Penicillium notatum 1 a new source of dextranase

Summary Two hundred and fifteen fungal strains were screened for extracellular dextranase production with a diffusion plate method. The best enzymatic activity (12–19 DU ml^–1) was achieved byPenicillium notatum 1, a species for which the dextranase productivity has not yet been published. Some of the parameters affecting enzyme production have been standardized. The enzyme in crude state was relatively stable, its maximal activity was at 50°C and at pH 5.0. Conidia of the selected strain were mutagenized, and isolated mutants were tested for production of dextranase in submerged culture. The most active mutant,P. notatum 1-I-77, showed over two-times higher dextranase activity than the parentP. notatum 1     

Determination of 5-hydroxy-N-methylpyrrolidone and 2-hydroxy-N-methylsuccinimide in human urine

A method for simultaneous determination of 5-hydroxy-N-methylpyrrolidone and 2-hydroxy-N-methylsuccinimide in urine is described. These compounds are metabolites of N-methyl-2-pyrrolidone, a powerful and widely used organic solvent. 5-Hydroxy-N-methylpyrrolidone and 2-hydroxy-N-methylsuccinimide were purified from urine by adsorption to a C₈ solid-phase extraction column and then elution by ethyl acetate–methanol (80:20). After evaporation, the samples were derivatised at 100°C for 1 h by bis(trimethylsilyl)trifluoroacetamide. Ethyl acetate was then added and the samples were analysed by gas chromatography–mass spectrometry in the electron impact mode. The extraction recovery for 5-hydroxy-N-methylpyrrolidone was about 80% while that for 2-hydroxy-N-methylsuccinimide was about 30%. The intra-day precision for 5-hydroxy-N-methylpyrrolidone was 2–4% and the between-day precision 4–21% (4 and 60 μg/ml). The intra-day precision for 2-hydroxy-N-methylsuccinimide was 4–8% and the between-day precision 6–7% (2 and 20 μg/ml). The detection limit was 0.2 μg/ml urine for both compounds. The method is applicable for analysis of urine samples from workers exposed to N-methyl-2-pyrrolidone.     

Association between TNF α Gene Polymorphisms and the Risk of Duodenal Ulcer: A Meta-Analysis

Background

Epidemiological studies have evaluated the association between tumor necrosis factor α (TNF-α) single nucleotide polymorphisms (SNPs) and duodenal ulcer (DU), but the results remain inconclusive. The aim of this study was to perform a meta-analysis to investigate a more authentic association between TNF-α SNPs and DU.

Methods

We performed the meta-analysis by searching PubMed, Embase, and Web of Science databases from the first available year to Sep. 5, 2012. Additionally, checking reference lists from identified articles, reviews, and the abstracts presented at related scientific societies meetings were also performed. All case-control studies investigating the association between TNF-α SNPs and DU risk were included. The association was assessed by odds ratio (OR) with 95% confidence interval (CI). Publication bias was analyzed by Begg''s funnel plot and Egger''s regression test.

Results

A total of sixteen studies reporting TNF-α −308G/A, −1031T/C, −863C/A, −857C/T, and −238G/A polymorphism were included in our final meta-analysis. There was no statistically significant association between −308G/A polymorphism and DU in the overall study population, as well as subgroup analyses by ethnicity, study design, and H. pylori status. As for −1031T/C, −863C/A, −857C/T, and −238G/A, results of our meta-analyses showed no statistical evidence of significant association. Power calculation on the combined sample size showed that the statistical powers were all lower than 80% for all the meta-analyses.

Conclusions

The data suggests that there is no statistical evidence of significant association between the studied TNF-α SNPs and DU. However, this conclusion should be interpreted with caution as low statistical powers were revealed by power calculations. In future, larger sample-size studies with homogeneous DU patients and well-matched controls are required.     

Estimating the Size of HIV Key Affected Populations in Chongqing,China, Using the Network Scale-Up Method

Objectives

To estimate the average social network size in the general population and the size of HIV key affected populations (KAPs) in Chongqing municipality using the network scale-up method (NSUM).

Methods

A general population survey was conducted in 2011 through a multistage random sampling method. Participants aged between 18 and 60 years were recruited. The average social network size (c) was estimated and adjusted by known population method. The size of HIV KAP in Chongqing municipality was estimated using the adjusted c value with adjustment for the transmission effect using the scaled respect factor.

Results

3,026 inhabitants of Chongqing agreed to the survey, and 2,957 (97.7%) completed the questionnaire. The adjusted c value was 310. The estimated size of KAP was 28,418(95% Confidence Interval (CI):26,636∼30,201) for female sex workers (FSW), 163,199(95%CI:156,490∼169,908) for clients of FSW, 37,959(95%CI: 34,888∼41,030) for drug users (DU), 14,975(95%CI:13,047∼16,904) for injecting drug users (IDU) and 16,767(95%CI:14,602∼18,932) for men who have sex with men (MSM). The ratio of clients to FSW was 5.74∶1, and IDU accounted for 39.5% of the DU population. The estimates suggest that FSW account for 0.37% of the female population aged 15–49 years in Chongqing, and clients of FSW and MSM represent 2.09% and 0.21% of the male population aged 15–49 years in the city, respectively.

Conclusion

NSUM provides reasonable population size estimates for FSW, their clients, DU and IDU in Chongqing. However, it is likely to underestimate the population size of MSM even after adjusting for the transmission effect.     

Efficacy of 6-amino-2-n-pentylthiobenzothiazole onTrichophyton in vitro and in vivo

In vitro and in vivo antifungal activities of synthetically parepared 6-animo-2-n-pentylthiobenzothiazole (APB) againstTrichophyton strains were studied. APB inhibited the growth of 3Trichophyton strains at 65 µg/ml. 2-Mercaptobenzothiazole was not effective at 125 µg/ml and ketoconazole inhibited the growth at 20–30 µg/ml. Treatment of experimental dermatophytosis in guinea pigs using 2.5% APB cream was studied in comparison to Canesten cream (1% clotrimazole). Dermatophytosis was considerably reduced after both APB and Canesten therapies.     

Determination of retinol and retinyl esters in human plasma by high-performance liquid chromatography with automated column switching and ultraviolet detection

A HPLC method with automated column switching and UV detection is described for the simultaneous determination of retinol and major retinyl esters (retinyl palmitate, retinyl stearate, retinyl oleate and retinyl linoleate) in human plasma. Plasma (0.2 ml) was deproteinized by adding ethanol (1.5 ml) containing the internal standard retinyl propionate. Following centrifugation the supernatant was directly injected onto the pre-column packed with LiChrospher 100 RP-18 using 1.2% ammonium acetate–acetic acid–ethanol (80:1:20, v/v) as mobile phase. The elution strength of the ethanol containing sample solution was reduced by on-line supply of 1% ammonium acetate–acetic acid–ethanol (100:2:4, v/v). The retained retinol and retinyl esters were then transferred to the analytical column (Superspher 100 RP-18, endcapped) in the backflush mode and chromatographed under isocratic conditions using acetonitrile–methanol–ethanol–2-propanol (1:1:1:1, v/v) as mobile phase. Compounds of interest were detected at 325 nm. The method was linear in the range 2.5–2000 ng/ml with a limit of quantification for retinol and retinyl esters of 2.5 ng/ml. Mean recoveries from plasma were 93.4–96.5% for retinol (range 100–1000 ng/ml) and 92.7–96.0% for retinyl palmitate (range 5–1000 ng/ml). Inter-assay precision was ≤5.1% and ≤6.3% for retinol and retinyl palmitate, respectively. The method was successfully applied to more than 2000 human plasma samples from clinical studies. Endogenous levels of retinol and retinyl esters determined in female volunteers were in good accordance with published data.     

Simultaneous determination of seven penicillins in muscle, liver and kidney tissues from cattle and pigs by a multiresidue high-performance liquid chromatographic method

A high-performance liquid chromatographic (HPLC) method based on solid-phase extraction (SPE) was developed for determination of amoxicillin, penicillin G (benzylpenicillin), ampicillin, oxacillin, cloxacillin, nafcillin and dicloxacillin in muscle, liver and kidney tissues of pigs and cattle. The compounds were extracted in aqueous solution by precipitation of organic materials with a mixture of sulphuric acid and sodium tungstate. The extract was cleaned up by SPE on a divinylbenzene-co-N-vinylpyrrolidone polymeric sorbent. Further clean-up was performed by liquid–liquid partition with diethyl ether. The extract was derivatised with benzoic anhydride and 1,2,4-triazole mercury (II) reagent. Chromatography was performed by reversed-phase gradient HPLC on a C₁₈ column with ultraviolet detection at 323 nm. The limits of detection estimated by a conservative model were in the range 8.9–11.1 μg/kg for amoxicillin, penicillin G, ampicillin, oxacillin, cloxacillin and nafcillin and 18.3–20.9 μg/kg for dicloxacillin. The mean recovery range was 66–77% for amoxicillin, 73–75% for penicillin G, 81–82% for ampicillin, 73–76% for oxacillin, 74–75% for cloxacillin, 66–72% for nafcillin and 58–65% for dicloxacillin.     

Candidal vaginitis in hormone-treated mice: Prevention by a chitin extract

In view of findings from previous studies that a chitin soluble extract (CSE) blocked adhesion of Candida albicans in vitro and in vivo and prevented thereby a short lived candidal infection in naive mice, we attempted in the present study to block by CSE the development of a persistent infection, induced in hormone-treated animals. Continuous oestrus phase was obtained in mice by repeated weekly subcutaneous injections with estradiol benzoate. Intravaginal inoculation of the hormone-treated mice with 10⁷–10¹⁰ C. albicans cells induced a persistent candidal infection. Fifty three mice were pretreated intravaginally prior to inoculation of C, albicans with 2.5, 5.0 or 10 mg/mouse of a CSE cream and followed up for development of infection in comparison to 30 untreated animals. Twenty four hrs post fungus inoculation the infection rate among the CSE treated mice was 11–23% VS 84% among the controls; the rate increased a week later to 97% among the controls VS 41–50% among the CSE treated. Administering the CSE to the mice prior — and post-yeast inoculation (37 mice), led to increased efficacy of the treatment. The data, indicating that CSE is an effective measure for preventing persistent candidal vaginitis, may open the way to consider a similar approach for prophylaxis of vaginitis in human susceptible populations.     

Cream fermentation by a mixed culture of lactococci entrapped in two-layer calcium alginate gel beads

This investigation was directed towards the development of a process which produces a fermented cream of greatly reduced cell number.Lactococcus lactis subsp.Lactis andLactococcus lactis subsp.lactis biovardiacetylactis were entrapped separately in normal or two-layer Ca-alginate gel beads. Pasteurized cream (31% fat content) was inoculated with free-cells and with normal or two-layer beads. When 8% of the total volume was occupied by the gel, there was 300–800 times more inoculum in this system and the fermentation time was considerably reduced (5h against 18h). When pH 5.0 was reached, the residual free-cell count was 150 and 1800 times less than for a classical inoculation method with free-cells for normal and two-layer beads respectively. This result was reproducible for several consecutive runs. Also, the problems linked to storage acidification (souring, wheying-off) appeared later and living lactic acid bacteria were maintained in the product.     

Simultaneous determination of six penicillins in cows'' raw milk by a multiresidue high-performance liquid chromatographic method

A high-performance liquid chromatographic method based on C₁₈ solid-phase extraction and ultraviolet detection at 323 nm of analytes derivatized with benzoic anhydride and 1,2,4-triazole mercuric chloride solution was developed for the simultaneous determination of amoxicillin, penicillin G (benzylpenicillin), ampicillin, oxacillin, cloxacillin and dicloxacillin residues in raw milk. The detection limit of the method was 1.3 μg/l for penicillin G; 1.4 μg/l for amoxicillin, oxacillin and cloxacillin, 1.5 μg/l for ampicillin and 2.7 μg/l for dicloxacillin. The mean recovery was 95–102% for amoxicillin, penicillin G and ampicillin, 92–98% for oxacillin and cloxacillin and 87–94% for dicloxacillin, measured by using an internal standard. The relative repeatability standard deviation was 4–9% on level 4–15 μg/l, respectively, 2–7% on level 30–40 μg/l.     

Benzoyl Peroxide and Sulfur: Foundation for Acne Management

One hundred and thirteen consecutive patients with acne were studied by qualified dermatologists during a trial of topical 10% benzoyl peroxide and 2%-5% sulfur cream. The results were considered “good” to “excellent” in both office and clinic situations. The method was remarkably free of undesirable side effects. The program has been adopted as a standard acne regimen at the dermatology clinic of the Royal Victoria Hospital, Montreal.     

Determination of gestrinone in human serum by liquid chromatography–electrospray tandem mass spectrometry

A rapid, sensitive and specific high-performance liquid chromatography–electrospray tandem mass spectrometric method has been developed for the determination of gestrinone (R 2323) in human serum using mifepristone (RU 486) as an internal standard. R 2323 was extracted from human serum by an ether extraction procedure. Multiple reaction monitoring was used to detect R 2323 and RU 486. The calibration curve was linear over the range of 3.5–177 ng/ml (r²≥0.99) with the limitation of detection of 0.8 ng/ml. The intra-day precision and accuracy, expressed as C.V. and RE, ranged from 2.3–13.7 to −4.8–3.0%. The inter-day precision and accuracy ranged from 5.5–14.8 to −6.7–3.1%. The mean recovery was 91.0% for R 2323, and 90.6% for the internal standard. The method was successfully applied to the pharmacokinetic study of R 2323.     

Simultaneous determination of citalopram, fluoxetine, paroxetine and their metabolites in plasma and whole blood by high-performance liquid chromatography with ultraviolet and fluorescence detection

A method for the simultaneous determination of the three selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, paroxetine and their metabolites in whole blood and plasma was developed. Sample clean-up and separation were achieved using a solid-phase extraction method with C₈ non-endcapped columns followed by reversed-phase high-performance liquid chromatography with fluorescence and ultraviolet detection. The robustness of the solid-phase extraction method was tested for citalopram, fluoxetine, paroxetine, Cl-citalopram and the internal standard, protriptyline, using a fractional factorial design with nine factors at two levels. The fractional factorial design showed two significant effects for paroxetine in whole blood. The robustness testing for citalopram, fluoxetine, Cl-citalopram and the internal standard revealed no significant main effects in whole blood and plasma. The optimization and the robustness of the high-performance liquid chromatographic separation were investigated with regard to pH and relative amount of acetonitrile in the mobile phase by a central composite design circumscribed. No alteration in the elution order and no significant change in resolution for a deviation of ±1% acetonitrile and ±0.3 pH units from the specified conditions were observed. The method was validated for the concentration range 0.050–5.0 μmol/l with fluorescence detection and 0.12–5.0 μmol/l with ultraviolet detection. The limits of quantitation were 0.025 μmol/l for citalopram and paroxetine, 0.050 μmol/l for desmethyl citalopram, di-desmethyl citalopram and citalopram-N-oxide, 0.12 μmol/l for the paroxetine metabolites by fluorescence detection, and 0.10 μmol/l for fluoxetine and norfluoxetine by ultraviolet detection. Relative standard deviations for the within-day and between-day precision were in the ranges 1.4–10.6% and 3.1–20.3%, respectively. Recoveries were in the 63–114% range for citalopram, fluoxetine and paroxetine, and in the 38–95% range for the metabolites. The method has been used for the analysis of whole blood and plasma samples from SSRI-exposed patients and forensic cases.     

Measurement of dexfenfluramine metabolism in rat liver microsomes by gas chromatography–mass spectrometry

A specific and useful method was developed for the determination of dexfenfluramine metabolism by microsomal systems utilising GC–MS. The synthesis of two metabolites 1-(3-trifluoromethylphenyl)propan-2-ol (‘alcohol') and 1-(3-trifluoromethylphenyl)-1,2-propanediol (‘diol') via straightforward routes, were confirmed by MS and NMR spectra. The conditions for extraction from alkalinised microsomal mixtures of the metabolites nordexfenfluramine, 1-(3-trifluoromethylphenyl)propan-2-one (‘ketone'), alcohol and diol, their conversion to trifluoroacetate derivatives and analysis by GC–MS–SIM are described. Calibration curves were constructed between 48 and 9662 nM and fitted to quadratic equations (r²>0.999). The method precision was good over low (121 nM) medium (2415 nM) and above medium (9662 nM) concentrations for all metabolites; the within- and day-to-day coefficients of variation ranged between 2.5–12.4% and 6.7–17.5%, respectively. The accuracy, measured as bias, was very good both within- and day-to-day (range: −0.4–12.6%, 0.8–18.9%). For most metabolites, the C.V. for the assay and bias increased at 121 nM. Dexfenfluramine metabolism by rat liver microsomes was investigated using the assay method and showed a concentration dependent increase in nordexfenfluramine and ketone metabolites over the substrate range of 5–200 μM.     

Simultaneous determination of artemether and its major metabolite dihydroartemisinin in plasma by gas chromatography–mass spectrometry-selected ion monitoring

A sensitive, selective, and reproducible GC–MS–SIM method was developed for determination of artemether (ARM) and dihydroartemisinin (DHA) in plasma using artemisinin (ART) as internal standard. Solid phase extraction was performed using C₁₈ Bond Elut cartridges. The analysis was carried out using a HP-5MS 5% phenylmethylsiloxane capillary column. The recoveries of ARM, DHA and ART were 94.9±1.6%, 92.2±4.1% and 81.3±1.2%, respectively. The limit of quantification in plasma was 5 ng/ml (C.V.≤17.4% for ARM and 15.2% for DHA). Calibration curves were linear with R²≥0.988. Within day coefficients of variation were 3–10.4% for ARM and 7.7–14.5% for DHA. Between day coefficients of variations were 6.5–15.4% and 7.6–14.1% for ARM and DHA. The method is currently being used for pharmacokinetic studies. Preliminary data on pharmacokinetics showed C_max of 245.2 and 35.6 ng/ml reached at 2 and 3 h and AUC_0–8h of 2463.6 and 111.8 ngh/ml for ARM and DHA, respectively.     

Determination of ritodrine in biological fluids of the pregnant sheep by fused-silica capillary gas chromatography using electron-capture detection

A sensitive and selective gas chromatographic assay method employing splitless injection, fused-silica capillary columns and electron-capture detection is reported for the quantitation of the tocolytic drug, ritodrine, in a variety of biological fluids obtained from the pregnant ewe and fetus. This method has improved sensitivity and selectivity over previously published assay procedures. A 25 m × 0.31 mm I.D., cross-linked 5% phenylmethylsilicone, fused-silica capillary column was employed for all analyses. Linearity of response was observed over the range 2.5–75 ng of ritodrine base per 0.05–0.5 ml of biological fluid, representing ≈ 1–75 pg at the detector. The coefficient of variation was less than 10% over the range 2.5–75 ng of added ritodrine. The minimum quantifiable amounts is ≈ 2.5 ng from a 0.5-ml biological fluid sample. Applicability of this method to biological fluids, obtained from ovine subjects, is demonstrated by the analysis of samples obtained during the course of ritodrine placental transfer studies.     

Nitrogen fixation of field-inoculatedLeucaena leucocephala (Lam.) de Wit estimated by the15N and the difference methods

The amount of nitrogen fixed byLeucaena leucocephala (Lam.) de Wit was assessed on an Alfisol at the International Institute of Tropical Agriculture located in southwestern Nigeria. Estimated by the difference method, nitrogen fixation of leucaena inoculated with Rhizobium strain IRc 1045 was 133 kg ha^–1 in six months. Inoculation with Rhizobium strain IRc 1050 gave a lower nitrogen fixation of 76 kg ha^–1. Fertilization with 40 and 80 kg N ha^–1 inhibited nitrogen fixation by 43–76% and 49–71%, respectively. Estimates with the¹⁵N dilution method gave nitrogen fixation of 134 kg ha^–1 in six months when leucaena was inoculated with Rhizobium strain IRc 1045 and 98 kg ha^–1 for leucaena inoculated with Rhizobium strain IRc 1050. This nitrogen fixation represented 34–39% of the plant nitrogen. Inoculated leucaena derived 5–6% of its nitrogen from applied fertilizer and 56–54% from soil.     

Pimecrolimus Cream 1% in the Management of Atopic Dermatitis in Pediatric Patients: A Meta-Analysis

Objective

To evaluate the efficacy and safety of pimecrolimus cream 1% in the treatment of AD in the pediatric population.

Methods

PubMed, EMBASE, Web of Science and Cochrane library databases were searched till July 2013. The randomized and nonrandomized blinded studies of pimecrolimus cream 1% applied twice daily with Jaded score ≥3 in pediatric patients with AD were included. The efficacy outcomes included investigator global assessment (IGA), eczema area and severity index (EASI) scores, pruritus and care giver''s assessments and flares free period. Adverse events were reviewed to assess the safety.

Results

Out of 81 studies, 7 were selected that enrolled 2,170 pediatric patients. The pooled analysis reported that pimecrolimus was no better to vehicle reducing eczema at day-8, day-26 and six weeks (OR 4.95, 95% CI 2.79–8.80), (OR 9.69, 95% CI 4.12–22.83) and (OR 3.83. 95% CI 1.94–7.56), respectively in children. Similarly, pimecrolimus did not show beneficial effects when analyzed for mild or absent pruritus at day 4 (OR 8.29, 95% CI 3.88–17.72 favoring vehicle), day 43 (OR 1.81 95% CI 1.13–2.89 favoring vehicle) and 1 week (OR 2.29, 95%CI 1.45 to 3.60 favoring vehicle) as compared with vehicle. One study comparing pimecrolimus with tacrolimus found no significant difference in achieving mild or absent pruritus (OR 0.94, 95% CI 0.44–1.99). More patients showed an improvement in overall disease in vehicle group at day 8 (OR 3.30, 95% CI 2.03–5.35), day 29 (OR 14.14, 95% CI 6.87–29.13) and day 43 (OR 4.11, 95% CI 2.59–6.52) as compared with pimecrolimus 1% group, as assessed by caregivers. No significant difference was seen between the total AEs in both groups (pimecrolimus vs vehicle/tacrolimus) (OR 1.19, 95% CI 0.85, 1.65)

Conclusion

The results of the present meta-analysis showed that pimecrolimus cream 1% was not significantly better to vehicle for AD in pediatrics population.     

Telmisartan anti‐cancer activities mechanism through targeting N‐cadherin by mimicking ADH‐1 function

This study aimed to investigate if Telmisartan as a novel N‐cadherin antagonist, can overcome cell migration of cancer cells. We investigated the mechanism and influence of Docetaxel and Telmisartan (as an analogous to ADH‐1, which is a well‐known N‐cadherin antagonist) on cancer cells. The effect of ADH‐1 and Telmisartan on cell attachment in PC3, DU145, MDA‐MB‐468 cell lines using recombinant human N‐cadherin was studied. Cell viability assay was performed to examine the anti‐proliferative effects of Telmisartan, ADH‐1 and Docetaxel. Migration was examined via wound healing assay, and apoptosis was determined by flow cytometry. The expression of AKT‐1 as a downstream gene of N‐cadherin signalling pathway was assayed by real‐time PCR. Treatment of PC3, MDA‐MB‐468 and DU145 cells with Telmisartan (0.1 µM) and ADH‐1 (40 µM) resulted in 50%, 58% and approximately 20% reduction in cell attachment to N‐cadherin coated plate respectively. It shows reduction of cell attachment in PC3 and MDA‐MB‐468 cell lines appeared to be more sensitive than that of DU145 cells to the Telmisartan and ADH‐1 treatments. Telmisartan (0.1 µM) and Docetaxel (0.01 nM) significantly reduced cell migration in PC3 and MDA‐MB‐468 cell lines compared with the control group. Using Real‐time PCR, we found that Telmisartan, Docetaxel and ADH‐1 had significant influence on the AKT‐1 mRNA level. The results of the current study for the first time suggest that, Telmisartan, exerts anti‐proliferation and anti‐migration effects by targeting antagonistically N‐cadherin. Also, these data suggest that Telmisartan as a less expensive alternative to ADH‐1 could potentiate Docetaxel anticancer effects.     

Control of the production of individual fusicoccins at different dissolved oxygen concentrations

The regulatory effect of different concentrations of dissolved oxygen on the production of fusicoccins by the fungus Fusicoccum amygdali Del. was studied. The maximum output of total fusicoccins was obtained by using a profiled dissolved oxygen tension (DOT) regime, in which the DOT was maintained at 15–20% during the biomass growth phase and at 5–8% during the fusicoccins production phase. In comparison with the profiled regime, the maintenance of DOT at 15–20% during the whole fermentation shortened the fusicoccins production phase. The fermentation performance at a low DOT (5–8%) inhibited both the accumulation of biomass and the production of fusicoccins. At high DOT (40–50%), an accelerated accumulation of the biomass with an expressed autolysis of mycelia took place, and the production of fusicoccins was lowered. The qualitative composition of individual fusicoccins varied substantially at different DOTs. Fusicoccins, A, C, D, J, H, 16-O-demethyl-J, detretpentenylfusicoccin and some minor fusicoccin metabolites were found in the fermentation broth using the method of liquid secondary ion mass spectrometry. It was established that the profiled DOT regime (15–20% to 5–8%) provided both the maximum concentration of fusicoccins and an enhanced accumulation of the main metabolite – fusicoccin A (FC A). The performance of the fermentation at a DOT of 15–20% decreased the content of FC A by 2–6% in comparison with the profiled DOT regime, and increased the content of fusicoccin C to 14–20% of the total fusicoccins. Fermentation at DOT of 5–8% was characterized by the highest content of the precursors of FC A, the less oxidized fusicoccins H and J, the contents of which were in range 7–12% and 16–17% of total fusicoccins, respectively.