Synthesis and characterization of certain thiourea derivatives starting from 1,2,4-triazoline-3-thiones as potential antibacterial and antifungal agents.

Several N-substituted-N'-[4-(4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thione -5-yl ) phenyl[thioureas were synthesized in order to examine their antibacterial and antifungal activities. The structures and purity of the synthesized compounds were confirmed by UV, IR and mass spectral data and elemental analysis. However, they were found not to possess significant antibacterial or antifungal activity.

Synthesis of 3-methyl-4-[(2,4-dihydro-4-substituted-3H-1,2,4-triazole-3-thione-5-yl) phenylhydrazono]-5-isoxazolone and evaluation of their antimicrobial activities.

3-Methyl-4-[(2,4-dihydro-4-substituted-3H-1,2,4-triazole-3-thione-5-yl) phenylhydrazono]-5-isoxazolone derivatives have been synthesised. The structure of these compounds was determined using spectral data and elemental analyses. These compounds were tested for antimicrobial activity.

Synthesis and structure elucidation of some 4-substituted benzylidene amino-5-[3(5)-methyl-5(3)-phenyl-1H-1-pyrazolyl]-2,4-dihydro-3H-1,2,4- triazole-3-thione derivatives with their antimicrobial activities.

A new series of 4-substituted benzylideneamino-5[3(5)-methyl-5(3)-phenyl-1H-1-pyrazolyl]-2 ,4-dihydro-3H- 1,2,4-triazole-3-thione was synthesized by reaction of I with suitable aldehyde and tested for their antimicrobial activities against six microorganisms. Most of the compounds showed antibacterial activity against Gram positive bacteria.

Evaluation of some arylhydrazones of p-aminobenzoic acid hydrazide as antimicrobial agents and their in vitro hepatic microsomal metabolism.

Benzoic acid p-amino-[(substituted phenyl/pyridyl) methylene] hydrazide derivatives were synthesised by interaction of p-aminobenzoic acid hydrazide with various aromatic aldehydes. The structures of the compounds were elucidated by use of their UV, IR, 1H-NMR and mass spectral data. These compounds were also evaluated for antimicrobial activity. The in vitro hepatic microsomal metabolism of benzoic acid p-amino-[(4-fluorophenyl)methylene]hydrazide (2d), a selected prototype from these compounds was also carried out.

Effect of oral administration of kefir on serum proinflammatory cytokines on 5-FU induced oral mucositis in patients with colorectal cancer.

In order to investigate the effect of kefir consumption on mucositis induced by 5-FU based chemotherapy (CT), we monitored the systemic immune response by measurement of the serum proinflammatory cytokine levels and we evaluated the anti-microbial effect of kefir with an agar diffusion method. Forty patients with colorectal cancer were included in this randomized prospective study. On the first 5 days of each CT cycle, the study group received oral lavage with kefir and then swallowed 250 ml of kefir while control group received oral lavage with 0.09% NaCl twice a day. Before and after every cycle of CT, the oral mucosa was assessed. Serum proinflammatory cytokine levels were evaluated before the initiation and after the third and the sixth cycle. Kefir was administered in 99 out of 205 courses. Mucositis developed in 27.3% of the courses given with kefir administration and in 21.7% of the courses given with 0.9% NaCl oral rinses. The difference between the two groups was not statistically significant (p > 0.05). When we compared the serum proinflammatory cytokine levels of the two groups at the baseline and following the third and the sixth cycles, we again found no statistically significant difference (p > 0.05). Kefir consumption at the mentioned doses made no statistically significant effect on serum proinflammatory cytokine levels and on the incidence of mucositis development in cancer patients. Under in vitro conditions, kefir inhibits only Staphylococcus epidermidis.

Effect of the function of polymorphonuclear leukocytes and interleukin-1 beta on wound healing in patients with diabetic foot infections.

OBJECTIVES: This study was carried out prospectively to determine the effect on prognosis of phagocytic activity index (PAI) and intracellular killing activity (IKA) of polymorphonuclear leukocytes (PMNL), and the levels of interleukin-1 beta (IL-1beta) on prognosis in patients with diabetic foot infection (DFI). METHODS: The evaluation of PAI and IKA in PMNL and the levels of IL-1beta were performed at the beginning and in the second and fourth weeks of therapy in all diabetic patients, who were categorized into a healing group (HG) and a non-healing group (NHG) on the basis of therapy results. RESULTS: Sixty-six cases (38 diabetic patients and 28 non-diabetic controls) were included in the study. Full recovery was observed in 23 HG patients, whereas 15 (NHG) patients were unresponsive to treatment and nine patients were subjected to amputation at the end. At the baseline, PAI, IKA and IL-1beta levels in HG were not significantly different compared to those of NHG, but at weeks 2 and 4, PAI and IKA levels were significantly higher and IL-1beta levels were significantly lower than those in NHG. On the other hand, at the baseline, PAI and IKA values in HG were significantly lower and IL-1beta levels were significantly higher in comparison with the controls. However, no significant difference was observed at week 2 or 4. CONCLUSION: Our results suggest that the PMNL functions and IL-1beta regulation deteriorated in patients with DFI, and that such deteriorations might indicate inefficient therapeutic responses in patients with diabetes mellitus.

Streptococcus mutans in plaque from margins of conventional and high copper amalgam restorations.

Levels of Streptococcus mutans in plaque samples from margins of conventional and high copper amalgam restorations were compared in fourteen patients, each having one conventional amalgam filling in each quadrant and one high copper amalgam filling on the contra-lateral side were examined. The percentage of S. mutans of total CFU count in plaque was higher on conventional amalgam than on high copper amalgam. The difference was statistically significant (p < 0.01).

In vitro effect of amikacin, imipenem, cefodizime, IFNalpha-2a alone and combinations of antibiotics with IFNalpha-2a on polymorphonuclear leukocyte function in chronic hepatitis patients.

The in vitro effect of amikacin (8 microg/ml), imipenem (30 microg/ml), cefodizime (10 microg/ml), interferon alpha-2a (IFNalpha-2a) (10 IU/ml) and antibiotic combinations with IFNalpha-2a on polymorphonuclear leukocyte (PMN) functions (phagocytosis and intracellular killing of Candida albicans blastospores) was investigated in chronic hepatitis B patients. Phagocytosis and candidacidal activity was not affected after pretreatment of PMNs with amikacin and imipenem (p > 0.05). Phagocytic activity was enhanced after pretreatment of PMNs with cefodizime and IFNalpha-2a compared with that of control PMNs (p < 0.05), but candidacidal activity was not affected by the same drugs (p > 0.05). Phagocytic and intracellular activity of PMNs were not affected by combinations of IFNalpha-2a and antibiotics (p > 0.05).

In vitro effects of clarithromycin on human polymorphonuclear leukocyte functions.

BACKGROUND: It has been shown that antibacterial agents affect polymorphonuclear leukocytes (PMNs), which are active in the body's first line of defense, in different ways. However, few studies have investigated the effects of tablet dosage forms as opposed to pure powder forms. There is a need to demonstrate the clinical relevance of previous results with commercially available products. METHODS: We examined the effects of clarithromycin solutions, prepared separately from either pure powder or commercially available tablets (250 mg), on human PMNs. The in vitro effects of each solution, adjusted to therapeutic concentration (1 mg/l), on PMN adherence, chemotaxis, phagocytosis, candidacidal capacity and superoxide production were studied. RESULTS: Solutions prepared from pure clarithromycin powder did not affect the adherence, phagocytosis or superoxide production of PMNs, but did inhibit (p<0.05) chemotaxis and candidacidal capacity. By contrast, a decrease (p<0.05) in all functions except phagocytosis was observed with solutions prepared from the tablet dosage form of clarithromycin. CONCLUSION: The results of this study suggest that the tablet dosage form of clarithromycin may have a more pronounced inhibitory effect on human PMN functions than solutions prepared from the pure powder form.

Effect of fluconazole on human polymorphonuclear leucocyte functions ex vivo against Candida albicans.

Polymorphonuclear leucocytes (PMNs) are important components of host defence against fungi. We investigated the ex vivo effect of fluconazole on chemotaxis, adherence, superoxide anion (O-2) generation and intracellular killing of Candida albicans blastoconidia after the administration of fluconazole (300 mg per os) to healthy volunteers. With regard to chemotaxis in response to zymosan-activated serum (ZAS), as measured using an agarose gel technique, fluconazole neither increased, nor decreased the chemotaxis of PMNs. The adherence was significantly enhanced after exposure of PMNs to fluconazole under ex vivo conditions, whereas, O-2 production after stimulation of PMNs with ZAS was not affected by fluconazole. The effect of fluconazole on intracellular killing of C. albicans blastoconidia by PMNs was determined by viable colony count, after release of yeast cells from disturbed neutrophils. Fluconazole under in vitro conditions, at a therapeutic concentration, significantly increased the intracellular killing of C. albicans by PMNs at 30 min when compared with the results obtained in ex vivo experiments (p < 0.001). During 90 min of exposure, no significant difference was found between in vitro and ex vivo conditions (p > 0.05).