Impacto del Servicio de Farmacia en la disminución de errores en la medicación en pediatría / Impact of the pharmaceutical actions to decrease medication errors in pediatrics

Estudio descriptivo de errores de medicación en el Tecnológico de Monterrey, Hospital San José Tec Salud, Escuela de Medicina y Ciencias de la Salud.Objetivo: Describir las intervenciones farmacéuticas que contribuyen a tener una tasa de error de medicación por debajo de los estándares internacionales.Material y métodos: Se consideró como error de medicación cualquier fallo en el proceso de medicación. Se revisaron prescripciones por el método de reporte de incidentes en expedientes de pacientes de 0-17 añosA de los últimos 12 meses (2017-2018).Resultados: Se detectaron 776 errores de 6.119 prescripciones (2,47%). El error más común fue aquel relacionado con la dosificación (60,3%). No se reportaron errores que resultaran en daño letal al paciente. El grupo terapéutico con mayor incidencia de errores fue el de los antibióticos seguido de los analgésicos.Conclusión: La intervención multidisciplinaria con el farmacéutico en el proceso de medicación permite una detección oportuna de errores que impacta la seguridad del paciente. (AU)

Descriptive and retrospective study of medical errors at, San Jose Monterrey Hospital School of medicine and Health science.Objective: To describe pharmaceutical interventions in order to keep a low incidence of medical errors.Material and methods: Medical error was defined as any unintended error in medication. We present a 12 Month (2017-2018) retrospective study using incident reports.Results: We identified 776 medication errors over a total of 6,119 reviewed prescriptions. (2.4%) The most frequent errors in prescription were dosage associated (60.3%). No lethal outcomes were reported. The most common group of medication errors were antibiotics followed by analgesics.Conclusion: Involving pharmacists in checking drug prescriptions has been the main factor for detecting and improving pediatric dosages leading to an important improvement in patient safety. (AU)

Competition between Superconductor - Ferromagnetic stray magnetic fields in YBa2Cu3O7-x films pierced with Co nano-rods.

Superconductivity and ferromagnetism are two antagonistic phenomena that combined can lead to a rich phenomenology of interactions, resulting in novel physical properties and unique functionalities. Here we propose an original hybrid system formed by a high-temperature superconducting film, patterned with antidots, and with ferromagnetic nano-rods grown inside them. This particular structure exhibits the synergic influence of superconductor (SC) - ferromagnetic (FM) stray fields, in both the superconducting behaviour of the film and the three-dimensional (3D) magnetic structure of nano-rods. We show that FM stray fields directly influence the critical current density of the superconducting film. Additional functionalities appear due to the interaction of SC stray fields, associated to supercurrent loops, with the non-trivial 3D remanent magnetic structure of FM nano-rods. This work unravels the importance of addressing quantitatively the effect of stray magnetic fields from both, the superconductor and the ferromagnet in hybrid magnetic nano-devices based on high temperature superconductors.

Characterization of a protein kinase C gene in Sporothrix schenckii and its expression during the yeast-to-mycelium transition.

The yeast-to-mycelium transition in Sporothrix schenckii has been shown to respond to protein kinase C (PKC) effectors, indicating the involvement of PKC in this regulation. In this study, we identified the presence of two pkcl-like genes in S. schenckii. Using fungal genomic DNA as template and primers targeted to conserved sequences in the Saccharomyces cerevisiae pkc1 gene, two partially overlapping extra long polymerase chain reaction (XL-PCR) products were obtained. These XL-PCR products were sequenced and found to encode part of the C3/C4 domains of two different PKC-like proteins. The presence of two different genes was confirmed by Southern blot analysis. These two genes were named pkcSs-1 and pkcSs-2. The sequence of the pkcSs-2 gene was completed and revealed an open reading frame of 3942 nucleotides interrupted by five introns. A transcript of 8.7 kb was detected in northern blot analysis of poly A+ RNA. The pkcSs-2 gene encodes a protein of 1194 amino acids and 132.84 kDa that contains the characteristic structure and domains of other fungal PKCs reported to date. Using reverse transcription-PCR (RT-PCR), the pkcSs-2 gene was found to be expressed at all intervals tested during the yeast-to-mycelium transition.

Presence of a pertussis toxin-sensitive G protein alpha subunit in Sporothrix schenckii.

As an initial step in the study of the role of G proteins in signal transduction in Sporothrix schenckii, we identified a Galphai subunit using different experimental approaches. Western blots of fungal membrane preparations using anti-Galphacommon and anti-Galphai1-Galphai2 antibodies identified a band of approximately 41 kDa. Pertussis toxin-catalyzed adenosine diphosphate (ADP)-ribosylation of these membrane fractions confirmed the presence of a protein substrate of 41 kDa. A 357 bp polymerase chain reaction (PCR) product obtained using fungal DNA as template and primers targeted to conserved Galphai sequences, was used as a probe to isolate a clone from an S. schenckii genomic library. A partial sequence for a Galphai subunit was obtained from this clone. The sequence was completed using the rapid amplification of cDNA ends (RACE) technique with mycelium and yeast cDNA. The cDNA sequence revealed a 1059 bp open reading frame encoding a 353 amino acid Galphai subunit of 41 kDa, more than 90% identical to the CPG-1 of Cryphonectria parasitica, and GNA-1 of Neurospora crassa. The genomic sequence was obtained by PCR using fungal DNA, and revealed a 1250 bp sequence and the presence of three introns. These results provide evidence for the first time of the presence and expression of a Galphai homolog in a pathogenic dimorphic fungus.

Different protein kinase C isoforms are present in the yeast and mycelium forms of Sporothrix schenckii.

Protein kinase C (PKC) plays an important role in the control of proliferation and differentiation of a wide range of cell types, and fungi are no exception. Previous results reported by us on the effects of the phorbol ester, 12-myristate-13-acetate phorbol (PMA) and other PKC effector molecules, on dimorphism in Sporothrix schenckii suggested the presence of this enzyme in the fungus and its involvement in the control of morphogenetic transitions. The work summarized here confirms the presence of PKC in yeast and mycelium extracts of S. schenckii. Different isoforms of this enzyme were found to be present in the yeast and mycelium forms of the fungus and were identified by Western blot analysis using affinity purified anti-PKC isoforms specific antibodies: the gamma and zeta isoforms were detected in both the yeast and mycelium forms of the fungus, while the beta isoform was only detected in the yeast form. The presence of PKC was confirmed biochemically by measuring total enzyme activity in both forms of the fungus. No significant differences were observed for the PKC activity level recorded for both the mycelium and yeast forms of the fungus (p < or = 0.05). These data confirm the presence of PKC activity in Sporothrix schenckii and constitutes the first evidence concerning the differential expression of PKC isoforms in the mycelium and yeast forms of a dimorphic fungus, supporting the possible involvement of this important signal transduction enzyme in the control of morphogenesis in this fungus.

Calcium stimulates molecular and cellular events during the yeast-to-mycelium transition in Sporothrix schenckii.

Calcium ions (Ca2+) have been identified as mediators of proliferative and morphogenetic processes in many eukaryotic cells. The effects of these ions on the cellular and macromolecular processes that accompany the dimorphic transition from the yeast-to-mycelial form of Sporothrix schenckii have been studied. Ca2+ were found to stimulate germ tube formation and growth in these cells at an optimal concentration of 1.0 mM. Studies concerning the effects of this cation on the molecular processes that precede germ tube formation revealed that the earliest molecular event which was stimulated by 1.0 mM Ca2+ was RNA synthesis. An increased incorporation of radioactivity into RNA in the presence of 1.0 mM Ca2+ was first observed at 0-3 h, and subsequently at all other times tested, following inoculation. A stimulation in rRNA and tRNA synthesis was detected in the presence of 1.0 mM Ca2+. The incorporation of radioactivity into proteins was stimulated 3-5 h following induction in the presence of Ca2+ suggesting a specific effect of Ca2+ on protein synthesis. This increased incorporation takes place prior to the start of DNA synthesis. Incorporation of radioactivity into DNA was also stimulated in the presence of Ca2+, 6 and 9 h after inoculation. This stimulation resulted in nuclear division taking place with a shorter lag period and proceeding with increased kinetics. The results reported here are evidence that Ca2+ plays a role in the control of the early molecular and cellular processes that accompany the yeast-to-mycelium transition in S. schenckii and offer an explanation of how Ca2+ can control the expression of the dimorphic potential of this fungus.

Effects of calcium ions on the germination of Sporothrix schenckii conidia.

Sporothrix schenckii conidia were induced to germinate in varying concentrations of added calcium. Calcium had a stimulatory effect on the process and a calcium concentration of 1 mM was found to be optimal. Measurements of radioactive calcium uptake confirmed that uptake was taking place during the germination of conidia to the mycelial form of the fungus. Three calcium uptake peaks were observed, the first occurred 10 min after inoculation and the other two peaks coincided with the first 2 cycles of DNA synthesis in these cells. Ionophore A23187 and cobalt sulfate inhibited germination of S. schenckii conidia and altered the normal calcium uptake pattern in these cells. On the other hand, phorbol 12-myristate-13-acetate, a stimulator of protein kinase C (PKC) activity, stimulated germination in medium without calcium. This suggests that PKC activation might account for the germination of conidia in the absence of added calcium. The effects of increasing the calcium concentration on RNA and protein synthesis were also studied. A stimulation of RNA synthesis was found at all times tested with maximum stimulation 6 h after inoculation. A stimulation in protein synthesis was also observed but only after 12 h incubation.

An unusual niche for an opportunistic fungus.

An acrylic on canvas painting from the collection of the Institute of Puerto Rico Culture was found to be stained with light brown spots. Under ultraviolet light it was evident that these spots covered the entire painting. Scotch tape samples from different areas of the painting were taken. In almost all of these samples, septated hyphae were observed to surround the canvas fibers and in most of them, spiny or rough-surfaced conidia were also observed. A sample from the canvas which was incubated over a Sabourand agar plate yielded a fungus very similar to the one observed in the tape samples after subculturing in potato dextrose agar. Slide cultures and culture characteristics provided evidence that this fungus was a species of Scopulariopsis. This fungus has been implicated in human disease and in this case, it was the cause of the deterioration of the painting.

Calcium uptake and efflux during the yeast to mycelium transition in Sporothrix schenckii.

A study was made of calcium metabolism during germ tube formation in Sporothrix schenckii yeast cells. A net efflux of calcium was observed very early in the transformation process and remained constant thereafter. The efflux of calcium in yeast cells induced to form germ tubes was twice that observed in yeast cells not induced to form germ tubes. Two peaks of calcium uptake were observed in germ tube forming yeast cells at 30 and 300 minutes following inoculation, while non-induced yeast cells, a continuous increase in uptake was observed which ultimately reached higher values than the ones obtained in germ tube forming cells. Substances which affect calcium metabolism in other cells such as cobalt ions, ionophore A23187 and compound R24571 were observed to inhibit germ tube formation and calcium uptake. In addition, ionophore A23187 was found to increase calcium efflux to approximately twice the control values. The inhibition of germ tube formation brought about by substances which inhibit calcium uptake or increase efflux suggests that the intracellular calcium concentration in these cells must be precisely regulated for the yeast to mycelium transition to occur.

Effects of zinc on macromolecular synthesis and nuclear division during the yeast to mycelium transition in Sporothrix schenckii.

Zinc ions (10 mM) have been reported previously to inhibit the yeast to mycelium transition in Sporothrix schenckii. Yeast cells of this fungus were harvested, selected by filtration and allowed to form germ tubes in a basal medium with glucose in the presence of 10 mM zinc and the effects of this ion on protein, RNA and DNA synthesis and nuclear division recorded. All of these processes were affected by the addition of 10 mM zinc to the medium. Nevertheless, the inhibition of protein synthesis was observed earlier than that of RNA or DNA synthesis and was of a greater magnitude than that observed for both of these processes. Protein synthesis was inhibited within the first hour after inoculation, at which time this process begins in the control cells. RNA synthesis was inhibited during the 3 to 6 h interval after inoculation, that is, 3 h after the start of this process in the control cells. After 9 h of incubation, the inhibition of protein synthesis had reached its maximum at 70%, while that of RNA synthesis was only 52%. DNA synthesis was slightly inhibited, with maximum inhibition being observed 9 h after inoculation. Nuclear division in cells forming germ tubes in the presence of 10 mM zinc took place with a 3 h delay in relation to the control cells. These observations suggest that the inhibition of protein synthesis might be the most important mechanism by which zinc inhibits the yeast to mycelium transition in S. schenckii.

Yeast cell cycle of Sporothrix schenckii.

Unbudded yeast cells from exponentially growing Sporothrix schenckii were harvested, selected by filtration and allowed to form buds in basal medium with glucose at pH 7.2. These cells undergo bud formation and cell duplication at 25 degrees C earlier than at 35 degrees C. The time of cell duplication at 25 degrees C was dependent upon the initial cell concentration. These cells carried out RNA and protein synthesis before cell evagination as early as 10 min after inoculation, and DNA synthesis during the 6 to 9 h period after inoculation, prior to nuclear division and bud formation. Nuclear division and bud formation seemed to occur concomitantly during the 9 to 12 h period after inoculation and were inhibited by the addition of hydroxyurea (0.1 M) to the medium. The preferred site for bud formation was the pole opposite the birth scar. Septum formation was evidenced at the mother cell-bud junction. A light septum first appeared in medium sized buds followed by a dark septum in large buds.

Molecular and cellular events during the germination of conidia of Sporothrix schenckii.

Hyaline, non pigmented microconidia of Sporothrix schenckii were harvested and allowed to form germ tubes in a basal medium with glucose at pH 4.0 and 25 degrees C. These conditions supported only the development of the mycelial form of Sporothrix schenckii in a reproducible, synchronized manner which allowed further analysis of the early cellular events occurring during the germination of the conidia. The relationship between macro-molecular synthesis (DNA, RNA and protein synthesis) and nuclear division, hyphal growth and septum formation were established. Following inoculation, protein synthesis was observed after 10 minutes followed by RNA synthesis, after 1 h and DNA synthesis after 2 h. The first nuclear division was observed during the 9 to 12 h interval after inoculation. Germ tube formation slightly preceeded nuclear division and was first evidenced 9 h after the induction of germination but was not completed until 12 h after inoculation. Septation was first observed in the germ tubes 0.25 micron from the mother cell-germ tube function 9 h after induction of germination.

Molecular and cellular events during the yeast to mycelium transition in Sporothrix schenckii.

Unbudded singlets from exponentially growing yeast cells of Sporothrix schenckii were harvested, selected by filtration and allowed to form germ tubes in a basal medium with glucose at pH 4.0 and 25 degrees C. These conditions supported only the development of the mycelial form of S. schenckii in a reproducible manner which allowed further analysis of the early cellular events occurring during the yeast-to-mycelium transition. The relationship between macromolecular synthesis (DNA and RNA synthesis) and nuclear division, hyphal growth and septum formation were investigated during germ tube formation. RNA synthesis started 0 to 3 h after the induction of germ tube formation, followed by DNA synthesis and the first nuclear division, which took place between 3 and 6 h. Germ tube formation followed nuclear division and was first evidenced 6 h after the induction of germ tube formation, but was not completed until 12 h after inoculation. Septation was first observed in these germ tubes at the mother cell-germ tube junction 6 h after induction. Addition of hydroxyurea, an inhibitor of DNA synthesis, to the medium, also inhibited nuclear division and germ tube growth, suggesting that these processes in S. schenckii are dependent upon DNA synthesis.

Effects of caffeine, cyclic 3', 5' adenosine monophosphate and cyclic 3', 5' guanosine monophosphate in the development of the mycelial form of Sporothrix schenckii.

The kinetics of the development of the mycelial form of Sporothrix schenckii from yeast cells and conidia in a minimal basal medium with glucose at pH 4.0 and 25 degrees C were established. Germ tube formation was used as the index of germination for both yeast cells and conidia. Yeast cells were first observed to develop germ tubes after 3 h of incubation, reaching 92 +/- 5%, after 12 h of incubation. Germ tubes were first detected in conidia after 9 h of incubation, and 12 h after inoculation 92 +/- 6% of the conidia had germ tubes. After 24 h of incubation, fully developed, sporulating mycelia were observed from both yeast cells and conidia. A delay in germ tube formation from yeast cells was observed when But2cAMP (10 mM) and But2cGMP (10 mM) were added to the medium. Also the addition of caffeine, a cyclic nucleotide phosphodiesterase inhibitor, inhibited the yeast to mycelial transition. Conidial germination into the mycelial form was also inhibited when cAMP, But2cAMP and caffeine were added to the medium. These results suggest the possible involvement of cyclic nucleotides in the control of dimorphism in S. schenckii.

Effects of divalent cations and functionally related substances on the yeast to mycelium transition in Sporothrix schenckii.

In a minimal basal medium with glucose at pH 4.0 and 25 degrees C, a lowering of the magnesium and zinc concentrations or increase in the calcium concentration of the medium favoured the yeast-mycelium transition in Sporothrix schenckii. Addition of zinc (1 and 10 mM) inhibited mycelial development and induced reversion to a yeast-like morphology. EDTA and EGTA also delayed germ tube formation, possibly by their calcium-chelating effects or by altering intracellular concentrations of this or other ions. Ionophore X537A also caused a delay in germ tube formation, possibly by interfering with magnesium metabolism in these cells.

Effects of pH, temperature, aeration and carbon source on the development of the mycelial or yeast forms of Sporothrix schenckii from conidia.

Culture conditions for the exclusive development of the mycelial and the yeast forms of Sporothrix schenckii from conidia in a rich, defined medium were established. Only the mycelial morphology developed when the pH of the medium was adjusted between 4.0 and 5.0 and the conidia were incubated at 25 degrees C, regardless of aeration. When the pH of the medium was adjusted between 6.5 and 8.0 and the conidia were incubated with aeration at 35 degrees C, only the yeast form was obtained. Using these culture conditions conidia were inoculated in a buffered-salts medium with vitamins with or without added carbohydrates as carbon sources. After incubation, the form obtained was recorded and the amount of growth determined on a dry weight basis. Development of the mycelial form was observed with all of the carbon sources tested (glucose, fructose, mannose, arabinose, maltose, sucrose and starch) while the yeast form developed only when glucose or another hexose was added to the medium. These observations indicated that in S. schenckii the development of conidia into a specific form is dependent on the interrelationship between the available nutrients and the culture conditions and that no specific parameter seemed to be exclusively determinant of the morphology obtained.