RESUMEN
Hemax® is an epoetin alfa product developed by Biosidus S.A. in Argentina at the end of the 1980s and has been present in that market since 1991. The initial presentation was a lyophilized powder containing albumin as stabilizer, to best adapt to environmental conditions in developing countries; more recently, a prefilled syringe, albumin-free presentation was developed, since this presentation has become the preferred standard in many markets. The primary objective was to compare the pharmacokinetic profile of different formulations of epoetin alfa after a single subcutaneous administration to healthy volunteers of 40 000 IU of Eprex/Erypo® and Hemax® PFS. This clinical trial was conceived following an open-label, randomized, three-way three-period cross-over balanced, and sequential design. The study was conducted on 24 healthy volunteers. To analyze similarity between Hemax® PFS and the innovator product, Eprex®, area under the curve (AUC) and Cmax of both products have been compared. The 90% CI lower limit for the geometric mean ratios was higher than 80% for any comparisons, and the 90% CI upper limit for these geometric ratios was below 125% for all the comparisons made, thus demonstrating equivalence between both products. The comparison between Hemax® PFS and Eprex® resulted in similar 90% CI for Cmax , AUC(0-120 h) and AUC(0-inf) ratios, all of them within the 80-125% interval, with a power above 95% for each ratio. These findings suggest biosimilar patterns for absorption velocity (with Tmax close to 15 h), absorption extent, and elimination (with an elimination half-life close to 25-30 h for each formulation).
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Eritropoyetina , Humanos , Epoetina alfa/farmacocinética , Voluntarios Sanos , Área Bajo la Curva , Proteínas Recombinantes , Equivalencia Terapéutica , Inyecciones SubcutáneasAsunto(s)
COVID-19 , Humanos , Corticoesteroides/uso terapéutico , SARS-CoV-2 , Respiración ArtificialAsunto(s)
COVID-19 , Eritropoyetina , Enfermedad Crítica , Humanos , Proteínas Recombinantes , SARS-CoV-2RESUMEN
The putative Pueyo's vaccine was a commercial venture that obtained marketing authorization in 1946, a turbulent period of Argentine history. After a few months, health authorities withdrew financial support from the state to buy the vaccine and required patients to sign a written consent to receive that product. An independent investigation did not find any evidence of benefit in non-clinical and clinical evaluation of the putative vaccine.
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Medios de Comunicación de Masas , Vacunas , Humanos , Mercadotecnía , Tuberculosis , Vacunas contra la Tuberculosis , IncertidumbreRESUMEN
BACKGROUND: The prenylated flavonoid 2', 4'-dihydroxy-5'-(1'â³, 1'â³-dimethylallyl)-8-prenylpinocembrin (8PP, formerly 6PP) shows antifungal activity, inhibits rhodamine 6G efflux and reverses fluconazole (FCZ) resistance in azole-resistant Candida albicans overexpressing cdr1, cdr2 and mdr1 transporters. PURPOSE AND DESIGN: In this paper, we tried to characterize 8PP in vitro interactions on the cell growth and lethality of C. albicans. We also initiated preliminary in vivo toxicological studies on mice. METHODS: The effects of 8PP and FCZ on cell growth and viability of C. albicans were evaluated by CLSI guidelines. The checkerboard assay was used to search for interactions on cell growth. The time-kill assay was used to study fungicidal effects. Acute toxicity was evaluated at a single dose schedules. RESULTS: From the checkerboard design, and using a starting inoculum of 103CFU/ml, the fractional inhibitory concentration (FIC) of FCZ and 8PP could be determined as 0.11 and 0.50, respectively, with a FIC index value (FICI) of 0.61. This FICI and the isobologram showing a concave shape suggests an additive interaction between them. At a higher starting inoculum (105CFU/ml), C. albicans growth and viability were decreased by FCZ, 8PP and their combination in a concentration-dependent way. For FCZ, minimum fungicidal concentration (MFC) and FC50 (the concentration that kills 50% of the fungal cells) were 4-fold reduced (280-70µM) in combination with 125µM 8PP. A decrease of 3 log units in viable counts with respect to control was reached (3.65 ± 1.05 , p< 0.0001). Thus, both fungistatic compounds when combined achieved an almost complete fungicidal effect at lower concentrations respecting of each of them alone. In preliminary toxicological assessment, lethal dose 50% (LD50) for 8PP by the i.p. route was 357 and 245mg/kg, for female and male adult albino mice, respectively. FCZ LD50 was 785 and 650mg/kg for female and male animals, respectively CONCLUSIONS: In vitro results suggest additive interactions between 8PP and FCZ with respect to C. albicans cell growth. Besides killing per se, 8PP helps FCZ to achieve an almost complete fungicidal effect, which would be crucial to eradicate fungal infections.
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Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Fabaceae/química , Flavanonas/farmacología , Fluconazol/farmacología , Animales , Antifúngicos/administración & dosificación , Antifúngicos/toxicidad , Azoles/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Farmacorresistencia Fúngica/efectos de los fármacos , Femenino , Flavonoides/química , Flavonoides/farmacología , Masculino , Ratones Endogámicos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Prenilación , Pruebas de Toxicidad AgudaRESUMEN
UNLABELLED: In recent years, several cases of torsade de pointes have been associated with many opioids. However, to present no cases have been reported with tramadol. OBJECTIVE: To evaluate the effect of tramadol on QT-interval in the clinical setting. RESEARCH DESIGN AND METHODS: Medical history and comorbidities predisposing to QT interval prolongation were registered for patients requiring medical assistance that involved tramadol administration. Ionograms and ECGs were performed at baseline and intratreatment; QT interval was analyzed after correction with Bazzet, Fridericia, Framinghan and Hogdes formula. RESULTS: 115 patients were studied (50.4% males) All patients had received tramadol 150-400 mg/day during 3.0-5.0 days at the moment of intratreatment control. Plasma concentrations of tramadol were 201-1613 ng/mL. Intratreatment electrocardiographic control, as mean ± SD (range), showed QTcB 372±32 (305 to 433), QTcFri 356±37 (281 to 429), QTcFra 363±33 (299 to 429), QTcH 362±30 (304 to 427), ΔQTcB 26±40 (-73 to 110), ΔQTcFri 24±48 (-97 to 121), ΔQTcFra 22±42 (-81 to 109) and .QTcH 22±38 (-68 to 110) ms. QTc interval presents high correlation with plasma tramadol concentrations (for .QTc, R>0.77). Renal failure was associated with a relative risk for ΔQTc > 30 ms of 1.90 (IC95% 1.31-2.74) and for ΔQTc > 60 ms of 4.74 (IC95% 2.57-8.74). No patient had evidence of arrhythmia during the present study. CONCLUSION: Tramadol produces QTc interval prolongation in good correlation with plasma drug concentrations; renal failure is a risk factor for higher concentration and QT prolongation by tramadol.
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Analgésicos Opioides/efectos adversos , Analgésicos Opioides/sangre , Síndrome de QT Prolongado/sangre , Síndrome de QT Prolongado/inducido químicamente , Tramadol/efectos adversos , Tramadol/sangre , Anciano , Anciano de 80 o más Años , Argentina/epidemiología , Estudios de Cohortes , Electrocardiografía/efectos de los fármacos , Femenino , Humanos , Síndrome de QT Prolongado/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prevalencia , Estudios ProspectivosRESUMEN
In previous studies, 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin, a prenylated flavonoid isolated from Dalea elegans roots, showed activity against multiresistant Staphylococcus aureus and Candida albicans, as well as an uncoupling effect on mitochondria and antioxidant activity. The aim of this study was to evaluate the inhibitory effects of 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin and fluconazole on the efflux of rhodamine 6 G in azole-resistant C. albicans 12-99 that expresses multidrug transporters Cdr1p, Cdr2p, and Mdr1p. The effect of fluconazole and 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin on rhodamine 6 G efflux was assessed in both azole-sensitive and azole-resistant C. albicans. Between 1 and 1000 µM, 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin inhibited rhodamine 6 G efflux only in azole-resistant C. albicans 12-99 in a concentration-dependent manner (IC50 = 119 µM); a competitive effect was observed. It also showed selectivity of action in comparison with other flavanones (6-prenylpinocembrin, isolated from aerial parts of D. elegans, pinocembrin, naringenin, and hesperetin, all at 250 µM). To check the possible implications of the inhibition of azole efflux on cell growth, antifungal assays were conducted. Minimal inhibitory concentration values were 150 µM for 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin and higher than 400 µM for fluconazole. The combination of both compounds at either inhibitory or subinhibitory concentrations was significantly more effective than each compound separately. Minimal inhibitory concentration for fluconazole decreased by more than 400 times in the presence of 100 µM 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin, reversing azole resistance and giving values similar to those of azole-sensitive C. albicans. These data are consistent with a dual action of 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin: direct antifungal effect on azole-resistant C. albicans 12-99 and inhibition of azole transporters, which results in reversion of fluconazole resistance.
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Candida albicans/efectos de los fármacos , Farmacorresistencia Fúngica/efectos de los fármacos , Fabaceae/química , Flavanonas/farmacología , Fluconazol/farmacología , Rodaminas/química , Antifúngicos/farmacología , Recuento de Colonia Microbiana , Proteínas Fúngicas/química , Humanos , Concentración 50 Inhibidora , Proteínas de Transporte de Membrana/química , Pruebas de Sensibilidad Microbiana , Componentes Aéreos de las Plantas/química , Raíces de Plantas/química , Prenilación , Verapamilo/farmacologíaRESUMEN
BACKGROUND: Amylase is synthesized in submandibular glands (SMG) and released into the oral cavity to degrade carbohydrates in the mouth. Bitter taste receptors (T2R) belong to the G-protein coupled receptor (GPCR) family and are expressed in the taste cells and also in the digestive tract. METHODS: The activity of amylase secreted by murine SMG was measured, detecting maltose by Bernfeld's method. Amylase and T2R6 were detected by imunohistochemistry and Western blot. The expression of Ggustducin, Gi, and phospholipase Cß2 was also studied by Western blot. cAMP levels were measured by radioimmunoassay and inositol monophosphate production was quantified by ELISA. RESULTS: Theophylline, denatonium and cycloheximide exerted a dose-dependent inhibition on amylase secretion. This effect was reverted by preincubating SMG with an anti-Gαi antibody. cAMP production was increased by the same compounds, an effect that was also abrogated by an anti-Gαi antibody. Bitter compounds reduced inositol monophosphate formation in SMG and H-89, a protein kinase A inhibitor, reverted this action, revealing that this protein kinase down regulates phospholipase C activity. GENERAL SIGNIFICANCE: We demonstrated that theophylline, denatonium and cycloheximide inhibit salivary amylase secretion, activating an intracellular signaling pathway that involves cAMP and phospholipase C, that cross talks via protein kinase A.
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Amilasas/metabolismo , Transducción de Señal , Glándula Submandibular/enzimología , Animales , Western Blotting , AMP Cíclico/metabolismo , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C , Glándula Submandibular/metabolismoRESUMEN
BACKGROUND: Pandemic influenza A H1N1 2009 virus presents a new challenge to health authorities and communities worldwide. In Argentina, the outbreak was at its peak by the end of June 2009, during the southern winter. A systematic analysis of samples from patients with pandemic H1N1 2009 studied in our laboratory (Virology Laboratory, Hospital de Niños R Gutiérrez, Buenos Aires, Argentina) detected two patients presenting intratreatment emergence of the H275Y neuraminidase mutation, which confers resistance to oseltamivir. METHODS: Complementary DNAs, including the 275 codon, were obtained by reverse transcriptase PCR using viral RNAs extracted from nasopharyngeal or tracheal aspirates. Conventional sequencing and pyrosequencing were performed on each sample. In order to measure the virus susceptibility to oseltamivir, 50% inhibitory concentration determinations were performed by chemiluminescence. RESULTS: Sequential samples of two paediatric patients under oseltamivir treatment were analysed. Pretreatment samples were composed of 100% oseltamivir-sensitive variants. In case 1, the oseltamivir-resistant variant was found 8 days after the beginning of treatment. In case 2, the viral population became resistant on the second day of treatment, with 83% of the viral population bearing the mutation and this reached 100% on the seventh day. CONCLUSIONS: We describe the intratreatment emergence of oseltamivir resistance in two paediatric patients. Pyrosequencing allowed us to detect variant mixtures, showing the transition of the viral population from sensitive to resistant.
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Farmacorresistencia Viral/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/tratamiento farmacológico , Pandemias , Antivirales/farmacología , Argentina/epidemiología , Niño , Preescolar , ADN Complementario/farmacología , Farmacorresistencia Viral/genética , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/epidemiología , Masculino , Mutación , Neuraminidasa/uso terapéutico , Oseltamivir/farmacología , ARN Viral/efectos de los fármacos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
To describe utilization of a biosimilar product containing filgrastim (Neutromax), data of 414 myeloma or lymphoma patients subjected to autologous SCT between 1998 and 2007 were analyzed. Filgrastim was used for mobilization of progenitors (5 days at 300 microg/day) and for the recovery of neutropenia after transplantation (100 microg/day, since day +5). In 2003, the excipient mannitol was replaced by sorbitol. A mean dose of 9.47 x 10(6)CD34(+)cells/kg was infused; 100 neutrophils/mm(3) required 5-day treatment; 500 neutrophils/mm(3), 6 days and 1000 neutrophils/mm(3), 7 days. Neutromax effect in SCT is similar to reports with other brands. No difference was found between formulations.
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Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma/terapia , Mieloma Múltiple/terapia , Neutropenia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios Transversales , Femenino , Filgrastim , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes , Acondicionamiento Pretrasplante , Adulto JovenRESUMEN
Blastoferon, in the following referred to as the test product, is a pharmaceutical product of interferon beta la (CAS 220581-49-7) currently marketed as a biosimilar to the innovator Interferon beta la product (referred to as the reference product). Pharmacokinetics and pharmacodynamIcs assays are critically relevant to demonstrate similarity between biopharmaceuticals. The aims of the present study were to investigate the bioavailability (BA) of the test product (either absolute or relative to the innovator product) and to compare the extent of increase of neopterin concentration following administration of either product. Two studies were performed: initially, an absolute BA assay with i.v. and s.c. injection of test product to 12 healthy subjects. Second, a formal relative BA study with s.c. injections of 88 microg of both products to 24 healthy volunteers. Blood samples for pharmacokinetic and pharmacodynamic profiling were drawn at different intervals after injection. Interferon beta (IFNB) concentrations were determined by ELISA. In the absolute BA study, a single s.c. dose of 44 microg of the test product resulted in a median bioavailable fraction of 29%, a median T(max) of 4 h (4-6) and a C(max) of 3.69 (3.27-4.41) IU x ml(-1). In the relative BA study, values for the test product were: median T(max) of 3 h (2-18), C(max) of 5.39 (4.99-6.31) IU x ml(-1), AUC (0-72) of 142.86 (134.16-190.15) IU x h x ml(-1) and AUC(0-infinity) of 190.95 (174.23-303.13) IU x h x ml(-1). The corresponding values for the innovator product were: T(max) of 3 h (1-24), C(max) of 4.44 (4.12-5.40) IU x ml(-1), AUC(0-72) of 128.77 (121.18-170.92) IU x h x ml(-1) and AUC(0-affinity) of 192.61 (183.04-286.46) IU x h x ml(-1). The AUC(0-72) ratio was 111% (CI 90%: 106-116), the AUC(0-affinity) was 99% (CI 90%: 92-107) and the C(max) ratio was 121% (CI 90%: 112-131). IFNB1a increased neopterin levels in both studies. Both products induced side-effects commonly reported for IFN with no serious adverse events. This study presents pharmacokinetics parameters of the test product and demonstrates similar bioavailability of IFNB1a for both pharmaceutical products.
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Factores Inmunológicos/farmacocinética , Interferón Tipo I/farmacocinética , Adulto , Área Bajo la Curva , Disponibilidad Biológica , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Inyecciones Intravenosas , Inyecciones Subcutáneas , Interferón Tipo I/administración & dosificación , Interferón Tipo I/efectos adversos , Masculino , Neopterin/sangre , Proteínas Recombinantes , Equivalencia TerapéuticaRESUMEN
The prenylated flavanone 2'-4'-dihidroxy-5'-(1" '-dimethylallyl)-6-prenylpinocembrin) (6PP), isolated from the roots of Dalea elegans, shows antimicrobial activity. The aim of this study was to evaluate mitochondrial toxicity and antioxidant properties of 6PP. Addition of micromolar concentrations of 6PP to rat liver mitochondria, stimulated O2 uptake in state 4 and inhibited it in state 3 when malate-glutamate was the respiratory substrate, and inhibited O2 uptake in state 3 when succinate was the substrate. Highest concentration of 6PP also inhibited O2 uptake in state 4 in the latter case; in both conditions, respiratory control index values were decreased. This flavanone collapsed the mitochondrial membrane potential in a concentration-dependent manner. 6PP also inhibited F0F1-ATPase activity in coupled mitochondria and in submitochondrial particles. In the latter, this compound also inhibited NADH oxidase and succinate dehydrogenase activities. HEp-2 cells were incubated for 24 h with 6PP in presence or absence of 0.5% albumin. As measured by reduction of the mitochondrial-related probe MTT, in the albumin-free condition, 6PP was cytotoxic in a concentration-dependent manner; on the other hand, albumin decreased 6PP effect. In addition, in rat liver microsomes 6PP: (1) inhibited the enzymatic lipid peroxidation, (2) exhibited significant scavenging activity, measured by DPPH reduction assay and (3) demonstrated significant antioxidant activity by decreasing the reduction of Mo(VI) to Mo(V). We suggest that 6PP impairs the hepatic energy metabolism by acting as mitochondrial uncoupler and by inhibiting enzymatic activities linked to the respiratory chain. 6PP also exerts both antioxidant and antiradical activities. Due to its cytotoxicity, this molecule, and its future structure developments, can be considered as a potentially promising therapeutic agent, for instance in cancer chemotherapy.
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Antineoplásicos/farmacología , Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , Fabaceae/química , Flavanonas/farmacología , Flavonoides/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Flavanonas/química , Flavanonas/aislamiento & purificación , Flavonoides/química , Flavonoides/aislamiento & purificación , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Mitocondrias Hepáticas/metabolismo , Membranas Mitocondriales/efectos de los fármacos , Membranas Mitocondriales/metabolismo , Estructura Molecular , Complejos Multienzimáticos/antagonistas & inhibidores , NADH NADPH Oxidorreductasas/antagonistas & inhibidores , Oxígeno/antagonistas & inhibidores , Oxígeno/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Raíces de Plantas/química , Prenilación , ATPasas de Translocación de Protón/antagonistas & inhibidores , Ratas , Ratas Wistar , Succinato Deshidrogenasa/antagonistas & inhibidores , Células Tumorales CultivadasRESUMEN
To determine the ability of monocyte phagosomal acidification in chronic paracoccidioidomycosis, 13 patients were recruited at different times during follow-up and compared with 18 normal controls. Eight patients were studied at diagnosis, six of them also during treatment and five additional patients after ending treatment. Phagosomal acidification of monocytes, triggered by challenge with opsonized zymosan, was evaluated with acridine orange and expressed as percentage of orange-stained intracellular particles, as mean +/- SE. In comparison with controls, acidification was severely impaired before treatment (33 +/- 11% vs. 67 +/- 6%) and reached values similar to controls during treatment (73 +/- 6%, n = 6). In addition, phagosomal acidification of the patients studied after treatment (63 +/- 4%) had no difference when compared with controls. This study demonstrates that phagosomal acidification is perturbed among chronic paracoccidioidomycosis patients and reverses with antifungal treatment.
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Monocitos/metabolismo , Paracoccidioidomicosis/inmunología , Fagosomas/metabolismo , Naranja de Acridina/metabolismo , Adulto , Antifúngicos/uso terapéutico , Células Cultivadas , Humanos , Concentración de Iones de Hidrógeno , Masculino , Microscopía Fluorescente/métodos , Persona de Mediana Edad , Monocitos/citología , Paracoccidioidomicosis/tratamiento farmacológico , Zimosan/inmunología , Zimosan/metabolismoRESUMEN
OBJECTIVE: The National Institute of Social Services for Retirees and Pensioners (NISSRP) is a nationwide health care financing agency and service provider in Argentina. Among its services, the NISSRP provides outpatient drug coverage to more than 3.3 million beneficiaries, mainly senior citizens and disabled persons. In 1997, to help cope with its rising costs, the NISSRP agreed to transfer the risk for the cost of outpatient medications and cancer-treatment drugs to a consortium of pharmaceutical companies in exchange for a fixed monthly payment. The objective of this study was to determine the impact that this new approach had on three things: (1) the level of expenditures for the medicines that were included in the agreement, (2) the pattern of nonrational prescribing for NISSRP beneficiaries, and (3) this pattern's relationship with macroeconomic variables and the pattern of prescribing for Argentina as a whole. METHODS: We compared outpatient-medicine consumption in 1999 with consumption before the agreement went into effect. RESULTS: The actual amount that NISSRP beneficiaries spent out-of-pocket climbed from US$ 336.13 million in 1996 to US$ 473.36 million in 1999, an increase of almost 41%. The nominal amount "spent" by the NISSRP in 1999 was US$ 601.11 million, versus a real amount of US$ 374.75 million in 1996, an "increase" of 60% (that increase for the NISSRP was only theoretical since the agreement specified the fixed monthly amount that the NISSRP would have to pay to the pharmaceutical consortium). In contrast with the increased real spending by NISSRP beneficiaries, Argentina's economy remained stable over the assessed period, with the consumer price index even falling by 0.8%. We found high levels of nonrational drug use in the NISSRP system in both 1996 and 1999, indicating a serious ongoing problem. CONCLUSIONS: An agreement with pharmaceutical companies, like the one we have described, might add an element of financial predictability for institutions such as the NISSRP. However, such an agreement can easily result in an increased economic burden for health care beneficiaries, and without any improvement in the services that they receive. This type of agreement requires extensive mechanisms for control, follow-up, and updating, and it also risks making nonrational drug prescribing the accepted rule. While perhaps feasible, the requirements for this kind of agreement are actually very difficult to put into place, requiring additional efforts from institutions such as the NISSRP.
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Industria Farmacéutica/economía , Personal de Salud/economía , Medición de Riesgo/economía , Anciano , Argentina , Industria Farmacéutica/estadística & datos numéricos , Economía/estadística & datos numéricos , Honorarios Farmacéuticos/estadística & datos numéricos , Personal de Salud/estadística & datos numéricos , Humanos , Honorarios por Prescripción de Medicamentos/estadística & datos numéricos , Medición de Riesgo/estadística & datos numéricosRESUMEN
PURPOSE: Langerhans cell histiocytosis (LCH) is a rare disease with variable prognosis in which lesions and clinical features suggest that pro- and anti-inflammatory cytokines may be involved in its pathogenesis. The authors wished to evaluate whether serum levels of interleukin-1 receptor agonist (IL-1Ra) and tumor necrosis factor-alpha (TNF-alpha) are elevated in children with LCH and decrease after chemotherapy. PATIENTS AND METHODS: Circulating levels of IL-1Ra and TNF-alpha were measured in 23 and 8 children with LCH, respectively, and 7 pediatric controls using commercially available ELISA kits. All patients fulfilled the Histiocyte Society LCH Protocols criteria for diagnosis, stratification, and treatment. RESULTS: Pretreatment concentrations of IL-1Ra and TNF-alpha were found to be significantly elevated in patients with LCH compared with controls. Among LCH substages, a significant difference in IL-1Ra values was observed between individuals with single-system single-site disease vs. multisystem disease with risk-organ dysfunction. In all eight patients evaluated, IL-1Ra levels decreased after 6 weeks of chemotherapy. Lower values of TNF were observed in three patients after treatment. A positive and significant correlation between IL-1Ra and TNF serum concentrations was found. CONCLUSIONS: Patients with LCH have elevated levels of IL-1Ra and TNF, which decrease after chemotherapy.
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Histiocitosis de Células de Langerhans/sangre , Sialoglicoproteínas/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Etopósido/administración & dosificación , Femenino , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Histiocitosis de Células de Langerhans/patología , Humanos , Lactante , Proteína Antagonista del Receptor de Interleucina 1 , Masculino , Valor Predictivo de las Pruebas , Prednisolona/administración & dosificación , Receptores de Interleucina-1/antagonistas & inhibidores , Proteínas Recombinantes , Vinblastina/administración & dosificaciónRESUMEN
OBJECTIVE: The National Institute of Social Services for Retirees and Pensioners (NISSRP) is a nationwide health care financing agency and service provider in Argentina. Among its services, the NISSRP provides outpatient drug coverage to more than 3.3 million beneficiaries, mainly senior citizens and disabled persons. In 1997, to help cope with its rising costs, the NISSRP agreed to transfer the risk for the cost of outpatient medications and cancer-treatment drugs to a consortium of pharmaceutical companies in exchange for a fixed monthly payment. The objective of this study was to determine the impact that this new approach had on three things: (1) the level of expenditures for the medicines that were included in the agreement, (2) the pattern of nonrational prescribing for NISSRP beneficiaries, and (3) this pattern's relationship with macroeconomic variables and the pattern of prescribing for Argentina as a whole. METHODS: We compared outpatient-medicine consumption in 1999 with consumption before the agreement went into effect. RESULTS: The actual amount that NISSRP beneficiaries spent out-of-pocket climbed from US$ 336.13 million in 1996 to US$ 473.36 million in 1999, an increase of almost 41 percent. The nominal amount "spent" by the NISSRP in 1999 was US$ 601.11 million, versus a real amount of US$ 374.75 million in 1996, an "increase" of 60 percent (that increase for the NISSRP was only theoretical since the agreement specified the fixed monthly amount that the NISSRP would have to pay to the pharmaceutical consortium). In contrast with the increased real spending by NISSRP beneficiaries, Argentina's economy remained stable over the assessed period, with the consumer price index even falling by 0.8 percent. We found high levels of nonrational drug use in the NISSRP system in both 1996 and 1999, indicating a serious ongoing problem. CONCLUSIONS: An agreement with pharmaceutical companies, like the one we have described, might add an element of financial predictability for institutions such as the NISSRP. However, such an agreement can easily result in an increased economic burden for health care beneficiaries, and without any improvement in the services that they receive. This type of agreement requires extensive mechanisms for control, follow-up, and updating, and it also risks making nonrational drug prescribing the accepted rule. While perhaps feasible, the requirements for this kind of agreement are actually very difficult to put into...
Objetivos. El Instituto Nacional de Servicios Sociales para Personas Jubiladas y Pensionadas (INSSPJP) es una agencia nacional que financia y provee servicios de salud en Argentina. Entre los servicios que provee figura la cobertura del costo de medicamentos adquiridos por la vía ambulatoria a más de 3,3 millones de beneficiarios, principalmente personas de edad avanzada o discapacitadas. En 1997, con el fin de ayudar a sufragar el aumento de los costos, el INSSPJP acordó transferir el riesgo de los costos de los medicamentos para pacientes ambulatorios y para el tratamiento del cáncer a un consorcio de compañías farmacéuticas a cambio de una cuota mensual fija. El objetivo del presente estudio es determinar qué impacto ha tenido esta medida en tres aspectos: 1) el nivel del gasto en los medicamentos abarcados por el acuerdo; 2) la tendencia a prescribir medicamentos de forma no racional para beneficiarios del INSSPJP y 3) la relación que muestra esta tendencia con las variables macroeconómicas y los patrones de prescripción en toda la Argentina. Métodos. Comparamos el consumo de medicamentos por pacientes ambulatorios en 1999 con el consumo antes de la entrada en vigor del acuerdo. Resultados. La cantidad que los beneficiarios del INSSPJP gastaron de su bolsillo aumentó de $US 336,13 millones en 1996 a $US 473,36 millones en 1999, aumento que equivale a casi 41%. La cantidad nominal "gastada" por el INSSPJP en 1999 fue de $US 601,11 millones, frente a la cantidad real gastada en 1996, que fue de $US 374,75 millones. Esto representa un "aumento" de 60% (el aumento para el INSSPJP es solo teórico, ya que en el acuerdo se especificaba la cantidad mensual fija que esta entidad tendría que pagarle al consorcio de compañías farmacéuticas). A diferencia del aumento del gasto real que afectó a los beneficiarios del INSSPJP, la economía argentina permaneció estable durante el período estudiado, cuando el índice de precios al consumidor hasta se redujo en 0,8%. Hallamos un uso frecuente de medicamentos de forma irracional en el sistema del INSSPJP tanto en 1996 como en 1999, dato que apunta a la presencia de un problema importante. Conclusiones. Un acuerdo con compañías farmacéuticas como el aquí descrito podría aportar un elemento de pronosticabilidad para instituciones tales como el INSSPJP. No obstante, un acuerdo de este tipo bien podría aumentar la carga económica de los beneficiarios de las prestaciones de salud, sin que mejoren en modo alguno los servicios que reciben. Los acuerdos de este tipo exigen que haya complejos mecanismos de control, seguimiento y actualización, y al mismo tiempo acarrean el peligro de que la prescripción irracional de medicamentos se convierta en práctica habitual. Aunque su factibilidad no es de dudar, los mecanismos que exigen estos acuerdos son muy difíciles de implantar y su puesta en marcha plantea la necesidad de medidas adicionales por parte de instituciones como el INSSPJP
Asunto(s)
Humanos , Anciano , Industria Farmacéutica/economía , Personal de Salud/economía , Medición de Riesgo/economía , Argentina , Industria Farmacéutica/estadística & datos numéricos , Economía/estadística & datos numéricos , Honorarios Farmacéuticos/estadística & datos numéricos , Personal de Salud/estadística & datos numéricos , Honorarios por Prescripción de Medicamentos/estadística & datos numéricos , Medición de Riesgo/estadística & datos numéricosRESUMEN
This short review address the concept of cytokine and cytokine families, their relationship with CNS, cytokine effects on nervous system (namely, sickness behavior) and the cellular source of brain cytokines. In addition, it provides selected data on the role of cytokines in mental disorders such as depression, schizophrenia, Alzheimer's disease and AIDS-related dementia.
Asunto(s)
Citocinas/inmunología , Trastornos Mentales/inmunología , Humanos , Receptores de Citocinas/inmunología , Rol del EnfermoRESUMEN
VRCTC-310-ONCO, an agent based on the snake phospholipase A2 (crotoxin), is currently under clinical development. After phase I study in patients by intramuscular administration, the interest of intravenous (IV) dosing arose. To evaluate IV administration of VRCTC-310-ONCO in rabbits, ten animals were subjected to surgical implant of fixed jugular catheter, by which they received daily IV doses of 0.03 mg/kg body weight of VRCTC-310-ONCO for 30 days (n = 8) or saline (n = 2). The procedure was well tolerated in all rabbits. One of the animals died after the sixth dose of VRCTC-310-ONCO with CNS involvement; two additional rabbits required dose-reduction. All other rabbits achieved 30 days of treatment and were sacrificed. All rabbits (even controls) developed lymphocytosis and mild anaemia, without changes in blood neutrophils. No changes were found in serum transaminases (GOT and GPT), cholesterol, triglycerides, and y-glutamyl transpeptidase. At necropsy, chronic granulation tissue was found surrounding the implant in all rabbits. VRCTC-3 10-ONCO-treated rabbits presented generalised and marked swelling of hepatocytes, with areas of cytoplasmic vacuolisation. No abnormalities were found in kidney, heart, lung, spleen, adrenal gland, uterus, testes and ovary. Additional studies with IV route for VRCTC-310-ONCO, including humans, are required to define its toxicity in the clinical setting.