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Biomedical subjects

M Renoux

Publications and source records attributed to M Renoux.

At least 19 recordsLinked to original sources

[Candida tropicalis arthritis of the shoulder associated with articular chondrocalcinosis].

A case of infection of the scapulohumeral joint following articular infiltrations is reported in a female patient with alcohol-related cirrhosis of the liver. Joint destruction occurred despite appropriate treatment with fluconazole. Candida tropicalis joint infections are seen mainly in immunocompromised hosts and usually cause little destruction of the joint. Most are the result of dissemination via the bloodstream. Preexisting chondrocalcinosis in the patient reported here may have been a contributing factor to the development of extensive joint destruction.

Aged

Paradoxal pharmacologic effects observed with beta-blocker agents on cardiac cells in culture.

The direct effects of propranolol and metoprolol were studied on cultured neonatal rat ventricular myocytes by recording cellular contraction with a video signal analyzer of cells movements. The experiments were performed on 3-d-old cultures forming a synchronously beating monolayer. The spontaneous beating frequency of preparations depended on cultures and varied from 100 to 330 beats/min with a peak for the interval 140 to 149 beats/min. Propranolol and metoprolol were tested at 1, 5, 10 microM and 10, 50, 100 microM, respectively. At these doses the two beta-blockers induced chronotropic and inotropic effects in the same range. The two agents induced rapid and short-lasting negative inotropic effects, which were dose-dependent and delayed negative chronotropic effects even with the lowest doses. In some preparations paradoxal effects were evidenced: an increase of the amplitude or frequency of the contractions was observed. The results obtained with 5 microM propranolol or 50 microM metoprolol could be separated in two groups depending on the basal beating rate (less than or greater than to 150 beats/min). In cultures with a rapid frequency, the drugs had a marked negative chronotropic effect and, surprisingly, a positive inotropic effect was observed. These findings confirm the interdependence of the two parameters frequency and amplitude of contraction on this model, and evidence the interest of taking into account the control parameters before any interpretation.

Adrenergic beta-Antagonists

Role of the N-terminal arginine in the histamine-releasing activity of substance P, bradykinin and related peptides.

A series of substance P (SP)- and bradykinin (BK)-related peptides have been compared for their histamine-releasing activities on rat peritoneal mast cells. Some of these peptides only differed in the N-acetylation of the N-terminal arginine residue or by the removal of charged residue at the N-terminal. The aim was to examine the role of the N-terminal positive charges in the histamine-releasing activity of compounds that are selective for the SP receptor (named NK-1) or for the B2 type bradykinin receptor. Only compounds with positive charges at the N-terminal caused non-cytotoxic histamine release from rat mast cells. It is suggested that SP- and BK-related peptides caused histamine release by a mechanism which appeared to be non-specific and not related to the activation of mast cell NK-1 or B2 receptors, respectively. Our results show that NK-1 agonists or B2 antagonists devoid of histamine-releasing activity, which could be of potential use in the clinic, can be obtained by removing the positively charged N-terminal aminoacids or by N-acetylation of the N-terminal arginine.

Animals

Sodium diethyldithiocarbamate protects against the MPTP-induced inhibition of immune responses in mice.

The effects of 1-methyl-4-phenyl - 1,2,3,6-tetrahydropyridine (MPTP) on immune parameters, and the restorative influence of sodium diethyldithiocarbamate (DTC) or deprenyl were evaluated in mice. The concentrations of dopamine (DA), 3-methoxytyramine (3-MT), 3-4-dihydroxyphenyl acetic acid (DOPAC), and homovanillic acid (HVA), were concomitantly measured in the striatum. MPTP depressed T-cell responses. DTC restored these responses as well as the concentration of striatal DA. Deprenyl had no effect on the concentrations of DA and its metabolites, yet it modified the immune responses alike MPTP. The findings suggest a dopamine pathway could be involved in the brain-controlled immunostimulation afforded by DTC.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Interleukin-1 secretion by lipopolysaccharide-stimulated alveolar macrophages. Relationships to cell numbers--influence of smoking habits.

Interleukin-1 (IL-1) release by alveolar macrophages (AMs) from 29 patients with primary bronchogenic carcinoma, lung metastases, acute pneumonitis, and chronic infection was evaluated in response to a standard stimulus, lipopolysaccharide (LPS). The results were compared to those of AMs from normal smokers or nonsmokers (volunteers). AMs derived from healthy smokers secreted significantly more IL-1 than AMs from nonsmokers. In contrast, AMs from smokers affected with primary lung cancer have lost their capacity of secreting high levels of IL-1, whereas IL-1 secretion was high in nonsmokers with hematogenous metastases. AMs release high IL-1 levels in patients with acute bacterial infections. A significant correlation exists between numbers of AMs and IL-1 levels in normal individuals, a relationship which disappears in patients. These observations suggest that AMs in inflammatory lung disease, even discrete, have an increased capacity to secrete IL-1 on stimulation with LPS. They also suggest that an intrinsic dysfunction of AMs may accompany primary bronchogenic carcinoma. The influence of tobacco in modifying the functions of AMs is stressed.

Adult

Histamine-releasing activity of endogenous peptides on mast cells derived from different sites and species.

We have examined the cytological and functional characteristics of mast cells grown in tissue culture from the bone marrow of mice and rats and compared them with mast cells isolated from the peritoneal cavity of these animals. In both species, bone marrow-derived mast cells (considered to be a model of mucosal mast cells) have fewer cytoplasmic granules and lower histamine content than peritoneal mast cells. Sprague-Dawley rat peritoneal mast cells were responsive to various endogenous peptides and to compound 48/80. However, peritoneal mast cells isolated from BDF1 mice (a strain widely used to obtain bone marrow-derived mast cells) were not responsive to the same secretagogues. Rat and mouse bone marrow-derived mast cells obtained from Sprague-Dawley rats and BDFI1 mice were also hyporesponsive to calcium ionophore as compared to peritoneal mast cells and unresponsive to compound 48/80 and peptides. Despite the similarity of the functional characteristics of mouse and rat bone marrow-derived mast cells, mouse bone marrow-derived mast cells could not be used as a model of responsiveness to peptides for rat mucosal mast cells because of the differences in responsiveness between the peritoneal mast cells in the two species. Obtention of homogeneous rat bone marrow-derived mast cells may provide a useful tool to study the functional heterogeneity in an intraspecies system since most of our knowledge on mast cell physiology and pharmacology is derived from studies on rat peritoneal mast cells.

Animals

Imuthiol influences on cytotoxic T cells and NK activity in +/+ and athymic nude BALB/c mice.

The effects of imuthiol (sodium ditiocarb, DTC) on the expression of cytotoxic responses (CTL) and natural killer (NK) activity were evaluated in aged and young euthymic mice, and in nu/nu BALB/c mice. Imuthiol generated CTL and concomitantly reduced NK activity in nu/nu mice, suggesting that the agent can generate T cells in athymic nude animals. Treatment for up to 4 months augmented spleen NK and CTL activities in young or aged euthymic mice, but the generation of CTL in old animals was increased by long-term treatments better than by a single injection. The capacity of imuthiol to activate specific and nonspecific cytotoxic functions in euthymic mice may contribute to enhancement of resistance in vivo against transformed cells after treatment with this agent.

Adjuvants, Immunologic

Histamine release from rat peritoneal mast cells by kinin antagonists.

Kinins are known to be potent releasers of histamine. In the present study, the B2 antagonist analogues of bradykinin (BK) and kallidin (KD): [( Thi6,9,D-Phe8]KD, [Thi5,8,D-Phe7]BK) were also found to be potent releasers of histamine from rat mast cells and not to exert any antagonistic effect. Similarly, two B1 receptor antagonists, des-Arg10-[Leu9]KD and des-Arg9-[Leu8]BK, were shown to promote histamine release and acted only as agonists. The order of potency of these analogues was the following: [Thi6,9,D-Phe8]KD greater than [Thi5,8,D-Phe7]BK greater than des-Arg10- [Leu9]KD greater than des-Arg9-[Leu8]BK. The high activity of some of these compounds suggests that (1) the potency of kinins for histamine release from rat mast cells not only increases in parallel with the number of positively charged amino acids (Lys, Arg) but also, because of others factors such as peptide conformation, receptor binding affinity or receptor accessibility, (2) the histamine release by kinins is either a non-specific effect not mediated by receptors or, if receptors are involved, these sites may be different from other kinin receptors (i.e. B1 or B2).

Animals

Study of histamine release induced by acute administration of antitumor agents in dogs.

The effects of eight antitumoral drugs known to cause anaphylactoid side effects in clinical use were studied in dogs. Blood pressure, heart rate, and blood and plasma histamine levels were monitored. L-asparaginase, methotrexate, 5-fluorouracil, bleomycin, and cisplatin had no effect on these parameters. Doxorubicin, Vehem (teniposide), and Vepeside (etoposide) induced hypotension, tachycardia, and a rise in histamine levels. In the cases of Vehem and Vepeside, the excipient (respectively, cremophor EL and tween 80) induced the same effects. These agents, like elliptinium, which had been previously studied, induce nonspecific histamine release--unlike the other drugs studied. The mechanism of clinically observed anaphylactoid side effects is discussed in the light of these findings.

Anaphylaxis

Early changes in immune parameters induced by an acute nonantigenic inflammation in mouse: influence of imuthiol.

Calcium pyrophosphate (CaPP)-induced pleurisy, may represent one of the simplest expressions of inflammation in that the irritant is a non-diffusible, non-antigenic and non-pyrogenic agent. Spleen or lymph node T or B cell numbers and activities, as well as NK activity, were modified at distance by CaPP-pleurisy. An intense increase in blood polymorphonuclear cells was also triggered by the inflammatory process. Treatment with imuthiol (sodium diethyldithiocarbamate), an agent known to be active on the T-cell lineage, restored towards control values the inflammatory response and tended to normalize white blood cell percentages altered by the inflammatory process. The findings suggest imuthiol could be employed as a virtually nontoxic and non-steroidal anti-inflammatory agent.

Animals

Histamine release and local responses of rat and human skin to substance P and other mammalian tachykinins.

Substance P and two recently identified neurokinins, substance K and neuromedin K as well as the nonmammalian tachykinin kassinin were compared for histamine-releasing abilities from rat mast cells, plasma extravasation effects on rat skin, and wheal and flare responses on human skin. Among the four tachykinins, a significantly dose-dependent histamine release from rat mast cells and a flare response in human skin was observed only with substance P, indicating the possible implication of histamine in this response. On the other hand, the four peptides were similarly active on the wheal response (plasma extravasation produced by increased permeability of capillaries and venules) in human skin and on the plasma extravasation in the rat skin, suggesting a dissociation of effects and possibly of receptors.

Animals

Peptides and histamine release from rat peritoneal mast cells.

Various vasoactive peptides were compared for their histamine releasing effects on rat mast cells. Neurotensin, substance P (SP), and kallidin were the most active natural peptides, followed by bradykinin; neurokinin A and B, bombesin, angiotensin and tuftsin were practically inactive. Several kinins and tachykinin-related peptides were tested in an attempt to characterize the receptors mediating histamine liberation. The order of potency of the kinins was the following: kallidin greater than [Tyr(Me)8]bradykinin = bradykinin greater than [desArg10]kallidin greater than desArg9-bradykinin, the same as that found in smooth muscle possessing receptors of the B2 type. Tachykinin-related peptides were potent stimulants and followed the order: [D-Tryp7,9,10]SP-(1-11) greater than [D-Pro2,D-Tryp7,9,10]SP-(1-11) greater than SP-(1-11) greater than SP-(1-9) greater than [D-Pro4,D-Tryp7,9,Leu11]SP-(4-11) greater than SP-(1-7) greater than SP-(4-11) greater than neurokinin A = neurokinin B, indicating that: (a) undecapeptide antagonists of SP behave as superagonists; (b) both N- and C-terminal portions of SP-(1-11) are essential for activity; and (c) receptors for the tachykinins mediating histamine release appear to be of the SP-P type.

Animals