Autonomous Defense Based on Biogenic Nanoparticle Formation in Daunomycin-Producing .

Daunomycin is a chemotherapeutic agent widely used for the treatment of leukemia, but its toxicity toward healthy dividing cells limits its clinical use and its production by fermentation. Herein, we describe the development of a specialized cultivation medium for daunomycin production, including a shift to oil rather than sugar as the primary carbon source. This achieved an almost threefold increase in daunomycin yields, reaching 5.

The Daunomycin: Biosynthesis, Actions, and the Search for New Solutions to Enhance Production.

Daunorubicin (DNR) is an anthracycline antibiotic originating from soil-dwelling actinobacteria extensively used to treat malignant tumors. Over the decades, extensive attempts were made to enhance the production of anthracyclines by introducing genetic modifications and mutations in combination with media optimization, but the target production levels remain comparatively low. Developing an appropriate culture medium to maximize the yield of DNR and preventing autotoxicity for the producing organism remains a challenge.

Extracts of Strains from Bee Bread Inhibit the Growth of spp. In Vitro.

Honey bees coexist with fungi that colonize hive surfaces and pollen. Some of these fungi are opportunistic pathogens, but many are beneficial species that produce antimicrobial compounds for pollen conservation and the regulation of pathogen populations. In this study, we tested the in vitro antimicrobial activity of strains isolated from bee bread against (associated with European foulbrood disease) and three species that cause stonebrood disease.

Crude Extracts of Strains (Ascomycota) Affect Honey Bee () Resistance to Chronic Bee Paralysis Virus.

Viruses contribute significantly to the global decline of honey bee populations. One way to limit the impact of such viruses is the introduction of natural antiviral compounds from fungi as a component of honey bee diets. Therefore, we examined the effect of crude organic extracts from seven strains of the fungal genus in honey bee diets under laboratory conditions.

Prograf five milligrams versus Tacrolimus medis in healthy volunteers: a bioequivalence study.

For FDA approval, bioequivalence of a generic version of Tacrolimus must be demonstrated in a randomized, two-treatments, two-periods, two-sequences, single-dose crossover study in healthy adult volunteers. Currently there are at least 3 differents generic equivalent for Tacrolimus, that are approved by the EMA and the FDA, with a USA market share of nearly 50%. However, the market share of generic immunosuppressive drugs in the Middle East region is still very low due to the reluctance of the physician to accept Tacrolimus generics, considered to be a narrow therapeutic window drug, that are approved using the standard bioequivalence criteria of 80% to 125%.

Switchability of neoral and equoral according to Food and Drug Administration rules and regulations.

According to the US Food and Drug Administration (FDA), if a drug product contains a drug substance that is chemically identical and is delivered to the site of action at the same rate and extent as another drug product, then it is equivalent and can be substituted (switchable) for that drug product. Methods used to define bioequivalence as stated by the FDA rules (FDA 21 CFR 320, 24) are (1) pharmacokinetic (PK) studies in healthy volunteers, (2) comparative clinical trials, and (3) pharmacodynamic (PD) studies (bioactivity). We evaluated the switchability of Equoral (IVAX-USA) with Neoral (Novartis Switzerland using all FDA rules.

Combination treatment of rat adjuvant-induced arthritis with methotrexate, probiotic bacteria Enterococcus faecium, and selenium.

The effects of the probiotic bacteria Enterococcus faecium (EF) and selenium were studied on methotrexate (MTX) treatment in rats with adjuvant arthritis. Arthritic rats were treated orally with the following substances: lyophilized EF (15 mg/kg/day, 5 days a week), sodium selenite pentahydrate (SSe; 0.050 mg/kg containing 0.

The effects of Enterococcus faecium and selenium on methotrexate treatment in rat adjuvant-induced arthritis.

The effects of probiotic bacteria Enterococcus faecium (EF) and selenium were studied on methotrexate (MTX) treatment in rats with adjuvant arthritis (AA). Arthritic rats were preventive treated orally with the following substances: lyophilized EF (15mg/kg/day, 5 days a week); sodium selenite pentahydrate (SSe, 0.050mg/kg containing 0.

The role of generics in transplantation: TM-MMF versus Cellcept in healthy volunteers.

Because several studies having revealed a relation between early graft rejection and long-term graft survival, potential benefits have been attributed to MMF. The cost of the drug is, however, prohibitive, which renders its long-term use in countries with limited income. We thus compared the pharmacokinetic profiles of a new MMF generic formulation (MM-Cept developed by Ivax CR) with those of Cellcept (Hoffman La Roche) in healthy volunteers.

The pharmacokinetics of equoral versus neoral in stable renal transplant patients: a multinational multicenter study.

We studied the pharmacokinetics (PKs) of the new generic cyclosporine formulation, Equoral capsules, after the switch from original formulation Neoral capsules in stable renal transplant patients. The study was carried out in accordance with the basic principles defined in the US 21 CFR Part 312.20 and the principles of the Declaration of Helsinki.

Cyclosporine blood level monitoring. Cross-reactivity of anti-cyclosporine A monoclonal with its sulphate metabolite: an in vitro study.

Cyclosporine is metabolized in the liver by the Cytochrom P450 system. Many of the metabolites have been identified and thoroughly studied. However the sulphate metabolite is the least known.

Effects of the entomopathogenic fungus Metarhizium anisopliae and its secondary metabolites on morphology and cytoskeleton of plasmatocytes isolated from the greater wax moth, Galleria mellonella.

The effects of Metarhizium anisopliae infection and three different secondary metabolites released by the fungus, destruxin A and E and cytochalasin D, on the morphology and cytoskeleton of plasmatocytes of the greater wax moth Galleria mellonella were studied. Plasmatocytes isolated from M. anisopliae infected larvae exhibited impairment of attachment, spreading and cytoskeleton formation accompanied with the occurrence of blebbing and pycnotic nuclei.

Effects of the peptide mycotoxin destruxin E on insect haemocytes and on dynamics and efficiency of the multicellular immune reaction.

Destruxins (DTXs) are cyclic peptide toxins secreted by the entomopathogenic fungus Metarhizium anisopliae var. anisopliae. The effects of DTX E, the most active compound of this family on haemocytes, the immunocompetent insect cells, and on the dynamics and efficacy of the multicellular defense of insect hosts have been investigated.

Effects of beauverolide L and cyclosporin A on humoral and cellular immune response of the greater wax moth, Galleria mellonella.

The effects of beauverolide L and cyclosporin A, cyclic peptidic metabolites, produced by several genera of entomopathogenic fungi on immune responses of last instar larvae of the greater wax moth Galleria mellonella have been examined. Intrahemocoelic injection of either metabolite-coated silica particles or dissolved metabolites in a concentrations ranging between 10 and 30 micrograms per larvae caused no mortality but activated humoral responses in G. mellonella larvae.

Detection of a P-glycoprotein related pump in Chironomus larvae and its inhibition by verapamil and cyclosporin A.

A membrane associated ATP-dependent efflux pump, similar in function to mammalian P-glycoprotein, was detected in anal papillae of Chironomus riparius larvae. Immunohistochemical analysis of larval tissues, using monoclonal antibodies against P-glycoprotein, was supplemented by functional in vivo and in vitro assays which confirmed the existence of a mechanism for transporting xenobiotic substances. The in vitro ATPase activity of homogenate fractions increased in the presence of typical P-glycoprotein substrates (vinblastine, actinomycin D or ivermectin).

Destruxin Ed1 a cyclopeptide from the fungus Metarhizium anisopliae.

A new destruxin Ed1 has been isolated from the entomopathogenic fungus Metarhizium anisopliae. Its structure was deduced from the NMR and mass spectral data.

Effects of destruxins, cyclic depsipeptide mycotoxins, on calcium balance and phosphorylation of intracellular proteins in lepidopteran cell lines.

The influence of the destruxin E, cyclodepsipeptidic mycotoxin produced by the filamentous entomopathogenic fungus Metarhizium anisopliae, on calcium fluxes and protein phosphorylation of in vitro cultivated lepidopteran cell lines have been studied. The use of the fluorescent calcium indicator Fura 2 AM did not show a fast increase in the level of cytosolic calcium in lepidopteran and human cell lines treated with dtx E. In contrast, 45Ca+2 assays detected a late but significant calcium influx in insect cells exposed to dtx E and A for at least 30 min.

Fine mapping of randomly distributed multiple deletions of mitochondrial DNA in a case of chronic progressive external ophthalmoplegia.

Multiple deletions of mitochondrial DNA have been detected by Southern blotting in the skeletal muscle of a 42-year-old woman with chronic progressive external ophthalmoplegia. A PCR method, using several combinations of primers covering the whole mtDNA as well as sequence analysis, disclosed the wide spectrum of these multiple deletions differing in size, location and sequence at the breakpoint junction. Most involved the major region between the two replication origins.

Cyclosporins from Tolypocladium terricola.

New natural cyclosporins were isolated from the mycelium of surface cultivated fungus Tolypocladium terricola. The chemical structures of [Leu4] CS and [MeLeu1] CS = cyclosporin-J, were deduced from the NMR and mass spectral data. Biological activity of new cyclosporins is reported based on the proliferative mitogen stimulation test.

Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis.

The penetration of amikacin into the cerebrospinal fluid (CSF) was studied with 16 children (mean age, 1 year and 9 months; range, 4 months to 8 years) with community-acquired bacterial meningitis. Amikacin was given intravenously at a dose of 7.5 mg/kg of body weight twice daily.

Beauverolides L and La from Beauveria tenella and Paecilomyces fumosoroseus.

New beauverolides L and La were isolated and identified from the entomopathogenic fungi, Beauveria tenella and Paecilomyces fumosoroseus. Their structures, cyclo-[3-hydroxy-4-methyldecanoyl-L-phenylalanyl-L-alanyl-D-leucyl ], and cyclo-[3-hydroxy-4-methyldecanoyl-L-phenylalanyl-L-alanyl-D-allo-i soleucyl] were deduced from HPLC and GC-mass spectrometric analyses of their hydrolysates and NMR and mass spectral data.