Stability of tedizolid phosphate-sodium rifampicin and tedizolid phosphate-meropenem admixtures in intravenous infusion bags stored at different temperatures.

This is a report on the chemical stability and physical compatibility of intravenous tedizolid phosphate 0.8 mg/mL-sodium rifampicin 2.4 mg/mL and tedizolid phosphate 0.8 mg/mL-meropenem 4 mg/mL combinations in polypropylene 0.9% sodium chloride infusion bags stored at different storage conditions. Triplicate solutions of both admixtures were prepared in 0.9% sodium chloride polypropylene infusion bags and stored under light protection at room temperature (25±2 °C), refrigeration (2-8 °C) or freezing (-15 - -25 °C) conditions. The study was performed using a validated and stability-indicating liquid chromatography (LC) method. For both admixtures and for all storage conditions, at least 90% of the initial drug concentration of tedizolid phosphate remained unchanged throughout the entire study period. Stability of sodium rifampicin at 25±2 °C was determined to be seven hours and six days when it was stored at 2-8 °C. Under the same storage conditions, meropenem was stable for 12 h or 6 days, respectively. Under freezing conditions, sodium rifampicin was stable throughout all 28 days, while stability of meropenem was only 8 days. Solutions of 0.8 mg/mL tedizolid phosphate admixtured with 2.4 mg/mL rifampicin or 4 mg/mL meropenem, in polypropylene 0.9% sodium chloride infusion bags, are stable for at least 7 or 12 hours, respectively, when stored at 25±2 °C. When stored at 2-8 °C, stability was increased to 6 days for both admixtures.

Treatment response and long term follow up in nineteen dogs diagnosed with chronic enteropathy in Australia.

Chronic enteropathy (CE) in dogs is common worldwide, but little data is available from Australia. The aim of this study was to describe treatment response and long-term outcome in a cohort of dogs with CE. Dogs were prospectively enrolled at Murdoch University and the University of Melbourne. After diagnostic investigation to rule out diseases other than CE, dogs underwent sequential therapeutic trials until achieving a clinical response (diet then antibiotics, and finally immunosuppressants). Success was defined as 75% reduction of clinical severity for a minimum of five weeks. A total of 21 dogs were enrolled, and 19 completed the study. One dog was euthanised for lack of response to treatment and one excluded for lack of owner compliance. Most dogs responded to diet (n = 10), followed by antibiotics (n = 7) and immunosuppressants (n = 2). Long-term remission (median 21.1 months, [3.0-44.7]) was achieved in eight out of ten dietary responders without additional treatment. In contrast, only two dogs with antibiotic response remained in long-term remission, of which one needed on-going antibiotic treatment. Longer term remission was achieved in the two dogs treated with immunosuppressants with on-going low dose therapy. This study concludes that most dogs referred for CE in Australia respond to dietary treatment (even after previous dietary interventions), and remission is long-term compared to dogs treated with an antibiotic. Furthermore, the need for long-term antibiotics in some dogs to maintain response may lead to antibiotic resistance. This study supports adequate dietary trials for CE in dogs, and a need for alternative second-line treatments.

Atypical E2Fs inhibit tumor angiogenesis.

Atypical E2F transcription factors (E2F7 and E2F8) function as key regulators of cell cycle progression and their inactivation leads to spontaneous cancer formation in mice. However, the mechanism of the tumor suppressor functions of E2F7/8 remain obscure. In this study we discovered that atypical E2Fs control tumor angiogenesis, one of the hallmarks of cancer. We genetically inactivated atypical E2Fs in epithelial and mesenchymal neoplasm and analyzed blood vessel formation in three different animal models of cancer. Tumor formation was either induced by application of 7,12-Dimethylbenz(a)anthracene/12-O-Tetradecanoylphorbol-13-acetate or by Myc/Ras overexpression. To our surprise, atypical E2Fs suppressed tumor angiogenesis in all three cancer models, which is in a sharp contrast to previous findings showing that atypical E2Fs promote angiogenesis during fetal development in mice and zebrafish. Real-time imaging in zebrafish displayed that fluorescent-labeled blood vessels showed enhanced intratumoral branching in xenografted E2f7/8-deficient neoplasms compared with E2f7/8-proficient neoplasms. DLL4 expression, a key negative inhibitor of vascular branching, was decreased in E2f7/8-deficient neoplastic cells, indicating that E2F7/8 might inhibit intratumoral vessel branching via induction of DLL4.

Synergistic functions of E2F7 and E2F8 are critical to suppress stress-induced skin cancer.

E2F transcription factors are important regulators of the cell cycle, and unrestrained activation of E2F-dependent transcription is considered to be an important driver of tumor formation and progression. Although highly expressed in normal skin and skin cancer, the role of the atypical E2Fs, E2F7 and E2F8, in keratinocyte homeostasis, regeneration and tumorigenesis is unknown. Surprisingly, keratinocyte-specific deletion of E2F7 and E2F8 in mice did not interfere with skin development and wound healing. However, the rate for successful isolation and establishment of E2f7/8-deficient primary keratinocyte cultures was much higher than for wild-type keratinocytes. Moreover, E2f7/8-deficient primary keratinocytes proliferate more efficiently under stress conditions, such as low/high confluence or DNA damage. Application of in vivo stress using the DMBA/TPA skin carcinogenesis protocol revealed that combined inactivation of E2f7/8 enhanced tumorigenesis and accelerated malignant progression. Loss of atypical E2Fs resulted in increased expression of E2F target genes, including E2f1. Additional loss of E2f1 did not rescue, but worsened skin tumorigenesis. We show that loss of E2F7/8 triggers apoptosis via induction of E2F1 in response to stress, indicating that the tumor-promoting effect of E2F7/8 inactivation can be partially compensated via E2F1-dependent apoptosis. Importantly, E2F7/8 repressed a large set of E2F target genes that are highly expressed in human patients with skin cancer. Together, our studies demonstrate that atypical E2Fs act as tumor suppressors, most likely via transcriptional repression of cell cycle genes in response to stress.

Indicadores de calidad en el proceso de almacenamiento y dispensación de medicamentos en un Servicio de Farmacia Hospitalaria / Quality indicators in the storage and dispensing process in a Hospital Pharmacy

Objetivo. Establecer indicadores para evaluar la calidad de los procesos de almacenamiento y dispensación relacionados con los sistemas semiautomáticos de carrusel vertical (SSADV) y horizontal (SSADH). Material y métodos. Estudio observacional descriptivo entre enero-diciembre de 2012. Definición de indicadores de calidad, se estableció un valor objetivo planificado (OP) y se calculó el valor en el año 2012 (VO). Resultados. Se definieron y calcularon 5 indicadores de calidad en el proceso de almacenamiento y dispensación de medicamentos relativos a: indicador 1, error de llenado de carro de unidosis: OP (< 1,67%), VO (1,03%); indicador 2, precisión del llenado de los carros de unidosis utilizando un SSADV: OP (< 15%); VO (11,5%); indicador 3, fiabilidad del inventario de medicamentos en el proceso de entradas de medicamentos en un SSADH: OP (< 15%); VO (6,53%); indicador 4, fiabilidad del inventario de medicamentos en el proceso de preparación de pedidos de planta de medicamentos en un SSADH: OP (< 10%), VO (1,97%); indicador 5, precisión del proceso de preparación de pedidos de medicamentos de las unidades clínicas utilizando el SSADH: OP (< 10%), VO (10,41%). Conclusiones. El establecimiento de indicadores ha permitido valorar la calidad en términos de seguridad, de precisión y fiabilidad de los sistemas semiautomáticos para el almacenamiento y dispensación de medicamentos (AU)

Objective. To establish indicators for the evaluation of the quality of the storage and dispensing processes related to semiautomatic vertical (SAVCS) and horizontal (SAHCS) carousel systems. Material and Methods. Descriptive observational study conducted between January-December 2012. Definition of quality indicators, a target value is established and an obtained value is calculated for 2012. Results. Five quality indicators in the process of storage and dispensing of drugs were defined and calculated: indicator 1, error filling unidose trolleys: target (< 1.67%), obtained (1.03%); indicator 2, filling accuracy unidose trolleys by using an SAVCS: target (< 15%), obtained (11.5%); indicator 3, reliability of drug inventory in the process of drug entries using an SAHCS: target (< 15%), obtained (6.53%); indicator 4, reliability of drug inventory in the picking process of orders replacement stock of clinical units using an SAHCS: target (< 10%), obtained (1.97%); indicator 5, accuracy of the picking process of drug orders using an SAHCS: target (< 10%), obtained (10.41%). Conclusions. Establishing indicators has allowed the quality in terms of safety, precision and reliability of semiautomatic systems for storage and dispensing drugs to be assessed (AU)

[Quality indicators in the storage and dispensing process in a Hospital Pharmacy]. / Indicadores de calidad en el proceso de almacenamiento y dispensación de medicamentos en un Servicio de Farmacia Hospitalaria.

OBJECTIVE: To establish indicators for the evaluation of the quality of the storage and dispensing processes related to semiautomatic vertical (SAVCS) and horizontal (SAHCS) carousel systems. MATERIAL AND METHODS: Descriptive observational study conducted between January-December 2012. Definition of quality indicators, a target value is established and an obtained value is calculated for 2012. RESULTS: Five quality indicators in the process of storage and dispensing of drugs were defined and calculated: indicator 1, error filling unidose trolleys: target (<1.67%), obtained (1.03%); indicator 2, filling accuracy unidose trolleys by using an SAVCS: target (<15%), obtained (11.5%); indicator 3, reliability of drug inventory in the process of drug entries using an SAHCS: target (<15%), obtained (6.53%); indicator 4, reliability of drug inventory in the picking process of orders replacement stock of clinical units using an SAHCS: target (<10%), obtained (1.97%); indicator 5, accuracy of the picking process of drug orders using an SAHCS: target (<10%), obtained (10.41%). CONCLUSIONS: Establishing indicators has allowed the quality in terms of safety, precision and reliability of semiautomatic systems for storage and dispensing drugs to be assessed.