N-methylisatin-beta-thiosemicarbazone derivative (SCH 16) is an inhibitor of Japanese encephalitis virus infection in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>During the early and mid part of 20^thcentury, several reports described the therapeutic effects of N-methylisatin-β-Thiosemicarbazone (MIBT) against pox viruses, Maloney leukemia viruses and recently against HIV. However, their ability to inhibit flavivirus replication has not been investigated. Hence the present study was designed to evaluate the antiviral activity of 14 MIBT derivatives against Flaviviruses that are prevalent in India such as Japanese Encephalitis Virus (JEV), Dengue-2 (Den-2) and West Nile viruses (WNV).</p> <p>Results</p> <p>Amongst the fourteen Mannich bases of MIBT derivatives tested one compound – SCH 16 was able to completely inhibit <it>in vitro </it>Japanese encephalitis virus (JEV) and West Nile virus (WNV) replication. However no antiviral activity of SCH 16 was noted against Den-2 virus replication. This compound was able to inhibit 50% of the plaques (IC₅₀) produced by JEV and WNV at a concentration of 16 μgm/ml (0.000025 μM) and 4 μgm/ml (0.000006 μM) respectively. Furthermore, SCH 16 at a concentration of 500 mg/kg body weight administered by oral route twice daily was able to completely (100%) prevent mortality in mice challenged with 50LD₅₀JEV by the peripheral route. Our experiments to understand the mechanism of action suggest that SCH 16 inhibited JEV replication at the level of early protein translation.</p> <p>Conclusion</p> <p>Only one of the 14 isatin derivatives -SCH 16 exhibited antiviral action on JEV and WNV virus infection <it>in vitro</it>. SCH 16 was also found to completely inhibit JEV replication <it>in vivo </it>in a mouse model challenged peripherally with 50LD₅₀of the virus. These results warrant further research and development on SCH 16 as a possible therapeutic agent.</p

Transactivation and signaling functions of Tat are not correlated: biological and immunological characterization of HIV-1 subtype-C Tat protein

BACKGROUND: Of the diverse subtypes of Human Immunodeficiency Virus Type-1 (HIV-1), subtype-C strains cause a large majority of infections worldwide. The reasons for the global dominance of HIV-1 subtype-C infections are not completely understood. Tat, being critical for viral infectivity and pathogenesis, may differentially modulate pathogenic properties of the viral subtypes. Biochemical studies on Tat are hampered by the limitations of the current purification protocols. Tat purified using standard protocols often is competent for transactivation activity but defective for a variety of other biological functions. Keeping this limitation in view, we developed an efficient protein purification strategy for Tat. RESULTS: Tat proteins obtained using the novel strategy described here were free of contaminants and retained biological functions as evaluated in a range of assays including the induction of cytokines, upregulation of chemokine coreceptor, transactivation of the viral promoter and rescue of a Tat-defective virus. Given the highly unstable nature of Tat, we evaluated the effect of the storage conditions on the biological function of Tat following purification. Tat stored in a lyophilized form retained complete biological activity regardless of the storage temperature. To understand if variations in the primary structure of Tat could influence the secondary structure of the protein and consequently its biological functions, we determined the CD spectra of subtype-C and -B Tat proteins. We demonstrate that subtype-C Tat may have a relatively higher ordered structure and be less flexible than subtype-B Tat. We show that subtype-C Tat as a protein, but not as a DNA expression vector, was consistently inferior to subtype-B Tat in a variety of biological assays. Furthermore, using ELISA, we evaluated the anti-Tat antibody titers in a large number of primary clinical samples (n = 200) collected from all four southern Indian states. Our analysis of the Indian populations demonstrated that Tat is non-immunodominant and that a large variation exists in the antigen-specific antibody titers. CONCLUSION: Our report not only describes a simple protein purification strategy for Tat but also demonstrates important structural and functional differences between subtype-B and -C Tat proteins. Furthermore, this is the first report of protein purification and characterization of subtype-C Tat

HLA-B∗57 and Gender Influence the Occurrence of Tuberculosis in HIV Infected People of South India

Background. Substantial evidence exists for HLA and other host genetic factors being determinants of susceptibility or resistance to infectious diseases. However, very little information is available on the role of host genetic factors in HIV-TB coinfection. Hence, a longitudinal study was undertaken to investigate HLA associations in a cohort of HIV seropositive individuals with and without TB in Bangalore, South India. Methods. A cohort of 238 HIV seropositive subjects were typed for HLA-A, B, and DR by PCR-SSP and followed up for 5 years or till manifestation of Tuberculosis. HLA data of 682 HIV Negative healthy renal donors was used as control. Results. The ratio of males and females in HIV cohort was comparable (50.4% and 49.6%). But the incidence of TB was markedly lower in females (12.6%,) than males (25.6%). Further, HLA-B*57 frequency in HIV cohort was significantly higher among females without TB (21.6%, 19/88) than males (1.7%, 1/59); P = 0.0046; OR = 38. CD4 counts also were higher among females in this cohort. Conclusion. This study suggests that HIV positive women with HLA-B*57 have less occurrence of TB as compared to males

Enterovirus 75 Encephalitis in Children, Southern India

Recent outbreaks of enterovirus in Southeast Asia emphasize difficulties in diagnosis of this infection. To address this issue, we report 5 (4.7%) children infected with enterovirus 75 among 106 children with acute encephalitis syndrome during 2005–2007 in southern India. Throat swab specimens may be useful for diagnosis of enterovirus 75 infection

Implementación de la estrategia de segmentación de clientes para el incremento en el uso de la tarjeta de crédito de una entidad bancaria

RESUMEN La tesis en la modalidad de suficiencia profesional denominada “Implementación de la estrategia de segmentación de clientes para el incremento en el uso de la tarjeta de crédito de una entidad bancaria” presenta el problema general: ¿Cómo la implementación de la estrategia de segmentación de los clientes incrementará el uso de la tarjeta de crédito de una entidad bancaria?, del cual se plantea el objetivo general: Implementar la estrategia de segmentación de clientes para incrementar el uso de la tarjeta de crédito de una entidad bancaria. Se desarrolla un caso de éxito en una entidad bancaria que se sustenta en los aportes teóricos acerca de la Segmentación de Clientes desde el punto de vista del Marketing, el CRM y la Estadística; también se presenta las bases de la teoría de administración aplicada a la Gestión de Campañas. En el desarrollo del caso se realizó dos segmentaciones: por nivel de consumo (Heavy, Medium, Light Transactor) y por consumo en giros comerciales (Viajeros, Retail, Buen comer, etc) lo que impactó positivamente en el conocimiento del cliente y en la formulación de estrategias comerciales innovadoras que originó buenos resultados en el incremento de uso de la tarjeta de crédito. PALABRAS CLAVE: segmentación, tarjeta de crédito, entidad bancaria, marketing, CRM, gestión de campañas, conocimiento del cliente.ABSTRACT The thesis in the modality of professional sufficiency denominated "Implementation of the strategy of the customer segmentation for the increase in the use of the credit card of a bank" presents the general problem: How the implementation of the strategy of customer segmentation will increase the use of the credit card of a bank?, which propose the general objective: Implement the strategy of customer segmentation to increase the use of the credit card of a bank. It developed a success case in a bank that is based on theoretical contributions on the Customer Segmentation from the point of view of Marketing, CRM and Statistics; it also presents the bases of management theory applied to Campaign Management. In the development of the case, there were two segmentations: by level of consumption (Heavy, Medium, Light Transactor) and by commercial spins consumption (Travellers, Retail, God eating, et cetera.) which positively impacted the customer knowledge and formulation of innovative commercial strategies that resulted in good results for the increase of credit card use. KEYWORDS: segmentation, credit card, banking, CRM, campaign management, customer knowledge

Enterovirus 75 encephalitis in children, Southern India

Recent outbreaks of enterovirus in Southeast Asia emphasize difficulties in diagnosis of this infection. To address this issue, we report 5 (4.7%) children infected with enterovirus 75 among 106 children with acute encephalitis syndrome during 2005–2007 in southern India. Throat swab specimens may be useful for diagnosis of enterovirus 75 infection

Chikungunya Virus and Central Nervous System Infections in Children, India

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus best known for causing fever, rash, arthralgia, and occasional neurologic disease. By using real-time reverse transcription–PCR, we detected CHIKV in plasma samples of 8 (14%) of 58 children with suspected central nervous system infection in Bellary, India. CHIKV was also detected in the cerebrospinal fluid of 3 children

HLA-B * 57 and Gender Influence the Occurrence of Tuberculosis in HIV Infected People of South India

Background. Substantial evidence exists for HLA and other host genetic factors being determinants of susceptibility or resistance to infectious diseases. However, very little information is available on the role of host genetic factors in HIV-TB coinfection. Hence, a longitudinal study was undertaken to investigate HLA associations in a cohort of HIV seropositive individuals with and without TB in Bangalore, South India. Methods. A cohort of 238 HIV seropositive subjects were typed for HLA-A, B, and DR by PCR-SSP and followed up for 5 years or till manifestation of Tuberculosis. HLA data of 682 HIV Negative healthy renal donors was used as control. Results. The ratio of males and females in HIV cohort was comparable (50.4% and 49.6%). But the incidence of TB was markedly lower in females (12.6%,) than males (25.6%). Further, HLA-B * 57 frequency in HIV cohort was significantly higher among females without TB (21.6%, 19/88) than males (1.7%, 1/59); P = 0.0046; OR = 38. CD4 counts also were higher among females in this cohort. Conclusion. This study suggests that HIV positive women with HLA-B * 57 have less occurrence of TB as compared to males

Establishment of reference CD4+ T cell values for adult Indian population

<p>Abstract</p> <p>Background</p> <p>CD4+ T lymphocyte counts are the most important indicator of disease progression and success of antiretroviral treatment in HIV infection in resource limited settings. The nationwide reference range of CD4+ T lymphocytes was not available in India. This study was conducted to determine reference values of absolute CD4+ T cell counts and percentages for adult Indian population.</p> <p>Methods</p> <p>A multicentric study was conducted involving eight sites across the country. A total of 1206 (approximately 150 per/centre) healthy participants were enrolled in the study. The ratio of male (N = 645) to female (N = 561) of 1.14:1. The healthy status of the participants was assessed by a pre-decided questionnaire. At all centers the CD4+ T cell count, percentages and absolute CD3+ T cell count and percentages were estimated using a single platform strategy and lyse no wash technique. The data was analyzed using the Statistical Package for the Social Scientist (SPSS), version 15) and Prism software version 5.</p> <p>Results</p> <p>The absolute CD4+ T cell counts and percentages in female participants were significantly higher than the values obtained in male participants indicating the true difference in the CD4+ T cell subsets. The reference range for absolute CD4 count for Indian male population was 381-1565 cells/μL and for female population was 447-1846 cells/μL. The reference range for CD4% was 25-49% for male and 27-54% for female population. The reference values for CD3 counts were 776-2785 cells/μL for Indian male population and 826-2997 cells/μL for female population.</p> <p>Conclusion</p> <p>The study used stringent procedures for controlling the technical variation in the CD4 counts across the sites and thus could establish the robust national reference ranges for CD4 counts and percentages. These ranges will be helpful in staging the disease progression and monitoring antiretroviral therapy in HIV infection in India.</p

Diagnostic markers of acute encephalitis syndrome and COVID-associated multisystem inflammatory syndrome in children from Southern India.

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1β, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation