Errores de prescripción en la Unidad de Mezclas Oncológicas del Servicio de Farmacia de la Clínica Ricardo Palma, Lima – 2019

El presente trabajo de investigación tuvo como objetivo identificar los errores de prescripción detectados en los esquemas de tratamiento oncológicos atendidos en la Unidad de Mezclas Oncológicas del Servicio de Farmacia de la Clínica Ricardo Palma, Lima – 2019. Es un estudio de tipo observacional, retrospectivo y descriptivo. Se evaluaron 1835 esquemas de tratamiento oncológico, de enero a diciembre del 2019, y luego analizados para detectar los errores de prescripción haciendo uso de una ficha de recolección de datos en base a la información necesaria que debe poseer una prescripción médica en quimioterapia. El 41 % de los esquemas de tratamiento oncológico presentaron errores de prescripción. En conclusión, los tipos de errores de prescripción identificados y cuantificados en los esquemas de tratamiento oncológico en la Unidad de Mezclas Oncológicas del Servicio de Farmacia de la Clínica Ricardo Palma en el año 2019, de acuerdo a los datos del paciente fueron: peso y talla (71,2 %) y nombres completos y N° DNI (27,5 %); referente a los datos del medicamento los principales fueron: tipo y volumen del diluyente (49,5 %) y dosis (35,3 %). La frecuencia de fármacos oncológicos implicados en los errores de prescripción fueron Cisplatino (8,6 %), Trastuzumab (8,6 %) y Fluoruracilo (7,8 %)

B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial

INTRODUCTION: An over-expression of CD19 has been shown in B cells of systemic sclerosis (SSc) and B cells are thought to contribute to the induction of skin fibrosis in the tight skin mouse model. The aim was to define the outcome on safety and the change in skin score after rituximab therapy in SSc patients and to correlate the clinical characteristics with the levels of interleukin (IL)-6 and with the immune cell infiltrate detected by immunohistochemistry. METHODS: Nine patients with SSc with mean age 40.9 +/- 11.1 years were treated with anti-CD20, 1 g at time 0 and after 14 days. Skin biopsy was performed at baseline and during the follow-up. B-cell activating factor (BAFF) and IL-6 levels were also determined at the follow-up times. RESULTS: After 6 months patients presented a median decrease of the skin score of 43.3% (range 21.1-64.0%), and a decrease in disease activity index and disease severity index. IL-6 levels decreased permanently during the follow up. After treatment, a complete depletion of peripheral blood B cells was observed in all but 2 patients. Only 3 patients presented CD20 positive cells in the biopsy of the involved skin at baseline. CONCLUSIONS: Anti-CD20 treatment has been well tolerated and SSc patients experienced an improvement of the skin score and of clinical symptoms. The clear fall in IL-6 levels could contribute to the skin fibrosis improvement, while the presence of B cells in the skin seems to be irrelevant with respect to the outcome after B cell depletion

Measuring transcutaneous bilirubin: a comparative analysis of three devices on a multiracial population

BACKGROUND: Hyperbilirubinemia can lead to potentially irreversible bilirubin-induced neurotoxicity. Transcutaneous bilirubin (TcB) determination has become a valuable aid in non invasive screening of neonatal jaundice. The aim of this study is to compare the performance of three most widespread transcutaneous bilirubinometers on a multiracial population of term and late pre-term neonates. METHODS: Bilirubin concentration was determined using traditional photometric determination and transcutaneously with Bilicheck, BiliMed and JM-103, in random order. Total serum bilirubin (TSB) was determined over a wide concentration range (15,8–0,7 mg/dl) with a mean of 9,5 mg/dl. Related TcB values using Bilicheck (TcB-BC), BiliMed (TcB-BM), and JM-103 (TcB-JM) are reported in Table 1. RESULTS: A multiracial population of 289 neonates was enrolled with a gestational age ranging from 35 to 41 weeks; birth weight ranging from 1800to 4350 grams; hours of life ranging from 4 to 424. In the total study population correlation analysis using Pearson coefficients showed good results for Bilicheck (r = 0.86) and JM-103 (r = 0.85) but poor for BiliMed (r = 0,70). Similar results were found for the non-Caucasian neonates subgroup. Bilicheck and JM-103 had a greater area under the curve than BiliMed when TSB =14 mg/dl was chosen as a threshold value both for the total study population and the non-Caucasian subgroup. CONCLUSIONS: Bilicheck and JM-103, but not BiliMed, are equally reliable screening tools for hyperbilirubinemia in our multiracial neonatal population

Levetiracetam enhances the Temozolomide effect on glioblastoma stem cell proliferation

Glioblastoma Multiforme (GBM) is a highly aggressive brain tumor in which cancer cells with stem cell-like features, called Cancer Stem Cells (CSCs), were identified. CSCs show a high capacity to resist to standard therapies, finally leading to a poor prognosis. Thus, the development of efficient strategies targeting these cells are urgently needed. We have previously demonstrated the presence of two CSC populations in GBM, one derived from the GBM area called enhanced lesion (GCSC) and the other one from the brain area adjacent to the tumor margin (PCSC), that greatly differ in their growth properties and tumor-initiating ability. Tumor recurrence occurs in tissue neighboring GBM suggesting a growing relevance for this area in translational research. To date the most effective chemotherapies to treat GBM are alkylating agents such as temozolomide (TMZ). Epigenetic mechanisms are increasingly recognized as a major factor contributing to pathogenesis of cancer including glioblastoma. Histone deacetylase (HDAC) inhibitors can interfere with TMZ activity by modulating methylguanine methyltransferase (MGMT) expression, resulting in increased TMZ efficacy. Levetiracetam (LEV), an antiepileptic drug, is known to modulate the transcription of HDAC, ultimately silencing MGMT.Since TMZ is the chemotherapeutic agent most widely used in newly diagnosed adult glioblastoma patients, we evaluated its effects on the proliferation rate of both GCSC and PCSC deriving from five patients, in comparison with the effects of other drugs such as etoposide, irinotecan and car-boplatin. Our results demonstrated that TMZ was the less efficient agent, hence we verified the pos-sibility to increase the effect of TMZ by combining it with LEV. Here we show that LEV signifi-cantly enhances the inhibitory effect of TMZ on the proliferation of the GCSC deriving from four patients and of the PCSC deriving from two patients. This effect seems to be mediated by HDAC6 since its expression is up-regulated in the TMZ resistant cells and correlates with MGMT expression. Taken together our results suggest that GCSC and PCSC differ in their ability to respond to the combined chemotherapeutic treatment we used and that the manipulation of HDAC6 expression might be a potential strategy for treating glioblastoma and overcoming resistance to TMZ

First record of the occurrence of Partamona ailyae Camargo (Hymenoptera: Apidae) in Atlantic Forest

This is the first record of the stingless bee Partamona ailyae Camargo, 1980 in an area of the Atlantic Forest in Brazil. The morphological identification and COI and 12S sequences indicated that the samples collected in the Atlantic Forest and other areas of the range of distribution belong to the same biological species. The data revealed low intraspecific variation and high interspecific divergence, with no overlap of the taxa compared

Associação dos variantes dos genes bGH e Pit-1 com características de produção leiteira em touros Gir leiteiro

The objective of this study was to obtain genetic marker information in the Gyr breed by analyzing bGH and Pit-1 gene polymorphisms and to verify their association with milk production traits. One sample including 40 Gyr bulls were genotyped at two bGH gene restriction sites (bGH- AluI and bGH-MspI) and at one restriction site in the Pit-1 gene (Pit-1 HinfI). The bGH-MspI(-) allele was favorable for fat milk percentage. The heterozigous Pit-1 HinfI (+/-) bulls were superior for fat milk production, in relation to homozigous Pit-1 HinfI (+/+). The Pit-1 and bGH genes are strong candidates in the dairy cattle QTL search, and zebuine populations are promising samples for this purpose.O objetivo deste estudo foi obter informações dos marcadores genéticos na raça Gir pela análise dos polimorfismos nos genes bGH e Pit-1, e verificar suas associações com características de produção leiteira. Uma amostra de 40 touros da raça Gir foi genotipada, nos dois sítios de restrição no gene bGH (bGH-AluI e bGH-MspI) e em um sítio de restrição no gene Pit-1 (Pit-1 HinfI). O alelo bGH-MspI(-) favoreceu a porcentagem de gordura no leite. Os touros heterozigotos Pit-1 HinfI (+/-) foram superiores quanto à produção de gordura no leite, em relação aos homozigotos Pit-1 HinfI (+/+). Os genes Pit-1 e bGH são fortes candidatos à pesquisa de QTLs em raças leiteiras e populações zebuínas representam uma amostra promissora para esse propósito

VAMP8 is a vesicle SNARE that regulates mucin secretion in airway goblet cells

Mucin secretion in the lung is regulated by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) exocytotic core, which has not been defined in airway goblet cells. In this study, the SNARE vesicle-associated membrane protein 8 (VAMP8) was found to be expressed in human airway epithelial goblet cells. VAMP8 knockdown by RNA interference techniques reduced airway epithelial mucin secretion induced by PAR agonists, neutrophil elastase and ATP. Basal (non-agonist elicited) mucin secretion was also reduced as a result of VAMP8 knockdown. Importantly, mucin secretion was reduced in the lungs of VAMP8 knockout mice compared to wild-type littermates. Our data suggest that VAMP8 is an essential SNARE in airway mucin granule exocytosis. Reduction of VAMP8 activity/expression may provide a novel therapeutic target to ameliorate airway mucus obstruction in lung diseases

Levetiracetam enhances the temozolomide effect on glioblastoma stem cell proliferation and apoptosis

Abstract BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor in which cancer cells with stem cell-like features, called cancer stem cells (CSCs), were identified. Two CSC populations have been previously identified in GBM, one derived from the GBM area called enhanced lesion (GCSCs) and the other one from the brain area adjacent to the tumor margin (PCSCs) that greatly differ in their growth properties and tumor-initiating ability. To date the most effective chemotherapy to treat GBM is represented by alkylating agents such as temozolomide (TMZ), whose activity can be regulated by histone deacetylases (HDACs) inhibitors through the modulation of O6-methylguanine-DNA methyltransferase (MGMT) expression. Levetiracetam (LEV), a relatively new antiepileptic drug, modulates HDAC levels ultimately silencing MGMT, thus increasing TMZ effectiveness. However, an improvement in the therapeutic efficacy of TMZ is needed. METHODS: Cell proliferation was investigated by BrdU cell proliferation assay and by Western Blot analysis of PCNA expression. Apoptosis was evaluated by Western Blot and Immunofluorescence analysis of the cleaved Caspase-3 expression. MGMT and HDAC4 expression was analyzed by Western Blotting and Immunofluorescence. Statistical analysis was performed using the Student's t test and Mann-Whitney test. RESULTS: Here we evaluated the effect of TMZ on the proliferation rate of the IDH-wildtype GCSCs and PCSCs derived from six patients, in comparison with the effects of other drugs such as etoposide, irinotecan and carboplatin. Our results demonstrated that TMZ was less effective compared to the other agents; hence, we verified the possibility to increase the effect of TMZ by combining it with LEV. Here we show that LEV enhances the effect of TMZ on GCSCs proliferation (being less effective on PCSCs) by decreasing MGMT expression, promoting HDAC4 nuclear translocation and activating apoptotic pathway. CONCLUSIONS: Although further studies are needed to determine the exact mechanism by which LEV makes GBM stem cells more sensitive to TMZ, these results suggest that the clinical therapeutic efficacy of TMZ in GBM might be enhanced by the combined treatment with LEV

Avian haemosporidians in the cattle egret (Bubulcus ibis) from central-western and southern Africa: high diversity and prevalence

We described the geographic distribution of 82 haemosporidian lineages (Plasmodium, Haemoproteus, and Leucocytozoon) in the cattle egret sampled in five countries in central-western and southern Africa. Seventy-three lineages have not previously been reported. We determined the prevalence of three haemosporidians in the samples. We investigated the influence of the internal environment of the host and environmental variables on the Plasmodium diversity and whether environmental variables may explain spatial variations in the prevalence of Plasmodium. We screened DNA from 509 blood samples from nestlings in 15 African colonies for infection by sequencing the cytochrome b gene of parasites. The molecular phylogenetic analysis was performed using Bayesian methods and including sequences from the MalAvi and GeneBank databases. We found 62 new Plasmodium lineages in a clade with MYCAME02, which is a lineage described in waterbirds and recently identified in birds of prey as Plasmodium paranucleophilum. Two Haemoproteus lineages identified in cattle egret formed a distinct group with Haemoproteus catharti and MYCAMH1 (Haemoproteus spp.). Seven Leucocytozoon lineages found in the cattle egret clustered with Leucocytozoon californicus. We found different Plasmodium diversities among the colonies sampled, demonstrating that the internal environment of the host is not the primary determinant of diversity. A linear mixed-effects multivariate model showed that precipitation was positively associated with Plasmodium diversity when controlling for the effects of temperature, colony composition (mixed and non-mixed species) and country. Moreover, a generalized mixed model showed that temperature was positively associated with the prevalence of Plasmodium when controlling for precipitation, elevation and country. We conclude that the cattle egret is a good model for future haemosporidian studies, as we found a significant number of new lineages in this host, which occupies regions with different climate characteristics where environmental variables exert an influence on the diversity and prevalence of Plasmodium