Search PubMed⌕ Search

Biomedical subjects

G Palumbo

Publications and source records attributed to G Palumbo.

At least 55 records · Page 3Linked to original sources
PubMed1998

Pharmacokinetics of mitomycin C in pelvic stopflow infusion and hypoxic pelvic perfusion with and without hemofiltration: a pilot study of patients with recurrent unresectable rectal cancer.

This pilot study was conducted to evaluate the advantage in drug delivery for regional chemotherapy in patients with unresectable recurrent rectal carcinoma by different methods. For this research, the pharmacokinetic advantages of mitomycin C delivery by four different methods were compared: intraaortic infusion with aortic stopflow; intraaortic infusion with inferior vena cava stopflow; intraaortic infusion with aortic and inferior caval vein stopflow (hypoxic pelvic perfusion); and hypoxic pelvic perfusion with hemofiltration. The results of this study indicate that pelvic stopflow infusion followed by hypoxic pelvic perfusion significantly increases mitomycin C concentrations in the blood coming from the tumor site. Also, use of hemofiltration reduces mitomycin C levels in peripheral blood after high-dose regional chemotherapy. Further investigations involving more patients should be carried out in the future to validate these results.

Algorithms↗
PubMed1998

Inhibition by glass-ionomer cements of protein synthesis by human gingival fibroblasts in continuous culture.

The effects of several glass-ionomer cements (Baseline and Chem Fil of De Trey; Ketac Fil and Ketac Bond of ESPE; Vitrebond and Vitremer of 3 M) on the protein synthesis of cultured gingival fibroblasts were studied. The presence of cements in the culture medium inhibited protein synthesis, although the relative effectiveness varied significantly. The cements tested have been ranked in three groups, group A (Chem Fil and Ketac Fil), group B (Ketac Bond and Baseline) and group C (Vitrebond and Vitremer), showing 50, 75 and 100% reduction in protein synthesis, respectively. Incubation of cells with medium previously conditioned by Baseline and Ketac Fil caused only transient inhibition of protein synthesis followed by almost complete recovery. This recovery was not observed when the medium was conditioned with Vitrebond. A characterization of the factors determining the inhibitory effect of one cement in each group was attempted. The cements, irrespective of the type, produced small but reproducible decreases in the pH of the medium but released fluoride ions to a different extent. Both changes in the pH of the medium and in the fluoride concentration inhibited protein synthesis by cultured gingival fibroblasts. The different action of cements can be explained, at least in part, by a differing release of fluoride ions.

Aluminum Silicates↗
PubMed1998

Effects of vitamin E and HMG-CoA reductase inhibition on cholesteryl ester transfer protein and lecithin-cholesterol acyltransferase in hypercholesterolemia.

BACKGROUND: The enzyme lecithin-cholesterol acyl transferase (LCAT) esterifies free cholesterol on high-density lipoprotein (HDL) and the cholesteryl ester transfer protein (CETP) transfers cholesteryl ester to very-low-density lipoprotein (VLDL) and low-density lipoproteins (LDL). Using statins, contradictory findings have been made regarding CETP activity in normolipidemic individuals and in those with familial dysbetalipoproteinemia. In contrast, LCAT activity appears to be unaffected by simvastatin. Antioxidants have also been proposed for the use of anti-atherosclerotic treatment, because the oxidation of LDL may have a key role in the pathophysiology of atherogenesis. OBJECTIVE: To investigate, in hypercholesterolemic patients, whether a combination of pravastatin with the antioxidant, vitamin E, has greater effects on the activity of CETP and of LCAT than does pravastatin alone. METHODS: This placebo-diet-controlled multicenter trial included 220 hypercholesterolemic patients who were assigned randomly to groups to receive: diet and 20-40 mg pravastatin (n = 52), diet and alpha-tocopherol (n = 60), or diet associated with placebo (n = 52). Plasma LCAT activity was determined using excess exogenous substrate, containing [3H]cholesterol. Plasma CETP activity was measured in the supernatant fraction after precipitation of endogenous apo B-containing lipoproteins with phosphotungstate-Mg2+. The exchange of cholesteryl esters between [14C]cholesteryl ester-labeled LDL and unlabeled HDL was measured during a 16-h incubation, while LCAT was inhibited. RESULTS: The addition of pravastatin to the diet induced a significant decrease in plasma CETP activity (P < 0.05); this effect was less evident in the group cotreated with vitamin E. For the first time, it was shown that CETP concentrations increased significantly after vitamin E alone (P < 0.05). No significant differences in the plasma activity of LCAT were observed among the groups. CONCLUSIONS: Pravastatin reduced CETP activity, but not that of LCAT. Addition of vitamin E prevented the decrease in CETP activity and had no effect on LCAT activity. The mechanism responsible for these effects is unknown, but could involve the prevention of radical-induced damage to CETP by vitamin E.

Antioxidants↗
PubMed1998

The neuroactive steroid allopregnanolone suppresses hypothalamic gonadotropin-releasing hormone release through a mechanism mediated by the gamma-aminobutyric acidA receptor.

The central nervous system (CNS) is able to synthesize and/or metabolize steroid hormones. These neuroactive steroids are capable of modulating several brain functions and, among these, they seem to regulate the hypothalamic-pituitary-gonadal (HPG) axis. Indeed, recent observations have shown that 5 alpha-pregnane-3 alpha-ol-20-one (allopregnanolone), one of the most abundant naturally occurring neuroactive steroids, suppresses ovulation and sexual behaviour when administered within the CNS. The present study was undertaken to evaluate the effects of allopregnanolone and its inactive stereoisomer, 5 alpha-pregnane-3 beta-ol-20-one, upon the release of gonadotropin-releasing hormone (GnRH) from individually-incubated hemihypothalami. Allopregnanolone suppressed GnRH release in a concentration-dependent manner with maximal activity in the nanomolar range, a range at which this neurosteroid is capable of playing a biological action. The specificity of allopregnanolone suppression of GnRH release was provided by the lack of effect of its known inactive stereoisomer. To evaluate the involvement of gamma-aminobutyric acidA (GABAA) receptor, we examined the effects of two neurosteroids with GABA-antagonistic properties, pregnanolone sulfate (PREG-S) and dehydroepiandrosterone sulfate (DHEAS), and of bicuculline, a selective antagonist of the GABA binding site on the GABAA receptor, on allopregnanolone (10 nM)-suppressed GnRH release. Both PREG-S and bicuculline overcame the inhibitory effects of allopregnanolone on GnRH release, whereas DHEAS did not. To substantiate the involvement of the GABAA receptor further, we tested the effects of muscimol, a selective agonist for this receptor, which suppressed GnRH release. In conclusion, allopregnanolone suppressed hypothalamic GnRH release in vitro and this effect appeared to be mediated by an interaction with the GABAA receptor. We speculate that the inhibitory effect of allopregnanolone on the HPG axis may also be caused by its ability to suppress hypothalamic GnRH release.

Animals↗
PubMed1998

Induction of ovulation in thalassemic patients.

The authors studied 19 thalassemic patients: 14 patients with secondary amenorrhea (group A), 5 patients with primary amenorrhea (group B) and 1 patient with anovulation (group C). All the patients underwent three cycles of induction of ovulation with FSH. The level of 17 beta-estradiol and the diameter of follicles were evaluated every three days. Normal gonadal function was maintained in three patients with positive response at Step 1 of the treatment.

Amenorrhea↗
PubMed1998

Osteopenia in female beta-thalassemic patients.

Sixty-four women with thalassemia major aged 13-28 years were studied. 49 patients had primary amenorrhea and 15 had secondary amenorrhea. Bone density of the spine was performed using lunar DPX. The Z score was used to evaluate the degree of osteopenia. In 82% of the patients a Z score less than -2 was found. BMD correlated negatively with the duration of amenorrhea and age of thalassemic patients.

Absorptiometry, Photon↗
PubMed1998

T-cell acute lymphoblastic leukemia occurring in a patient with acute promyelocytic leukemia.

Secondary acute lymphoblastic leukemia (sALL) following acute myeloid leukemia (AML) is a rare event; only eight cases have been reported. We report a patient with acute promyelocytic leukemia (APL), in hematological and molecular remission who developed T-ALL three years after the diagnosis of APL. The morphological, cytochemical, phenotypical and molecular features of this T-ALL were different from those of the previous APL. The absence of t(15;17), negative PML/RAR alpha at reverse transcription polymerase chain reaction (RT-PCR) analysis and presence of TcR delta support the hypothesis that the T-ALL in this sALL case originated from a different clone from that of the APL cells.

Adult↗
PubMed1997

Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions.

To determine whether oxidized LDL enhances atherogenesis by promoting monocyte recruitment into the vascular intima, we investigated whether LDL accumulation and oxidation precede intimal accumulation of monocytes in human fetal aortas (from spontaneous abortions and premature newborns who died within 12 h; fetal age 6.2+/-1.3 mo). For this purpose, a systematic assessment of fatty streak formation was carried out in fetal aortas from normocholesterolemic mothers (n = 22), hypercholesterolemic mothers (n = 33), and mothers who were hypercholesterolemic only during pregnancy (n = 27). Fetal plasma cholesterol levels showed a strong inverse correlation with fetal age (R = -0.88, P < 0.0001). In fetuses younger than 6 mo, fetal plasma cholesterol levels correlated with maternal ones (R = 0.86, P = 0.001), whereas in older fetuses no such correlation existed. Fetal aortas from hypercholesterolemic mothers and mothers with temporary hypercholesterolemia contained significantly more and larger lesions (758,651+/-87,449 and 451,255+/-37,448 micron2 per section, respectively; mean+/-SD) than aortas from normocholesterolemic mothers (61,862+/-9,555 micron2; P < 0.00005). Serial sections of the arch, thoracic, and abdominal aortas were immunostained for recognized markers of atherosclerosis: macrophages, apo B, and two different oxidation-specific epitopes (malondialdehyde- and 4-hydroxynonenal-lysine). Of the atherogenic sites that showed positive immunostaining for at least one of these markers, 58.6% were established lesions containing both macrophage/foam cells and oxidized LDL (OxLDL). 17.3% of all sites contained only native LDL, and 13.3% contained only OxLDL without monocyte/ macrophages. In contrast, only 4.3% of sites contained isolated monocytes in the absence of native or oxidized LDL. In addition, 6.3% of sites contained LDL and macrophages but few oxidation-specific epitopes. These results demonstrate that LDL oxidation and formation of fatty streaks occurs already during fetal development, and that both phenomena are greatly enhanced by maternal hypercholesterolemia. The fact that in very early lesions LDL and OxLDL are frequently found in the absence of monocyte/macrophages, whereas the opposite is rare, suggests that intimal LDL accumulation and oxidation contributes to monocyte recruitment in vivo.

Adult↗
PubMed1997

Occurrence of the same peroxidative compounds in low density lipoprotein and in atherosclerotic lesions from a homozygous familial hypercholesterolemic patient: a case report.

Oxidative modification of low density lipoprotein (LDL) and its byproducts may play a fundamental role in atherosclerosis. We report an in vitro analysis of LDL peroxidative compounds in an homozygous familial hypercholesterolemic (HFH) patient who subsequently died. During the autopsy, we analyzed lipids extracted directly from different atherosclerotic plaques, and we also provided an immunocytochemical analysis using the specific monoclonal antibody MDA2 (directed against malondialdeyde-lysine epitopes of oxidized LDL). The results showed that the same species of peroxidative compounds were present both in LDL in vitro and in lipids extracted directly from atherosclerotic lesions. Moreover, the immunocytochemistry analysis revealed a positive staining of atherosclerotic plaques, confirming the presence of LDL oxidation-specific epitopes. Although observation of a single case is necessarily limited, our findings are consistent with the hypothesis that oxidative modification of LDL is involved in human atherogenesis.

Adult↗
PubMed1997

Glycosylation enhances oxygen radical-induced modifications and decreases acetylhydrolase activity of human low density lipoprotein.

BACKGROUND: Posttranslational nonenzymatic glycosylation of native low-density lipoprotein (n-LDL) occurs both in vitro and in vivo in diabetic patients. Glycosylated LDL (glc-LDL) behave similarly to oxidized LDL in some respects. In fact, unlike n-LDL, uptake the glc-LDL can occur in part by the "scavenger" receptor(s), as also demonstrated for oxidized LDL. The enzyme acetylhydrolase, carried by LDL, catabolizes platelet activating factor (PAF). This enzymatic activity is inhibited in oxidized LDL. However, it is unknown whether glc-LDL have reduced acetylhydrolase activity. OBJECTIVE: The first aim of the study was to investigate whether glc-LDL were more susceptible than n-LDL to oxidative modification, and which different oxygen radical species were involved in the phenomenon. Moreover, in order to investigate whether glycosylation may affect acetylhydrolase, we also measured this enzymatic activity in both n- and glc-LDL. METHODS: In vitro glc-LDL and n-LDL were exposed to the oxidants xanthine/xanthine oxidase (X/XO; 2 mM and 100 mU/ml, respectively), or CuSO4 (10 microM) for 18 hs at 37 degrees C. Parallel experiments were done in the presence of the superoxide radical scavenger superoxide dismutase (SOD; 330 U/ml), the hydrogen peroxide scavenger catalase (1000 U/ml), or the hydroxyl radical scavenger dimethylthiourea (10 mM) or dimethylsulfoxide (1 mM). Standards of PAF and lyso-PAF were visualized with iodine vapors after separation by thin layer chromatography. The distribution of label was determined by an imaging scanner. Labeled products were then isolated from the chromatography plate, and the amount of 3H-lyso-PAF formed was determined by liquid scintillation counting. RESULTS: Glc-LDL were more susceptible than n-LDL to lipid peroxidation (n-LDL 22.9 +/- 3.4 vs 34.8 +/- 4.2* nmoles/MDA/mg of protein in glc-LDL oxidized by X/XO and n-LDL 28.9 +/- 4.2 vs 40.4 +/- 4.1* in glc-LDL oxidized by CuSO4, *p < 0.05 vs n-LDL). SOD, but not other scavengers, prevented peroxidation, indicating an obligatory role for superoxide radicals. Oxidation of glc-LDL also induced a higher degree of apolipoprotein-B100 modifications than n-LDL, with increased electrophoresis mobility and decreased TNBS reactivity. These effects were similarly prevented by SOD. Finally, acetylhydrolase activity was significantly lower in glc-LDL than in n-LDL. CONCLUSION: Glycosylation increases LDL oxidation due to superoxide radicals, and also reduces acetylhydrolase activity. These phenomenona may contribute to enhance and/or accelerate the progression of atherosclerosis in diabetic patients.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Decreased low-density lipoprotein oxidation after repeated selective apheresis in homozygous familial hypercholesterolemia.

Familial hypercholesterolemia was the first genetic disorder recognized to cause myocardial infarction. Patients with homozygous familial hypercholesterolemia have rapidly progressive coronary atherosclerosis with angina pectoris, myocardial infarction, or sudden death at a young age. Selective apheresis on dextran sulfate cellulose columns reduces mortality and may induce regression of coronary lesions. These patients have both increased levels and prolonged circulation residence time of low-density lipoprotein (LDL), which is not removed by cellular receptor. LDL oxidation may play a pivotal role in atherogenesis. LDL undergoes oxidation before being taken up by macrophages and then transformed into arterial wall foam cells. The aim of this study was to investigate LDL oxidation in eight homozygous patients with familial hypercholesterolemia during repeated LDL apheresis. LDL lipid peroxidation, estimated by conjugated-diene absorbance at 234 nm, lipid peroxides, and malondialdehyde showed an increased resistance against oxidation after repeated LDL apheresis. This phenomenon was also observed in the oxidative indexes of protein moiety of LDL (apolipoprotein-B100 fragmentation, trinitrobenzenesulfonic acid reactivity, and electrophoresis agarose mobility). Similarly, cholesteryl esterification was decreased after LDL apheresis. Thus selective LDL apheresis not only decreases the pool of LDL, but it also induces changes that render LDL less susceptible to oxidation. This phenomenon might contribute to reduce coronary atherosclerosis and thus mortality of these particular patients.

Apolipoprotein B-100↗
PubMed1997

Fibroblast growth and polymorphonuclear granulocyte activation in the presence of a new biologically active sol-gel glass.

The search for chemical devices to be used in clinical orthopaedics must find substances that are biocompatible and do not elicit inflammatory responses in vivo. To this end, a new form of glass has been prepared, composed of 8.1% CaO, 2.9% P2O5, 6.7% N2O5 and 82.3% SiO2, using sol-gel procedures. In order to evaluate the in vitro biocompatibility of this glass, the proliferation of cultured murine fibroblasts and the activation of human polymorphonuclear leukocytes has been studied. The performance of the sol-gel glass has been compared with that of a biocompatible non-resorbable soda-lime glass. Unlike the soda-lime glass, the sol-gel glass neither caused the inhibition of fibroblast growth nor elicited a marked inflammatory response by polymorphonuclear leukocytes, as demonstrated by chemiluminescence assay for reactive oxygen metabolites.

Journal Article↗
PubMed1997

A simple and rapid purification procedure minimizes spontaneous oxidative modifications of low density lipoprotein and lipoprotein (a).

Usual purification procedures of LDL and Lp(a) require numerous, extensive and prolonged sample handlings: this greatly increases the possibility of spontaneous oxidation. We have developed a method which, making use of two short-run ultracentrifugations in vertical rotors alternated by two rapid column-chromatography steps (SRUC), significantly shortens the preparation time to 3.5 h (LDL) and does not demand additional instrumentation or particular accuracy. Purification of Lp(a) requires a further wheat germ agglutinin chromatographic step, which can be accomplished within 30 min. More importantly, the method significantly reduces spontaneous oxidation as compared with classical isolation procedures. LDL isolated by the standard sequential method exhibits more extensive apolipoprotein B100 degradation, lipid peroxidation, and endogenous antioxidant (vitamin E) loss than the same lipoproteins obtained by means of the SRUC. This procedure may have be particularly valuable in experiments evaluating the effects of oxygen radical-induced modifications, especially in vitro.

Adolescent↗
PubMed1997

Circulating serum lectins of patients with IgA nephropathy stimulate IL-6 release from mesangial cells.

Previously, the authors reported that the serum of patients with immunoglobulin (Ig) A nephropathy stimulated peripheral leukocytes, and this effect was inhibited by nominal haptens for lectins. In vitro studies have shown that lectins can bind to rat mesangial cells and cause their activation. This study was performed to investigate whether the serum of IgA nephropathy patients contains lectins that activate mesangial cells, i.e., induce release of interleukin (IL)-6, a nephritogenic cytokine. The serum of patients was adsorbed by affinity chromatography on resins loaded with lectin-binding sugars. After adsorption, serum supernatant was collected and the resins were then eluted. Human mesangial cells were conditioned with native serum, post-adsorption supernatant, and eluate (all three at 10%) for 24 h, and the release of IL-6 was determined by ELISA. Normal serum was used as control. Incubation of mesangial cells with IgA nephropathy patients serum raised average IL-6 release from 8.5 pg/mL to 274.1 pg/mL. Adsorption in beta-D-glucose and N-acetyl-D-glucosamine caused a fall in the activity of patients' serum, to 17.0 and 63.7 pg/mL, respectively, and the activity lost was recovered in the eluate (185.2 and 142.7 pg/mL, respectively). Neither adsorption on N-acetyl-D-galactosamine nor on fucosylamine was associated with any effect on serum activity; accordingly, no activity was found in the eluates. Serum of patients with non-IgA mesangiocapillary nephritis did not stimulate mesangial cells. These results show that the serum of IgA nephropathy patients contains specific lectins that stimulate IL-6 nephropathy by mesangial cells and are, therefore, potential nephritogenic.

Adult↗
PubMed1996

Simultaneous determination of rufloxacin, fenbufen and felbinac in human plasma using high-performance liquid chromatography.

A simple, specific and sensitive high-performance liquid chromatographic method has been developed for the simultaneous determination of rufloxacin, fenbufen and felbinac in human plasma. Plasma, spiked with internal standard, was vortex-mixed for 1 min with a mixture of dichloromethane-diethyl ether (80:20, v/v). The evaporated extract was dissolved in 0.02 M NaOH. Drugs were resolved at room temperature on a 5 microns Zorbax SAX column (250 x 4.6 mm I.D.) equipped with a 20 x 4.6 mm anion-exchange Vydac AXGU (10 microns particle size) precolumn. The mobile phase consisted of acetonitrile and phosphate buffer (pH 7.0), delivered at a flow-rate of 1.2 ml/min. Detection was made at 280 nm. 2-[4-(2'-Furoyl)phenyl]propionic acid was used as internal standard. The calibration curve was linear from 0.2 to 10 micrograms/ml for rufloxacin, from 0.5 to 30 micrograms/ml for fenbufen and from 0.2 to 10 micrograms/ml for felbinac, respectively. The detection limit was 0.1 microgram/ml for rufloxacin, 0.3 microgram/ml for fenbufen and 0.1 microgram/ml for felbinac, respectively.

Anti-Infective Agents↗
PubMed1996

Adverse events in the treatment of hypertensive patients.

We evaluated frequency and type of adverse events (AE) and measures adopted in outpatients attending a hospital hypertension unit in a two-part study: (1) a retrospective review of the charts of the 412 patients seen in 1991 with at least one follow-up visit and (2) a prospective study of the 491 patients seen in 1993 with at least one follow-up visit for whom physicians were asked to fill out an AE form. In 1991 18.6% of patients spontaneously reported an AE; those with an AE were older (p<0.001) than those without and included a greater proportion of females (p<0.002). This retrospective analysis of AE is reproducible as demonstrated by a blind review of 30 randomly selected charts undertaken by two independent observers (McNemar's test:p=ns). In 1993 AE were reported by 24.4% of patients who had more follow-up visits (p<0.001) and included a higher proportion of females (p=0.016) than the subgroup without AE. AE were different in the two studies (p<0.001), more specific and drug-related in 1993. AE were usually considered as mild or moderate (87.4%), the drugs most often involved were calcium antagonists and ACE-inhibitors and the measure adopted was switching to another substance (44%). The frequency of AE reporting varied widely between different physicians.

Journal Article↗