Search PubMed⌕ Search

Biomedical subjects

M Ferro

Publications and source records attributed to M Ferro.

At least 19 recordsLinked to original sources

Identification of the melatonin-binding site MT3 as the quinone reductase 2.

The regulation of the circadian rhythm is relayed from the central nervous system to the periphery by melatonin, a hormone synthesized at night in the pineal gland. Besides two melatonin G-coupled receptors, mt(1) and MT(2), the existence of a novel putative melatonin receptor, MT(3), was hypothesized from the observation of a binding site in both central and peripheral hamster tissues with an original binding profile and a very rapid kinetics of ligand exchange compared with mt(1) and MT(2). In this report, we present the purification of MT(3) from Syrian hamster kidney and its identification as the hamster homologue of the human quinone reductase 2 (QR(2), EC ). Our purification strategy included the use of an affinity chromatography step which was crucial in purifying MT(3) to homogeneity. The protein was sequenced by tandem mass spectrometry and shown to align with 95% identity with human QR(2). After transfection of CHO-K1 cells with the human QR(2) gene, not only did the QR(2) enzymatic activity appear, but also the melatonin-binding sites with MT(3) characteristics, both being below the limit of detection in the native cells. We further confronted inhibition data from MT(3) binding and QR(2) enzymatic activity obtained from samples of Syrian hamster kidney or QR(2)-overexpressing Chinese hamster ovary cells, and observed an overall good correlation of the data. In summary, our results provide the identification of the melatonin-binding site MT(3) as the quinone reductase QR(2) and open perspectives as to the function of this enzyme, known so far mainly for its detoxifying properties.

Amino Acid Sequence↗

Synthesis of ionones and carvone analogues: olfactory properties and preliminary toxicity assays.

Vilsmeier reagents react with alpha/beta-ionones and carvone to produce aldehydes 7-11 in a one-step procedure. The indene derivative 11, which came from the double iminoalkylation of carvone and ring closure with the elimination of dimethylamine, was practically odourless, while all the others had peculiar odours which were very different from the starting material. The cytotoxicity data of 9 and 10, which are the most promising potential perfume ingredients, are also reported.

Alkenes↗

Differentiation of O-acetyl and O-carbamoyl esters of N-acetyl-glucosamine by decomposition of their oxonium ions. Application to the structure of the nonreducing terminal residue of Nod factors.

Nod factors are substituted N-acyl chito-oligomers secreted by plant symbiotic bacteria of the Rhizobium family. Substitutions on the oligosaccharide core specify their recognition by host plants. A method using tandem mass spectrometry is proposed to locate the O-acetyl and O-carbamoyl substituents on the nonreducing terminal residue of the chito-oligomers. As model compounds, all the positional isomers of monoacetyl and monocarbamoyl esters of 1-O-methyl-N-acetyl-alpha-D-glucosamine were synthesized. Oxonium ions (MH - CH3OH)+ were generated by liquid secondary ion mass spectrometry (LSIMS) and their decomposition was recorded on a tandem magnetic instrument. Large differences were observed in the relative abundances of ions resulting from elimination of water and of the O-ester substituent from metastable oxonium ions. Deuterium exchange reactions indicated parallel elimination pathways involving either exchangeable or carbon-linked hydrogens. The intensity ratios of some of the ions generated by collisions with helium atoms allowed the isomers to be distinguished. The main dissociation routes were identified. Metastable and collision-induced decomposition of the B1 ions from Nod factors of Sinorhizobium meliloti and Azorhizobium caulinodans resembled that of the 6-O-substituted N-acetylglucosamine models. Decomposition of the B1 ion from Mesorhizobium loti and Rhizobium etli Nod factors, was similar to that of 3-O-carbamoyl N-acetyl-glucosamine and different to that of the 4-O isomer. 6-O- and 3-O-carbamoylation specified by the nodU and nolO genes, respectively, of Rhizobium. sp. NGR234 were confirmed.

Acetylglucosamine↗

Steroid and cyclophosphamide in IgA nephropathy.

BACKGROUND: IgA nephropathy is associated with a wide spectrum of possible lesions. Therefore, different responses to anti-inflammatory or immunosuppressive therapies should be expected with acute inflammatory changes, which are predominantly reversible, and with prevalently sclerotic lesions. METHODS: The effects of a combined schedule of prednisone and cyclophosphamide was analysed in the specific subset of IgA nephropathy patients with acute inflammatory histologic changes associated with haematuria and proteinuria. Two groups of patients, with similar histologic lesions and clinical presentation, were considered. The first group (12 patients) was treated within 1 week after renal biopsy; starting with three pulses of methylprednisolone (1 g) followed by oral prednisone (0.8 mg/kg body weight for 2 weeks, 0.6 mg/kg for another 2 weeks, 0.4 mg/kg for an additional 4 weeks, then slowly tapered by 5 mg each month until discontinuation) and 1.5 mg/kg cyclophosphamide for 2 months. A second sample of eight untreated patients served as a control group. Treated and untreated patients had diffuse mesangial proliferation with florid crescents (8-60% in treated and 10-40% in untreated patients) with mild degree of glomerular sclerosis and interstitial changes. Basal creatinine (167 micromol/l, range 79-371 vs 132 micromol/l, range 79-256) and proteinuria (3.0 g/24 h, 1.0-4.9 vs 3.3 g/24 h, 1.0-13.7) were not statistically different between treated and untreated patients respectively. Nine treated and six untreated patients were hypertensive. Blood pressure treatment did not include ACE-inhibitors. RESULTS: Untreated patients' 5-year renal survival, as assessed by the Kaplan-Meier method, was found to be significantly lower than treated patients (37.5 vs 91.6%, log-rank P=0.01 and Breslow test P=0.008; relative risk to reach the endpoint of a 100% increase in serum creatinine=3.58, P=0.03). CONCLUSION: This short course of therapy with prednisone and cyclophosphamide has been effective in a subset of IgA nephropathy patients with florid glomerular changes and major urinary abnormalities, turning off phlogistic activity and preventing subsequent progression toward renal failure.

Adolescent↗

Inhibition of class-3 aldehyde dehydrogenase and cell growth by restored lipid peroxidation in hepatoma cell lines.

Hepatoma cells have a below-normal content of polyunsaturated fatty acids; this reduces lipid peroxidation and the production of cytotoxic and cytostatic aldehydes within the cells. In proportion to the degree of deviation, hepatoma cells also show an increase in the activity of Class-3 aldehyde dehydrogenase, an enzyme important in the metabolism of lipid peroxidation products and also in that of several drugs. When hepatoma cells with different degrees of deviation were enriched with arachidonic acid and stimulated to peroxidize by ascorbate/iron sulphate, their growth rate was reduced in proportion to the quantity of aldehydes produced and to the activity of aldehyde dehydrogenase. Therefore, 7777 cells, less deviated and with low Class-3 aldehyde dehydrogenase activity, were more susceptible to lipid peroxidation products than JM2 cells. It is noteworthy that repeated treatments with prooxidant also caused a decrease in mRNA and activity of Class-3 aldehyde dehydrogenase, contributing to the decreased growth and viability. Thus, Class-3 aldehyde dehydrogenase could be considered relevant for the growth of hepatoma cells, since it defends them against cell growth inhibiting aldehydes derived from lipid peroxidation.

Aldehyde Dehydrogenase↗

Structure of the Mesorhizobium huakuii and Rhizobium galegae Nod factors: a cluster of phylogenetically related legumes are nodulated by rhizobia producing Nod factors with alpha,beta-unsaturated N-acyl substitutions.

Rhizobia are symbiotic bacteria that synthesize lipochitooligosaccharide Nod factors (NFs), which act as signal molecules in the nodulation of specific legume hosts. Based on the structure of their N-acyl chain, NFs can be classified into two categories: (i) those that are acylated with fatty acids from the general lipid metabolism; and (ii) those (= alphaU-NFs) that are acylated by specific alpha,beta-unsaturated fatty acids (containing carbonyl-conjugated unsaturation(s)). Previous work has described how rhizobia that nodulate legumes of the Trifolieae and Vicieae tribes produce alphaU-NFs. Here, we have studied the structure of NFs from two rhizobial species that nodulate important genera of the Galegeae tribe, related to Trifolieae and Vicieae. Three strains of Mesorhizobium huakuii, symbionts of Astragalus sinicus, produced as major NFs, pentameric lipochitooligosaccharides O-sulphated and partially N-glycolylated at the reducing end and N-acylated, at the non-reducing end, by a C18:4 fatty acid. Two strains of Rhizobium galegae, symbionts of Galega sp., produced as major NFs, tetrameric O-carbamoylated NFs that could be O-acetylated on the glucosamine residue next to the non-reducing terminal glucosamine and were N-acylated by C18 and C20 alpha,beta-unsaturated fatty acids. These results suggest that legumes nodulated by rhizobia synthesizing alphaU-NFs constitute a phylogenetic cluster in the Galegoid phylum.

Acylation↗

[Usefulness of long-term follow-up of patients operated on for cryptorchidism].

BACKGROUND: Cryptorchidism, testicular ectopia and rectractile testicle are different pathologies with conceivable different prognosis. As a matter of fact spermiogram used in these patients for the prognosis is really worse in bilateral cryptorchid than ectopic patients, because the tubular damage is present in the former than in the latter. It does not mean, anyway, that direct correlation exists between age of the patient at the operation and fertility. METHODS: 171 patients operated on for cryptorchidism or testicular ectopia at the Pediatric Surgery Department of the Regional Hospital of Treviso during the years 1974-1983 under-went follow-up at the age of 18 years with clinical evaluation, hormonal dosage (testosterone and gonadotropin after stimulus as GnRH) and spermiogram. RESULTS AND CONCLUSIONS: The present study does not differ from many other studies about hormonal levels and spermiograms of cryptorchid patients; it underlines long term follow-up utility of patients operated on for cryptorchidism and stresses the need of an eventual psychological evaluation of these patients.

Adolescent↗

Smoking as a risk factor for end-stage renal failure in men with primary renal disease.

BACKGROUND: It is not known whether smoking increases the risk of end-stage renal failure (ESRF) in patients with primary renal disease. METHODS: We performed a retrospective multicenter case-control study including 582 patients from nine centers in Germany, Italy and Austria. The diseases investigated were IgA glomerulonephritis (IgA-GN) as a model of inflammatory renal disease and autosomal dominant polycystic kidney disease (ADPKD) as a model of non-inflammatory renal disease. Cases were patients who had progressed to ESRF and controls were patients who were not in ESRF, that is, whose serum-creatinine failed to progress to >3 mg/dl during the observation period and who did not require renal replacement therapy. Matching for renal disease (IgA-GN, ADPKD), gender, age at renal death and region of residence resulted in 102 individually matched pairs (IgA-GN N = 54, ADPKD N = 48). Multiple conditional logistic regression was used to estimate adjusted odds ratios for independent tobacco effects. RESULTS: In men (matched pairs: IgA-GN N = 44, ADPKD N = 28), a significant dose-dependent increase of the risk to progress to ESRF was found (non-adjusted). The baseline risk was defined as <5 pack-years (PY): (i) 5 to 15 PY, odds ratio 3.5 (95% CI 1.3 to 9.6), P = 0.017; (ii) >15 PY = 5.8 (2.0 to 17), P = 0.001. Systolic blood pressure, ACE inhibitor treatment and age at diagnosis emerged as potential confounders. After adjustment, the risk for ESRF in men with >5 PY was highly increased for patients without ACE inhibitor treatment [10.1 (2.3 to 45), P = 0.002] but not with ACE inhibitor treatment [1.4 (0.3 to 7.1), P = 0.65]. CONCLUSION: Smoking increases the risk of ESRF in men with inflammatory and non-inflammatory renal disease.

Adult↗

[Cachexia during dialysis].

In the Italian language, the term cachexia is a rather picturesque synonym of "marasma senile", "senile marasmus", an old definition involving not only old-age, but specifically senility, the end of the ageing process and marasmus, a stagnant and hopeless situation in which all superior organised functions have disappeared. The problem of cachexia during dialysis is complex and several discordant opinions exist at this regard, partly accounted by different definitions of this sluggish entity (or non entity). Actually, the basic question is very simple: is cachexia the cause or the effect of failure of dialysis treatment? The aim of this study was an evaluation of epidemiological data from the Dialysis and Transplantation Registry of Piedmont, a northern Italian Region with about 4,350,000 inhabitants, 22 public dialysis Centers, open acceptance to dialysis since the mid seventies, a multiple choice dialysis system developed in the eighties. In the period 1981-1995, 764 patients died in conditions of cachexia. This figure is 20.9% of all deaths recorded, 27.4% over age 65 and 34.7% over age 75. Despite a likewise significant increase in age and presence of comorbid factors, an improvement of patients survival, that reach statistical significance in the old age group (> or = 65 yrs), was observed.

Aged↗

Effect of oxidative stress by iron on 4-hydroxynonenal formation and proliferative activity in hepatomas of different degrees of differentiation.

It has been shown previously that oxidative stress by ferrous iron in vitro leads to an inhibition of proliferation of murine ascites tumour cells in vivo. This effect is associated with increased lipid peroxidation in terms of formation of the highly reactive aldehyde 4-hydroxynonenal (HNE), which has been shown to inhibit the proliferation of numerous tumours and to induce differentiation. It was the purpose of this article to study the occurrence and metabolism of HNE and its inducibility by oxidative stress in hepatomas of different degrees of differentiation to find further evidence for a possible role of HNE in proliferation and/or differentiation, because it is known that in hepatoma cells with a very low degree of differentiation basal lipid peroxidation is hardly detectable, while in normal hepatocytes the basal level of thiobarbituric acid reactive substances (TBArS) is rather high. MH1C1 hepatoma cells and Yoshida AH-130 hepatoma cells were chosen as highly differentiated and poorly differentiated tumour cells, respectively, and rat hepatocytes served as a control for normal liver phenotype. Ferrous histidinate (Fe/His) did not have a cytotoxic effect on Yoshida and MH1C1 cells, as measured by the LDH release test. In cell culture studies Fe/His revealed a dose dependent inhibition of the proliferation of Yoshida cells. The incorporation of 3H-thymidine into DNA of these cells was also inhibited by Fe/His in a dose-dependent manner, while the precursor uptake into the cytoplasm was unaffected. The basal levels of HNE were in the order: hepatocytes > MH1C1 cells > Yoshida cells. Both hepatocytes and Yoshida cells responded to the presence of Fe/His with increased formation of TBArS. Compared with hepatocytes the response of the Yoshida cells was greatly reduced. The response of cells to Fe/His with respect to HNE formation was decreased in the order: hepatocytes > MH1C1 cells > Yoshida cells, but in this case the differences were not very pronounced. The metabolic capacity of the cells to consume HNE was also decreased in the order: hepatocytes > MH1C1 cells > Yoshida cells. In this case the differences were very pronounced. These findings support the view that Yoshida cells with a low degree of differentiation and a low basal level of HNE are released from an inhibitory effect of HNE operative in hepatocytes and that HNE is causally involved in the iron induced inhibition of proliferation of poorly differentiated hepatoma cells.

Aldehydes↗

Nod factors of Azorhizobium caulinodans strain ORS571 can be glycosylated with an arabinosyl group, a fucosyl group, or both.

In addition to the previously described arabinosylated Nod factors, Azorhizobium caulinodans can also produce fucosylated Nod factors and Nod factors that are both arabinosylated and fucosylated. The presence of a plasmid carrying extra copies of a subset of nod genes as well as bacterial growth conditions influence the relative proportion of carbamoylated, fucosylated, and arabinosylated Nod factors. By using a root hair formation assay, we demonstrate that the Nod factor glycosylations are important for biological activity on Sesbania rostrata roots.

Arabinose↗

Sinorhizobium teranga bv. acaciae ORS1073 and Rhizobium sp. strain ORS1001, two distantly related Acacia-nodulating strains, produce similar Nod factors that are O carbamoylated, N methylated, and mainly sulfated.

We have determined the structures of Nod factors produced by strains representative of Sinorhizobium teranga bv. acaciae and the so-called cluster U from the Rhizobium loti branch, two genetically different symbionts of particular Acacia species. Compounds from both strains were found to be similar, i.e., mainly sulfated, O carbamoylated, and N methylated, indicating a close relationship between host specificity and Nod factor structure, regardless of the taxonomy of the bacterial symbiont.

Bacterial Proteins↗

Comparative evaluation of cytotoxicity and metabolism of four aldehydes in two hepatoma cell lines.

The metabolism of acetaldehyde (ACA), benzaldehyde (BA), propionaldehyde (PA) and valeraldehyde (VA) has been studied in two hepatoma cell lines, the rat HTC and mouse Hepa 1c1c7 cells. The cytotoxicity of the four aldehydes to these two cell lines has been compared. The end-points for evaluating cytotoxicity were 1) total macromolecular content (TMC) of confluent cultures, and 2) colony forming ability of dividing cells. These two assay systems had different sensitivities for the toxicity of aldehydes, probably due to different numbers of target cells. The activities of aldehyde dehydrogenases (NAD- and NADP-dependent, ALDH), alcohol dehydrogenase and aldehyde reductase were markedly greater in the HTC cell line compared to the Hepa 1c1c7 cell line, especially with BA as substrate. The cytotoxicities of aldehydes were generally stronger in the HTC cell line than in the Hepa 1c1c7 cell line; with the CF test. Particularly, BA was highly toxic to the HTC cells, which possessed the highest ALDH levels. Moreover, the treatment with (diethylamino)benzaldehyde, an ALDH inhibitor, completely abolished the toxicity of BA. Taken together, all these findings suggest that several cell lines expressing different aldehyde metabolizing activities could be used especially in the pre-screening phase to distinguish the metabolism-dependent cytotoxic effects from the metabolism independent effects.

Acetaldehyde↗

[The complement system in kidney diseases].

The multifaceted relations between complement system and immune-mediated nephropathies are reviewed. Several conditions in which either the complement activation induces renal damage without hypocomplementemia or hypocomplementemia occurs in the absence of circulating IC are reported as well as disorders in which immune complexes promote hypocomplementemia. The complement system is involved in the clearance of immune complexes, both modifying the immune complex size and favouring the physiologic neutralization by the erythrocyte transport system. In certain pathological conditions the immune complex intrinsic characteristic or genetic abnormalities prevent efficient removal from the blood stream. The purpose of the present review is to summarize these conditions, briefly describing their pathological consequences, and indicate a simple scheme to correctly interpret the biochemical abnormalities of the complement system in nephropathology.

Complement System Proteins↗

[Phimosis: when does it require surgical intervention?].

One of the most recurrent questions in pediatric age is the phimosis; this is a frequently underestimated problem and its resolution often cause a lot of discomforts in babies and parents. In many countries it has been treated on the roots of ancient sanitary measures (circumcision) whereas in others it's routinely treated with painful and useless maneuvers; instead, until three years of age this don't represents a problem but the normal situation of the baby. Herein the authors report the results of topic corticosteroid treatment of fimosis in 83 patients aged 1-14 years, with good outcome in 86.7% of cases. Therapy and results are discussed.

Administration, Topical↗