N-alpha-Aminoacyl Colchicines as Promising Anticancer Agents.

BACKGROUND: In the last years, many efforts have been made to find colchicine derivatives with reduced toxicity. Additionally, the deregulation of amino acid uptake by cancer cells provides an opportunity to improve anticancer drug effectiveness. OBJECTIVE: To design new colchicine derivatives with reduced cytotoxicity and enhanced selectivity by means of introducing aminoacyl groups. METHODS: 34 colchicine analogues bearing L- and D-amino acid pendants were synthetized and characterized by NMR, IR and MS techniques. Cytotoxicity and antimitotic properties were assessed by spectrophotometry and cell cycle assays. Oncogene downregulation was studied by RTqPCR whereas in vivo studies were performed in SCID mice. RESULTS: Compounds exhibit high antiproliferative activities at the nanomolar level while being, in general, less cytotoxic than colchicine. Most compounds inhibit the polymerization of tubulin in a way similar to colchicine itself, with L-amino acid derivatives being the most active in the inhibition of tubulin polymerization. All selected compounds caused cell cycle arrest at the G2/M phase when tested at 1 µM. More specifically, Boc-L-proline derivative 6 arrested half of the population and showed one of the highest Selectivity Indexes. Derivatives 1 (Boc-glycine), 27 (D-leucine) and 31 (Boc-glycine-glycine) proved fairly active in downregulating the expression of the c-Myc, hTERT and VEGF oncogenes, with compound 6 (Boc-L-proline) having the highest activity. This compound was shown to exert a potent anti-tumor effect when administered intraperitoneally (LD50 > 100 mg/kg for 6, compared with 2.5 mg/kg for colchicine). CONCLUSION: Compound 6 offers an opportunity to be used in cancer therapy with less toxicity problems than colchicine.

Enhanced covalent p-phenylenediamine crosslinked graphene oxide membranes: Towards superior contaminant removal from wastewaters and improved membrane reusability.

The increasing depletion of freshwater necessitates the re-use and purification of wastewaters. Among the existing separation membrane materials, graphene oxide (GO) is a promising candidate, owing to its tunable physicochemical properties. However, the widening of GO membranes pore gap in aqueous environments is a major limitation. Crosslinking agents can be incorporated to alleviate this problem. This study describes a comparative analysis of uncrosslinked and p-Phenylenediamine (PPD) crosslinked GO membranes' water purification performance. Dip-coating and dip-assisted layer-by-layer methods were used to fabricate the uncrosslinked and crosslinked membranes respectively. The covalent interaction between GO and PPD was confirmed by Fourier Transform Infra-Red and X-ray Photoelectron Spectroscopy. The excellent membrane topographical continuity and intactness was assessed by means of Scanning Electron Microscopy, while water contact angle measurements were undertaken to evaluate and confirm membrane hydrophilicity. The improvement impact of the crosslinker was manifested on the enhancement of the stability and performance of the membranes during nanofiltration tests of aqueous solutions of methylene blue in a homemade nanofiltration cell operated at 1 bar.

Effects on tubulin polymerization and down-regulation of c-Myc, hTERT and VEGF genes by colchicine haloacetyl and haloaroyl derivatives.

Several colchicine analogues in which the N-acetyl residue has been replaced by haloacetyl, cyclohexylacetyl, phenylacetyl and various aroyl moieties have been synthesized. The cytotoxic activities of the synthesized compounds have been measured on three tumor cell lines (HT-29, MCF-7 and A549) and on one non-tumor cell line (HEK-293). These compounds exhibit high antiproliferative activities at the nanomolar level, in many cases with a higher potency than colchicine itself. Some of the compounds, particularly the haloacetyl derivatives, inhibit the polymerization of tubulin in a similar manner as colchicine. As regards the cell cycle, the most active compounds are the chlorobenzoyl and bromobenzoyl derivatives, which cause cell cycle arrest at the G2/M phase when tested at 20 nM, and the bromoacetyl derivative, which arrests the cell cycle at 15 nM. In addition, these colchicine derivatives have shown fairly active downregulating the expression of the c-Myc, hTERT and VEGF genes, as well as VEGF protein secretion, at very low concentrations.

Interactions of long-chain homologues of colchicine with tubulin.

Several colchicine analogues in which the N-acetyl residue has been replaced by aliphatic, straight-chain acyl moieties, have been synthesized. These compounds show high cytotoxic activity at the nanomolar level against the tumoral cell lines HT-29, MCF-7 and A549. Some of them exhibit activities in the picomolar range against the HT-29 line and are thus two to three orders of magnitude more cytotoxic than colchicine. In this specific cell line, the activities were found to be closely related to the length of the acyl carbon chain, an increase in the latter giving rise to an increase in the cytotoxicity with a maximum in the range of 10-12 carbon atoms, followed by a decrease in activity with still longer chains. Some of the compounds inhibit microtubule assembly and induce the formation of abnormal polymers and present in most cases better apparent affinity constants than colchicine. In addition, at IC50 concentrations the analogues block the cell cycle of A549 cells in the G2/M phase. Molecular docking studies suggest that, while interactions of the colchicine analogues with the colchicine binding site at ß-tubulin are still present, the increase in the acyl chain length leads to the progressive development of new interactions, not present in colchicine itself, with the neighboring α-tubulin subunit. Indeed, sufficiently long acyl chains span the intradimer interface and contact with a hydrophobic groove in α-tubulin. It is worth noting that some of the compounds show cytotoxicity at concentrations three orders of magnitude lower than colchicine. Their pharmacological use in cancer therapy could possibly be performed with lower dosages and be thus endowed with less acute toxicity problems than in the case of colchicine.

Use of micellar liquid chromatography for rapid monitoring of fungicides post harvest applied to citrus wastewater.

A method based on micellar liquid chromatography has been developed to simultaneously monitor four pesticides largely post-harvest applied to citrus: thiabendazole, pyrimethanil, o-phenylphenol and imazalil. Water samples were filtered and directly injected without other treatment, thus avoiding extraction steps. The composition of the mobile phase was optimized using a chemometrical approach to achieve and excellent resolution to 0.07 mol/L SDS/5%, V/V 1-pentanol buffered at pH3. Mobile phase run through a C18 column at 1 mL/min at room temperature. The detection was performing by UV-Visible absorbance using a wavelength program: 0-10 min, 305 nm (for thiabendazole); 10-12; 265 nm (for pyrimethanil) and 12-18, 220 nm (o-phenylphenol and imazalil). The developed method was validated following the guidelines of the US Environmental Protection Agency in terms of: quantitation range, (0.5-4 to 15 µg/mL), linearity (r(2)>0.9995), sensitivity (LOD, 0.18-1.4 µg/mL), precision (<9.2%), trueness (93.9%-103.7%), and ruggedness (<9.9%). It was found that the fungicides remain up to eight days in surface water at outdoor conditions. The method was used to screen the presence of the analytes in several waste water samples, and was proved to be useful in routine analysis.

Validación de la capacidad del proceso de pasteurización de la albúmina humana para inactivar virus / Validation of the capacity of the human albumin pasteurization process for virus inactivation

La validación de la capacidad de aclaramiento viral de los procesos de fabricación de productos biológicos constituye un requisito regulatorio en Cuba. Se recomienda introducir la pasteurización en los procesos de producción de la albúmina como un método capaz de inactivar virus; por ello, el objetivo del estudio fue validar la capacidad de inactivación viral de la etapa de pasteurización del proceso de producción de la albúmina humana al 20 y 25 por ciento. Los modelos virales que abarcan los posibles contaminantes de la materia prima, se diluyeron 1:10 en la albúmina en sus 2 concentraciones y se sometieron a tratamiento térmico a 60 °C durante 10 h. Se tomaron muestras a diferentes intervalos de tiempo para la confección de las curvas de cinética de inactivación. Se determinó el factor de reducción aportado por la pasteurización para cada virus. El tratamiento a 60 °C de la albúmina al 20 y 25 por ciento disminuyó significativamente la carga viral inicial con que se retó la etapa, con valores de p< 0,002 y p< 0,021, respectivamente, y se obtuvieron factores de reducción superiores a 4 log del título de todos los virus. La etapa de pasteurización le aportó a la albúmina humana al 20 y 25 por ciento un adecuado nivel de seguridad(AU)

The validation of the capacity of viral clearance in the manufacturing processes of biopharmaceuticals is a regulatory requirement in Cuba. It is recommended to introduce the pasteurization in the manufacturing processes of serum albumin as a method of inactivating viruses. The objective of this study was to validate the capacity of viral inactivation in the phase of pasteurization of the 20 percent and 25 percent human albumin production process The viral models covering the possible pollutants of the raw materials were diluted at 1:10 in albumin in 2 concentrations and they were heat-treated at 60 °C for 10 h. Several samples at different time intervals were taken to design the inactivation kinetic curves. The reduction factor of pasteurization for each virus was estimated. The treatment of 20 percent and 25 percent albumin at 60 °C decreased significantly the initial viral load in the stage, with p< 0.002 and p< 0.021 respectively. The reduction factors exceeded 4 log of the titers of all viruses. The stage of pasteurization gave adequate level of safety to the 20 percent and 25 percent human albumin(AU)

Validación de la capacidad del proceso de pasteurización de la albúmina humana para inactivar virus / Validation of the capacity of the human albumin pasteurization process for virus inactivation

La validación de la capacidad de aclaramiento viral de los procesos de fabricación de productos biológicos constituye un requisito regulatorio en Cuba. Se recomienda introducir la pasteurización en los procesos de producción de la albúmina como un método capaz de inactivar virus; por ello, el objetivo del estudio fue validar la capacidad de inactivación viral de la etapa de pasteurización del proceso de producción de la albúmina humana al 20 y 25 por ciento. Los modelos virales que abarcan los posibles contaminantes de la materia prima, se diluyeron 1:10 en la albúmina en sus 2 concentraciones y se sometieron a tratamiento térmico a 60 °C durante 10 h. Se tomaron muestras a diferentes intervalos de tiempo para la confección de las curvas de cinética de inactivación. Se determinó el factor de reducción aportado por la pasteurización para cada virus. El tratamiento a 60 °C de la albúmina al 20 y 25 por ciento disminuyó significativamente la carga viral inicial con que se retó la etapa, con valores de p< 0,002 y p< 0,021, respectivamente, y se obtuvieron factores de reducción superiores a 4 log del título de todos los virus. La etapa de pasteurización le aportó a la albúmina humana al 20 y 25 por ciento un adecuado nivel de seguridad

The validation of the capacity of viral clearance in the manufacturing processes of biopharmaceuticals is a regulatory requirement in Cuba. It is recommended to introduce the pasteurization in the manufacturing processes of serum albumin as a method of inactivating viruses. The objective of this study was to validate the capacity of viral inactivation in the phase of pasteurization of the 20 percent and 25 percent human albumin production process The viral models covering the possible pollutants of the raw materials were diluted at 1:10 in albumin in 2 concentrations and they were heat-treated at 60 °C for 10 h. Several samples at different time intervals were taken to design the inactivation kinetic curves. The reduction factor of pasteurization for each virus was estimated. The treatment of 20 percent and 25 percent albumin at 60 °C decreased significantly the initial viral load in the stage, with p< 0.002 and p< 0.021 respectively. The reduction factors exceeded 4 log of the titers of all viruses. The stage of pasteurization gave adequate level of safety to the 20 percent and 25 percent human albumin

Combined therapy with idebenone and deferiprone in patients with Friedreich's ataxia.

Iron chelators are a new therapeutical approach for patients with Friedreich's ataxia, on the basis that oxidative cell damage that occurs in these patients is due to the increasing deposits of mitochondrial iron pools. The objective of the study was to evaluate the effects of the combined therapy of idebenone and low oral doses of deferiprone on the neurological signs and cardiac function parameters. This study was designed as a prospective open-label single-arm study. Twenty Friedreich's ataxia patients were treated with idebenone (20 mg/kg/day) and deferiprone (20 mg/kg/day) for 11 months. Patients were evaluated before the start and throughout the study with the International Cooperative Ataxia Rating Scale (ICARS) scores, echocardiographic measurements and MRI (magnetic resonance imaging) techniques to asses brain iron deposits in the dentate nucleus. No significant differences were observed in total ICARS scores when comparing baseline status and the end of the study in the whole group of patients. Posture and gait scores increased significantly after 11 months of therapy (Wilcoxon's test, p = 0.04) and kinetic function improved significantly (Wilcoxon's test, p = 0.015). Echocardiography data showed a significant reduction of the interventricular septum thickness (Wilcoxon's test, p = 0.04) and in the left ventricular mass index (Wilcoxon's test, p = 0.038) after the start of the therapy. The MRI values in the dentate nucleus showed a statistically significant reduction (Wilcoxon's test p = 0.007) between baseline conditions and after 11 months of the therapy. Combined therapy with idebenone and deferiprone in patients with FDRA indicates a stabilizing effect in neurologic dysfunctions due to an improvement in the kinetic functions, with a worsening of gait and posture scores. Heart hypertrophy parameters and iron deposits in dentate nucleus improved significantly. Combined therapy was well tolerated with mild side effects, apart from the risk of neutropenia and progressive reduction of plasma iron parameters.

Coenzyme Q(10)-responsive ataxia: 2-year-treatment follow-up.

We assessed the clinical outcome after coenzyme Q(10) (CoQ(10)) therapy in 14 patients presenting ataxia classified into two groups according to CoQ(10) values in muscle (deficient or not). We performed an open-label prospective study: patients were evaluated clinically (international cooperative ataxia rating scale [ICARS] scale, MRI, and videotape registration) at baseline and every 6 months during a period of 2 years after CoQ(10) treatment (30 mg/kg/day). Patients with CoQ(10) deficiency showed a statistically significant reduction of ICARS scores (Wilcoxon test: P = 0.018) after 2 years of CoQ(10) treatment when compared with baseline conditions. In patients without CoQ(10) deficiency, no statistically significant differences were observed in total ICARS scores after therapy, although 1 patient from this group showed a remarkable clinical amelioration. Biochemical diagnosis of CoQ(10) deficiency was a useful tool for the selection of patients who are good candidates for treatment as all of them responded to therapy. However, the remarkable clinical response in 1 case without CoQ(10) deficiency highlights the importance of treatment trials for identification of patients with CoQ(10)-responsive ataxia.

Role of IL-10 promoter polymorphisms in the development of severe aorto-iliac occlusive disease.

Aortic severe occlusive disease (ASO) is a peripheral manifestation of atherosclerosis with an inflammatory component. Interleukin (IL)-10 is an anti-inflammatory cytokine that plays a key role in the development of atherosclerosis, promoting the stability of the atherosclerotic plaque. Several polymorphisms within the 5' region of the IL-10 gene have been related to altered transcriptional activity and protein levels. We aimed at studying two microsatellites, IL-10R and IL-10G, at -4 and -1.2 Kb, and three single nucleotide polymorphisms at positions -1082A/G, -819C/T and -592C/A in a collection of 94 ASO patients and 519 ethnically matched controls. Our results show that the IL-10 proximal promoter haplotype IL-10G*11/ -1082G/ -819C/ -592C is more frequent in ASO patients than in controls (28.7% vs 16% p = 0.003; OR = 2.12). Therefore, our data suggest a role of the IL-10 gene on ASO susceptibility.

Environment-gene interaction in multiple sclerosis: human herpesvirus 6 and MHC2TA.

Multiple sclerosis (MS) is an inflammatory disorder affecting the central nervous system, in which both genetic and environmental factors interact. Among these environmental contributors, herpesvirus has been proposed as an important etiologic factor. CIITA is a transcription factor controlling the expression of MHC class II genes, the main genetic determinants of MS susceptibility. This gene has been described as a target of the immunoevasive strategies, and it is therefore an attractive candidate gene to be at the genetic-viral crossroads. Two polymorphisms in MHC2TA gene (rs4,774G/C and rs3,087,456A/G) were studied in two groups: one in 22 multiple sclerosis patients with active human herpes virus 6 (HHV-6A) replication (HHV-6A-positive), and the other of 77 patients with no detectable HHV-6A active infection (HHV-6A-negative); a Spanish healthy control group (n = 520) was also included as external control. An association of the rs4,774C allele with the HHV-6A-positive group was found when compared with the HHV-6A-negative (47.7% vs 18.8%, p = 0.0001; odds ratio = 3.94) and also with the control group (47.7% vs 25.5%, p = 0.001, odds ratio = 2.67). No significant differences were observed between HHV-6A-negative subjects and healthy controls. Our data suggest that a strong gene-environment interaction occurs between HHV-6A active replication and MHC2TA rs4,774C or another polymorphism in tight linkage disequilibrium with it. Besides, this report indicates that when patients are grouped based upon a well-defined molecular event, complex diseases may reveal themselves as being constituted by distinct entities in which some genes may have a strong influence.

FcRL3 and multiple sclerosis pathogenesis: role in autoimmunity?

BACKGROUND AND AIMS: A functional promoter polymorphism in the FcRL3 gene, -169 T/C, has been shown to regulate gene expression and to play a role in several autoimmune diseases. We aimed at testing for the first time whether this gene was involved in multiple sclerosis (MS) pathogenesis. METHODS: Case-control study performed with 400 Spanish MS patients and 508 healthy subjects. Genotyping of -169 T/C and -110 G/A was ascertained by using TaqMan MGB chemistry following manufacturer suggestions (Applied Biosystems, CA, USA). RESULTS: As previously seen for other autoimmune diseases, a significant difference was observed in the distribution of -169 T/C FcRL3 genotypes between MS patients and healthy controls (p = 0.03; chi(2) = 6.99). The -169 T allele, recently associated with increased susceptibility to Addison's disease, showed a parallel effect in MS [(TT+TC) vs. CC: p = 0.013; OR = 1.55 (1.08-2.54)]. CONCLUSIONS: An increased susceptibility associated to the -169 T allele was found when MS patients and controls were compared, supporting the role of the FcRL3 locus in MS predisposition and therefore extending the evidence of its general influence on autoimmunity.

Role of the MHC2TA gene in autoimmune diseases.

OBJECTIVES: Expression of major histocompatibility complex (MHC) class II genes is almost exclusively regulated by the class II transactivator. A promoter polymorphism (-168A/G, rs3087456) in the MHC2TA gene was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction in a northern European population. However, no evidence of association of this MHC2TA variant with the two autoimmune diseases could be subsequently detected in independent cohorts. AIM: To test the aforementioned single nucleotide polymorphism and another G-->C change (nt1614 from coding sequence, rs4774) to analyse the haplotype pattern in this MHC2TA gene. METHODS: A case-control study was performed with 350 patients with rheumatoid arthritis, 396 patients with multiple sclerosis, 663 patients with inflammatory bowel disease (IBD) and 519 healthy controls from Madrid. Genotyping was ascertained by using TaqMan assays-on-demand on a 7900HT analyser, following the manufacturer's suggestions (Applied Biosystems, Foster City, California, USA). Haplotypes were inferred with the expectation-maximisation algorithm implemented by the Arlequin software. RESULTS: No independent association with these autoimmune diseases was found for either polymorphism in the Spanish cohorts tested. However, when haplotypes were compared between patients with rheumatoid arthritis and controls, a significant difference in their overall frequency distribution was observed, evidencing a protective haplotype (-168A/1614C, p = 0.006; odds ratio (OR) 0.7) and a risk haplotype (-168G/1614C, p = 0.019; OR 1.6). Patients with multiple sclerosis mirrored these results, but no effect on IBD was identified. CONCLUSIONS: The MHC2TA gene influences predisposition to rheumatoid arthritis and multiple sclerosis, but not to IBD. The -168G allele is not an aetiological variant in itself, but a genetic marker of susceptibility/protection haplotypes.

MDR1 gene: susceptibility in Spanish Crohn's disease and ulcerative colitis patients.

BACKGROUND: The multidrug resistance MDR1 gene codes for a membrane transporter associated with inflammatory bowel disease. The polymorphism Ala893Ser/Thr (G2677T/A) previously showed significant association with Crohn's disease (CD) and the Ile1145Ile (C3435T) with ulcerative colitis (UC). We studied the association of both polymorphisms in an independent population to reveal the impact of the MDR1 gene on predisposition to inflammatory bowel disease. METHODS: Case-control study with 321 CD and 330 UC white Spanish patients recruited from the same center, and 352 healthy ethnically matched controls. RESULTS: A significant association of MDR1 C3435T with CD was observed (CC vs (CT + TT): P = 0.007; OR [95% CI] = 1.58 [1.12-2.23]). A CD susceptibility haplotype 2677T/C3435 was identified. No difference between UC patients as a whole and controls could be detected. CONCLUSIONS: New evidence supports the role of the MDR1 gene on CD susceptibility. Therefore, considering our results and those from others, the MDR1 gene behaves as a common risk factor for both CD and UC. We discovered that the C3435 allele conferring susceptibility to CD is different from the described 3435T UC risk allele.

Early B-cell Factor gene association with multiple sclerosis in the Spanish population.

BACKGROUND: The etiology of multiple sclerosis (MS) is at present not fully elucidated, although it is considered to result from the interaction of environmental and genetic susceptibility factors. In this work we aimed at testing the Early B-cell Factor (EBF1) gene as a functional and positional candidate risk factor for this neurological disease. Axonal damage is a hallmark for multiple sclerosis clinical disability and EBF plays an evolutionarily conserved role in the expression of proteins essential for axonal pathfinding. Failure of B-cell differentiation was found in EBF-deficient mice and involvement of B-lymphocytes in MS has been suggested from their presence in cerebrospinal fluid and lesions of patients. METHODS: The role of the EBF1 gene in multiple sclerosis susceptibility was analyzed by performing a case-control study with 356 multiple sclerosis patients and 540 ethnically matched controls comparing the EBF1 polymorphism rs1368297 and the microsatellite D5S2038. RESULTS: Significant association of an EBF1-intronic polymorphism (rs1368297, A vs. T: p = 0.02; OR = 1.26 and AA vs. [TA+TT]: p = 0.02; OR = 1.39) was discovered. This association was even stronger after stratification for the well-established risk factor of multiple sclerosis in the Major Histocompatibility Complex, DRB1*1501 (AA vs. [TA+TT]: p = 0.005; OR = 1.78). A trend for association in the case-control study of another EBF1 marker, the allele 5 of the very informative microsatellite D5S2038, was corroborated by Transmission Disequilibrium Test of 53 trios (p = 0.03). CONCLUSION: Our data support EBF1 gene association with MS pathogenesis in the Spanish white population. Two genetic markers within the EBF1 gene have been found associated with this neurological disease, indicative either of their causative role or that of some other polymorphism in linkage disequilibrium with them.

Role of interleukin 4 in Spanish multiple sclerosis patients.

Interleukin 4 is a Th2 cytokine with potent anti-inflammatory properties. Protection from autoimmune encephalomyelitis and multiple sclerosis has been achieved with IL-4 therapy and IL-4 deficient mice developed a more severe form of clinical disease. Four polymorphisms within the IL-4 gene are in strong linkage disequilibrium, including one in the promoter at -590, which controls transcriptional activity. An MS protective role for the heterozygous genotype was confirmed in Spain (exon-1+33 C/T: p=0.003, OR [CI]=0.57 [0.38-0.84]), probably indicative of an MS protection haplotype at 5q31 locus. No difference among MS clinical forms or age at onset was detected.

Intervención cognitivo conductual en un caso de fobia social / Cognitive behavioral intervention in a case of social phobia

La fobia social se define como un temor acusado y persistente a una o más situaciones sociales o actuaciones en público por la posibilidad de una evaluación negativa de los demás. Es un trastorno que suele provocar notable sufrimiento a la persona que lo padece, generándole importante interferencia en su funcionamiento general, especialmente por las numerosas conductas de evitación que implica. En el presente artículo se presenta el tratamiento de un caso de de fobia social (DSM-IV, APA, 1994), llevado a cabo en 16 sesiones. Las técnicas empleadas fueron la exposición gradual, el entrenamiento en relajación y el entrenamiento en autoinstrucciones. Los resultados muestran diferencias en las medidas empleadas: HAD, SAD, STAI, FNE, EA y CHS. El caso que se expone resulta de interés por el detalle en la exposición de la intervención realizada (AU)

Social Phobia is defined as a strong and persistent fear about one or more social situations or public appearance where the individual feels confronted with a likely negative evaluation from others. This disorder usually leads to a remarkable individual suffering, producing a relevant interference in his/her general functioning particularly due to the numerous avoiding behaviors involved. This paper describes the treatment of a case of social phobia (DSM-IV, APA, 1994) carried out during 16 sessions. Techniques used were gradual exposure, relaxation training and self-instructions training. Results show differences among assessment protocols used: HAD, SAD, STAI, FNE, EA, and CHS. The case shown is of special interest because of the detailed intervention (AU)

Inactivacion de virus ADN envueltos en la producción de hemoderivados (Albúmina e Inmunoglobulinas) / Inactivation of enveloped DNA virus in the production of hemoderivatives (albumin and immunoglobulins)

Se estudió la inactivación del virus herpes simple humano tipo 1 como modelo de virus ADN envueltos, durante las etapas de producción de las inmunoglobulinas intramuscular e intravenosa y la albúmina humana, las etapas del método de fraccionamiento alcohólico para la obtención de estos productos, así como los métodos de remoción y/o inactivación introducidos en el proceso de manufactura, pasteurización y cromatografía de intercambio iónico. El virus se cuantificó por efecto citopático. La obtención de valores de reducción acumulativos reportados en este trabajo demuestran que el método de fraccionamiento alcohólico utilizado en Cuba como variante del método de Cohn-Oncley, combinando métodos de inactivación/remoción, produce un nivel de inactivación de virus ADN envueltos que garantiza una alta seguridad biológica de estos productos para su uso en humanos (AU)

Inactivacion de virus ADN envueltos en la producción de hemoderivados (Albúmina e Inmunoglobulinas) / Inactivation of enveloped DNA virus in the production of hemoderivatives (albumin and immunoglobulins)

Se estudió la inactivación del virus herpes simple humano tipo 1 como modelo de virus ADN envueltos, durante las etapas de producción de las inmunoglobulinas intramuscular e intravenosa y la albúmina humana, las etapas del método de fraccionamiento alcohólico para la obtención de estos productos, así como los métodos de remoción y/o inactivación introducidos en el proceso de manufactura, pasteurización y cromatografía de intercambio iónico. El virus se cuantificó por efecto citopático. La obtención de valores de reducción acumulativos reportados en este trabajo demuestran que el método de fraccionamiento alcohólico utilizado en Cuba como variante del método de Cohn-Oncley, combinando métodos de inactivación/remoción, produce un nivel de inactivación de virus ADN envueltos que garantiza una alta seguridad biológica de estos productos para su uso en humanos