A case of cutaneous Scedosporium apiospermum infection in a patient on a janus kinase inhibitor.

Scedosporium apiospermum is a mold that is usually found in soil and polluted water, but has also been linked to contaminated ambient air in hospitals. This fungus typically behaves as a rare opportunistic pathogen affecting immunocompromised patients in whom disseminated disease can readily occur, causing shock and multiorgan failure. We report the first case of cutaneous Scedosporium apiospermum infection in a patient with rheumatoid arthritis treated with a Janus kinase inhibitor. We also reviewed other cutaneous manifestations of Scedosporium apiospermum reported between 2003 and 2022.

The Incidence of Pinworm (Enterobius Vermicularis) in Pre-school and School Aged Children in the Eastern Slovakia.

Helminth infections caused by Enterobius vermicularis have a cosmopolitan character and most often affect the paediatric pre-school and school age population. The presented study was conducted to determine the prevalence of E. vermicularis in the analyzed population of children in the Eastern Slovakia. The Graham's scotch tape method was used to investigate the presence of Enterobius vermicularis eggs in 390 specimens. The analyzed set consisted of 218 girls and 172 boys, divided by age into three groups - aged from 5 months to 2 years, aged from 3 to 6 years, and aged from 7 to 15 years. Investigation of perianal scotch tapes of children for the presence of E. vermicularis eggs revealed the prevalence of E. vermicularis was P = 3.59 %. Depending on the incidence of E. vermicularis infection, we detected no statistically significant difference (p> 0.05). The prevalence of E. vermicularis in boys was P = 4.07 %, and in girls P = 3.21 %. The highest prevalence of E. vermicularis was recorded in the group of children aged from 3 to 6 years (P = 5.03 %). Most of the samples were positive at age 4 and 5. The lowest prevalence was in the group of children aged from 5 months to 2 years (P = 0.97 %), and the prevalence of E. vermicularis in the group of children aged from 7 to 15 was P = 3.91 %. The difference in the incidence of E. vermicularis infection among different age groups of children was not statistically significant (p> 0.05). Enterobius vermicularis nematode infection and enterobiasis currently represents a major public health problem in Slovakia. At the present its occurrence is the most frequent in the paediatric population. Therefore it is important to introduce a targeted hygienic-epidemiological measure in children's collectives, what also should include proper and effective diagnostics and frequent recurrent therapy.

Medical Evaluation for Exposure Extremes: Cold.

Risk of injury in cold environments is related to a combination of athlete preparedness, preexisting medical conditions, and the body's physiologic response to environmental factors, including ambient temperature, windchill, and wetness. The goal of this section is to decrease the risk of hypothermia, frostbite, and nonfreezing cold injuries as well as to prevent worsening of preexisting conditions in cold environments using a preparticipation screening history, examination, and counseling. Cold weather exercise can be done safely with education, proper preparation, and appropriate response to changing weather conditions.

Medical Evaluation for Exposure Extremes: Cold.

Risk of injury in cold environments is related to a combination of athlete preparedness, preexisting medical conditions, and the body's physiologic response to environmental factors, including ambient temperature, windchill, and wetness. The goal of this section is to decrease the risk of hypothermia, frostbite, and nonfreezing cold injuries as well as to prevent worsening of preexisting conditions in cold environments using a preparticipation screening history, examination, and counseling. Cold weather exercise can be done safely with education, proper preparation, and appropriate response to changing weather conditions.

The relative stability of xylazine hydrochloride polymorphous forms.

All four known xylazine hydrochloride polymorphous forms were obtained and their relative stabilities were compared directly at three different temperatures. At higher temperatures, it is possible to determine the relative stability of all forms directly by measuring the changes in the composition of the mixtures of two polymorphous forms using powder x-ray diffraction methods. At lower temperatures, a solvent was added to the mixture and the changes in composition were determined. Polymorph transition temperatures were determined directly. To predict the transition temperature which was not found using the direct method, the polymorph melting data and determined transition temperatures were used. A phase stability diagram was constructed from the acquired data. The stability of all anhydrous polymorphous forms was compared in the presence of water vapor pressure that was higher than the equilibrium pressure.

Hydration and dehydration kinetics of xylazine hydrochloride.

From the experiments where mixture of xylazine hydrochloride hydrate H and anhydrous X were held at constant conditions, the stable form of xylazine hydrochloride can be found out. To determine equilibrium relative humidity, the unstable form of xylazine hydrochloride was inserted in thermostated humidity chamber and its weight was recorded by weighing the sample outside the chamber. The kinetic model and the rate constant for each condition were determined. The rate constants give information regarding the speed of the process at every experimentally used relative humidity. Thus using the data in coordinates k-p for each temperature it is possible to determine the water vapor pressure of the equilibrium. With this method the phase boundary for xylazine hydrochloride was determined and hydration enthalpy was calculated. The hydration rates of xylazine polymorphs A and X were investigated.

Decontamination by anaerobic stabilisation of the environment contaminated with enteronematode eggs Toxocara canis and Ascaris suum.

Investigations were carried out under operating conditions of Field Composting Factory in Brezno (Slovak Republic) to determine the effect of anaerobic stabilization of organic wastes from public areas on the survival of model helminth Toxocara canis and Ascaris suum eggs. Due to anaerobic conditions, low temperature, low C:N ratio and changes in physical and chemical properties of organic waste, less than 64% of A. suum eggs remained viable after 150 days of stabilisation. The anaerobic stabilisation had a greater effect on the viability of T. canis eggs than on A. suum eggs. The infectivity of T. canis eggs was confirmed by a follow-up experiment in laboratory mice. A small number of T. canis larvae were found in their brain and muscles on day 28 after infection. The results refer to the risks of dissemination, survival and potential spread of endoparasitic developmental stages in the environment through organic wastes subjected to low temperature stabilisation.

Discovery of small-molecule inhibitors of tyrosinase.

To identify novel inhibitors of tyrosinase, a fluorescent assay was developed which is suitable for high-throughput screening. In the assay, oxidation of the substrate by tyrosinase leads to the release of a fluorescent coumarin. Several small molecules were identified that inhibited mushroom tyrosinase in vitro and human tyrosinase in cell culture. These compounds may represent lead structures for therapies targeted at disorders of hyperpigmentation.

A preliminary investigation into the action of anagrelide: thrombopoietin-c-Mpl receptor interactions.

OBJECTIVE: Many studies have validated the clinical efficacy of anagrelide to reduce platelet counts in thrombocythemic conditions. With the ability to support human megakaryopoiesis in vitro using thrombopoietin (TPO), specific investigation of changes in platelet levels can be carried out in human systems. Using CD34(+) stem cells and murine BaF3 cells transfected with the human or murine TPO receptor, c-Mpl (BaF3mpl), the effect of anagrelide on cell differentiation, proliferation, and signaling was examined in the presence of TPO. METHODS: Inhibition of TPO-mediated cell differentiation by anagrelide was evaluated by fluorescein-activated cell sorting analysis. Cell proliferation was monitored by 3-(4,5-dimethylthiazol-2-yl)-5-3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays. Effect of anagrelide on TPO-mediated phosphotyrosine (pTyr) activity was examined by Western analysis of whole cell lysates. RESULTS: In the presence of TPO, anagrelide reduced the number of CD41(+) cells without a reduction in the total mononuclear cell number in a dose-dependent manner. Growth inhibition was also observed in BaF3 cells transfected with human c-Mpl. Anagrelide also reduced TPO-specific pTyr activity in a species-specific manner. No inhibitory effect could be demonstrated with interleukin-3 stimulation. CONCLUSION: Parallel dose-response effects were found in both CD41(+) number and TPO-specific pTyr activity. These results suggest that anagrelide reduces TPO-mediated megakaryocyte proliferation of CD34(+) cells through a mechanism that leads to inhibition of intracellular signaling events. Furthermore, data also suggest that it is a species-specific effect, with no inhibitory activity against the murine receptor. Because there is a less than 10% difference in DNA sequence homology between human and murine receptors, the difference in sequence-specific activity must reside in these amino acid differences.

A medication screening trial evaluation of reserpine, gabapentin and lamotrigine pharmacotherapy of cocaine dependence.

AIMS: To conduct a preliminary evaluation of the safety and efficacy of reserpine, gabapentin or lamotrigine versus an unmatched placebo control as a treatment for cocaine dependence. DESIGN: A 10-week out-patient study using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design. SETTING: The study was conducted at the Cincinnati Medication Development Research Unit (MDRU). PARTICIPANTS: Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty participants were enrolled, with 50 participants completing the final study measures. INTERVENTION: The targeted daily doses of medication were reserpine 0.5 mg, gabapentin 1800 mg and lamotrigine 150 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis. MEASUREMENTS: Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression scale--observer and self-report of cocaine use. Safety measures included adverse events, electrocardiograms (ECGs), vital signs and laboratory tests. FINDINGS: Subjective measures of cocaine dependence indicated significant improvement for all study groups. Urine BE results indicated a significant improvement for the reserpine group (P < 0.05) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. The medications appeared to be tolerated well. CONCLUSIONS: The present findings suggest that reserpine may be worthy of further study as a cocaine dependence treatment.

A placebo-controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments.

AIMS: To conduct a preliminary evaluation of the safety and efficacy of tiagabine, sertraline or donepezil versus an unmatched placebo control as a treatment for cocaine dependence. DESIGN: A 10-week out-patient study was conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design. SETTING: This study was conducted at the Cincinnati Medication Development Research Unit (MDRU) and at an affiliated site in Dayton, Ohio. PARTICIPANTS: Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty-seven participants were enrolled with 55 completing final study measures. INTERVENTION: The targeted daily doses of medication were tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis. MEASUREMENTS: Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression Scale-Observer and self-report of cocaine use. Safety measures included adverse events, ECGs, vital signs and laboratory tests. FINDINGS: Subjective measures of cocaine dependence indicated significant improvement for all study groups. Generalized estimating equations analysis indicated that the tiagabine group showed a trend toward a significant decrease in urine BE level from baseline to weeks 5-8 (P = 0.10) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. CONCLUSIONS: The present findings suggest that tiagabine may be worthy of further study as a cocaine dependence treatment.

An open-label pilot study of methylphenidate in the treatment of cocaine dependent patients with adult attention deficit/hyperactivity disorder.

A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID). Participants received individual substance abuse therapy throughout the trial. Safety measures included adverse events, vital signs, and electrocardiograms. Methylphenidate's efficacy was assessed by both objective and subjective measures. Seventy percent of the participants completed final study measures. Safety measures indicated that methylphenidate was well tolerated by the participants. Subjective efficacy measures suggested that participants evidenced improvement in both cocaine dependence and adult attention deficit/hyperactivity disorder symptoms. Quantitative benzoylecgonine indicated that only those participants categorized as being compliant showed improvement. A double-blind, placebo-controlled study of methylphenidate for this population may be warranted.

Reactivity of reduced [2Fe-2S] ferredoxins parallels host susceptibility to nitroimidazoles.

The kinetics of the electron transfer reaction between reduced [2Fe-2S] ferredoxins and select nitroimidazole antimicrobial agents is reported. The ferredoxins from the protozoan Trichomonas vaginalis and the cyanobacterium Anabaena sp. strain 7120 were studied because they are the proximal electron donors to nitroimidazoles in these two organisms with significantly different nitroimidazole susceptibilities. The rates of electron transfer from Anabaena ferredoxin to all nitroimidazoles were 1 to 2 orders of magnitude lower than for T. vaginalis ferredoxin. Quantitative structure-activity analysis of the kinetic data showed that the size of the alkyl substituent on the N-1 position of the imidazole ring strongly influenced the magnitude of the electron transfer rate constant. This implies that the distance between the iron-sulfur cluster and the nitro group of the imidazole is the critical variable in determining the rate of electron transfer. A correlation between the magnitude of the one-electron transfer rate constant with the susceptibility of the host organism to the cytotoxic effects of nitroimidazoles was also discovered. These results demonstrate that reductive activation is the most crucial step in determining the toxicity of nitroimidazoles.

The crystal structure of Trichomonas vaginalis ferredoxin provides insight into metronidazole activation.

Crystallographic studies revealing the three-dimensional structure of the oxidized form of the [2Fe-2S] ferredoxin from Trichomonas vaginalis (TvFd) are presented. TvFd, a member of the hydrogenosomal class of ferredoxins, possesses a unique combination of redox and spectroscopic properties, and is believed to be the biological molecule that activates the drug metronidazole reductively in the treatment of trichomoniasis. It is the first hydrogenosomal ferredoxin to have its structure determined. The structure of TvFd reveals a monomeric, 93 residue protein with a fold similar to that of other known [2Fe-2S] ferredoxins. It contains nine hydrogen bonds to the sulfur atoms of the cluster, which is more than the number predicted on the basis of the spectroscopic data. The TvFd structure contains a large dipole moment like adrenodoxin, and appears to have a similar interaction domain. Our analysis demonstrates that TvFd has a unique cavity near the iron-sulfur cluster that exposes one of the inorganic sulfur atoms of the cluster to solvent. This cavity is not seen in any other [2Fe-2S] ferredoxin with known structure, and is hypothesized to be responsible for the high rate of metronidazole reduction by TvFd.

Treatment of sanitary-important bacteria by bacteriocin substance V24 in cattle dung water.

Quantification of sanitary-important bacteria (e.g. Enterobacteriaceae), as well as indicators of environmental contamination, was assessed in samples of cattle dung from 25 cattle farms in 15 north-eastern Slovakia districts. The inhibitory effect of crude bacteriocin extract CBE V24 from Enterococcus faecalis V24 against Listeria monocytogenes Ohio and Yersinia enterocolitica YE85 was examined in cattle dung water with the aim of finding a new way of eliminating the health risk of the animal slurry. The following bacterial groups were quantified: Salmonella spp., Shigella-like spp. , Proteus spp., Enterobacter spp., Citrobacter spp., Pseudomonas spp. , Escherichia coli, Listeria spp., staphylococci, streptococci and enterococci (the average count ranged from 102 up to 104 cfu ml-1). Antagonistic effect of the crude bacteriocin from Enterococcus faecalis V24 in the range of 100-600 Arbitrary units per ml (AU ml-1) was shown against the following bacteria: Enterobacter cloacae, Ent. asburiae, Proteus spp., Salmonella spp., Acinetobacter lwoffi, L. monocytogenes as well as Y. enterocolitica YE85. During tests performed to study the inhibitory effect of the crude bacteriocin CBE V24 (concentration 800, 1600 AU ml-1) against L. monocytogenes Ohio and Y. enterocolitica YE85 in experimentally contaminated cattle dung, a reduction of 2.03 and 1.44 log cfu ml-1, respectively, was already noted after 1 h after crude bacteriocin CBE V24 addition.

Antimicrobial effect of enterocin CCM 4231 in the cattle slurry environment.

The antagonistic effect of enterocin CCM 4231 towards enterococci, staphylococci, Escherichia coli, listeriae and pseudomonads in the cattle slurry environment was assessed during periods of 1 and 2 weeks. The maximum decrease in the viable cells of enterococci and staphylococci (5.39 to 1.1 log CFU ml-1, and 4.3 to 2.3 log CFU ml-1, respectively) was detected on the second day after enterocin CCM 4231 addition to cattle slurry. E. coli cells, listeriae and pseudomonads decreased insignificantly. After 1 week, enterococci were completely inhibited. Staphylococci were suppressed by reaching a 1.8 log CFU ml-1 difference between the experimental and the control samples. A stable suppressive effect of enterocin CCM 4231 on the growth of listerial cells became significant with 2.59 log CFU ml-1 between the experimental and the control samples in the second week of bacteriocin addition. This was demonstrated in an experiment with enterocin addition to slurry which was sterilized and then inoculated with Listeria monocytogenes Ohio culture. Further possibilities of using bacteriocins for the treatment of animal waste are discussed.

Occurrence of bacteriocin production among environmental enterococci.

The occurrence of enteroccoci in cattle dung water from the basins of 25 cattle farms of 15 northeastern Slovakia districts was screened as well as bacteriocin production among selective enterococcal isolates. The average total count of enterococci detected reached 5.0 x 10(3) cfu ml-1. Enterococcus faecium was the predominant species (25%) followed by Ent. casseliflavus (19.2%), Ent. faecalis (9.6%), Ent. avium and Ent. durans (1.9%). The antagonistic activity of isolates showed a mainly antilisterial effect. Enterococcus faecalis V24 strain produced a heat stable, largely hydrophobic antimicrobial substance with best production in the range pH 4 to 7 and with a strong inhibitory effect even against Gram-negative bacteria.