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Biomedical subjects

M Bianchi

Publications and source records attributed to M Bianchi.

At least 163 records · Page 9Linked to original sources
PubMed1995

Neurotoxicity of advanced glycation endproducts during focal stroke and neuroprotective effects of aminoguanidine.

Cerebral infarction (stroke) is a potentially disastrous complication of diabetes mellitus, principally because the extent of cortical loss is greater in diabetic patients than in nondiabetic patients. The etiology of this enhanced neurotoxicity is poorly understood. We hypothesized that advanced glycation endproducts (AGEs), which have previously been implicated in the development of other diabetic complications, might contribute to neurotoxicity and brain damage during ischemic stroke. Using a rat model of focal cerebral ischemia, we show that systemically administered AGE-modified bovine serum albumin (AGE-BSA) significantly increased cerebral infarct size. The neurotoxic effects of AGE-BSA administration were dose- and time-related and associated with a paradoxical increase in cerebral blood flow. Aminoguanidine, an inhibitor of AGE cross-linking, attenuated infarct volume in AGE-treated animals. We conclude that AGEs may contribute to the increased severity of stroke associated with diabetes and other conditions characterized by AGE accumulation.

Animals↗
PubMed1995

Hexokinase mutations that produce nonspherocytic hemolytic anemia.

Among glycolytic enzyme defects, hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1; HK) deficiency is a very rare disease where the predominant clinical effect is nonspherocytic hemolytic anemia. Here we report the characterization at molecular level of the HK type I cDNA from a patient with hemolytic anemia due to hexokinase deficiency. PCR amplification and sequence of the cDNA revealed the presence of a deletion and of a single nucleotide substitution, both in heterozygous form. In particular, the deletion, 96 bp long, concerns nucleotides 577 to 672 in the HK cDNA sequence and was never found in the cDNAs of 14 unrelated normal subjects. The sequence of the HK allele without deletion showed a single nucleotide substitution from T to C at position 1667 which causes the amino acid change from Leu529 to Ser. This heterozygous mutation at nt 1667 was confirmed by direct sequencing of the patient genomic DNA, but when DNAs from 10 normal controls were examined by this technique the substitution at nt 1667 was never found. From these results we concluded that the patient is carrying a point mutation at nt 1667 of one HK allele and a 96 nt deletion in the other allele. In normal subjects two differences from the published cDNA sequence were documented.

Alleles↗
PubMed1995

Effects of chlomipramine and fluoxetine on subcutaneous carrageenin-induced inflammation in the rat.

We have previously shown that, after acute administration, antidepressant drugs exert anti-inflammatory actions in rats. In this study we evaluated the effects of 3 different doses of chlomipramine (10, 20, and 40 mg/kg i.p), and fluoxetine (5.0, 10, and 20 mg/kg i.p.) on subcutaneous carrageenin-induced inflammation. Both drugs dose-dependently reduced the inflammatory exudate, as well as the PGE2-like bio- and immunoactivity in the exudate. Chlomipramine dose-dependently reduced substance P concentrations in the exudate, whereas fluoxetine was effective only at the highest dose. Our results confirm that antidepressant drugs are able to reduce the development of inflammation in the rat and suggest that the inhibition of substance P production might play a role in mediating the anti-inflammatory effects of chlomipramine.

Animals↗
PubMed1995

CRH and the noradrenergic system mediate the antinociceptive effect of central interleukin-1 alpha in the rat.

After intracerebroventricular administration, both interleukin-1 alpha and corticotropin-releasing hormone increase nociceptive thresholds evaluated by the hot-plate test in the rat. Pretreatment with 6-hydroxydopamine or prazosin fully prevents the action of both substances. Moreover, the effect of interleukin-1 alpha is completely blocked by the intracerebroventricular administration of the corticotropin-releasing hormone antagonist alpha-helical CRH 9-41. Our results suggest an involvement of CRH and the noradrenergic system in the antinociceptive effect of central interleukin-1 alpha.

Animals↗
PubMed1995

Evaluation of maximal left ventricular performance in elite bicyclists.

Aim of this work was to study in a group of elite cyclists, undergoing laboratory testing, the trend of the left ventricular systolic and diastolic function, echocardiographically and Doppler derived, simultaneously with the evaluation of ergospirometric parameters during maximal exercise. We studied a group of male subjects, consisting of 10 professional elite bicyclists (mean age: 25.1 +/- 3.2 years) during competitive activity (VO2/kg max: 78.5 +/- 7.7 ml.kg.min-1). The maximal exercise test, conducted with Wind Loaded Simulator for optimisation of ergometric capacity, showed, at the end of exercise, at a speed of 49.2 +/- 2.4 km/h, a VO2max of 5365 +/- 543.4 ml/min, with a calculated Cardiac Output (CO) of 19.3 +/- 3.7 l/min. A linear regression relationship was found between VO2max and CO (r = 0.84; p < 0.0001) as well as between VO2max and maximal reached speed (r = 0.97; p < 0.0001). During the aerobic period a slight but significant increase in End Diastolic Volume (EDV) was observed due to the greater venous return from exercising muscles. At stop, in anaerobic period, the EDV remained substantially constant. Ejection Fraction (EF) also increased during exercise through the Frank-Starling mechanism activation. The slight, but not significant, increase in EF at stop level may be explained by an activation of homeometric control of contractility with a sympathetic modulation on myocardial fibres. The early diastolic mitral flow velocity (Peak E) increased significantly during exercise, in comparison with basal upright values. The left ventricular diastolic compliance observed in athletes permits a good left ventricular filling, particularly in early diastolic phase; this allows an excellent left ventricular systolic performance. Based on echocardiography and pulsed Doppler measurements, calculated cardiac output is underestimated by approximately 20%.

Adult↗
PubMed1995

[Treatment of metastatic osteosarcoma with verapamil, cyclosporine and chemotherapy. A case report].

Studies on the use of revertants to overcome MDR have aroused a great interest even if they failed to prove their actual usefulness. A case of 10 years and 6 months old boy is described. He suffered from osteoblastic osteosarcoma and underwent chemotherapy following CNR-NEO3 protocol, wide surgical resection and postoperative chemotherapy. Nineteen months after diagnosis he underwent the removal of a little subpleural nodule in the right lung. Forty-five days later, in the same site, a large local metastasis was observed together with many others secondaries localizations spred in both lungs. Because of the rapid evolution they were considered not suitable for surgical treatment. A cyclosporine and verapamil treatment in association with adryamicin and etoposide was begun with the aim overcoming multidrug resistance. Five treatments were provided. ECG monitoring during verapamil infusion did not show any trouble; mielotoxicity was mild, with no need of transfusions. A lung CT scan at the end of the therapy demonstrated an important decrease of the subpleural metastasis and the vanishing of lung nodules. Another surgical intervention was provided together with 2 postoperative chemotherapy treatments. Twenty-six months later no sign of the disease was observed. Association of verapamil and cyclosporine with chemotherapy allowed to get a good clinical response with a very low toxicity, in a critical situation in which chemotherapy alone did not seem to offer any real possibility.

Bone Neoplasms↗
PubMed1995

[Endoscopic surgery in ectopic pregnancy. Analysis of 105 cases].

A report on 105 cases of ectopic pregnancy resolved via endoscopy is presented. Surgical techniques for total salpingectomy (82), salpingotomy (11), tubal expression (6), partial salpingectomy (3), partial ooforectomy (2) and anexectomy (1) is described. The excellent postsurgical recovery and low incidence of complications are depicted, as well as the growing percentage of ectopic pregnancies resolved endoscopically in our Department.

Adult↗
PubMed1995

[Danazol and its effect on bone and lipid metabolism in patients with endometriosis].

Danazol is a synthetic steroid, derived from 17-alpha ethinyltestosterone and it is used primarily in the treatment of endometriosis. It effectiveness is due to a reversible hypoestrogenic and hyperandrogenic state, which lead to atrophy of the ectopic endometrial tissue. A prospective study was undertaken in 14 women of child-bearing age with laparoscopically confirmed pelvic endometriosis to evaluate the alterations produced in bone and lipid metabolism after a six month treatment with Danazol. Laboratory evaluation included: bone mineral density, urine hydroxiproline/creatinine and calcium/creatinine ratios, lipid profile, bone isoenzyme of alkaline phosphatases and plasma estradiol. A significant decrease in plasma estradiol levels was observed (p < 0.001). Decrease in HDL cholesterol and increase in LDL cholesterol levels were statistically significant after 3 and 6 months of medication (p < 0.001), but the lipoproteins returned to normal levels three months after discontinuing Danazol. The bone isoenzyme of alkaline phosphatases showed a progressive increase (p < 0.001) and there were no significant variations in the hydroxyproline/creatinine and calcium/creatinine ratios. The osteodensitometry remained unchanged at 6 months of therapy. We conclude that, even though Danazol produces hypoestrogenism and hyperandrogenism, the markers of bone loss did not change, it has no negative effect on bone mineral density, and the transient worsening of the lipid profile that it causes is reversible on discontinuation of medication.

Adolescent↗
PubMed1995

An inhibitor of macrophage arginine transport and nitric oxide production (CNI-1493) prevents acute inflammation and endotoxin lethality.

BACKGROUND: Nitric oxide (NO), a small effector molecule produced enzymatically from L-arginine by nitric oxide synthase (NOS), is a mediator not only of important homeostatic mechanisms (e.g., blood vessel tone and tissue perfusion), but also of key aspects of local and systemic inflammatory responses. Previous efforts to develop inhibitors of NOS to protect against NO-mediated tissue damage in endotoxin shock have been unsuccessful, largely because such competitive NOS antagonists interfere with critical vasoregulatory NO production in blood vessels and decrease survival in endotoxemic animals. Accordingly, we sought to develop a pharmaceutical approach to selectively inhibit NO production in macrophages while sparing NO responses in blood vessels. MATERIALS AND METHODS: The process of cytokine-inducible L-arginine transport and NO production were studied in the murine macrophage-like cell line (RAW 264.7). A series of multivalent guanylhydrazones were synthesized to inhibit cytokine-inducible L-arginine transport. One such compound (CNI-1493) was studied further in animal models of endothelial-derived relaxing factor (EDRF) activity, carrageenan inflammation, and lethal lipopolysaccharide (LPS) challenge. RESULTS: Upon activation with cytokines, macrophages increase transport of L-arginine to support the production of NO by NOS. Since endothelial cells do not require this additional arginine transport to produce NO, we reasoned that a competitive inhibitor of cytokine-inducible L-arginine transport would not inhibit EDRF activity in blood vessels, and thus might be effectively employed against endotoxic shock. CNI-1493, a tetravalent guanylhydrazone, proved to be a selective inhibitor of cytokine-inducible arginine transport and NO production, but did not inhibit EDRF activity. In mice, CNI-1493 prevented the development of carrageenan-induced footpad inflammation, and conferred protection against lethal LPS challenge. CONCLUSIONS: A selective inhibitor of cytokine-inducible L-arginine transport that does not inhibit vascular EDRF responses is effective against endotoxin lethality and significantly reduces inflammatory responses.

Animals↗
PubMed1995

Pre-B acute lymphoblastic leukemia in a patient with partial lipodystrophy and acanthosis nigricans.

In patients with lipodystrophies a post binding defect in insulin action has been described involving phosphorylation of the beta subunit of the insulin receptor, suggesting the presence of a genetically determined defect in insulin action; the receptor gene has been mapped to the distal short arm of chromosome 19 close to the break-point of a specific chromosome translocation frequently found in pre-B Acute Lymphoblastic Leukemia (ALL). We report on a 13 years old female patient with partial lipodystrophy, acanthosis nigricans and insulin resistance who developed a pre-B ALL. Since lipodystrophy and pre-B ALL are rare disorders, a possible causal relationship between the two diseases is suggested possibly mediated by a mutation in the insulin receptor gene.

Acanthosis Nigricans↗
PubMed1994

Fluoxetine reduces inflammatory edema in the rat: involvement of the pituitary-adrenal axis.

The acute effect of the non-tricyclic, pro-serotoninergic, antidepressant drug fluoxetine on inflammatory edema was evaluated in the rat. Fluoxetine significantly and dose dependently reduced the swelling induced by the injection of 10% brewer's yeast suspension in the hindpaw. Both adrenalectomy and hypophysectomy prevented the effect of fluoxetine. In contrast pretreatment with the corticotropin-releasing hormone antagonist alpha-helical CRH-(9-41) did not interfere with the anti-inflammatory action of fluoxetine. Moreover, the drug induced a significant increase of corticosterone plasma concentrations in vivo, whereas, in vitro, it did not stimulate beta-endorphin release from anterior pituitary cells. Our data suggest that fluoxetine exerts a potent anti-inflammatory action by inducing pituitary-adrenocortical activation via serotonin.

Adrenalectomy↗
PubMed1994

Mutational analysis of the DNA binding domain A of chromosomal protein HMG1.

We have mutated several residues of the first of the two HMG-boxes of mammalian HMG1. Some mutants cannot be produced in Escherichia coli, suggesting that the peptide fold is grossly disrupted. A few others can be produced efficiently and have normal DNA binding affinity and specificity; however, they are more sensitive towards heating and chaotropic agents than the wild type polypeptide. Significantly, the mutation of the single most conserved residue in the rather diverged HMG-box family falls in this 'in vitro temperature-sensitive' category, rather than in the non-folded category. Finally, two other mutants have reduced DNA binding affinity but unchanged binding specificity. Overall, it appears that whenever the HMG-box can fold, it will interact specifically with kinked DNA.

Amino Acid Sequence↗
PubMed1994

Functional differences between the two splice variants of the nucleolar transcription factor UBF: the second HMG box determines specificity of DNA binding and transcriptional activity.

The nucleolar transcription factor UBF consists of two proteins, UBF1 and UBF2, which originate by alternative splicing. Here we show that deletion of 37 amino acids within the second of five HMG box motifs in UBF2 is important for the dual role of UBF as transcriptional activator and antirepressor. UBF1 is a potent antirepressor and transcriptional activator, whereas the ability of UBF2 to counteract histone H1-mediated repression and to stimulate ribosomal gene transcription both in vivo and in vitro is at least one order of magnitude lower. The difference in transcriptional activity between UBF1 and UBF2 is due to their different binding to the ribosomal gene promoter and enhancer. Apparently, the presence of an intact HMG box2 modulates the sequence-specific binding of UBF to rDNA control elements. However, the interaction of UBF with rDNA does not entirely depend on sequence recognition. Both UBF isoforms bind efficiently to four-way junction DNA, indicating that they recognize defined DNA structures rather than specific sequences. The results demonstrate that the HMG boxes are functionally diverse and that HMG box2 plays an important role in specific binding of UBF to rDNA.

3T3 Cells↗
PubMed1994

Intermittent but not continuous inescapable footshock stress affects immune responses and immunocyte beta-endorphin concentrations in the rat.

It is well known that a variety of stressors influence immune responses. The opioid peptide-beta-endorphin (BE) is deeply involved in stress responses, is synthesized in cells of the immune system, and participates in the modulation of immune function. We analyzed the ability of two different stress paradigms to modulate the beta-endorphin concentrations in the immune cells and the immune response in the rat. Two and 24 h after the exposure to inescapable intermittent footshock (1.6 mA, 60 Hz, 1 s, every 5 s for 20 min) the concentrations of beta-endorphin in splenocytes, peripheral blood mononuclear cells and lymph node cells were significantly increased. In contrast, the exposure to a continuous footshock for 3 min did not affect the concentrations of the opioid peptide. Similarly, phytohemoagglutinin-induced proliferation of splenocytes and natural killer activity were significantly impaired only after the exposure to intermittent footshock stress. On the contrary, plasma corticosterone levels were similarly elevated after both paradigms of stress. The pretreatment with the corticotropin-releasing hormone (CRH) receptor antagonist prevented both the stress-induced increase of immunocyte BE and immunosuppression. In conclusion, our data suggest that intermittent and continuous footshock stressors activate different neuroendocrine responses and that CRH plays a central role in mediating the immune effects of the intermittent footshock stress. The possible relationship between the beta-endorphin changes and immunosuppression is discussed.

Acute Disease↗
PubMed1994

Chlomipramine differently affects inflammatory edema and pain in the rat.

In the rat, the acute administration of the antidepressant drug chlomipramine significantly reduces the edema and the hyperalgesia induced by yeast injection in the paw. However, the intensity and time course of the two effects differ. Moreover, adrenalectomy enhances the antinociceptive effect, whereas it does not affect the antiedema action of chlomipramine. Our data suggest a dissociation between the antiinflammatory and the analgesic effect of acute chlomipramine.

Adrenalectomy↗
PubMed1994

Localization and age-dependent expression of hexokinase mRNA in the rat brain.

Localization of mRNA encoding for the enzyme hexokinase and its regulation in aged animals was carried out in rat brain using the in situ hybridization technique. The highest levels of the hybridization signal were observed in the olfactory bulb, piriform cortex, tenia tecta, hippocampus and granular cells of the cerebellum. Other brain areas and nuclei including cerebral cortex, thalamus, hypothalamus, substantia nigra, subiculum, choroid plexus and superior colliculus displayed moderate to low density of transcripts. Correlation between relative hexokinase content and levels of its mRNA was found only for some brain regions such as caudate-putamen, geniculate nucleus, ventral and lateral thalamic nuclei, superior colliculus and granular cells of the cerebellum. In the cerebral cortex and hippocampus of old animals the expression of hexokinase was significantly increased at 18 and 24 months of age. From the present data we conclude that although hexokinase is an ubiquitous enzyme, sites of synthesis display a discrete and uneven localization in rat CNS and expression, in the aging brain, might be regulated to compensate for reduced oxidative phosphorylation in the brain tissue.

Aging↗
PubMed1994

Chlorimipramine and nortriptyline but not fluoxetine and fluvoxamine inhibit human polymorphonuclear cell chemotaxis in vitro.

We examined the ability of antidepressant drugs belonging to different classes to interfere with human polymorphonuclear cell migration in vitro. 1. The tricyclic antidepressant drugs chlorimipramine and nortriptyline were able to block, in a dose related fashion both spontaneous and formyl-methionyl-leucyl-phenylalanine stimulated migration. This effect was already evident at very low concentrations (10(-7)M). 2. The atypical non-tricyclic antidepressant drugs fluoxetine and fluvoxamine did not affect polymorphonuclear cell mobility. 3. The ability of antidepressant drugs to interfere with polymorphonuclear cell physiology seems to depend on their chemical structures.

Antidepressive Agents↗