteoid volume, osteoid surface, osteoblast surface, eroded surface, osteoclast surface, osteoid thickness. Dependence of histomorphometric indicators on sex and age was evaluated by multiple regression analysis, including sex, age, and also a quadratic term (age2) and two interaction terms (sex x age, sex x age2). BV/TV was mainly affected by age. In fact, a decrease in the amount of bone was found with increasing age in both males and females. The reduction appeared rather regular, with negligible differences between males and females. The other indicators were found to be age- and sex-independent. As a consequence, they did not give information on the possible changes of bone apposition and resorption processes due to aging. On the whole, histomorphometric indicators of trabecular bone of the normal Italian population do not greatly differ from those reported for most other caucasian people.

Adult↗
PubMed1990

Bone loss in response to long-term glucocorticoid therapy.

A number of studies have shown that an excess of glucocorticoids induces osteoporosis, but the mechanism(s) and the time course of the reduction of bone mass remain uncertain. In order to clarify this issue we carried out a longitudinal clinical and histomorphometric study of patients requiring long-term glucocorticoid treatment. In 23 patients (9 men, 10 post- and 4 premenopausal women) biochemical and bone histomorphometric investigations were carried out before and during treatment with 10-25 mg/day of prednisone. Histomorphometric analysis of bone biopsies of the iliac crest showed that the decrease of TBV (up to -27%, P less than 0.001) occurs predominantly within the first 5-7 months of treatment; during the subsequent stages, which include observations after 12 months of treatment, only minor changes were observed. Therefore trabecular bone loss can be satisfactorily described by a negative exponential function. None of the other histomorphometric parameters (osteoid surfaces, resorption surfaces, etc.) showed significant changes. However, the histological features of the bone biopsies during steroid therapy, showing a virtual lack of osteoblastic activity, ruled out an increase of bone resorption. Moreover, the dynamic study of the bone formation by double tetracycline labelling showed, in a small subgroup of patients, a decrease of the apposition rates (from 0.763 +/- 0.053 to 0.305 +/- 0.074 microns/day (mean +/- SE) after treatment). No significant changes, at any time during steroid treatment, were observed in serum alkaline phosphatase, 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone or urinary calcium excretion. Serum calcium increased significantly within the first 1-2 months of therapy and then it returned to baseline. Urinary hydroxyproline excretion decreased significantly within the first 1-2 months and continued to fall throughout the treatment. Thus, both biochemical and histological findings suggest that long-term glucocorticoid therapy causes a reduction of bone turnover, that the bone loss occurs predominantly within the first 6 months of treatment and that patients with lower bone mass have a lower rate of bone loss.

Adult↗
PubMed1990

Cigarette smoking increases gastric luminal prostaglandin F2 alpha and thromboxane B2 in healthy smokers.

Pentagastrin-stimulated gastric luminal prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, PGF2 alpha and thromboxane B2 (TxB2) were measured using a second antibody solid-phase enzyme immunoassay before, during and after cigarette smoking in healthy smokers. Smoking significantly increased PGF2 alpha and TxB2 concentration and output; in contrast no significant changes were found for PGE2 and 6-keto-PGF1 alpha levels. In addition, cigarette smoking caused a significant reduction in gastric juice volume and acid output but did not alter intragastric acidity. These findings may suggest a possible role of prostanoids in the response of the stomach to cigarette smoking.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Cellular localization of type I III and IV procollagen gene transcripts in normal and fibrotic human liver.

The authors have determined the cell types producing alpha 1 (I), alpha 2 (I), alpha 1 (III), and alpha 1 (IV) procollagen gene transcripts in adult human liver by in situ hybridization with [35S]-labeled RNA probes. The liver specimens comprised a total of 20 biopsies with normal histology and biopsies with fibrosis or cirrhosis at different clinical stages and of heterogeneous origins. In normal liver, procollagen type I, III, and IV transcripts were detected in stromal and vascular mesenchymal cells of portal tracts and central veins, as well as in some perisinusoidal cells of the lobule. In fibrotic liver, increased levels of these procollagen mRNAs were observed in the same locations, and particularly enhanced in stromal cells of fibrotic septa and portal tracts, as well as in perisinusoidal cells. Expression of alpha 1 (IV) procollagen RNA was additionally found in some vascular endothelial and bile duct epithelial cells. Although previously suggested as the major source of liver collagens, hepatocytes showed no significant procollagen transcript levels in any of our samples. Thus, procollagen synthesis does not appear to be a function of hepatocytes, but rather of mesenchymal, endothelial, and bile duct epithelial cells in adult human liver. These findings may have implications for the development of specifically targeted antifibrotic therapies.

Adult↗
PubMed1989

In situ hybridization for procollagen types I, III and IV mRNA in normal and fibrotic rat liver: evidence for predominant expression in nonparenchymal liver cells.

The expression of alpha 2(I), alpha 1(III) and alpha 1(IV) procollagen mRNA was analyzed in normal and CCl4-induced fibrotic rat liver by in situ hybridization using RNA probes. In normal liver, moderate amounts of alpha 2(I) and alpha 1(III) procollagen transcripts were found in sinusoidal cells, in stromal cells of the portal tracts and in the vicinity of central veins, whereas a1(IV) procollagen gene expression was below the threshold of detection. After 2 weeks of CCl4 treatment, increased transcription of alpha 2(I) and alpha 1(III) procollagen genes was observed in sinusoidal cells. At this stage, alpha 1(IV) procollagen mRNA was detectable in the same cell types and localization as alpha 2(I) and alpha 1(III) procollagen transcripts, although with a weaker signal. After 4 weeks, newly formed fibrous septa showed many cells intensely labeled by alpha 2(I), alpha 1(III) and alpha 1(IV) procollagen probes. Neither in normal liver nor at any stage of fibrosis was any hybridization signal above background observed in hepatocytes. These patterns suggest that in the liver Type I, Type III and Type IV procollagen expression takes place predominantly in nonparenchymal cells. Therefore, hepatocytes do not appear to be significantly involved in procollagen production in this experimental model of liver fibrosis.

Animals↗
PubMed1989

Vimentin expression of newly formed rat bile duct epithelial cells in secondary biliary fibrosis.

The intermediate filament profile and the growth fraction of hepatocytes and bile duct epithelial cells were studied in a rat model of biliary fibrosis secondary to common bile duct ligation and scission. Strong vimentin expression was observed in epithelial cells of newly formed bile ductules, while normal liver contained only few weakly positive bile duct epithelial cells. All epithelial cells reacted with a pan-cytokeratin antibody. A monoclonal antibody specific for human cytokeratin 7 selectively reacted with both normal and newly formed bile duct epithelial cells. The intermediate filament profile of hepatocytes was constant, showing no changes during proliferation or in periportal areas adjacent to excessive bile duct formations. The proliferation-associated antigen detected by the antibody Ki-67 was present in many hepatocytes, homogeneously distributed in the lobules, but was seen only in a small proportion of the epithelial cells of the newly formed bile ducts. We conclude that vimentin may serve as an indicator for cellular reorganization in the bile duct system, and that the epithelial cells of newly formed bile ductules in this particular model of secondary biliary fibrosis were most likely to be derived from an outgrowth of the biliary duct system and recruitment of preductular epithelial cells. No morphological or immunohistological evidence suggesting a derivation from hepatocytes by ductular metaplasia or from oval cells was obtained.

Animals↗
PubMed1989

Sensitivity of bone histomorphometry in the diagnosis of metabolic bone diseases.

Diagnostic sensitivity of bone histomorphometry was assessed in different metabolic bone diseases, after fixing the specificity at 75%, 90% and 95% reference levels. Sensitivity was particularly high in cases with greatly increased osteoid and/or resorption features, as in renal osteodystrophy (ROD). All the remodeling indicators were highly sensitive toward advanced or severe forms of mixed ROD (mROD). Osteoid indicators were the most sensitive parameters in ROD with predominant osteomalacia (oROD). Osteoclastic and several osteoid indicators were very sensitive in all grades of ROD with predominant hyperparathyroidism (hROD). Sensitivity was generally low in uremic patients without bone changes (wROD) and also in patients with idiopathic osteoporosis (OP). It is our recommendation, however, that for each individual patient the definite diagnosis should be based on both morphological, clinical and metabolic parameters.

Adult↗
PubMed1989

Individual growth curves and longitudinal growth charts between 0 and 3 years.

From a statistical viewpoint, the construction of longitudinal growth norms involves two classes of problems: (a) the choice of a mathematical function having a few constants as possible, but suitable for describing individual growth process in the growth period of concern; (b) the estimation of the mean growth constants for a homogeneous group of subjects, and of the covariance matrix of data collected longitudinally, to compute tolerance intervals which enable us to draw growth charts. Although growth constants should have some biological interpretation, the choice of functions rests mainly on the criterion of following observed growth as closely as possible. As to the second problem, the simplest situation implies that growth function is linear in the constants and all subjects have measures on the same prefixed occasions: in this case, multivariate Potthoff-Roy model (1964) directly applies. In longitudinal growth studies, however, it happens that subjects do not come for measurements at exactly the age specified: two-stage models seem to be more appropriate to this latter case. They consist of (a) fitting individual growth curve on each subject to obtain estimates of 1st-stage constants; (b) obtaining estimates of 2nd-stage constants, characteristic of the whole group of subjects, in terms of weighted averages of the estimates of the 1st-stage constants. This paper deals with the application of a two-stage model to the growth in length of 203 girls and 217 boys born in Naples between 1977 and 1981. Children, whose growth records are used to trace longitudinal standards, have been measured at birth, and at least 5 times in the course of a follow-up made up of 8 visits, between 3 months and 3 years of life.

Child, Preschool↗
PubMed1989

Cellular localization of laminin gene transcripts in normal and fibrotic human liver.

We have attempted to determine the cell types producing laminin in normal and fibrotic human liver by in situ hybridization to laminin B1 chain gene transcripts with [35S]-labeled RNA probes. In normal liver laminin transcripts were detected in vascular endothelial, in bile duct epithelial, and in portal tract mesenchymal cells as well as in perisinusoidal cells of the lobule. In fibrotic liver, expression of laminin RNA was increased in proliferating bile duct epithelial cells, stromal cells of fibrotic septa, and in perisinusoidal cells of the regenerating nodules. Although recently suggested as a major source of laminin, hepatocytes in none of our samples showed evidence for significant laminin B1 gene transcription. Thus laminin synthesis does not appear to be a function of hepatocytes, but rather of mesenchymal, endothelial, and bile duct epithelial cells in the liver. This pattern of laminin expression underlines the importance of the mesenchyme in conditioning the function and differentiation of the hepatic parenchymal compartment.

Biopsy↗
PubMed1989

Cardiac output with CO2 rebreathing method in CAPD patients.

The aim of this study is to evaluate cardiac output (CO) with CO2 rebreathing method (RCO2) in patients (pts) on CAPD. We have studied 15 pts on CAPD from at least 6 months, the mean (+/- SD) age was 55 +/- 4 years, mean (+/- SD) hemoglobin was 10 +/- 2 gr/dl. The respiratory tests excluded obstructive or restrictive broncopneumopathies. Electrocardiograms and B-mode echocardiograms were normal. RCO2 was evaluated using the FICK formula: CO = VCO2/CvCO2 - CaCO2 where VCO2 is CO2 production; CvCO2 is the CO2 content in venous mixed blood; CACO2 is arterial CO2. VCO2 was obtained by collecting expired air into a Douglas bag during respiration at rest for 4 minutes. CvCO2 was obtained after 10-15 seconds of respiration in a mixture of 7% CO2 in O2. CaCO2 was obtained at CO2 end-tidal capnogram. RCO2 was performed in CAPD with full and empty abdomen. The mean (+/- SD) CO was 2.3 +/- 1.04 l/min with both full and empty abdomen, values below those theoretically calculated, taking into account the age and body surface (4.7 +/- 0.6 l/min P less than 0.0005). The reduction of CO is not induced by left ventricular insufficiency, but such phenomenon could be attributed to a redistribution of body fluid between intra and extracellular, in favour of the intracellular compartment. Therefore the increase in hematocrit and total plasma proteins can be fictitious.

Aged↗
PubMed1989

S-adenosylmethionine inhibits collagen synthesis by human fibroblasts in vitro.

Previous studies have indicated that S-adenosylmethionine (SAMe), the precursor of methyl groups and thiols, exerts an anti-inflammatory activity. In order to clarify whether this molecule also has antifibrotic properties, we evaluated its pharmacological effects on human fibroblasts in vitro. Accordingly, fibroblasts between 5 and 10 subcultures were incubated for 24 h with different SAMe concentrations (from 0.005 to 626 microM). Fibroblast proliferation measured by incorporation of labeled thymidine was not affected by SAMe in the range of the tested concentrations. Moreover, cell viability assessed by trypan-blue exclusion test was greater than 98% in all cultures, without any difference between SAMe and control cultures. Collagen synthesis estimated by HPLC measurement of hydroxyproline in both media and cells was not modified by SAMe concentrations lower than 0.05 microM. On the other hand, SAMe concentrations higher than 0.05 microM significantly (p less than 0.01) reduced collagen synthesis as compared with untreated controls. This effect was not dose-dependent. In conclusion, this study indicates that SAMe addition to fibroblasts in the range of concentrations which can be found in vivo induces a marked decrease (about 50% of control value) in collagen synthesis with no adverse effects on cell proliferation and viability. These findings suggest further investigation of the potential antifibrotic role of SAMe.

Cell Division↗
PubMed1989

Sensitivity and predictive value of serum ferritin and free erythrocyte protoporphyrin for iron deficiency.

The sensitivity and predictive value of serum ferritin (SF) and free erythrocyte protoporphyrin (FEP) for iron deficiency (ID) was evaluated by studying 272 subjects with uncomplicated ID (174 with anemia and 98 without) in whom diagnosis was confirmed by the response to iron supplementation. Overall, the sensitivity, at 95% specificity, was 82% (79% in women, 94% in men) for SF and 61% (60% in women, 65% in men) for FEP. The sensitivity varied as a function of hemoglobin values, dropping from over 90% for both tests in the case of severe anemia, to approximately 70% for SF and less than 50% for FEP in the absence of anemia. The predictive value decreases more sharply for FEP than for SF with increasing hemoglobin levels. It is concluded that SF is preferable to FEP for the detection of ID, particularly in the absence of anemia. However, owing to the unsatisfactory predictive value at low prevalence, SF should be used as a screening test for ID without anemia only when the prevalence is at least 20%.

Adult↗
PubMed1988

Ontogenetic development of the 5 alpha-reductase in the rat brain: cerebral cortex, hypothalamus, purified myelin and isolated oligodendrocytes.

In the central nervous system of the rat, the 5 alpha-reductase, the enzyme which converts testosterone into dihydrotestosterone, appears to be concentrated in the white matter and in particular to be associated with myelin. In order to verify whether a temporal correlation might exist between the formation of myelin membranes and the variations of the 5 alpha-reductase activity observed in the brain, the enzymatic activity was studied in the cerebral cortex and in the hypothalamus of male rat in the age range of 3-60 days, in myelin purified from animals of 15-60 days of life and in oligodendrocytes (i.e. in the cells responsible for the formation of the myelin) isolated from the brain of adult and very young rats (7th day of life, when the myelination process is not yet initiated). The results show that the formation of 5 alpha-androstane-17 beta-ol-3-one (DHT) in the cerebral cortex and in the hypothalamus has a peak activity in the first two weeks of life, before the beginning of the myelination process; purified myelin has an enzymatic activity always much higher than that present in the cerebral cortex and in the hypothalamus and shows a peak in the formation of DHT in the first period of myelinogenesis, on the third week of life. Finally the oligodendrocytes of young rats possess a much higher ability to convert testosterone into the 5 alpha-reduced metabolites than the oligodendrocytes of adult animals. A possible involvement of this enzyme in the myelin function may be hypothesized.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1988

Antihypertensive effect of spirapril and felodipine during repeated administration to spontaneously hypertensive rats.

The antihypertensive activity of spirapril given alone or in combination with felodipine was investigated in spontaneously hypertensive rats (SHR) during a 3-week treatment regimen and for one week after drug withdrawal. Systolic blood pressure and heart rate were recorded once a week just before dosing and at varying time intervals up to 6 hr thereafter. Recordings were continued for one week after drug withdrawal. Spirapril alone at 1 and 5 mg/kg p.o. was found to produce dose-related antihypertensive effects throughout the treatment period. Felodipine alone at 5 mg/kg p.o. reduced blood pressure slightly more than did the low dose of spirapril. The combination of spirapril and felodipine induced a marked antihypertensive response which was greater than that observed in rats treated with either drug alone. One week after treatment withdrawal, blood pressure was at initial levels with no evidence of rebound phenomena. No significant heart rate changes were observed in the treated groups, as compared with the controls, except for an increase on the 1st day of treatment in rats given felodipine. These findings indicate that the combination of an angiotensin converting enzyme (ACE) inhibitor with a calcium antagonist leads to an effective control of hypertension over a prolonged period of treatment. Since the combination allows effectiveness with lower doses of ACE inhibitor, it is expected that the antihypertensive efficacy might be associated with a lower liability to untoward effects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Serum HBV DNA and intrahepatic hepatitis B core antigen (HBcAg) in chronic hepatitis B virus infection: correlation with infectivity and liver histology.

In this study we investigated the HBeAg/anti HBeAg status, the liver histological features, the intrahepatic localization of HBcAg, and the presence of serum HBV DNA in a group of 79 HBsAg-positive patients. We found a close relationship between the presence of HBV DNA and intrahepatic HBcAg in HBeAg-positive patients. Among the 56 anti-HBeAg-positive patients considered, 13 (23.2%) showed the presence of intrahepatic HBcAg and serum HBV DNA. In this group of patients, active viral replication was associated with a chronic inflammatory liver disease and particularly with CAH. Furthermore, a prevalent cytoplasmic localization of HBcAg was found in 66.6% of patients affected by CAH, showing that this peculiar distribution of HBcAg seems to be associated with a poor prognosis.

Adult↗
PubMed1987

Is determination of serum N-terminal procollagen type III peptide (sPIIIP) a marker of hepatic fibrosis?

Serum N-terminal procollagen type III peptide (sPIIIP) levels were evaluated in 58 patients affected by chronic liver disease, in order to assess the usefulness of sPIIIP as a marker of hepatic fibrosis. In 45 patients sPIIIP was also correlated to liver histology; biopsies were scored by two of the authors, without knowledge of diagnosis. Compared to normal controls, sPIIIP concentration was found to be significantly elevated in chronic active hepatitis (CAH) and in cirrhosis, but not in fatty liver. Patients affected by chronic persistent hepatitis (CPH) had values of sPIIIP higher than normal in four of 11 cases considered. A close correlation was found between sPIIIP values and histological parameters of inflammation, necrosis, and degeneration, while the relationship between sPIIIP levels and fibrosis was weaker. These data suggest that sPIIIP determination may reflect the extent of inflammatory changes in the liver; but it cannot be considered a reliable index of hepatic fibrosis.

Adult↗
PubMed1987

Antihypertensive activity of a new ACE-inhibitor, SCH 33844, during repeated administration in spontaneously hypertensive rats.

The antihypertensive activity of SCH 33844, a new angiotensin converting enzyme inhibitor, was investigated in conscious spontaneously hypertensive rats during a 3-week treatment regimen and for 1 week following drug withdrawal. SCH 33844 was given once daily at 2 dose levels (1 and 5 mg/kg orally) and its effects were compared with those of captopril (60 mg/kg orally). Systolic blood pressure was recorded twice weekly just before administration and at varying time intervals up to 6 hr after dosing; recordings were continued for 1 week after drug withdrawal. SCH 33844 was found to produce dose-related antihypertensive effects. Given at 1 mg/kg, the compound elicited small but significant blood pressure changes during the treatment. After drug withdrawal, systolic blood pressure returned to pre-drug levels within 1 week. SCH 33844 at 5 mg/kg, and captopril at 60 mg/kg, both reduced blood pressure markedly and to a similar extent. After each administration the effect was rapid in onset, lasted for over 6 hr and was not subject to tolerance. Drug withdrawal resulted in a gradual return of systolic blood pressure toward pre-treatment levels within 1 week, with no evidence of rebound phenomena. These results indicate that SCH 33844, like captopril, produces an effective antihypertensive action throughout a repeated dosing.

Angiotensin-Converting Enzyme Inhibitors↗