The antibiotic furagin and its derivatives are isoform-selective human carbonic anhydrase inhibitors.

The clinically used antibiotic Furagin and its derivatives possess inhibitory activity on human (h) carbonic anhydrases (CA, EC 4.2.1.1), some of which are highly expressed in various tissues and malignancies (hCA IX/XII). Furagin exhibited good hCA IX and XII inhibition with KIs of 260 and 57 nM, respectively. It does not inhibit off-target CA I and poorly inhibited CA II (KI = 9.6 µM). Some synthesised Furagin derivatives with aminohydantoin moieties as zinc binding group exhibited weak inhibition of CA I/II, and good inhibition of CA IX/XII with KIs ranging from 350 to 7400 and 150 to 5600 nM, respectively. Docking and molecular dynamics simulations suggest that selectivity for the cancer-associated CA IX/XII over CA II is due to strong H-bond interactions in CA IX/XII, involving the tail orientated towards hydrophobic area of the active site. These results suggest a possible drug repurposing of Furagin as anti-cancer agent.

Is it possible to find presence of lactose in pharmaceuticals? - Preliminary studies by ATR-FTIR spectroscopy and chemometrics.

Lactose and saccharose have the same molecular formula; however, the arrangement of their atoms is different. A major difference between lactose and saccharose with regard to digestion and processing is that it is not uncommon for individuals to be lactose intolerant (around two thirds of the population has a limited ability to digest lactose after infancy), but it is rather unlikely to be saccharose intolerant. The pharmaceutical industry uses lactose and saccharose as inactive ingredients of drugs to help form tablets because of their excellent compressibility properties. Some patients with severe lactose intolerance may experience symptoms of many allergic reactions after taking medicine that contains this substance. People who are specifically "allergic" to lactose (not just lactose intolerant) should not use tablets containing this ingredient. Fourier Transform Infrared (FTIR) spectroscopy has a unique chemical fingerprinting capability and plays a significant important role in the identification and characterization of analyzed samples and hence has been widely used in pharmaceutical science. However, a typical FTIR spectrum collected from tablets contains a myriad of valuable information hidden in a family of tiny peaks. Powerful multivariate spectral data processing can transform FTIR spectroscopy into an ideal tool for high volume, rapid screening and characterization of even minor tablet components. In this paper a method for distinction between FTIR spectra collected for tablets with or without lactose is presented. The results seem to indicate that the success of identifying one component in FTIR spectra collected for pharmaceutical composition (that is tablet) is largely dependent on the choice of the chemometric technique applied.

Multi-technique approach for qualitative and quantitative characterization of furazidin degradation kinetics under alkaline conditions.

Degradation of drug furazidin was studied under different conditions of environmental pH (11-13) and temperature (30-60°C). The novel approach of hybrid hard- and soft-multivariate curve resolution-alternating least squares (HS-MCR-ALS) method was applied to UV-vis spectral data to determine a valid kinetic model and kinetic parameters of the degradation process. The system was found to be comprised of three main species and best characterized by two consecutive first-order reactions. Furazidin degradation rate was found to be highly dependent on the applied environmental conditions, showing more prominent differences between both degradation steps towards higher pH and temperature. Complimentary qualitative analysis of the degradation process was carried out using HPLC-DAD-TOF-MS. Based on the obtained chromatographic and mass spectrometric results, as well as additional computational analysis of the species (theoretical UV-vis spectra calculations utilizing TD-DFT methodology), the operating degradation mechanism was proposed to include formation of a 5-hydroxyfuran derivative, followed by complete hydrolysis of furazidin hydantoin ring.

[Acute tonsillopharyngitis: the effectiveness of topical therapy].

The objective of the present study was to evaluate the clinical effectiveness of a furasol sore throat gargle solution for the treatment of acute tonsillopharyngitis. Forty patients presenting with acute tonsillopharyngitis were allocated to two groups, 20 subjects in each, by means of independent sequential randomization. Prior to the onset of the treatment, all the patients were examined for determining the species composition of pharyngeal microflora with the use of an «AutoScan4 System¼ analyzer («Siemens¼, USA) and estimating the resistance to antibacterial preparations (by the disk diffusion method). All the participants of the study were prescribed antibacterial therapy. In the patients of group 1 (study group), the antibacterial treatment of acute tonsillopharyngitis was supplemented by a furasol sore throat gargle solution whereas those of group 2 (controls) were treated without topical therapy. The quantitative evaluation of the severity of manifestations of the disease before and after the treatment was based on a 5-point visual-analog scale. It was shown that systemic antibacterial therapy resulted in the consistent decrease of the frequency of occurrence of pathogenic and potentially pathogenic microflora in the patients comprising both groups. Treatment with a furasol sore throat gargle solution did not lead to the appearance of bacterial species alien to the oropharynx, nor was it accompanied by the impairment of resistance of its mucous membrane to the colonization by microorganisms. The results of the study give evidence of the well apparent regression of the subjective signs of tonsillopharyngitis and the inflammatory changes in the mucous membrane of the pharynx in the patients given the topical treatment in the form of a furasol sore throat gargle solution in addition to antibacterial therapy. It is concluded that a furasol sore throat gargle solution can be recommended for the introduction into the combined treatment of the patients presenting with acute tonsillopharyngitis.

[Antibacterial therapy for acute cystitis in the age of growing pathogen resistance].

Acute cystitis refers to uncomplicated lower urinary tract infections, with the recurrence rates after the first cystitis episode being 50%. The basic treatment for the above diseases is antibacterial therapy, whose efficiency depends entirely on the right choice of a drug during initial empiric therapy. The paper gives the European Association of Urology guidelines and Russian guidelines, which are based on the results of both international (ARESC) and Russian (DARMIS) studies of urinary tract infection pathogens and their susceptibility to antibacterial drugs. Phosphomycin trometamol and furasidine potassium are the drugs of choice to treat acute cystitis in Russia now.

[Comparative efficacy of nitrofurans in children and adolescents with pyelonephritis in presence of crystalluria].

AIM: To evaluate the efficacy of nitrofurans in children and adolescents with pyelonephritis in the presence of crystalluria. SUBJECTS AND METHODS: The study included 50 patients aged 4-14 years with chronic pyelonephritis in the presence of dysmetabolism. The patients underwent general blood test, general urinalysis with an urocytogram, bacteriological examination of urine, biochemical test of serum (uric acid, calcium, phosphorus, magnesium, urea, and creatinine) and 24-hour urinary excretion (uric acid, oxalates, calcium, phosphorus, and magnesium) at hospital admission and over time. The treatment regimen for Group 1 patients after antibiotic therapy involved furamag, Group 2 received furagin. The drugs were used in a dosage of 2 mg/kg/day in 2 divided doses for 14 days. Complaints, major clinical manifestations, crystalluria patterns, and a number of laboratory findings were analyzed over time. RESULTS: The urinary sediment showed leukocyturia and bacteriuria in all the patients, oxaluria in 70% of the patients, uraturia in 10%, and mixed crystalluria in 20%. The main etiological agent of pyelonephritis was Escherichia coli (48.4%). Increased serum uric acid concentrations were revealed in 14% of the patients. Daily urine tests revealed hyperoxaluria, hyperuricosuria, and hypercalciuria in 86, 18, and 8% of the patients, respectively; urinary magnesium excretion was reduced in 86%. After treatment, Group 1 patients showed a more marked therapeutic effect in terms of a number of indicators (leukocyturia, crystalluria, uricosuria, magnesuria). CONCLUSION: The results of the study showed that the antibacterial therapy involving antibiotics and nitrofurans for an exacerbation of chronic pyelonephritis in the presence of crystalluria not only provides an anti-inflammatory effect, but also leads to reductions in the level of crystalluria and the urinary content of uric acid and calcium. There was a significantly marked reduction in crystalluria, serum uric acid, and urinary oxalates and calcium in the children taking furamag. Out of nitrofurans, furamag may be recommended as the drug of choice to treat urinary tract infections in the presence of crystalluria.

[Etiology of acute and chronic pyelonephritis in children in Khabarovsk region].

Microflora of urinary tract was studied in 419 children aged 1 - 17 years and hospitalized due to acute or chronic pyelonephritis. Etiology of inflammatory process was established in 57.8% of cases. According to our study, etiologic structure of causative agents of pyelonephritis did not differ from all-Russian data. The leading positions belonged to Gram-negative microorganisms from Enterobacteriaceae family: Escherichia coli, Proteus mirabilis, and Klebsiella spp. Results of the study point to high susceptibility of main causative agents of pyelonephritis to cephalosporins, aminoglycosides, and fluoroquinolones. High resistance to aminopenicillines was noted. In several isolates from Enterobacteriaceae family significant resistance to nalidixic acid and furazidin was observed.

Ciprofloxacin and furagin in acute cystitis: comparison of early immune and microbiological results.

Furagin (a nitrofurantoin analogue) has the same efficacy in treating acute cystitis as ciprofloxacin, however the duration of therapy is longer. We established a hypothesis that therapy with ciprofloxacin results in faster resolution of mucosal inflammation in comparison with furagin. Rates of urinary secretion of immunoglobulins class A, M and G and interleukin-8 (IL-8) were evaluated before and after initiation of therapy in adult women presenting with acute cystitis confirmed by urine culture. Women were randomised into two groups receiving either ciprofloxacin 250mg twice a day for 3 days (n=13) or furagin 100mg three times a day for 7 days (n=14). Median lengths of follow-up were 4 days and 5 days in the ciprofloxacin and furagin groups, respectively. Treatment with ciprofloxacin resulted in faster eradication of pathogens. No bacteria or nitrates were detected in the ciprofloxacin group, whilst leukocyte esterase was positive in only one case. In the furagin group there were four positive cultures, seven cases with positive nitrates and five cases with positive esterase. Secretion rates of all four substances dropped significantly, but the changes over time were similar in both groups.

[Usefulness of Uro-Vaxom in complex treatment of recurrent urinary tract infections in girls]. / Przydatnosc preparatu Uro-Vaxom w kompleksowym leczeniu nawracajacych zakazen ukladu moczowego u dziewczat.

Uro-Vaxom was used in the treatment of recurrent urinary tract infections in 35 girls. Most of them (34/35) tolerated the drug very well, no side effect were observed. We stopped administration of the Uro-Vaxom in one girl, during the first month of treatment because of vomiting. This way efficiency of Uro-Vaxom was evaluated in the treatment of recurrent urinary tract infections in 34 girls. Uro-Vaxom was found to be a valuable drug, supporting antibiotic therapy in recurrent urinary tract infections caused by E. coli.

Cytogenetic analysis of children under long-term antibacterial therapy with nitroheterocyclic compound furagin.

Cytogenetic analysis of chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) was performed in 109 blood samples from 95 pediatric patients with urinary tract infections (UTIs). Children were exposed to diagnostic levels of X-rays during voiding cystourethrography and subsequently treated for one to 12 months with low doses of furagin - N-(5-nitro-2-furyl)-allylidene-1-aminohydantoin. Furagin is 2-substituted 5-nitrofuran, chemically and structurally similar to well-known antibacterial compound nitrofurantoin. Increased frequencies of CAs were found in children undergoing voiding cystourethrography as compared with the unexposed, acentric fragments being the most frequent alteration (2.03 versus 0.88 per 100 cells, P=0.006). However, a significant decrease in the frequency of acentric fragments was determined with the time elapsed since X-ray examination was performed. A time-independent increase in SCE frequency was found in lymphocytes of children treated with furagin. Total CA frequency did not differ significantly between groups of children with various duration of furagin treatment. However, frequency of chromatid exchanges (triradials and quadriradials) increased significantly with duration of treatment.

A population-based case-control teratologic study of furazidine, a nitrofuran-derivative treatment during pregnancy.

OBJECTIVE: To study human teratogenic potential of furazidine treatment during pregnancy. DESIGN: Pair analysis of cases with congenital abnormalities and matched population controls. SETTING: The Hungarian Case-Control Surveillance of Congenital Abnormalities. PARTICIPANTS: 38,151 pregnant women who had newborn infants without any defects (population control group) and 22,865 pregnant women who had newborns or fetuses with congenital abnormalities between 1980 and 1996. RESULTS: In the case group, 157 (0.7%) and in the control group, 254 (0.7%) pregnant women were treated with furazidine. The case-control pair analysis did not indicate a teratogenic potential of furazidine use during the second to third months of gestation, i.e. in the critical period for major congenital abnormalities. CONCLUSION: Treatment with furazidine during pregnancy did not show teratogenic risk to the fetus.

[Pulmonary reaction after furazidin (Furagin). Case report]. / Plucna reakcja po furazydynie (Furagin). Opis przypadku.

For the first time in Poland we present the case of pulmonary reaction to furazidin which is by chemical structure closely related to nitrofurantoin. 63 years old woman presented generalized symptoms of acute hypersensitivity reaction induced by furazidin as well as features of chronic pulmonary fibrosis. After few months of treatment with this drug patients complained of weight loss, dyspnea on effort, non-productive cough, chills and fever. Radiological and functional evaluation of respiratory system confirmed features of lung fibrosis. Drug provocation test was positive. In vitro furazidin in low concentrations stimulated proliferation of patient's lymphocytes. After cessation of treatment we have observed rapid improvement of clinical, radiological, biochemical and functional parameters.

[Photosensitizing properties and antioxidant activity of furagin--an antimicrobial drug that is a derivative of nitrofuran]. / Fotosensibiliziruiushchie svoistva i antioksidantnaia aktivnost' furagina--antimikrobnogo lekarstvennogo preparata, proizvodnogo nitrofurana.

Photosensitizing effect of antimicrobial drug nitrofuran derivative--furagin N-(5-nitro-2-furil)-allylidencamino-hydantoin) under irradiation with light longer than 280 nm was found. The method of investigation is based on photochemiluminescence of Gly-Trp peptide in aqueous solution. Maximum photosensitizing efficiency was observed at the furagin concentration 0.08 mM when chemiluminescence yield was 33 times greater than photochemiluminescence of Gly-Trp peptide in absence of drug. It was shown that photochemiluminescence sensitized by furagin occurred via free radical way. Life time of the triplet state of furagin determined by flash photolysis was 40 microseconds. A comparison of experimental data with kinetic calculation allowed us to estimate the rate constant of triplet quenching by oxygen ((2.2 +/- 0.3)10(8) M-1.s-1) and the total rate constants of physical quenching and chemical reaction with Gly-Trp peptide ((2.0 +/- 0.4)10(8) M-1.s-1). It was also found in experiments with photochemiluminescence of Gly-Trp peptide sensitized by riboflavin (irradiation with monochromatic light 436 nm) that furagin possesses antioxidant properties twice reducing the intensity of chemiluminescence at the drug concentration 0.029 mM.

[Clinical evaluation of Uro-Vaxom in treatment of recurrent urinary tract infections in girls]. / Kliniczna ocena preparatu Uro-Vaxom w leczeniu nawracajacych zakazen ukladu moczowego u dziewczynek.

Uro-Vaxom was used in the treatment of recurrent urinary tract infections in 28 girls. Most of them (27/28) tolerated the drug very well, no side effects were observed. We stopped administration of the Uro-Vaxom in one girl during the first month of treatment because of vomiting. Uro-Vaxom efficiency was, therefore, evaluated in 27 girls. Uro-Vaxom was found to be a valuable drug, supplementing antibiotic therapy in recurrent urinary tract infections caused by E. coli.

[Results of conservative treatment for regressive vesicoureteral reflux in childhood]. / Wyniki postepowania zachowawczego we wstecznych odplywach pecherzowo-moczowodowych u dzieci.

The study involved 112 children with 169 confirmed vesicoureteric reflux grades I, II, III. During anti-bacterial treatment which lasted at last two years, spontaneous regression occurred in 82% of the vesicoureteral reflux. Renal scars were observed in 8% of the cases. Initially urinary tract infection was diagnosed in 84% of the children. This figure was reduced to 8% after anti-bacterial treatment. 54% of the observed children had associated diseases (anaemia, chronic enteropathy, bronchitis and pneumonia). The results confirmed the efficiency of anti-bacterial treatment in children with vesicoureteral reflux grades I, II, III.

[Effects of a new derivative of 5-alkyl-3N-furanones on the colonization resistance of the intestine in albino mice]. / Vliianie novogo proizvodnogo 5-alkil-3N-furanonov na kolonizatsionnuiu rezistentnost' kishechnika belykh myshei.

By its antagonistic function normal microflora provides the intestine with resistance to colonization with exogenic opportunistic and pathogenic microorganisms. The drug was effective in inducing a decrease in the intestine colonization resistance which in its turn leads to filling of free ecological niches with exogenic microflora. In this connection the suggestion that specification of a new chemical agent should include along with other criteria its effect on colonization resistance is valid. It was shown with the use of indicator microorganisms that when administered per os in doses of 40 and 80 mg/kg daily for 3 and 6 days, respectively, a new original compound 1929, a derivative of 5-alkyl-3H-furanones, with high antimicrobial activity induced no significant or more pronounced changes in the colonization resistance of the gastrointestinal tract of noninbred albino mice than furagin used as the reference drug.

[The effect of nitrofurans on the membrane apparatus of coccal bacteria]. / Deistvie nitrofuranov na membrannyi apparat bakterii kokkovoi gruppy.

Secondary membrane effects on the membrane apparatus of coccus bacteria were being studied. Cultivation of Micrococcus lysodeikticus and Staphylococcus aureus cells on subbacteriostatic concentrations of nitrofurans results in a lower biosynthesis of many membrane proteins, as well as in inhibiting the activity of respiratory enzymes, i. e. the specific concentration of cytochromes and specific activity of NADH-, malate-, lactate oxidases and some reductases drop. Some cytological changes were revealed, when cells were grown on solafur, furazolidone, and furacriline.