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Biomedical subjects

M Bianchi

Publications and source records attributed to M Bianchi.

At least 145 records · Page 8Linked to original sources
PubMed1997

[Treatment of sudden hearing loss].

A total of 27 patients affected by sudden idiopathic deafness (SID) and 3 with sudden idiopathic anacousia (SIA) were treated within 10 days of onset of the disorder. The treatment consisted of intramuscular or per os administration of corticosteriods for 10 days and the simultaneous administration of carbogene for 5 days. At the 5th day of corticosonic treatment, if audiometry did not reveal complete recovery, the treatment was associated for 7 days with Destrane 500 ml. The cases included neurosensorial deafness of 30 dB or more over at least 3 adjacent frequencies and arising over a 12 hour period. Soft cord deafness was not included in the study. The following variables were analyzed: 1) patient age; 2) extent of the hearing loss: average tone threshold for the frequencies of 500 -1000-2000 Hz equal to or better than 70 dB HL (group A); tone threshold ranging between 71 and 89 dB HL (group B), tone threshold ranging from 90 to 110 dB HL (group C), anacousia (group D); 3) audiometric curve; 4) presence or lack of vertigo. After treatment 25 subjects (83%) indicated a recovery ranging from good to complete. It is significant that among this 83% there were 12 subjects, 9 with profound deafness and 3 with anacousia. The therapeutic association adopted made it possible to achieve two-fold activity: anti-edemagene and hemorheological. The most highly implicated etiology for SID was viral causing not only neural but also endothelial damage and leading to acute microcirculatory insufficiency.

Adolescent↗
PubMed1996

Peripherally administered GM-CSF interferes with scopolamine-induced amnesia in mice: involvement of interleukin-1.

We studied the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on the classical behavioral test of scopolamine-induced amnesia for a passive avoidance response in the mouse. Pre-training intraperitoneal administration of this cytokine (1.25, 2.5, 5.0 or 10 micrograms/mouse) partially, although significantly, reduced the amnesic action of the muscarinic receptor antagonist. The peripheral administration of a specific interleukin-1 receptor antagonist (IL-1 ra, 50 micrograms/mouse i.p.) blocked the effect of GM-CSF. Our results suggest that GM-CSF is able to exert neuromodulatory actions and that it is involved (probably via IL-1) in the interactions between the immune system and the central nervous system.

Amnesia↗
PubMed1996

Involvement of beta-endorphin in the modulation of paw inflammatory edema in the rat.

This study investigates the role of the opiod receptors and of the opioid peptide beta-endorphin in the development of yeast-induced inflammation in the rat paw. Pretreatment with the opioid receptor antagonist naltrexone (10 mg/kg i.p.) exacerbates the paw edema, while morphine pretreatment (5 and 10 mg/kg) reduces it. In addition, the intravenous injection of a specific anti-beta-endorphin antibody aggravates the yeast-induced inflammation. On the contrary, both the kappa-opioid receptor antagonist MR 1452 (2.5, 5 and 10 mg/kg i.p.) and the delta-opioid receptor antagonist ICI 174-864 (2.5, 5 and 10 mg/kg i.p.) do not interfere with the inflammatory process. After intraplantar injection, naltrexone, morphine and the anti-beta-endorphin antibody do not interfere with the yeast-induced inflammatory edema. Our data suggest that beta-endorphin exerts an inhibitory regulation on the inflammatory responses through the activation of mu-opioid receptors probably located on immune cells, rather than in the paw.

Animals↗
PubMed1996

CNI-1493 inhibits monocyte/macrophage tumor necrosis factor by suppression of translation efficiency.

Tumor necrosis factor (TNF) mediates a wide variety of disease states including septic shock, acute and chronic inflammation, and cachexia. Recently, a multivalent guanylhydrazone (CNI-1493) developed as an inhibitor of macrophage activation was shown to suppress TNF production and protect against tissue inflammation and endotoxin lethality [Bianchi, M., Ulrich, P., Bloom, O., Meistrell, M., Zimmerman, G. A., Schmidtmayerova, H., Bukrinsky, M., Donnelley, T., Bucala, R., Sherry, B., Manogue, K. R., Tortolani, A. J., Cerami, A. & Tracey, K. J. (1995) Mol. Med. 1, 254-266, and Bianchi, M., Bloom, O., Raabe, T., Cohen, P. S., Chesney, J., Sherry, B., Schmidtmayerova, H., Zhang, X., Bukrinsky, M., Ulrich, P., Cerami, A. & Tracey, J. (1996) J. Exp. Med., in press]. We have now elucidated the mechanism by which CNI-1493 inhibits macrophage TNF synthesis and show here that it acts through suppression of TNF translation efficiency. CNI-1493 blocked neither the lipopolysaccharide (LPS)-induced increases in the expression of TNF mRNA nor the translocation of nuclear factor NF-kappa B to the nucleus in macrophages activated by 15 min of LPS stimulation, indicating that CNI-1493 does not interfere with early NF-kappa B-mediated transcriptional regulation of TNF. However, synthesis of the 26-kDa membrane form of TNF was effectively blocked by CNI-1493. Further evidence for the translational suppression of TNF is given by experiments using chloram-phenicol acetyltransferase (CAT) constructs containing elements of the TNF gene that are involved in TNF translational regulation. Both the 5' and 3' untranslated regions of the TNF gene were required to elicit maximal translational suppression by CNI-1493. Identification of the molecular target through which CNI-1493 inhibits TNF translation should provide insight into the regulation of macrophage activation and mechanisms of inflammation.

Base Sequence↗
PubMed1996

Suppression of proinflammatory cytokines in monocytes by a tetravalent guanylhydrazone.

An overproduction of proinflammatory cytokines by activated macrophages/monocytes mediates the injurious sequelae of inflammation, septic shock, tissue injury, and cachexia. We recently synthesized a tetravalent guanylhydrazone compound (CNI-1493) that inhibits cytokine-inducible arginine transport and nitric oxide (NO) production in macrophages, and protects mice against lethal endotoxemia and carrageenan-induced inflammation. During these investigations we noticed that CNI-1493 effectively prevented lipopolysaccharide (LPS)-induced NO production, even when added in concentrations 10-fold less than required to competitively inhibit L-arginine uptake, suggesting that the suppressive effects of this guanylhydrazone compound might extend to other LPS-induced responses. Here, we report that CNI-1493 suppressed the LPS-stimulated production of proinflammatory cytokines (tumor necrosis factor [TNF], interleukins 1beta and 6, macrophage inflammatory proteins 1alpha and 1beta) from human peripheral blood mononuclear cells. Cytokine suppression was specific, in that CNI-1493 did not inhibit either the constitutive synthesis of transforming growth factor beta or the upregulation of major histocompatibility complex class II by interferon gamma (IFN-gamma). In contrast to the macrophage suppressive actions of dexamethasone, which are overridden in the presence of IFN-gamma, CNI-1493 retained its suppressive effects even in the presence of IFN-gamma. The mechanism of cytokine-suppressive action by CNI-1493 was independent of extracellular L-arginine content and NO production and is not restricted to induction by LPS. As a selective inhibitor of macrophage activation that prevents TNF production, this tetravalent guanylhydrazone could be useful in the development of cytokine-suppressive agents for the treatment of diseases mediated by overproduction of cytokines.

Animals↗
PubMed1996

High-performance liquid chromatographic method for guanylhydrazone compounds.

A high-performance liquid chromatographic method has been developed for a series of aromatic guanylhydrazones that have demonstrated therapeutic potential as anti-inflammatory agents. The compounds were separated using octadecyl or diisopropyloctyl reversed-phase columns, with an acetonitrile gradient in water containing heptane sulfonate, tetramethylammonium chloride, and phosphoric acid. The method was used to reliably quantify levels of analyte as low as 785 ng/ml, and the detector response was linear to at least 50 micrograms/ml using a 100 microliters injection volume. The assay system was used to determine the basic pharmacokinetics of a lead compound, CNI-1493, from serum concentrations following a single intravenous injection in rats.

Animals↗
PubMed1996

High-level expression and purification of a human "mini"-hexokinase.

Human hexokinase type I is a 100-kDa enzyme with the catalytic site located in the C-terminal domain. We had previously expressed this domain in Escherichia coli, however only a small amount of the recombinant enzyme was catalytically active. To overcome this problem we have now expressed the "mini"-hexokinase using the pET expression system. An average of 1000 U of enzyme per liter of culture was obtained. The recombinant enzyme was purified to homogeneity by a combination of ion-exchange chromatography, affinity chromatography, and dye-ligand chromatography. The enzyme was unstable under ultrafiltration; thus, a multicolumn purification procedure was developed in order to avoid the ultrafiltration steps. The recombinant "mini"-hexokinase was found to have the same kinetic properties as the entire enzyme. Using the method described, the enzyme can be obtained in sufficient quantities for biophysical and biochemical investigations.

Blotting, Western↗
PubMed1996

Peripheral mononeuropathy affects hypothalamic and splenocyte beta-endorphin levels but not immune function in the rat.

Beta-endorphin and substance P levels were measured in the hypothalamus of rats 14 days after chronic constriction injury of right sciatic nerve. Furthermore, beta-endorphin concentrations in splenocytes, phytoemoagglutinin-induced proliferation of splenocytes, and natural killer activity were assessed. We observed a significant increase of beta-endorphin and substance P hypothalamic levels, and a significant decrease of beta-endorphin concentrations in the immune cells. In contrast, the peripheral mononeuropathy did not affect the immune function. This study presents a picture of central and peripheral peptide changes consistent with a painful condition, but different from what previously observed in rats which underwent peripheral nerve deafferentation or stressful conditions.

Animals↗
PubMed1996

Correlation of various Crohn's disease activity indexes in subgroups of patients with primarily inflammatory or fibrostenosing clinical characteristics.

Several activity indexes, including clinical variables, laboratory variables or both, have been proposed to assess the activity and severity of Crohn's disease (CD). Although activity indexes are commonly used in clinical trials, doubts exist as to whether it is correct to group together and quantify under the same numerical expression the very heterogeneous clinical manifestations of CD. The aim of our study was to try to establish a correlation between clinical and laboratory activity indexes of CD in subgroups of patients with primarily inflammatory or primarily fibrostenosing clinical characteristics. At least two activity indexes were calculated among 232 outpatient examinations in 61 CD patients. Indexes were classified as clinical, laboratory, or both. A close correlation was observed when indexes calculated on clinical variables were compared or when those that include only or prevalently laboratory parameters were compared. Conversely, the correlation between clinical and laboratory indexes tended to be poor. Taking into consideration the subgroups of patients, the correlation between clinical and laboratory indexes was high in primarily inflammatory disease but low in the primarily fibrostenosing form. The clinical activity of CD does not always reflect the quantity of inflammation measured by laboratory parameters. This is particularly true in primarily fibrostenosing disease. Different clinical patterns of CD should always be considered in the attempt to quantify with an activity index the activity and severity of disease.

Adult↗
PubMed1996

Left ventricular function during exercise in athletes and in sedentary men.

Aim of this study was to evaluate left ventricular function during exercise in 10 male elite runners and in 10 sedentary males. End-diastolic (EDV) and end-systolic volume (ESV), left ventricular ejection fraction (EF), early peak transmitral flow velocity (peak E), time-velocity integral of mitral inflow (m-TVI); mitral cross sectional area (m-CSA); mitral stroke volume (SV), and cardiac output (CO) were measured by echo-Doppler. We simultaneously analyzed: VO2max by spirometric method, mean arterial blood pressure (MAP) by sphygmomanometer, and heart rate (HR) by ECG. The parameters were measured under basal conditions (level 1), at 50% of maximal aerobic capacity (level 2), at peak of exercise (level 3) and during recovery. Ejection fraction in athletes increased significantly at peak of exercise through Frank-Starling mechanism. Stroke volume and cardiac output increased significantly in athletes at peak of exercise. Left ventricular diastolic function was superior in athletes versus controls: in fact, higher peak E in athletes enhanced early diastolic ventricular filling. Therefore, the athletes showed complex cardiovascular adjustments induced by training, which allowed an higher peak working power, a greater cardiac output, and VO2max when compared with an untrained control population.

Adult↗
PubMed1996

The dose-related effects of paracetamol on hyperalgesia and nociception in the rat.

1. We have studied the effects of 3 low doses of paracetamol (25, 50 and 100 mg kg-1 p.o.) on inflammatory hyperalgesia, inflammatory oedema, and nociceptive thresholds in rats. 2. At the lower dose (25 mg kg-1), paracetamol reduces only central hyperalgesia. 3. At the doses of 50 and 100 mg kg-1, paracetamol reduces also peripheral hyperalgesia; moreover, it enhances nociceptive thresholds to a mechanical stimulus in the non-inflamed paws. 4. Neither paw inflammatory oedema nor tail nociceptive thresholds to a thermal stimulus were modified by paracetamol administration. 5. Our results suggest that paracetamol can reduce hyperalgesia without affecting physiological nociception and inflammation.

Acetaminophen↗
PubMed1996

RU 486 reduces morphine-induced analgesia in mice, but steroid receptors are not involved.

The effects of subcutaneous pretreatment with the glucocorticoid/progesterone receptor antagonist RU 486 on the antinociceptive action of peripherally administered morphine were evaluated by the hot-plate test in mice. The steroid significantly reduced the analgesic effect of the opiate. Neither dexamethasone nor progesterone modified the effects of RU 486 on morphine-induced analgesia. Therefore, the present data indicate that the modulatory effect of RU 486 on morphine-induced analgesia does not involve the binding of this drug to classical steroid receptors.

Analgesia↗
PubMed1996

[Obstructive azoospermia and malformations of seminal tract].

About 10% of the cases of male infertility is represented by the obstruction of the seminal tract, which may be congenital or secondary to inflammatory events or surgery. The most frequent obstructive malformation of the seminal tract is the bilateral agenesia of the vas deferens. Such malformation is typical of the cystic fibrosis (CF), an autosomal recessive disorder determining chronic respiratory infections with bronchiectasia, and pancreatic failure. Recently the defective gene responsible for CF has been identified on the long arm of the chromosome 7. Congenital bilateral absence of the vas deferens (CBAVD) may be present in otherwise healthy males without clinical evidence of CF. Genetics studies demonstrated that most CBAVD display at least one detectable CF mutation, therefore this disease can be considered as an incomplete clinical form of CF. With the realization that a man with CBAVD may have CF, albeit a genital form, considerable care is required not only to document his specific mutations, but also to test his partner for CF mutations to evaluate the risk that their child would have CF. The association of chronic suppurating respiratory disease with obstructive azoospermia characterizes also the Young's syndrome. In this disease the obstruction could possibly be the result of defective epididymal sperm transport, related to an abnormality in the mucus. Despite some clinical common aspects, CF and Young's syndrome are two distinct entity. In fact, no CF mutations have been demonstrated in Young's syndrome. Congenital obstructive abnormalities of the vas deferens and epididymis are often associate to cryptorchidism (36-68% of the cases) and to patent processus vaginalis. The degree of testicular retention and processus vaginalis closure correlates well with the incidence of associated epididymal defects. Rare causes of congenital obstructive azoospermia are represent by the cyst of Müllerian or Wolffian origin. An obstruction to the progression of the sperm along the seminal tract can also be present in complex malformations, such as pseudohermaphroditism in which the infertility has a multifactorial etiology.

Cryptorchidism↗
PubMed1996

[Carcinoids in emergency surgery].

The authors report their experience of three cases of carcinoids of the gastroenteric tract which required emergency surgery. Two patients presented symptoms of acute appendicitis caused by appendicular carcinoid, whereas the third presented an occlusive syndrome due to ileal carcinoid.

Aged↗
PubMed1996

[Cholangiojejunostomy of the duct of the 3d segment. Palliative treatment of cholestatic jaundice caused by neoplastic obstruction of the hepatic hilus].

Cholangiojejunostomy of the duct of the III segment in the palliative treatment of mechanical jaundice from neoplastic obstruction of the hepatic hilus. The neoplastic obstruction of the liver hilus has an almost total absence of forewarning clinical signs and therefore results in surgery at a late stage when the patient is not susceptible to radical treatment. It is therefore necessary to use palliative treatment in order to resolve the serious jaundice, the main cause of a quick death. Among the palliative treatment the Authors report their experience of intrahepatic cholangiojejunostomy of the duct of the III segment that they consider the most suitable technique for its ease of execution, its constant anatomical situation and the peripheral position of the anastomoses in relation to the neoplastic lesion. This allows a lasting biliary decompression with a good residual life.

Anastomosis, Surgical↗
PubMed1995

Carbamazepine exerts anti-inflammatory effects in the rat.

In a first set of experiments, we evaluated the effects of different doses (5.0, 10, 20 and 40 mg/kg p.o.) of carbamazepine on nociceptive thresholds to thermal and mechanical stimuli, and on paw inflammatory hyperalgesia induced by the injection of brewer's yeast. Moreover, we studied the effect of carbamazepine on paw inflammatory edema by plethysmometry. Carbamazepine did not modify nociceptive latencies, but dose dependently reduced the hyperalgesia and the edema induced by the brewer's yeast injection in the rat hindpaw. In a second set of experiments, we studied the effects induced by the same doses of the drug on subcutaneous carrageenin-induced inflammation. Carbamazepine dose dependently reduced the inflammatory exudate, the prostaglandin E2-like activity in the exudate, and the substance P concentrations in the exudate. Our results demonstrate that carbamazepine is able to inhibit the development of different types of inflammation in the rat.

Animals↗
PubMed1995

Effects of interleukin-1 beta and interleukin-2 on amino acids levels in mouse cortex and hippocampus.

We measured the levels of glutamine, aspartic acid, glutamic acid and GABA in cortex and hippocampus of mice acutely treated with i.p. human recombinant interleukin-2 (IL-2) or human recombinant interleukin-1 beta (IL-1 beta). Administration of IL-2 (5.0 micrograms kg-1) induced a slight but statistically significant increase in glutamine concentrations in both brain areas, while similar administration of IL-1 beta (20 micrograms kg-1) significantly reduced the hippocampal levels of glutamine, glutamic acid and GABA. Our data suggest that brain amino acid pathways are involved in the central modifications induced by IL-1 beta.

Amino Acids↗