ABSTRACT
@#We have previously isolated a novel avian Orthobunyavirus, Kedah Fatal Kidney Syndrome (KFKS) virus from a broiler farm in Kedah, Malaysia in 2020 with a severe kidney lesion in chickens. The virus was designated as KFKS2_CS virus. Sequence analysis of partial nucleocapsid (N) and nonstructural (NSs) sequence of this virus showed the highest sequence identity with previous KFKS1 from Malaysia (100%) and 97% with a zoonotic Umbre (UMB) virus, which was reported to cause encephalitis in immunocompromised humans in India. Phylogenetic analysis revealed that this virus was clustered together with previous KFKS1 virus from Malaysia, UMB and Cristoli viruses. This study aimed to assess the zoonotic potential of this KFKS2_CS virus in vitro by determining its ability to inhibit the production of interferon (IFN) in human glioblastoma multiforme (GBM) brain cells using reverse-transcriptase polymerase reaction (RT-PCR). This virus blocked the production of interferon-a in this human brain cells. In conclusion, this KFKS2_CS virus may have a zoonotic potential and become a public health concern in the future.
ABSTRACT
Objective@#To explore the association between the efficacy of peg-IFN and the complexity of TP and RT regions of hepatitis B virus (HBV) in chronic hepatitis B.@*Methods@#Patients with HBeAg positive, HBV DNA positive chronic hepatitis B were given peg-interferon 180 μg once a week for subcutaneous injection, and baseline information was collected from baseline and after 12 weeks’ treatment. The baseline HBV DNA TP and RT fragments were amplified, database, high-throughput sequencing, and the average genetic distance calculation.@*Results@#Data of 108 patients were analyzed by logistic regression. RT area fragment Markov distance and TP area fragment Shannon quotient for HBV DNA response were calculated. ALT level is good for HBeAg response. HBsAg level is bad for HBsAg response.@*Conclusions@#The complexity of the baseline TP and RT regions may be associated with the efficacy of peg-interferon therapy for CHB.
ABSTRACT
In the present work, a recombinant Escherichia coli strain was used for the production of interferon α-2b in both shake flask and in bioreactor. The first part of this research was focused on the investigation of the effect of glucose concentration on the kinetics of cell growth, recombinant protein production and acetate formation. In general, glucose supplementation to culture medium enhanced cell growth when added in concentration between 0-20 g/L. Further increase in glucose level reduces biomass production and enhances acetate accumulation in culture. The results clearly demonstrated that maximal interferon production of 27.7 mg/L was achieved in culture supplemented with 20 g/L glucose. Further improvement in recombinant interferon production process was also achieved by scaling up from shake flask to 16-L stirred tank bioreactor. The maximal volumetric interferon production in bioreactor batch culture was 44.5. mg/L after only 6 hours.
ABSTRACT
La leucemia mieloide crónica (LMC) es un trastorno clonal que generalmente se diagnostica con facilidad porque las células leucémicas en más del 95 por ciento de los pacientes presentan una anomalía citogenética característica, el cromosoma Filadelfia (Ph). El embarazo no tiene un efecto adverso sobre la enfermedad, pero esta puede comprometer potencialmente la circulación placentaria por leucoestasis, puede provocar bajo peso al nacer, nacimiento prematuro y aumento de la mortalidad. El mesilato de Imatinib se usa como terapia de primeria línea en estos pacientes pero existen numerosos reportes sobre su acción teratogénica. El interferón-á es considerado la droga de elección en el tratamiento durante el embarazo. Se describen dos pacientes con diagnóstico de LMC y embarazo tratadas con interferón-a; la primera al diagnóstico de la enfermedad y la segunda a los 3 años de tratamiento con mesilato de Imatinib, el cual suspendió un mes antes de la gestación. Los dos embarazos se desarrollaron satisfactoriamente al igual que los fetos y nacieron dos niños con buena vitalidad que actualmente están sanos y con un desarrollo psicomotor normal
Chronic myeloid leukemia (CML) is a clonal dysfunction with easy diagnosis since more than 95 percent of the leukemia cells present a citogenetic chromosome Philadelphia (Ph) anomaly. The pregnancy has no adverse effect on the illness, but the leucoestasis potentially can commit the placental circulation and cause underweight born, premature birth and the increase of mortality. The imatinib mesylate is the first line therapy for the disease but there are numerous reports about its teratogenic action. The alpha-interferon is the drug of election for treatment during pregnancy. Two patients with CML and pregnancy treated with alpha-interferon are described. The first one treated at diagnosis and the second one after 3 years of treatment with imatinib mesylate which was suspended one month before. The two pregnancies developed satisfactorily same as the fetuses and two children were born with good vitality and healthy with normal psychomotor development
Subject(s)
Humans , Female , Pregnancy , Pregnancy Complications, Hematologic/prevention & control , Interferon-alpha/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/prevention & control , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapyABSTRACT
El Interferón alfa (IFN-alfa), se utiliza junto a otros antivirales en el tratamiento de la hepatitis C crónica. Se han descrito alteraciones autoinmunes durante su uso, destacándose las enfermedades del tiroides y la diabetes mellitus tipo 1 (DM 1), entre otras. Se presenta el caso de una paciente con hepatitis C crónica que a los 6 meses de tratamiento con IFN-alfa y Ribavirina, manifestó síntomas graves de coma, cetoácidosis metabólica, hiperglucemía y deshidratación. Se diagnosticó el inicio de una DM 1 secundaria a la administración del IFN-alfa. No tenía antecedentes personales o familiares de factores genéticos predisponentes para el desarrollo de ésta enfermedad. Fue tratada en una Unidad de Urgencias Medicas, donde recibió medicamentos para el control de sus manifestaciones. Se suspendió la administración de IFN-alfa y se mantiene con tratamiento ambulatorio, aplicándose la insulina en dosis fraccionada, ajustada a los valores de glucemia
Interferon a (IFN-a), is used together with other antivirals in the treatment of chronic hepatitis C. Autoimmune disorders have been described during its use, particularly thyroid diseases and type 1 diabetes mellitus (DM1), among others. We report the case of a patient with chronic hepatitis C, showing severe symptoms of coma, metabolic ketoacidosis, hyperglycemia and dehydration after 6 months of treatment with IFN-aand ribavirin. The beginning of a secondary DM 1 at the administration of IFN-a was diagnosed. There was no personal or family history of genetic factors predisposing to the development of this disease. The patient was treated in an Emergency Medical Unit (MEU) where medication to control its manifestations was received. Administration of IFN-a was suspended and the ambulatory treatment is maintained, applying insulin in fractional doses adjusted to blood glucose values
Subject(s)
Humans , Female , Middle Aged , Diabetes Mellitus, Type 1/chemically induced , Hepatitis C/drug therapy , Interferon-alpha/adverse effects , Interferon-alpha/therapeutic useABSTRACT
La policitemia Vera se encuentra entre las neoplasias mieloides según la clasificación más reciente de la Organización Mundial de la Salud (OMS). Sus criterios diagnósticos han tenido variaciones en los últimos años y en este trabajo se realiza un análisis de estos criterios, así como de la respuesta a los tratamientos empleados en 349 pacientes atendidos en el Instituto de Hematología e Inmunología en los últimos 40 años. Se sugiere, dada su factibilidad y eficacia, continuar utilizando por el momento la clasificación OMS del 2001, y de acuerdo con la experiencia acumulada, se propone el tratamiento con medicamentos de primera y segunda líneas según la edad y las características clínicas de cada enfermo
The Polycythemia vera is located among the myeloid neoplasms according to the more recent classification of the HWO. Its diagnostic criteria have underwent variations in past years and in present paper authors made an analysis of such criteria, as well as of the response to treatments applied in 349 patients seen in the Institute of Hematology and Immunology during the past 40 years. Due to feasibility and effectiveness, for the moment, is has been suggested to carry on with the use of the classification of WHO of 2001, and according to the experience gained, it is proposed the treatment with first and second line drugs by age and the clinical features of each patient
Subject(s)
Humans , Male , Female , International Classification of Diseases/standards , Polycythemia Vera/diagnosis , Polycythemia Vera/therapy , Case Reports , International Classification of Diseases/methodsABSTRACT
El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: El presente estudio estuvo dirigido a determinar la evolución virológica, bioquímica e histológica de los pacientes con hepatitis crónica C bajo terapia combinada Interferón a 2b recombinante más ribavirina e identifica los principales factores asociados a las tasas obtenidas de respuesta virológica sostenida. MÉTODOS: Ensayo clínico-terapéutico fase IV, abierto, no controlado y multicéntrico rectorado por el Instituto de Gastroenterología y el Centro de Ingeniería Genética y Biotecnología en el período comprendido de mayo de 2001 a mayo de 2006. La muestra estuvo conformada por 122 pacientes con hepatitis crónica C que cumplieron con criterios de inclusión y exclusión predeterminados. Se utilizó interferón a 2b recombinante (3 millones de unidades 3 veces por semana) más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal) durante 48 sem. RESULTADOS: Se obtuvo una tasa de respuesta virológica y bioquímica sostenida a la semana 72 de 32,8 y 50,8 por ciento respectivamente. Un 41,3 por ciento del total de pacientes experimentó mejoría histológica a expensas de la reducción de la fibrosis y pocos cambios en la inflamación. CONCLUSIONES: Teniendo en cuenta la tasa de respuesta global obtenida, se consideró como tratamiento eficaz para la hepatitis crónica C y se recomendó profundizar en el conocimiento de las características de la infección en Cuba así como en opciones de tratamiento más eficaces para esta enfermedad
The hepatitis C virus becomes in leading cause of chronic hepatitis, hepatic cirrhosis, hepatocarcinoma and liver transplant at world level. OBJECTIVE: The aim of present study is to determine the virological, biochemical and histological course of patients presenting with Chronic hepatitis C under a combination of recombinant Interferon alfa-2b plus Ribavirin and to identify the main factors associated with the rates obtained of virological response. METHODS: A non-controlled and multicenter phase IV clinical-therapeutical trial was sponsored by the Institute of Gastroenterology and the Genetics and Biotechnology Engineering Center from May, 2002 to May, 2006. Sample included 122 patients diagnosed with chronic hepatitis C fulfilling the predetermined inclusion and exclusion criteria. Recombinant Interferon alfa-2b (3 millions of t.i.d units) was used plus Ribavirin (1000 or 1200 mg daily depending on the body weight) during 48 weeks. RESULTS: We achieved a sustained biochemical and virological response rate of 32,8 and 50,8 percent, respectively at week 72. A 41,3, percent from the total of patients had a histological improvement at the expense of reduction of fibrosis and a few changes in inflammation level. CONCLUSIONS: Raking into account the global response rate achieved this combined treatment was considered effectiveness for chronic hepatitis C and we recommended to deepen in the knowledge of infection in Cuba, as well as in more efficient treatment options for this disease
Subject(s)
Humans , Hepatitis C, Chronic/therapy , Interferon-alpha , Ribavirin/therapeutic use , Virology/analysisABSTRACT
Se evaluaron 43 pacientes adultos con leucemia mieloide crónica, Philadelphia positivo, que recibieron tratamiento con mesilato de imatinib como droga de segunda línea por resistencia o intolerancia al interferón alfa recombinante. La manifestación más frecuente al inicio de la enfermedad fue la esplenomegalia. El tratamiento con mesilato de imatinib se inició por resistencia (33; 76,7 por ciento) o intolerancia grado 3 o 4 (10; 23,3 por ciento). El mayor porcentaje de respuesta citogenética mayor (22; 91,7 por ciento) y completa (11; 61,1 por ciento) se alcanzó a los 18 y 24 meses de evolución. El 74,3 por ciento no mostró respuesta molecular y el 5,1 por ciento ya presentaba respuesta molecular antes del tratamiento; 9 (26,5 por ciento) mostraron pérdida de la remisión hematológica completa, de ellos, 7 fallecieron por progresión de la enfermedad. La sobrevida global fue de 90,7 por ciento, 83,3 por ciento, 82,6 por ciento y 78,9 por ciento a los 5, 6, 7 y 8 años de evolución, respectivamente. La sobrevida global y libre de eventos a los 3 años de iniciado el mesilato de imatinib fue de 92,3 por ciento y 81,8 por ciento, respectivamente. Se encontró diferencia significativa entre la sobrevida libre de eventos y el índice pronóstico de Sokal. Las reacciones clínicas secundarias más frecuentes fueron dolores óseos, musculares o ambos; y las hematológicas: anemia hemolítica autoinmune y trombocitopenia
Forty three patients presenting with chronic positive-Philadelphia myeloid leukemia were assessed treated with Imatinib Mesilate as a second line drug by resistance or intolerance to recombinant alpha Interferon. At onset, the more frequent manifestation of this condition was the splenomegalia. Imatinib Mesilate treatment was started by resistance (33; 7.6 percent) or 3 or 4 degree intolerance (10; 23.3 percent). The greater percentage of cytogenetic response (22; 91.7 percent) and complete (11; 61.1 percent) was achieved at 18 and 24 course months. The 74,3 percent hadn't ,molecular response and the 5,1 percent yet had it before treatment; 9 (26.5 percent) showed a loss of complete hematologic remission, from them, 7 deceased from disease progression. Global survival was of 90.7 percent, 83,3 percent
Subject(s)
Humans , Interferon-alpha/adverse effects , Interferon-alpha/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Mesylates/therapeutic useABSTRACT
Interferon-alpha is known to inhibit the vascular endothelial cell proliferation and migration in vitro.It has been used systemically for the treatment of choroidal neovascular membrane proliferation.However, significant side effects in systemic administration limit the dosage and duration of its use. It has been suggested that reducing systemic side effects and maintenance of high intraocular concentration would be achieved with the direct intravitreal injection of Interferon-alpha.Thus, this study was undertaken to estimate the toxicity and safe dose of Interferon-alpha when it is given intravitreally in rabbits. Normal saline, Interferon-alpha 50, 000IU, 100, 000IU, 200, 000IU and 300, 000 IU were given intravitreally to 10 rabbit eyes.Toxicity was assessed by serial ERGs after 7 and 14 days.Animals were sacrificed at 14 days after injection for histopathologic study. The ERG was flattened at 14 days in 300, 000IU of Interferon-alpha group.On histologic examination, inflammatory reaction of vitreous and retina remained at an insignificant level upto 200, 000IU, but increased in dose dependent manner above this dose, resulting in prominent reaction in 300, 000IU group. Therefore, we suggest that 200, 000IU of Interferon-alpha may be the safe dose when administered intravitreally in rabbits, and 300, 000IU may be the toxic dose.
Subject(s)
Rabbits , Choroid , Endothelial Cells , Interferon-alpha , Intravitreal Injections , Membranes , RetinaABSTRACT
Interferons(IFNs) exhibit an antiproliferative effect on many normal and transformed cells and have in vivo antitumor activity in a variety of cancers. Recent clinical studies have suggested major activity with IFNs, especially in advanced squamous cell carcinoma of the skin and cervix. With the objective of exploring how the IFNs might work in squamous carcinoma cell line, we studied the effect of IFN-a on cervical cancer cell lines. The effect of IFNs on apoptosis and cell cycle of cervical cancer cell lines(C33A, CaSki, SiHa, HeLa, ME-180) was analysed by flow cytometry in time dependent manner. Results were as follows: (1) According to cell count of studied cancer cell lines treated with 2,000 IU/ml IFN-a for 7 days exposure, IFN-a had the antiproliferative effect on all five tested cervical cancer cell lines. Also this antiproliferative effect was confirmed by WST-1 assay. (2) The effect of IFN-a on apoptosis of each cultute was analysed by flow cytometry after 3 days and 7 days exposure with 2,000 IU/ml IFN-a, Apoptosis was not induced by IFN-a treatment. (3) The effect of IFN-a on the cell cycle of each culture was analysed by flow cytometry after 3 days exposure with 2,000 IU/ml IFN-a. As compared to control cells, treatment with IFN-a resulted in a higher proportion of cells in S phase with lower portion of cells with G2/M phase. (4) Time course of IFN-a effect on HPV 16 and HPV 18 E6 mRNA levels was evaluated by northern blot analysis. In CaSki cell line, HPV 16 E6 mRNA expression induced by IFN-a was not inhibited. But in HeLa cell line, HPV 18 E6 inRNA expression was inhibited. IFN-a appears to have the antiproliferative effect on all five tested cervical cancer cell lines and the antiproliferative effect of IFN-a seemed to be induced not by apoptosis but by disruption on specific cell cycle. Also regulation of HPV E6 mRNA expression induced by IFN-a is not directly related to the mechanisms of the antiproliferative effect of IFN-a in cancer cell lines.
Subject(s)
Female , Humans , Apoptosis , Blotting, Northern , Carcinoma, Squamous Cell , Cell Count , Cell Cycle , Cell Line , Cervix Uteri , Flow Cytometry , HeLa Cells , Human papillomavirus 16 , Human papillomavirus 18 , RNA, Messenger , S Phase , Skin , Uterine Cervical NeoplasmsABSTRACT
A 13-month-old boy had irregularly shaped, erythematous to dusky red, slightly raised patches and plaques on the left antecubital fossa and arm for 7 months. The lesions were firm and tender. Histopathologically the lesion consisted of small, circumscribed, angiomatous tufts and lobules with a cannonball appearance scattered throughout dermis, a characteristic feature of tufted angioma. For 15 weeks, interferon-a intralesional injections have been performed and the lesions showed an improvement.
Subject(s)
Humans , Infant , Male , Arm , Dermis , Hemangioma , Injections, Intralesional , Interferon-alphaABSTRACT
Locally advanced cancer of the uterine cervix is a major cause of death worldwide. Standard treatment with rdiolherepy for locally advanced cancer of the uterine cnvix has a response rate of less than 50%. Resently concurrent chcmoradirothcrpay has been introduced but with some contvovesy. Interferon and retinoic acid are inducible proteins which posses many hiologic activities such as, antiproliferative, immunomodulatory and antineoplastic properties. Combination of interferon and retinoic acid has produced high response rates especially for patients with squamous cell carcinoma . And they may potentiate the radiation cytotoxicity as adiosensitizer. This study was underaken to assess the clinical efficacy of combination regimen with interferon-alpha2a, 13-cis-retinoic acid and radiotherapy from Dec. 1988 to Dex. 1994 at Severance hospital Yonsei uniersity. Twenty seven patients of locally advanced squamous cell carcionma of the uterine cervix enrolled in this study are evaluated for response and toxicity. The results were as follow: 1. Preliminary results of interferon-alpha2a 13-cis-retinoic acid and radiotherapy are 46.7% of response rate(33.3% complete response)and those of concurrent chemoradiotherapy are 41.7% of response rate(46.7% complete response). 2. Major toxicity of interferon-alpha2a, 13-cis-retinoic acid and radiotherapy is fever(60.0%), and only case of grade 2 anemia and one case of grade 1 AST/ALT elevation was noted. There was no grade 3 or 4 toxicity. Systemic interferon-alpha2a, 13-cis-retinoc acid and radiotherapy is highly active, well tolerated therapy for locally advanced cervical cancer.
Subject(s)
Female , Humans , Anemia , Carcinoma, Squamous Cell , Cause of Death , Cervix Uteri , Chemoradiotherapy , Interferons , Isotretinoin , Radiotherapy , Tretinoin , Uterine Cervical NeoplasmsABSTRACT
Locally advanced cancer of the uterine cervix is a major cause of death worldwide. Standard treatment with rdiolherepy for locally advanced cancer of the uterine cnvix has a response rate of less than 50%. Resently concurrent chcmoradirothcrpay has been introduced but with some contvovesy. Interferon and retinoic acid are inducible proteins which posses many hiologic activities such as, antiproliferative, immunomodulatory and antineoplastic properties. Combination of interferon and retinoic acid has produced high response rates especially for patients with squamous cell carcinoma . And they may potentiate the radiation cytotoxicity as adiosensitizer. This study was underaken to assess the clinical efficacy of combination regimen with interferon-alpha2a, 13-cis-retinoic acid and radiotherapy from Dec. 1988 to Dex. 1994 at Severance hospital Yonsei uniersity. Twenty seven patients of locally advanced squamous cell carcionma of the uterine cervix enrolled in this study are evaluated for response and toxicity. The results were as follow: 1. Preliminary results of interferon-alpha2a 13-cis-retinoic acid and radiotherapy are 46.7% of response rate(33.3% complete response)and those of concurrent chemoradiotherapy are 41.7% of response rate(46.7% complete response). 2. Major toxicity of interferon-alpha2a, 13-cis-retinoic acid and radiotherapy is fever(60.0%), and only case of grade 2 anemia and one case of grade 1 AST/ALT elevation was noted. There was no grade 3 or 4 toxicity. Systemic interferon-alpha2a, 13-cis-retinoc acid and radiotherapy is highly active, well tolerated therapy for locally advanced cervical cancer.