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Biomedical subjects

M Altamura

Publications and source records attributed to M Altamura.

At least 19 recordsLinked to original sources
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↗
PubMed1997

In vitro effects of recombinant human granulocyte-macrophage colony-stimulating factor (RhGM-CSF) on polymorphonuclear cell (PMN) and monocyte (MO) functional capacities in ovarian cancer patients versus human volunteers.

Human polymorphonuclear cells (PMN) and monocytes (MO) from four ovarian cancer patients and seventeen normal donors were in vitro pretreated with different concentrations (25, 50 and 100 IU, respectively) of rhGM-CSF. Phagocytosis and killing of PMN and MO as well as PMN polarization were evaluated in cancer patients before treatment (T0) and at the end of each chemotherapeutic cycle (T1, T2, T3 and T4, respectively) in comparison with normal donors. RhGM-CSF did not affect phagocytosis and killing of PMN and MO. On the other hand, this cytokine was per se endowed with the capacity to enhance PMN polarization in both cancer patients (at T2 interval) and normal donors.

Aged↗
PubMed1995

2-Substituted penems with amino acid-related side chains: synthesis and antibacterial activity of a new series of beta-lactam antibiotics.

A new series of 6-(hydroxyethyl)penems 2-substituted with amino acid-related side chains was synthesized. The nature of the amino acyl derivative proved to be crucial both from a synthetic point of view, as beta-lactam ring opening can compete with C-2 nucleophilic substitution, and for antibacterial activity. Primary amino acid amides emerged as the most suitable side chains for enhancing permeability through a Gram-negative outer membrane. In vitro activity of the new 2-[(aminoamido)methyl]penems 3a-u was influenced by the nature and position of the amide moiety, the ring size for cyclic amides, and the configuration of the amino acid. Compounds bearing amides derived from small N-methyl amino acids (such as 3a) or from cyclic amino acids (such as prolinamide 3p and 4-hydroxyprolinamide 3r) showed broad spectrum in vitro activity against both Gram-positive and Gram-negative microorganisms.

Amino Acids↗
PubMed1995

Structure-activity relationship of new 2-substituted penem antibiotics.

The antibacterial activities of three new penems with 4-hydroxyprolinamide, 1-prolinamide and N-methyl-N-2-propionamide substituents, respectively, in position 2 and of their stereoisomers were examined against Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli and Pseudomonas aeruginosa. All substitutes conferred a broad antibacterial spectrum on the penem moiety. Changes in stereoisomerism selectively improved the activity against E. coli, S. aureus or enterococci. The structure-activity relationships of each compound were discussed in relation to minimum inhibitory concentrations, penicillin-binding protein (PBP) affinity and outer membrane permeability coefficient in E. coli. In this microorganism, PBP 2 was the target for all compounds. Changes in stereoisomerism influenced the affinity for PBPs 1A/B and 2. All antibiotics easily permeated the outer membrane of E. coli and, within each group of compounds, the penetration rate correlated with the antibacterial activity.

Anti-Bacterial Agents↗
PubMed1993

Supplementation of male inhibitory material to lipid A activated human mononuclear cell supernatants contributes to the suppression of polymorphonuclear cell phagocytosis.

Human normal peripheral blood mononuclear cells were stimulated with lipid A (LA), the biologically active moiety of bacterial lipopolysaccharides. LA-activated supernatants were able to suppress polymorphonuclear cell (PMN) phagocytosis of Candida albicans. This inhibitory activity was enhanced by the supplementation of male inhibitory material (MIM) to active supernatants. The addition of a recombinant human anti-interleukin-1 beta monoclonal antibody to activated supernatants in the absence or presence of MIM diminished or abrogated, respectively, the suppressive effect on PMN function. The mechanisms and the significance of MIM-mediated inhibition of phagocytosis under these circumstances are discussed.

Adult↗
PubMed1992

Crystalline lactulose in the therapy of hepatic cirrhosis. Evaluation of clinical and immunological parameters. Preliminary results.

Crystalline lactulose (Laevolac Cristalli, CAS 4618-18-2), a pure form of the disaccharide widely employed in the therapy of complications of liver cirrhosis, was administered, after a pharmacological wash-out of 10 days and following a randomized design, to 10 cirrhotic patients for 30 days at the dosage of 60 g/d, while another 10 subjects with similar characteristics received no treatment. Besides the parameters usually monitored for the evaluation of liver function and state of hepatic encephalopathy, immunological patterns such as lymphocyte subpopulations CD3, CD4, CD8, CD16(NK), CD25 and antibacterial activity against Ty2 strain of Salmonella typhi were evaluated. At the end of the study (day 30) a significant decrease of blood ammonia was observed, as expected, only in the group treated with lactulose with respect to the control group, as well as a significant increase of CD16 and antibacterial activity (1/3); an enhanced level of CD25, although not significant, was also noticed in the treated group with respect to the control group. These findings seem to show an effect of activation on cell-mediated immune system depressed during liver cirrhosis, produced by lactulose. Further studies are needed to confirm these data and to clarify the possible mechanisms involved.

Adult↗
PubMed1991

Effects of acetyl-L-carnitine oral administration on lymphocyte antibacterial activity and TNF-alpha levels in patients with active pulmonary tuberculosis. A randomized double blind versus placebo study.

Acetyl-L-carnitine (ALC), a drug for the treatment of ageing-related neuroendocrine dysfunctions, was orally administered--2 gm/day for 30 days--to 10 patients with active pulmonary tuberculosis (TBC). Lymphocyte-mediated antibacterial activity and serum levels of tumor necrosis factor (TNF)-alpha were evaluated before and after treatment, comparing the values with those of 10 TBC patients receiving placebo. Results show that by day 30, antibacterial activity remained unmodified or increased in ALC-treated subjects, while decreased in the placebo group. No influence of ALC on TNF-alpha levels was detectable. These data suggest that the host's immune responses to M. tuberculosis infection can be selectively modulated by drugs acting on the neuroendocrine axis.

Acetylcarnitine↗
PubMed1991

Effects of benzodiazepines on the immune system.

Benzodiazepines (BDZ) are psychotropic drugs largely used in patients with affective disorders. As far as their effects on the immune system are concerned, a few studies have been carried out until now. Diazepam is inhibitory in vitro for the phagocytic functions and the antibody synthesis, being its action mediated via specific receptors on immunocompetent cells. On the contrary, alprazolam results to be enhancing for the antibacterial activity exerted by normal human peripheral blood T lymphocytes in vitro. Taken together, these data point out the different role which BDZ play on the immune response.

Alprazolam↗
PubMed1991

Role of thymic hormones in neuroimmunomodulation. Their use in patients with phobic disorders.

Many evidences support the existence of a bilateral connection between the thymic gland and the hypothalamic-pituitary-adrenal axis (HPAA). In this respect, neurohormones such as the adrenal corticotropin hormone and glucocorticoids cause thymic involution, while the growth hormone and the prolactin upregulate thymic functions. On the other hand, a thymic hormone, the thymosin fraction 5, activates the HPAA, thus closing-up the regulatory loop between immune system and nervous system. In this review, a clinical trial with two thymic hormones (Timostimolina and Thymopentin) in agoraphobic patients with phagocytic dysfunctions is reported. Results obtained indicate that both substances lead to a partial and temporary immunological recovery, since a further depression of phagocytic activities occurs in coincidence with panic attack. The use of alternative immunomodulators in these patients is discussed.

Adjuvants, Immunologic↗
PubMed1991

Somnogenic cytokines with special reference to interleukin-1.

Cytokines (CKs) are involved in the mechanisms of sleep induction, and, in particular, interleukin-1 (IL-1) and tumor necrosis factor-alpha seem to play an important role in the slow-wave sleep. Here are reported two cases of normal sleep and altered sleep in which plasma levels of IL-1 beta have been determined. In the subject with a normal sleep a dramatic increase of this CK has been observed, while beta-endorphin levels were reduced. In the light of these findings, the role of sleep in the host protection is discussed.

Arousal↗
PubMed1991

Are TNF-alpha and IL-1 beta relevant in the pathogenesis of migraine without aura?

Migraine without aura (MWA) is a clinical condition characterized by multiple immune deficits, which may play an important role in the pathogenesis of the disease. In this respect, previous studies have demonstrated that patients with MWA exhibit profound dysfunctions of phagocytosis and killing exerted by polymorphonuclear cells (PMN) and monocytes. This may correlate with the increased frequency of infectious processes observed in these patients. The overall results suggested to evaluate the presence of circulating cytokines (CKs) in subjects affected by MWA. In particular, the present data point out an exaggerated spontaneous release of tumor necrosis factor (TNF)-alpha in a group of MWA individuals, which correlates with detectable levels of bacterial lipopolysaccharides (LPS) in their plasma. In view of the different biological activities displayed by TNF-alpha in the host, such as effects on the nervous and vascular systems, hemodynamics modifications and demyelinating properties, the intervention of this CK in the pathogenesis of MWA will be discussed.

Humans↗
PubMed1990

Administration of thymopentin to patients with phobic disorders improves depressed phagocytic functions.

Seven patients with phobic disorders were administered with a synthetic thymic extract, thymopentin (TP-5), in order to correct depressed polymorphonuclear cell (PMN) and monocyte phagocytosis and killing capacities. Subcutaneous administration (50 mg, three times weekly, for a period of 8 wks) of TP-5 resulted in a significant increase in phagocytic function with no change in the phagocytic capacity of PMN. These data support the concept that immunomodulators can achieve a correction of immune deficiencies associated with phobic disorders.

Adult↗
PubMed1990

Circulating immune complexes and autoantibodies in canine leishmaniasis.

In sera of 35 dogs with generalised leishmaniasis elevated levels of circulating immune complexes were detected by the 125I-C1q binding test. Furthermore, anti-heart muscle and anti-smooth muscle antibodies were detected by an indirect immunofluorescence technique in sera of infected dogs.

Animals↗
PubMed1989

Diazepam inhibits phagocytosis and killing exerted by polymorphonuclear cells and monocytes from healthy donors. In vitro studies.

The effect of a benzodiazepine (BDZ), diazepam on human polymorphonuclear cell (PMN) and monocyte phagocytosis and killing from healthy volunteers has been evaluated. Diazepam is able to inhibit in vitro both functions exerted by PMN and monocytes at 10(-5) and 10(-6) M concentrations/ 4 x 10(6) phagocytes. 10(-7) M concentration was not effective in all the instances. These results are discussed for their possible clinical implications, since previous studies have shown that in patients with phobic disorder there is evidence for reduced phagocytosis and killing capacities.

Adult↗
PubMed1989

Bacteriological and histological study of 40 loose cemented hip prostheses.

The causes of the loosening of a hip prosthesis may be inflammatory, mechanical, immunitary or due to detritus. A bacteriological and histological study, in cases where further surgery was needed, may clearly contribute to the aetiopathogenesis of failure. Loose hip prostheses removed at operation were studied from a bacteriological and, in particular, histological point of view. There results were then correlated to clinical, radiographic and laboratory data obtained during follow-up. Inflammation proved to be a constant histological finding. The hyalinosis observed in 22 cases revealed significant analogies with histological pictures of silicotic granuloma, for which an immunitary pathogenesis is the current hypothesis. Thus, it is our belief that this correlation is suggestive of an immunitary based approach in cases where hip prostheses fail due to loosening.

Activities of Daily Living↗