Pharmacokinetics and efficacy of teicoplanin against intramammary infections in sheep.

The pharmacokinetics of teicoplanin were evaluated in 10 healthy sheep. After intravenous injection it showed monophasic behaviour, with a short mean (sd) elimination half-life (5 [0.24] hours). After intramuscular injection its bioavailability was 100 per cent but it was absorbed slowly; its elimination half-life was satisfactorily slow (9.23 [0.74] hours). Its efficacy was evaluated in 26 crossbreed sheep with milk positive to strains of Staphylococcus aureus, coagulase-negative staphylococci and Streptococcus agalactiae, and clinical signs of disease. In 19 of them a single intramuscular dose of 6 mg/kg bodyweight resulted in a complete resolution of the clinical signs, and no microorganisms were detected in milk by the fifth day; in the other seven sheep, with more severe intramammary infections, three consecutive daily intramuscular doses of 6 mg/kg bodyweight were necessary. There were no local or systemic side effects and no relapses during 30 days after the treatments in any of the sheep.

Efficiency of Calamintha officinalis essential oil as preservative in two topical product types.

AIMS: To verify the efficiency of Calamintha officinalis essential oil as natural preservative in two current formulations. METHODS AND RESULTS: The 1.0 and 2.0% (v/v) C. officinalis essential oil was assayed for its preservative activity in two product types (cream and shampoo). The microbial challenge test was performed following the standards proposed by the European Pharmacopoeia Commission (E.P.) concerning topical preparations using standard micro-organisms and in addition wild strains, either in single or mixed cultures were used. The results clearly demonstrated that the C. officinalis essential oil at 2.0% concentration reduced the microbial inoculum satisfying the criterion A of the E.P. in the cream formulation and the criterion B in the shampoo formulation. Standard and wild strains showed a behaviour similar, both in cream and in shampoo formulation, with no significant difference (gerarchic variance, P > 0.05). CONCLUSION: C. officinalis essential oil confirmed its preservative properties but at higher concentration than that shown in previous studies on cetomacrogol cream. SIGNIFICANCE AND IMPACT OF THE STUDY: The nature of the formulation in which an essential oil is incorporated as preservative could have considerable effect on its efficacy.

[Thermal water of Alì Terme, Italy]. / Alì terme e le sue acque termali.

In this paper the history of the thermal water of Alì Terme (Sicily-Italy) and their beneficial effects are reported. Chemical and bacteriological investigations have been conducted for assay of thermophiles sulphur bacteria. As regards the chemical characteristics, traditional investigations have been carried out together with determination of H2S.

Evaluation of antiherpesvirus-1 and genotoxic activities of Helichrysum italicum extract.

The antiherpes virus-1 and genotoxic activities of diethyl ether extract from flowering tops of Helichrysum italicum (Compositae) were investigated. The extract showed significant antiviral activity at concentrations ranging from 400 to 100 microg/ml. This activity was not due to cytotoxic effect of the extract since Vero cells exhibited altered morphology or growth characteristics indicative of cytotoxic effects at higher concentration (800 microg/ml). Moreover H. italicum extract showed no DNA-damaging activity at concentrations up to 2000 microg/disk.

In vitro anti-mycotic activity of some medicinal plants containing flavonoids.

Aqueous, ethanolic and petroleum ether extracts of Citrus sinensis L. (Osbeck), Euphrasia officinalis L., Glycyrrhiza glabra L., Matricaria recutita L., Rosa canina L. and Ruta graveolens L. have been studied. The antimycotic activity was evaluated "in vitro" on strains of Candida albicans isolated from clinical samples obtained in the course of acute vaginitis.

Fatty acid profiles in pigmented and non-pigmented strains of S. marcescens.

Wild, pigmented strains of Serratia marcescens and their non-pigmented mutants were compared on the basis of fatty acid profiles and lipid content. Classic biochemical tests show only minor differences, as well as fatty acid ratio C18:C16. The total amount of lipid synthesized and the saturated/unsaturated fatty acids ratio disclose a sharp total lipid reduction and a high percentage of unsaturated fatty acids in the pigmented strains, placing them in separated clusters compared with the nonpigmented mutants. It is hypothesized that the synthesis of the polyacetate required for the completion of the prodigiosin molecule may result in waste of methyl groups and thus affect the total amount of lipids.

Synthesis and in vitro antimicrobial and antitumoral screening of novel lipophilic isoniazid analogues. VI.

Various kinds of lipophilic analogues of isonicotinic acid hydrazide (Isoniazid) were synthesized and in vitro explored in a search for antimycobacterial agents with extended activity spectrum against pathogens responsible for the AIDS-associated diseases. The primary in vitro screening showed that a) isonicotinoylhydrazones 1a, 1b, 1d, 1e are more active than the parent drug against non-tubercular mycobacteria (MIC ranging between 0.5 and 4 micrograms/ml), b) isonicotinohydrazides 6b and 6e display interesting antibacterial activity on some Gram + and Gram-strains, and c) trifluoromethyl-containing compounds 1a and 2c inhibit the growth of several human tumor cell lines at doses between 10(-5) and 10(-6) M. On the contrary, none of the tested analogues significantly counteracts the cytopathogenicity induced by HIV and HSV viruses.

2-(4-Pyridyl)-delta 2-1,3,4-oxadiazolines from isonicotinoylhydrazones and diazomethane as potential antimycobacterial and anti-HIV agents. V.

The 5-aryl-4-methyl-2-(4-pyridyl)-delta 2-1,3,4-oxadiazolines 3, previously synthesized along with isomer 4-aryl-1-methoxy-1-(4-pyridyl)-2,3-diaza-1,3-butadienes 2 from benzaldehyde isonicotinoylhydrazones and diazomethane, were tested for in vitro activity against both M. tuberculosis and some atypical mycobacterial strains as well as against human immunodeficiency virus (HIV-1). Some halophenyl derivatives, 3e, 3g, 3i, 3j, were found to display MIC ranges from 1 to 10 (micrograms/ml against H 37 Rv and a clinical isolate tubercular strain, whereas against M. avium (MAC) the MICs were higher than 20 micrograms/ml. When the combinations of oxadiazolines with ethambutol, acting as inhibitor of cell wall synthesis, were assayed on MAC strain a synergistic effect was demonstrated for 3g and 3h trifluoromethyl derivatives. The antimycobacterial profiles of 2 and 3 analogues are compared and discussed. As shown by compounds 2, no substantial anti-HIV in vitro activity was found in selected delta 2-oxadiazolines; a moderate cytotoxicity, however, appears to be a common property.

Halogenated isoniazid derivatives as possible antimycobacterial and anti-HIV agents--III.

As part of a research directed to the synthesis of novel isoniazid derivatives with potential activity on mycobacteria and HIV virus, the acetophenone-isonicotinoylhydrazones 3 and the 4-aryl-1-methoxy-1-(4-pyridyl)- 2,3-diaza-1,3-butadienes 5, obtained by reaction between isonicotinoylhydrazones and diazomethane, have been prepared and tested for such activities. Both classes of derivatives showed interesting growth inhibitory activity on non-tubercular mycobacteria, including the emerging M. avium. Such activity appears to be linked to fluorine and/or chlorine presence on benzene rings. In contrast, none of the compounds submitted to the anti-AIDS in vitro screening, displayed any protection against HIV-1 virus-induced cytopathic effect in T4-lymphocyte cell lines.

Halogenated isoniazid derivatives as possible antitubercular and antineoplastic agents. Note 1.

Halogenated arylhydrazones, 2-aryl-4-thiazolidinones and their 1,1-dioxides containing isoniazid (INI) moieties were prepared and explored for antimicrobial (against bacteria, Candida and mycobacteria) and antitumor activities. None of the tested compounds showed any marked antimicrobial effect. Furthermore, among the compounds submitted to NCI in vitro primary antitumor screening, those bearing 3-fluoro or -chlorophenyl substituents were found to possess selective inhibitory effects on the growth of non small cell lung cancer, whereas those with para-phenyl substituents displayed selective effects, sometimes statistically significant, against leukemias.

N-trifluoroacetyl derivatives as pharmacological agents. V. Evaluation of antiinflammatory and antimicrobial activities of some N-heterocyclic trifluoroacetamides.

Following the investigation on pharmacological aspects of N-trifluoroacetyl compounds some heterocyclic trifluoroacetamides were prepared and explored as potential antiinflammatory-analgesic and antimicrobial agents. The trifluoroacetamides 3, 4, 5, and 6 reached significant activity in the hot plate analgesic test; the same 4 and 5, along with 7 and 8 showed inhibitory properties in the adjuvant arthritis test; only 7 however, displayed a significant dose-dependent activity in the carrageenin edema test. In addition the parent heterocyclic amines were similarly explored for comparison. Test for antimicrobial activity were carried out in parallel. Among the examined compounds, only 4-aminomorpholine and 2-aminobenzimidazole were found active when assayed against gram+ and gram- bacteria and mycetes.

Antibacterial activity of some African medicinal plants.

The antimicrobial activity of some drugs utilized in traditional African medicine and selected on the basis of medicinal folklore reports, have been studied, within a screening program. The distribution of the antimicrobial activity among gram-positive, gram-negative bacteria, yeasts and mycoplasma is reported.

Piperazin-2,5-diones N,N'-substituted. III. Synthesis and pharmacological activities of some 1-aryl-4-arylidene (or heteroarylidene)aminopiperazin-2,5-dione derivatives.

The synthesis, antimicrobial and antitumor activities of new N,N'-substituted-2,5-dioxopiperazine derivatives are reported. The biological investigation showed that only the compounds containing the 5-nitrofurylidene moiety were active against some bacteria. All tested compounds showed no significant antitumor activity against lymphocytic murine leukemia P 388.

Evaluation of cefotaxime concentrations in rat cerebral areas and serum by microbiological method and HPLC.

The aim of the investigation was to verify the reliability and sensitivity of High Performance Liquid Chromatography (HPLC), compared to the classic microbiological method of plate diffusion, in evaluating cefotaxime concentrations in some cerebral areas and serum of the rat. The mean concentration of cefotaxime in the serum (after acute administration of 15 mg/kg i.m.) was 20 micrograms/ml with the microbiological method and 23 micrograms/ml with HPLC. No antibiotic was detectable, with both methods, in the cerebral areas. The results with both methods are in good accordance, although the HPLC technique is more sensitive and accurate.

[3,3'-bi-1,3-thiazolidine]-4,4'-dione system. III. Evaluation of the antimicrobial and antitumor properties of 2,2'-disubstituted derivatives and their 1,1'-disulfones.

A series of dl and meso 2,2'-disubstituted-[3,3'-bis-1,3-thiazolidine]-4,4'-diones and their 1,1'-disulfone derivatives have been tested for their antimicrobial activity against gram-positive, gram-negative and Candida strains and for antitumor activity against leukemic P.388 tumor system in mice. None of the tested bi-thiazolidinones showed any significant antitumor properties; only few 1,1'-disulfones exhibited some antibacterial activity.

[N-substituted p-fluorobenzencarboxyamides. Evaluation of the in vitro antimicrobial activity]. / p-Fluorobenzencarbossiamide N-sostituite. Valutazione dell'attività antimicrobica in vitro.

As part of our investigations on fluorine containing compounds of potential pharmacological interest, a series of N-substituted p-fluorobenzencarboxyamides, analogs of previously studied p-fluorobenzensolfonamides, was prepared. The in vitro antibacterial and antimycotic properties were also assayed. The replacement of the sulfonamide group with an isosteric carboxyamide one, was found to confer to trifluoromethylsubstituted compounds good activity against some strains of yeasts (Candida) and hyphomycetes (Tricophyton, Aspergillus, Microsporum, Epidermophyton). These compounds however are not very active against the gram-positive and gram-negative bacteria on which the corresponding sulfonanilides showed significant activity.

[N-substituted p-fluorobenzene sulfonamides with antimicrobial activity. I]. / p-Fluorobenzensolfonamidi N-sostituite ad attività antimicrobica. Nota I.

In an extension of the investigations on fluorine derivatives of potential pharmacological interest, some new p-fluorobenzensulfonanilides were synthesized and screened in vitro against many species of Gram-positive and Gram-negative bacteria and against some strains of Candida albicans. Some of these compounds exhibited significant antibacterial activity. The relation between activity and structure revealed that the presence of chloro and trifluoromethyl groups in the aniline ring increases activity against Gram-positive bacteria. The acute toxicity in mice was also determined.