Search PubMed⌕ Search

Biomedical subjects

M Altamura

Publications and source records attributed to M Altamura.

At least 19 recordsLinked to original sources
PubMed2004

Maturation of fish erythrocytes coincides with changes in their morphology, enhanced ability to interact with Candida albicans and release of cytokine-like factors active upon autologous macrophages.

Erythrocytes from the rainbow trout Salmo gairdneri Richardson (Salmo g.R.) were classified into immature and mature populations, respectively, by measuring longitudinal diameters. More elongated fish erythrocytes (FE), classified as mature cells, were those interacting with Candida albicans (CA) in a higher frequency in terms of either binding to the fungus or its intracellular engulfment. At the same time, in the rosetting phenomenon more elongated mature FE surrounded macrophages (Mø) phagocytosing CA. Finally, FE activated by CA released in the supernatants cytokine-like factors able to modulate Mø functions. In particular, these active supernatants were analyzed for their capacity to inhibit Mø migration Macrophage Inhibition Factor (MIF) activity and enhance Mø phagocytosis. Both activities were detected in supernatants from CA stimulated FE but not in control supernatants. MIF activity could play a role in the accumulation of Mø in the context of functional rosettes, while the factor enhancing Mø phagocytosis could promote clearance of CA in a more efficacious way.

Animals↗
PubMed2003

Allergic and pseudoallergic reactions induced by glucocorticoids: a review.

Glucocorticoids (GCs) represent the most effective treatment for autoimmune and allergic diseases, even if collateral effects are not rare, especially endocrine and immunosuppressive manifestations. Moreover, these drugs can develop adverse immunological reactions of I, III or IV type. Though immediate adverse reactions caused by systemic therapy with GCs are not very frequent, the possible beginning of anaphylactic and pseudo-anaphylactic manifestations in patients undergoing therapy with these drugs has to be considered. It has been observed that immediate adverse reactions usually are happened in asthmatic patients and in patients obliged to assume GCs again and again because of their pathology (e.g, kidney transplant). Other risk factors resulted to be female sex and hypersensibility to acetylsalicylic acid (ASA). Both in the cases of pseudo-allergic and allergic reactions, the pharmacological principle is hardly the responsible agent for the reaction; instead the excipients in drugs are often implicated (succinate salt, sulphites and carboxy-methyl-cellulose). It is possible that the IgE-response is highly specific for a fixed GC molecule as well depending on the way of administration and its salification. Moreover, it has been hypothesized that in patients with a first type allergic reaction to GCs there is a fourth type, sensitization to GCs, which is not usually diagnosed and even comes before IgE sensitization. Third type hypersensibility reactions may occur, too. Since GCs are large-scale drugs, also in emergency medicine and reanimation, allergic sensitization towards them, although infrequent, gives many interventionist problems. In the light of this feature, it seems of crucial importance to verify the tolerance toward other GC molecules. And in particular, it has been noted that patients presenting immediate reactions to hydrocortisone (HC) and methylprednisolone (MP) could tolerate prednisone and prednisolone per os and second-generation GCs, such as desamathazone and betamethazone. Nevertheless, second-generation GCs must not be considered safe; in fact, the beginning of allergic manifestations has been pointed out even towards them.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

The immunocompromised host: immune alterations in splenectomized patients and clinical implications.

The spleen plays a paramount role in the host protection against invading microorganisms. In support of the above concept, in splenectomized patients there is increasing evidence of overwhelming postsplenectomy infections (OPSI). OPSI are caused by Streptococcus pneumoniae in about 80% of cases, but also Gram-negative bacteria are implicated in a certain number of cases. Therapeutically, penicillin and pneumococcal vaccines represent valid therapeutic approaches in Gram-positive OPSI. However, the effectiveness of polyvalent polysaccharide pneumococcal vaccines is still debated and, thus, other therapeutic strategies should be validated for combating OPSI. According to our personal data, a deficit of phagocytic activities and of T helper (h)-1 cells is very frequent in splenectomized patients. In sera, we found reduced levels of both Interferon-gamma and Interleukin (IL)-4. These data are in accordance with the recent observation on the protective role of T cells against S. pneumoniae. In fact, patients deficient in IL-12 develop severe pneumococcal infections and undergo apoptosis of Th(1) cells.

Animals↗
PubMed2002

Fish immunology. I. Binding and engulfment of Candida albicans by erythrocytes of rainbow trout (Salmo gairdneri Richardson).

The role of fish erythrocytes (FE) as phagocytic cells has poorly been investigated, until now. Here, we have focussed our attention on the interplay between rainbow trout (Salmo gairdneri Richardson) erythrocytes and Candida albicans (CA). At the same time, the intervention of autologous head kidney macrophages (MO) in the CA processing by FE has been studied. Data show that CA particles bind to FE, which, in turn, are able to engulf but not kill them. In the presence of MO, a decrease of FE with bound CA occurs and, in some microscopic images, FE form rosettes with MO. Phagocytosis of CA is higher in rosetting MO than in non-rosetting ones. According to our findings, it appears that FE represent a reservoir of engulfed CA and rosetting is an efficacious phenomenon of presentation of pathogens to MO, where an effective clearance of them can take place.

Animals↗
PubMed2002

Evaluation of the innate immune response in pups during canine parvovirus type 1 infection.

In two pups (A and B) naturally infected with canine parvovirus type 1 (CPV1) phagocytic responses were evaluated over a period of two weeks (day 0 = T0; day 3 = T1; day 7 = T2; day 14 = T3). CPV1 infection led to a marked reduction of monocyte (MO) phagocytosis in both pups. Also MO killing was impaired and in pup B this function was totally absent. Polymorphonuclear (PMN) phagocytosis values of both pups fluctuated within normal ranges, as well as PMN killing of pup A. In pup B, killing exerted by PMN was absent at T0, then increased but again dropped below normal ranges at T3. The described alterations of phagocytic functions may be regarded as possible viral mechanisms of immune evasion.

Animals↗
PubMed2002

Fish immunology. II. Morphologycal and cytochemical characterization and phagocytic activities of head kidney macrophages from rainbow trout (Salmo gairdneri Richardson).

In Salmo gairdneri Richardson trouts, a comparison was made between macrophages (MO) derived from head kidney and peripheral blood monocytes. Morphologically and cytochemically no differences were observed between these two types of mononucleated cells. On the other hand, in parallel studies the ability of trout erythrocytes to engulf Candida albicans (CA) was evaluated and compared to the MO phagocytosis. In erythrocytes, engulfment is preceded by binding to CA and cell membrane invagination, while this was not the case for MO. Finally, MO stimulated with lipopolysaccharides (LPS) did not modify their phagocytic capacities, thus suggesting a lack of LPS receptors or a tolerance to LPS.

Animals↗
PubMed2001

Mass spectrometry and combinatorial chemistry: a short outline.

The rapid evolution of combinatorial chemistry in recent years has led to a dramatic improvement in synthetic capabilities. The goal is to accelerate the discovery of molecules showing affinity against a target, such as an enzyme or a receptor, through the simultaneous synthesis of a great number of structurally diverse compounds. This is done by generating combinatorial libraries containing as many as hundreds or thousands of compounds. The need to test all these compounds led to the development of high-throughput screening (HTS) techniques, and also high-throughput analytical techniques capable of assessing the occurrence, structure and purity of the products. In order to be applied effectively to the characterization of combinatorial libraries, an analytical technique must be adequately sensitive (to analyse samples which are typically produced in nanomole amounts or less), fast, affordable and easy to automate (to minimize analysis time and operator intervention). Although no method alone can meet all the analytical challenges underlying this task, the recent progress in mass spectrometric (MS) instrumentation renders this technique an essential tool for scientists working in this area. We describe here relevant aspects of the use of MS in combinatorial technologies, such as current methods of characterization, purification and screening of libraries. Some examples from our laboratory deal with the analysis of pooled oligomeric libraries containing n x 324(n = 1, 2) compounds, using both on-line high-performance liquid chromatography/MS with an ion trap mass spectrometer, and direct infusion into a triple quadrupole instrument. In the first approach, MS and product ion MS/MS with automatic selection of the precursor were performed in one run, allowing library confirmation and structural elucidation of unexpected by-products. The second approach used MS scans to characterize the entire library and also precursor ion and neutral loss scans to detect selectively components with given structural characteristics.

Combinatorial Chemistry Techniques↗
PubMed2001

Splenectomy and sepsis: the role of the spleen in the immune-mediated bacterial clearance.

Over the past few years, many observations of overwhelming post splenectomy bacterial infections have been reported. Streptococcus pneumoniae is the aetiologic agent in about 80% of cases, but also gram-negative bacteria are involved in the development of fatal infections in splenectomized patients. Functionally, the spleen plays a fundamental role in bacterial clearance either by antibody response or macrophage bactericidal capacity. At the same time, there is evidence that the spleen also contributes to bacterial endotoxin detoxification. Finally, the mechanisms responsible for gram-positive and gram-negative sepsis in the splenectomized host and possible therapeutical approaches able to neutralize bacterial products endowed with noxious effects are discussed.

Bacteria↗
PubMed2001

A syndrome characterized by psychiatric disorders, recurrent mucosal infections and natural immunity deficits: clinical approach.

The authors summarize their own previous work on the identification of a subset of patients characterized by psychiatric disorders, recurrency of mucosal infections and impaired natural immunity. The diagnostic approach to these patients based on the close collaboration between infectivologists, immunologists and psychiatrists is described with the aim to find out combined treatments for the amelioration of clinical manifestations.

Humans↗
PubMed2001

Immune responses to fungal infections and therapeutic implications.

Host responses to fungi result from a coordinate interplay between innate and adaptative immune system. Neutrophils and monocytes are involved in the non specific clearance of yeasts (e.g. Candida albicans and Cryptococcus neoformans), while T helper 1 type responses are protective via release of interferon gamma. By contrast, T helper 2 responses (IL-4 and IL 10 release) correlate with disease exacerbation and pathology. IL-12 production which enhances T helper 1 type responses seem to exert a beneficial role in the course of Candida infection. In particular, its production from neutrophilis may support memory T helper 1 cell responses of the fungus. With respect to anti-Candida vaccines several approaches are in progress, such as use of heat-killed Candida albicans in combination with adjuvants, purified peptides and proteins and immunogenic peptide-lipid conjugates. Furthermore, exogenous IL-12 may play an important role in inducing a T helper 1 anticandidal response, also replacing neutrophils in neutropenic patients. At the same time, granulocyte-colony stimulating factor has exhibited therapeutic efficacy in experimental and human models of fungal infection.

Animals↗
PubMed2000

Regio- and stereoselective cycloadditions of cyclic nitrones to maleic diamide forced in a peptide: synthesis of potent ligands of human NK-2 receptor.

The regioselectivity and the stereoselectivity induced by relatively small peptidomimetic maleic diamide 1 in cycloaddition reactions with cyclic nitrones 2-5 was studied. The high regio- and stereoselectivity observed, sensibly increased by nonpolar solvents, was the effect of a double-asymmetric induction produced by the nitrone substituent on the pseudopeptidic tether. A new class of potent human tachykinin NK-2 receptor ligands was synthesized.

Dipeptides↗
PubMed2000

Solid-phase synthesis of MEN 11270, a new cyclic peptide kinin B2 receptor antagonist.

An efficient synthesis of the cyclic decapeptide MEN 11270 [H-DArg1-Arg2 Pro3-Hyp4-Gly5-Thi6-Dab7-DTic8-Oic9-Arg10 c(7gamma - 10alpha)] was developed. Two three-dimensional orthogonal strategies were applied and compared: Fmoc/Tos/Boc (procedure A) and Fmoc/Pmc/Dde (procedure B). Both resulted in a 23-step strategy comprising the stepwise solid-phase chain assembly of the linear protected peptide, partial deprotection, solution-phase cyclization and final full deprotection. The stepwise assembly of the linear peptide was optimized by double coupling and acylation time prolongation for critical residues (Tic, Dab, Thi, Pro). O-(7-azabenzotriazol-1-yl)-N,N,N',N' tetramethyluronium (HATU) was preferred as coupling reagent for Dab. In the cyclization step, the partial racemization of Arg10 (31% using 1-ethyl-3-(3'-dimethyl-aminopropyl) carbodiimide/1-hydroxybenzotriazole (EDC/HOBt) as activation system) was reduced to 3% with HATU. The final deprotection was performed in the presence of dimethylsulfide (procedure A) and thiocresol (procedure B) as scavengers, to avoid the sulfation of Hyp side chain. The final compound and the main by-products were characterized by mass spectroscopy (MS), nuclear magnetic resonance (NMR) and racemization test. Procedure B produced operationally simpler and more efficient results than A (28% overall yield versus 4%).

Amino Acids↗
PubMed2000

Evaluation of the natural immunity in pups inoculated with a modified-live canine parvovirus type 2b (CPV-2b) strain.

Three pups 2-4 months old were vaccinated subcutaneously with the modified live canine parvovirus, CPV-2b/29-97 strain. During an observation period of two weeks pups remained clinically health, exhibiting a vigorous post-vaccinal active serological response (haemoagglutinating inhibiting antibody titers for CPV-2 ranging from 1:2560 to 1:5120 at 21 days post inoculation). Phagocytosis and killing of Candida albicans exerted by polymorphonuclear cells and monocytes did not undergo significant modifications 3-6 days post vaccination up to 30 days. Antibacterial activity mediated by peripheral blood lymphocytes (Salmonella typhi was used as a target) was slightly, but not significantly decreased 3 days post vaccination. Conclusively, in pups the CPV type 2b vaccine seems to be safe as far as natural immune responses are concerned, while its immunogenicity is preserved.

Animals↗
PubMed2000

Synthesis and biological activity of the penem antibiotic MEN 10700 and its orally absorbed ester MEN 11505.

The synthesis and biological properties of the new penem antibiotic MEN 10700 (6) and of its selected oral prodrug MEN 11505 (8f) are described. MEN 10700 showed a broad spectrum of activity, with high potency both on Gram-positive and Gram-negative strains. It also exhibited good antibacterial activity toward anaerobes and on strains selected for their resistance to other antibacterial agents (cefotaxime- or ceftazidime-resistant Gram-negative strains, ciprofloxacin-resistant E. coli, extended spectrum beta-lactamase producing and cephalosporinase inducible enterobacteria). MEN 10700 showed a very high stability to enzymatic degradation by renal dehydropeptidase DHP-I. After oral administration in rats of the pivaloyloxymethyl ester prodrug MEN 11505, the relative bioavailability of MEN 10700 was calculated as F=43%.

Administration, Oral↗
PubMed1999

Nonpeptide antagonists for kinin receptors.

Kinins are a family of small peptides acting as mediators of inflammation and pain in the peripheral and central nervous system. The two main 'kinins' in mammals are the nonapeptide bradykinin (BK, Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) and the decapeptide kallidin (KD, [Lys0]-BK, Lys1-Arg2-Pro3-Pro4-Gly5-Phe6-Ser7-Pro8-Phe9- Arg10). Their biological actions are mediated by two distinct receptors, termed B1 and B2. Kinin B and B2 receptor antagonists may be useful drugs endowed with analgesic and anti-inflammatory properties, with potential use in asthma, allergic rhinitis and other diseases. The first nonpeptide kinin B2 receptor antagonist, WIN 64338, was reported in 1993. Despite its low selectivity, the compound provided a reference for pharmacological and modeling studies. Several quinoline and imidazo[1,2-a]pyridine derivatives have been shown by Fujisawa to possess high affinity and selectivity for kinin B2 receptors. Among them, FR 173657 displayed excellent in vitro and in vivo antagonistic activity, while FR 190997 emerged as the first nonpeptide agonist for B2 receptor. Two structurally related Fournier compounds were recently published. Other kinin B2 receptor ligands were obtained by rational design, through library screening or from natural sources. The only example of a nonpeptide kinin B1 receptor ligand has been reported in a patent by Sanofi.

Amino Acid Sequence↗
PubMed1998

MEN 10700, a new penem antibiotic: in-vitro activity and its correlation with beta-lactamase stability, PBP affinity and diffusion through the bacterial cell wall.

The in-vitro activity of MEN 10700, a novel penem, was compared with that of imipenem, ritipenem, ampicillin/sulbactam, cefotaxime, ciprofloxacin and amikacin against 1088 strains taken from 21 genera, including Gram-negative, Gram-positive and anaerobic bacteria. MIC data showed that MEN 10700 was very active against staphylococci and streptococci (MIC90 < or = 0.5 mg/L) and against most members of the Enterobacteriaceae (MIC90 < or = 2 mg/L), with reduced activity only against Providencia stuartii (MIC90 = 8 mg/L). MEN 10700 was also active against anaerobic species such as Clostridium perfringens and Bacteroides fragilis as well as Moraxella catarrhalis. It was moderately active against Enterococcus faecalis and inactive against Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Aeromonas spp. and Acinetobacter spp. Its antibacterial spectrum was thus slightly narrower than that of imipenem, but compared favourably with those of a third-generation cephalosporin and ritipenem. MEN 10700 was highly stable to a number of beta-lactamases and was a poor inducer of class I enzymes. It bound penicillin-binding protein 2 with the highest affinity and easily permeated the outer membrane of Escherichia coli.

Anti-Bacterial Agents↗
PubMed1997

Successful treatment of herpes simplex virus (HSV) recurrent genital infection with recombinant human (rh) granulocyte-macrophage colony stimulating factor (GM-CSF): a case report.

In the present work, we describe the treatment with rhGM-CSF of a woman affected by HSV recurrent genital infection and not responsive to specific antiviral therapy. The therapeutic regimen consisted of a subcutaneous administration of 300 mg/day of rhGM-CSF for six days. Before treatment with rhGM-CSF, polymorphonuclear cell and monocyte functional capacities and the antibacterial activity exerted by T cells were profoundly depressed. After treatment, a normalization of immune functions and a progressive disappearance of clinical manifestations were observed.

Adult↗