Interleukin16 and Interleukin 28B Genes Polymorphism in HBV Infected Saudi pa...iosrjce
The course of hepatitis B virus (HBV) infection is variable depending on many factors. In this study,
we investigated single nucleotide polymorphisms of interleukin-28B and interleukin-16 as possible host factors
which may determine the occurrence of hepatocellular carcinoma (HCC) in Saudi patients. Chronic hepatitis B
(CHB) patients (75), HCC patients (42), and healthy controls (70) were analyzed for polymorphisms of the IL16
and IL28B genes using PCR and restriction fragment length polymorphism (RFLP). Results showed that HCC
and chronic HBV patients had higher prevalence of rs11556218TG genotype than controls. The rs11556218GG
genotype was higher among HCC (14.4%) compared to chronic HBV (2.7%) patients. The IL-16 genotype
rs4072111CT was higher among HCC (47.6%) and chronic HBV (46.7%) patients than controls (28.6%). The
rs4072111TT genotype was higher among HCC patients compared to the other two groups. The T allele
frequency was higher among HCC patients than controls. The CT and TT of the IL-28B rs12979860 genotype
were significantly less frequent in chronic HBV and HCC patients. The IL-28B rs8099917 TG genotype was
more frequent among HCC (19%) compared to chronic HBV (8%) patients. However, no significant difference
was detected in the allele distribution.
Comparison Between Antiviral Combination Therapies Against Hepatitis C Virus ...Mohammed Fathy Zaky
Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide. HCV genotype 4 is predominant in the Middle East and Africa, especially Egypt where 90% of HCV cases are genotype 4. The aim of this study is to compare the efficacy and safety of new antiviral combination therapies for treating HCV genotype 4 infection in Egyptian patients.
1. The document discusses the origin of HIV and evolution of resistance to AIDS, noting that chimpanzees and sooty mangabeys are naturally resistant to SIV and do not develop AIDS despite high viral loads.
2. It examines the receptors CCR5 and CXCR4 that HIV uses for entry and discusses whether R5, X4, or R5X4 variants are infectious via different routes of transmission.
3. The predominant virus transmitted is R5-tropic HIV which uses the CCR5 receptor and first infects memory CD4+ T cells and macrophages in the gut-associated lymphoid tissue.
Infection with a host-range mutant adenovirus 5 (Ad5hr) in rhesus macaques induced both innate and adaptive immune responses. There was a delayed increase in plasmacytoid dendritic cells and their interferon-alpha production in blood 2-6 weeks after infection. Ad5hr infection also transiently increased the frequencies of regulatory T cells and activated/proliferating CD4+ T cells in blood. Expression of proinflammatory cytokines like IFN-gamma, IL-1, CCL20 and TNF in blood was suppressed after Ad5hr infection. Ad5hr induced polyfunctional CD4+ and CD8+ T cell responses specific to the adenovirus hexon protein in all
1) Hepatitis C virus (HCV) infection affects 120-130 million people worldwide and is a leading cause of chronic liver disease and liver cancer.
2) The document describes a multidisciplinary team at the National Reference Center for Viral Hepatitis B, C and D that conducts clinical trials, cohort studies, and basic research on HCV.
3) The team uses new virological tools like next-generation sequencing and modeling to study HCV resistance and quasispecies evolution, and develops models to understand HCV-induced liver carcinogenesis.
Perrotti A.P. L'Ematologia nel III° Millennio: cosa è cambiato e cosa bisogna...Gianfranco Tammaro
DOTT. PERROTTI ALESSIO P. (Sessione del 26/11/2015) - Convegno "Lunch Meeting al Pasteur: What's New In..." - dal 01/10/2015 al 10/12/2015 - Studio Pasteur - Viale Pasteur, 66 - Roma
Sito: www.asmad.net
Canale Youtube: https://www.youtube.com/channel/UCIggSJlnC77uDHuX5TUoFHg
This study investigated the expression of CD44 standard (CD44st) and variant isoforms (CD44v) in human pancreatic cancer cell lines and normal pancreatic duct cells. Flow cytometry and immunocytochemistry showed that CD44st, CD44v3, CD44v4, CD44v5, and CD44v6 were moderately expressed in all pancreatic cancer cell lines tested. In contrast, normal pancreatic duct cells expressed very low levels of these CD44 variants. Stimulation of pancreatic cancer cells with growth factors did not affect CD44 expression, except IFNγ which downregulated CD44v6. The constitutive expression of CD44 variants seems associated with the malignant state of invasive pancreatic carcinoma.
This document discusses cancer care in Kashmir and South Asia. It provides information on the Hakim Sanaullah Cancer Centre in Kashmir and discusses challenges facing cancer treatment in the region like lack of resources, poverty, and late stage diagnoses. Statistics are presented on cancer incidence and mortality in South Asia countries compared to resources available for treatment.
Interleukin16 and Interleukin 28B Genes Polymorphism in HBV Infected Saudi pa...iosrjce
The course of hepatitis B virus (HBV) infection is variable depending on many factors. In this study,
we investigated single nucleotide polymorphisms of interleukin-28B and interleukin-16 as possible host factors
which may determine the occurrence of hepatocellular carcinoma (HCC) in Saudi patients. Chronic hepatitis B
(CHB) patients (75), HCC patients (42), and healthy controls (70) were analyzed for polymorphisms of the IL16
and IL28B genes using PCR and restriction fragment length polymorphism (RFLP). Results showed that HCC
and chronic HBV patients had higher prevalence of rs11556218TG genotype than controls. The rs11556218GG
genotype was higher among HCC (14.4%) compared to chronic HBV (2.7%) patients. The IL-16 genotype
rs4072111CT was higher among HCC (47.6%) and chronic HBV (46.7%) patients than controls (28.6%). The
rs4072111TT genotype was higher among HCC patients compared to the other two groups. The T allele
frequency was higher among HCC patients than controls. The CT and TT of the IL-28B rs12979860 genotype
were significantly less frequent in chronic HBV and HCC patients. The IL-28B rs8099917 TG genotype was
more frequent among HCC (19%) compared to chronic HBV (8%) patients. However, no significant difference
was detected in the allele distribution.
Comparison Between Antiviral Combination Therapies Against Hepatitis C Virus ...Mohammed Fathy Zaky
Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide. HCV genotype 4 is predominant in the Middle East and Africa, especially Egypt where 90% of HCV cases are genotype 4. The aim of this study is to compare the efficacy and safety of new antiviral combination therapies for treating HCV genotype 4 infection in Egyptian patients.
1. The document discusses the origin of HIV and evolution of resistance to AIDS, noting that chimpanzees and sooty mangabeys are naturally resistant to SIV and do not develop AIDS despite high viral loads.
2. It examines the receptors CCR5 and CXCR4 that HIV uses for entry and discusses whether R5, X4, or R5X4 variants are infectious via different routes of transmission.
3. The predominant virus transmitted is R5-tropic HIV which uses the CCR5 receptor and first infects memory CD4+ T cells and macrophages in the gut-associated lymphoid tissue.
Infection with a host-range mutant adenovirus 5 (Ad5hr) in rhesus macaques induced both innate and adaptive immune responses. There was a delayed increase in plasmacytoid dendritic cells and their interferon-alpha production in blood 2-6 weeks after infection. Ad5hr infection also transiently increased the frequencies of regulatory T cells and activated/proliferating CD4+ T cells in blood. Expression of proinflammatory cytokines like IFN-gamma, IL-1, CCL20 and TNF in blood was suppressed after Ad5hr infection. Ad5hr induced polyfunctional CD4+ and CD8+ T cell responses specific to the adenovirus hexon protein in all
1) Hepatitis C virus (HCV) infection affects 120-130 million people worldwide and is a leading cause of chronic liver disease and liver cancer.
2) The document describes a multidisciplinary team at the National Reference Center for Viral Hepatitis B, C and D that conducts clinical trials, cohort studies, and basic research on HCV.
3) The team uses new virological tools like next-generation sequencing and modeling to study HCV resistance and quasispecies evolution, and develops models to understand HCV-induced liver carcinogenesis.
Perrotti A.P. L'Ematologia nel III° Millennio: cosa è cambiato e cosa bisogna...Gianfranco Tammaro
DOTT. PERROTTI ALESSIO P. (Sessione del 26/11/2015) - Convegno "Lunch Meeting al Pasteur: What's New In..." - dal 01/10/2015 al 10/12/2015 - Studio Pasteur - Viale Pasteur, 66 - Roma
Sito: www.asmad.net
Canale Youtube: https://www.youtube.com/channel/UCIggSJlnC77uDHuX5TUoFHg
This study investigated the expression of CD44 standard (CD44st) and variant isoforms (CD44v) in human pancreatic cancer cell lines and normal pancreatic duct cells. Flow cytometry and immunocytochemistry showed that CD44st, CD44v3, CD44v4, CD44v5, and CD44v6 were moderately expressed in all pancreatic cancer cell lines tested. In contrast, normal pancreatic duct cells expressed very low levels of these CD44 variants. Stimulation of pancreatic cancer cells with growth factors did not affect CD44 expression, except IFNγ which downregulated CD44v6. The constitutive expression of CD44 variants seems associated with the malignant state of invasive pancreatic carcinoma.
This document discusses cancer care in Kashmir and South Asia. It provides information on the Hakim Sanaullah Cancer Centre in Kashmir and discusses challenges facing cancer treatment in the region like lack of resources, poverty, and late stage diagnoses. Statistics are presented on cancer incidence and mortality in South Asia countries compared to resources available for treatment.
This phase II trial tested a WT1 peptide vaccine (galinpepimut-S) in 22 adults with acute myeloid leukemia in first complete remission. The vaccine contained four WT1 peptides that induced CD4+ and CD8+ immune responses in 64% and 86% of patients respectively. Median overall survival was 62.5 months and immune responders showed a trend towards improved clinical outcomes. The vaccine was well-tolerated with common adverse events including injection site reactions and transient cytopenias. Upcoming randomized trials will evaluate clinical efficacy.
This study found that BST2, a host protein known to inhibit the release of viruses from infected cells, unexpectedly enhanced infection and release of human cytomegalovirus (HCMV). Cells expressing BST2 showed increased HCMV gene expression, viral DNA levels, and tegument protein entry shortly after infection. Knocking down BST2 reduced HCMV infection, indicating BST2 facilitates viral entry. This suggests HCMV employs BST2 to gain entry into cells like monocytes that express high BST2 levels, which may aid viral dissemination. Rather than counteracting BST2's antiviral function, HCMV appears to utilize BST2 to enhance its own infection of certain cell types.
Individualizing Therapy For Patients With Advanced Rccfondas vakalis
The document discusses individualizing therapy for patients with advanced renal cell carcinoma (RCC) based on prognostic factors and molecular markers. It describes that RCC has subtypes defined by genetic defects and pathways activated like HIF1-α and mTOR. Prognostic models integrate factors like TNM stage, Fuhrman grade and performance status. Biomarkers like CAIX, VEGF, COX-2 levels predict response to treatments targeting angiogenesis or mTOR. Molecular testing may help select therapies based on a tumor's genetic profile to maximize benefit for patients.
The document describes malaria immunology and epidemiology studies conducted in Papua New Guinea between 2004-2017. It involved several cohort and intervention studies with observational cohorts of approximately 500-2000 individuals. The studies aimed to understand immunity targets and mechanisms to malaria in order to rationalize vaccine development. They examined both antibody and cellular immune responses. Key findings included that γδ T cells are a major source of IFNγ response and certain NK cell receptors are associated with risk of high density infections.
This study used coreceptor-targeted inhibitors to investigate which coreceptors are used by HIV-1, SIV, HIV-2, and SHIV to enter primary cells. The inhibitors blocked entry via CCR5, CCR3, CCR2, and CXCR4. For most viruses, the main coreceptors were found to be CCR5 and CXCR4. However, some HIV-2 and SIV isolates could replicate using an alternative, undefined coreceptor. SIVrcm was found to use CCR2 as its primary coreceptor. The study helps elucidate coreceptor usage, which is important for understanding viral pathogenesis and developing animal models and vaccines.
BLOOD SCREENING :AntiHBc and NAT-Necessity or Luxuryicsp
- Screening of blood donations for transfusion has greatly reduced but not eliminated the risk of transmitting infections like HIV, HBV, and HCV due to the window period between exposure and detection.
- While developed countries widely use sensitive nucleic acid tests (NAT) to screen for viral RNA, most developing countries still lack adequate policies, funding, and infrastructure for comprehensive screening.
- Adding tests for hepatitis B core antibody (Anti-HBc) and NAT screening could further reduce residual transmission risks of HBV and HCV in Pakistan, but developing robust transfusion services and legislation is required first.
This document summarizes several studies on Fibroblast Growth Factor 23 (FGF23) and its relationship to outcomes in kidney disease. Elevated FGF23 levels were found to independently predict mortality and progression of chronic kidney disease. A prospective study of over 3,800 patients with stages 2-4 CKD found that higher FGF23 levels correlated with worse kidney function and were a strong independent risk factor for death, even after adjusting for other risk factors. However, elevated FGF23 predicted end-stage renal disease only before adjusting for estimated GFR and other kidney risk factors.
May r.j.-et-al.-2007-clinical-cancer-researchSellasCorp
This document summarizes a study identifying three HLA class II peptide epitopes from the Wilms' tumor 1 (WT1) oncoprotein that stimulate CD4+ T cell responses. One peptide (122-140) also contains a previously identified CD8+ epitope (126-134) and was modified to improve its ability to induce both CD4+ and CD8+ T cell responses against WT1-expressing tumor cells. Dendritic cells pulsed with these WT1 peptides were able to stimulate peptide-specific CD4+ T cell responses and cross-priming experiments showed the dendritic cells could present the peptides after processing tumor cell lysates. These WT1 CD4+ peptides may be useful for inclusion in
This phase 1 clinical trial tested different vaccination regimens combining an adjuvanted HIV protein vaccine (F4/AS01) and an adenovirus vector vaccine (Ad35-GRIN) in 146 healthy African adults. The vaccines were found to be generally well-tolerated and safe. Different regimens induced distinct immune response profiles: F4/AS01 primarily induced CD4+ T-cells while Ad35-GRIN primarily induced CD8+ T-cells. Co-administration of the vaccines resulted in strong, multifunctional immune responses against HIV from both T-cell types. Immune responses persisted for at least one year. The study provides support for combining protein and viral vector vaccines to generate comprehensive
This study characterized broadly neutralizing plasma antibodies obtained from an HIV-1 clade C infected elite neutralizer. The plasma neutralized 93% of HIV pseudoviruses from diverse clades. Mapping studies found the antibodies targeted unique epitopes on trimeric envelope glycoprotein not previously reported, including the V1 loop. Mutations in the V1 loop were associated with autologous virus escape, suggesting the antibodies exerted selection pressure leading to viral evolution. This identification of novel neutralizing epitopes on the trimeric envelope could inform immunogen design for antibody-based therapies and vaccines.
This study aimed to differentiate between invasive squamous cell carcinoma (SCC) and carcinoma-in-situ (CIS) of the uterine cervix using immunohistochemical markers. Tissue samples from 37 patients were stained for CD3, CD4, CD8, CD20, and CD138. Scoring showed decreased expression of CD8, CD20, and CD138 in invasive SCC compared to CIS, indicating differences in immune cell infiltration between invasive and non-invasive lesions. The results provide potential markers for differentiating invasive SCC from CIS of the cervix.
Lo que un reumatólogo debe saber de inmunoterapia contra el cáncer, abreviadoMauricio Lema
1. The document discusses various mechanisms of cancer immunotherapy including immune checkpoint inhibitors that target CTLA-4 and PD-1/PD-L1 pathways.
2. Key immunotherapy drugs discussed are ipilimumab, nivolumab, pembrolizumab, avelumab, and durvalumab which target CTLA-4 and PD-1/PD-L1 and have shown efficacy in treating cancers like melanoma, lung cancer, head and neck cancer, and kidney cancer.
3. Several clinical trials are summarized that demonstrate improved survival outcomes for immunotherapy compared to chemotherapy or standard treatments in various cancer types and treatment settings.
The document discusses the roles of dendritic cells and the dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) protein in both cis-infection and trans-infection of HIV. DC-SIGN binds to the gp120 envelope protein of HIV and allows dendritic cells to transport the virus to permissive CD4+ T cells in lymph nodes, facilitating trans-infection. Langerhans cells express the related Langerin protein instead of DC-SIGN, and transport HIV to Birbeck granules where it is degraded, thus protecting against epithelial infection in contrast to dendritic cells.
1) Chronic hepatitis C virus infection can cause a variety of extrahepatic manifestations including mixed cryoglobulinemia, a condition where low levels of cryoglobulins in the blood vessel can lead to inflammation.
2) Rituximab, a monoclonal antibody targeting CD20 found on B cells, has shown effectiveness in treating the symptoms of mixed cryoglobulinemia, particularly rashes and kidney involvement.
3) Combining rituximab treatment with pegylated interferon and ribavirin therapy may provide the best chance of achieving both clinical response and viral clearance for patients with mixed cryoglobulinemia caused by chronic hepatitis C infection.
The document discusses rationales for pursuing a cure for HIV, including that lifelong antiretroviral therapy does not restore full life expectancy and carries risks of toxicity and side effects. It outlines two potential strategies for a cure: sterilizing cure, which eliminates all HIV-infected cells, and functional cure, which controls HIV in the absence of therapy. It reviews examples of each from bone marrow transplantation and elite controllers. Measuring and targeting the latent HIV reservoir in resting immune cells is key to a cure.
International standards for screening blood donations require testing for hepatitis B, hepatitis C, HIV, syphilis, and malaria. While screening has improved blood safety, risks remain as new infectious agents may emerge and current tests have window periods where early infections are not detected. In Pakistan, screening is not uniform across centers and some use substandard methods, like pooling donor samples, which increases transmission risk. Future directions include fully implementing standard screening tests, minimizing residual risks through new tests, encouraging healthy volunteer donors, and increasing awareness of transfusion risks.
This document summarizes genetic research into factors influencing hepatitis C virus (HCV) infection outcomes. It discusses Dr. Annwyne Houldsworth's work studying polymorphisms in the interleukin-12B (IL-12B) and superoxide dismutase 2 (SOD-2) genes. The results showed that HCV-infected individuals with the IL-12B genotype expressing lower IL-12 levels were more likely to have chronic infection. Additionally, HCV-infected individuals with the SOD-2 TT genotype, associated with higher antioxidant activity, had higher rates of viral clearance compared to those with chronic infection. This research suggests genetic differences in immune response genes can impact HCV infection resolution or progression to chronic disease.
Towards Digitally Enabled Genomic Medicine: the Patient of TomorrowLarry Smarr
The document summarizes a keynote speech by Dr. Larry Smarr on his vision of digitally enabled genomic medicine and how he has been quantifying his own health metrics over 10 years to serve as a model patient of the future. Some of the metrics he tracks include weight, blood pressure, caloric intake/burn, over 100 blood variables, his gut microbiome, and 1 million SNPs in his human DNA. Through this self-quantification, he discovered he has a genetic predisposition and symptoms of Crohn's disease.
This document lists over 60 potential factors that are known to cause false positive HIV antibody test results. These factors include naturally occurring antibodies, viral infections like hepatitis B, autoimmune diseases, organ transplants, blood transfusions, and various medical treatments. False positives can also be caused by cross-reactivity with antibodies against other viruses or proteins as well as certain laboratory testing issues. Proper screening and confirmatory testing is necessary to avoid incorrect HIV diagnoses due to false positive initial test results from these many different sources.
1) O documento discute a história e situação atual da malária no Brasil, com foco na região amazônica.
2) Apesar de reduções significativas nos casos desde 2000, a malária ainda representa um desafio de saúde pública devido a fatores como a presença do vetor Anopheles darlingi e migrações humanas.
3) Perspectivas para o controle incluem melhorias no diagnóstico, tratamento, controle vetorial e gestão local dos programas de malária.
A malária é uma doença parasitária causada por três espécies de Plasmodium que afetam o homem através da picada do mosquito Anopheles. O ciclo da doença envolve uma fase no fígado e outra nas hemácias humanas, com a produção e disseminação de parasitas no sangue a cada 48, 72 ou 36 horas, dependendo da espécie. A transmissão ocorre quando os mosquitos ingerem gametócitos durante uma picada em um humano infectado e os esporozoítos são posteriormente inoculados em outro
This phase II trial tested a WT1 peptide vaccine (galinpepimut-S) in 22 adults with acute myeloid leukemia in first complete remission. The vaccine contained four WT1 peptides that induced CD4+ and CD8+ immune responses in 64% and 86% of patients respectively. Median overall survival was 62.5 months and immune responders showed a trend towards improved clinical outcomes. The vaccine was well-tolerated with common adverse events including injection site reactions and transient cytopenias. Upcoming randomized trials will evaluate clinical efficacy.
This study found that BST2, a host protein known to inhibit the release of viruses from infected cells, unexpectedly enhanced infection and release of human cytomegalovirus (HCMV). Cells expressing BST2 showed increased HCMV gene expression, viral DNA levels, and tegument protein entry shortly after infection. Knocking down BST2 reduced HCMV infection, indicating BST2 facilitates viral entry. This suggests HCMV employs BST2 to gain entry into cells like monocytes that express high BST2 levels, which may aid viral dissemination. Rather than counteracting BST2's antiviral function, HCMV appears to utilize BST2 to enhance its own infection of certain cell types.
Individualizing Therapy For Patients With Advanced Rccfondas vakalis
The document discusses individualizing therapy for patients with advanced renal cell carcinoma (RCC) based on prognostic factors and molecular markers. It describes that RCC has subtypes defined by genetic defects and pathways activated like HIF1-α and mTOR. Prognostic models integrate factors like TNM stage, Fuhrman grade and performance status. Biomarkers like CAIX, VEGF, COX-2 levels predict response to treatments targeting angiogenesis or mTOR. Molecular testing may help select therapies based on a tumor's genetic profile to maximize benefit for patients.
The document describes malaria immunology and epidemiology studies conducted in Papua New Guinea between 2004-2017. It involved several cohort and intervention studies with observational cohorts of approximately 500-2000 individuals. The studies aimed to understand immunity targets and mechanisms to malaria in order to rationalize vaccine development. They examined both antibody and cellular immune responses. Key findings included that γδ T cells are a major source of IFNγ response and certain NK cell receptors are associated with risk of high density infections.
This study used coreceptor-targeted inhibitors to investigate which coreceptors are used by HIV-1, SIV, HIV-2, and SHIV to enter primary cells. The inhibitors blocked entry via CCR5, CCR3, CCR2, and CXCR4. For most viruses, the main coreceptors were found to be CCR5 and CXCR4. However, some HIV-2 and SIV isolates could replicate using an alternative, undefined coreceptor. SIVrcm was found to use CCR2 as its primary coreceptor. The study helps elucidate coreceptor usage, which is important for understanding viral pathogenesis and developing animal models and vaccines.
BLOOD SCREENING :AntiHBc and NAT-Necessity or Luxuryicsp
- Screening of blood donations for transfusion has greatly reduced but not eliminated the risk of transmitting infections like HIV, HBV, and HCV due to the window period between exposure and detection.
- While developed countries widely use sensitive nucleic acid tests (NAT) to screen for viral RNA, most developing countries still lack adequate policies, funding, and infrastructure for comprehensive screening.
- Adding tests for hepatitis B core antibody (Anti-HBc) and NAT screening could further reduce residual transmission risks of HBV and HCV in Pakistan, but developing robust transfusion services and legislation is required first.
This document summarizes several studies on Fibroblast Growth Factor 23 (FGF23) and its relationship to outcomes in kidney disease. Elevated FGF23 levels were found to independently predict mortality and progression of chronic kidney disease. A prospective study of over 3,800 patients with stages 2-4 CKD found that higher FGF23 levels correlated with worse kidney function and were a strong independent risk factor for death, even after adjusting for other risk factors. However, elevated FGF23 predicted end-stage renal disease only before adjusting for estimated GFR and other kidney risk factors.
May r.j.-et-al.-2007-clinical-cancer-researchSellasCorp
This document summarizes a study identifying three HLA class II peptide epitopes from the Wilms' tumor 1 (WT1) oncoprotein that stimulate CD4+ T cell responses. One peptide (122-140) also contains a previously identified CD8+ epitope (126-134) and was modified to improve its ability to induce both CD4+ and CD8+ T cell responses against WT1-expressing tumor cells. Dendritic cells pulsed with these WT1 peptides were able to stimulate peptide-specific CD4+ T cell responses and cross-priming experiments showed the dendritic cells could present the peptides after processing tumor cell lysates. These WT1 CD4+ peptides may be useful for inclusion in
This phase 1 clinical trial tested different vaccination regimens combining an adjuvanted HIV protein vaccine (F4/AS01) and an adenovirus vector vaccine (Ad35-GRIN) in 146 healthy African adults. The vaccines were found to be generally well-tolerated and safe. Different regimens induced distinct immune response profiles: F4/AS01 primarily induced CD4+ T-cells while Ad35-GRIN primarily induced CD8+ T-cells. Co-administration of the vaccines resulted in strong, multifunctional immune responses against HIV from both T-cell types. Immune responses persisted for at least one year. The study provides support for combining protein and viral vector vaccines to generate comprehensive
This study characterized broadly neutralizing plasma antibodies obtained from an HIV-1 clade C infected elite neutralizer. The plasma neutralized 93% of HIV pseudoviruses from diverse clades. Mapping studies found the antibodies targeted unique epitopes on trimeric envelope glycoprotein not previously reported, including the V1 loop. Mutations in the V1 loop were associated with autologous virus escape, suggesting the antibodies exerted selection pressure leading to viral evolution. This identification of novel neutralizing epitopes on the trimeric envelope could inform immunogen design for antibody-based therapies and vaccines.
This study aimed to differentiate between invasive squamous cell carcinoma (SCC) and carcinoma-in-situ (CIS) of the uterine cervix using immunohistochemical markers. Tissue samples from 37 patients were stained for CD3, CD4, CD8, CD20, and CD138. Scoring showed decreased expression of CD8, CD20, and CD138 in invasive SCC compared to CIS, indicating differences in immune cell infiltration between invasive and non-invasive lesions. The results provide potential markers for differentiating invasive SCC from CIS of the cervix.
Lo que un reumatólogo debe saber de inmunoterapia contra el cáncer, abreviadoMauricio Lema
1. The document discusses various mechanisms of cancer immunotherapy including immune checkpoint inhibitors that target CTLA-4 and PD-1/PD-L1 pathways.
2. Key immunotherapy drugs discussed are ipilimumab, nivolumab, pembrolizumab, avelumab, and durvalumab which target CTLA-4 and PD-1/PD-L1 and have shown efficacy in treating cancers like melanoma, lung cancer, head and neck cancer, and kidney cancer.
3. Several clinical trials are summarized that demonstrate improved survival outcomes for immunotherapy compared to chemotherapy or standard treatments in various cancer types and treatment settings.
The document discusses the roles of dendritic cells and the dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) protein in both cis-infection and trans-infection of HIV. DC-SIGN binds to the gp120 envelope protein of HIV and allows dendritic cells to transport the virus to permissive CD4+ T cells in lymph nodes, facilitating trans-infection. Langerhans cells express the related Langerin protein instead of DC-SIGN, and transport HIV to Birbeck granules where it is degraded, thus protecting against epithelial infection in contrast to dendritic cells.
1) Chronic hepatitis C virus infection can cause a variety of extrahepatic manifestations including mixed cryoglobulinemia, a condition where low levels of cryoglobulins in the blood vessel can lead to inflammation.
2) Rituximab, a monoclonal antibody targeting CD20 found on B cells, has shown effectiveness in treating the symptoms of mixed cryoglobulinemia, particularly rashes and kidney involvement.
3) Combining rituximab treatment with pegylated interferon and ribavirin therapy may provide the best chance of achieving both clinical response and viral clearance for patients with mixed cryoglobulinemia caused by chronic hepatitis C infection.
The document discusses rationales for pursuing a cure for HIV, including that lifelong antiretroviral therapy does not restore full life expectancy and carries risks of toxicity and side effects. It outlines two potential strategies for a cure: sterilizing cure, which eliminates all HIV-infected cells, and functional cure, which controls HIV in the absence of therapy. It reviews examples of each from bone marrow transplantation and elite controllers. Measuring and targeting the latent HIV reservoir in resting immune cells is key to a cure.
International standards for screening blood donations require testing for hepatitis B, hepatitis C, HIV, syphilis, and malaria. While screening has improved blood safety, risks remain as new infectious agents may emerge and current tests have window periods where early infections are not detected. In Pakistan, screening is not uniform across centers and some use substandard methods, like pooling donor samples, which increases transmission risk. Future directions include fully implementing standard screening tests, minimizing residual risks through new tests, encouraging healthy volunteer donors, and increasing awareness of transfusion risks.
This document summarizes genetic research into factors influencing hepatitis C virus (HCV) infection outcomes. It discusses Dr. Annwyne Houldsworth's work studying polymorphisms in the interleukin-12B (IL-12B) and superoxide dismutase 2 (SOD-2) genes. The results showed that HCV-infected individuals with the IL-12B genotype expressing lower IL-12 levels were more likely to have chronic infection. Additionally, HCV-infected individuals with the SOD-2 TT genotype, associated with higher antioxidant activity, had higher rates of viral clearance compared to those with chronic infection. This research suggests genetic differences in immune response genes can impact HCV infection resolution or progression to chronic disease.
Towards Digitally Enabled Genomic Medicine: the Patient of TomorrowLarry Smarr
The document summarizes a keynote speech by Dr. Larry Smarr on his vision of digitally enabled genomic medicine and how he has been quantifying his own health metrics over 10 years to serve as a model patient of the future. Some of the metrics he tracks include weight, blood pressure, caloric intake/burn, over 100 blood variables, his gut microbiome, and 1 million SNPs in his human DNA. Through this self-quantification, he discovered he has a genetic predisposition and symptoms of Crohn's disease.
This document lists over 60 potential factors that are known to cause false positive HIV antibody test results. These factors include naturally occurring antibodies, viral infections like hepatitis B, autoimmune diseases, organ transplants, blood transfusions, and various medical treatments. False positives can also be caused by cross-reactivity with antibodies against other viruses or proteins as well as certain laboratory testing issues. Proper screening and confirmatory testing is necessary to avoid incorrect HIV diagnoses due to false positive initial test results from these many different sources.
1) O documento discute a história e situação atual da malária no Brasil, com foco na região amazônica.
2) Apesar de reduções significativas nos casos desde 2000, a malária ainda representa um desafio de saúde pública devido a fatores como a presença do vetor Anopheles darlingi e migrações humanas.
3) Perspectivas para o controle incluem melhorias no diagnóstico, tratamento, controle vetorial e gestão local dos programas de malária.
A malária é uma doença parasitária causada por três espécies de Plasmodium que afetam o homem através da picada do mosquito Anopheles. O ciclo da doença envolve uma fase no fígado e outra nas hemácias humanas, com a produção e disseminação de parasitas no sangue a cada 48, 72 ou 36 horas, dependendo da espécie. A transmissão ocorre quando os mosquitos ingerem gametócitos durante uma picada em um humano infectado e os esporozoítos são posteriormente inoculados em outro
Este documento presenta la lista de personas aptas para participar en un curso de capacitación a distancia para certificadores realizado por el INEP en Brasil. Se informa que los seleccionados recibirán un correo electrónico con información para acceder al curso, y que la conclusión del mismo no garantiza que serán contratados como certificadores, debido a que hubo más voluntarios de los necesarios. A continuación se lista el nombre de todas las personas aptas.
Este documento discute a malária, uma doença infecciosa transmitida por mosquitos do gênero Anopheles e causada por protozoários do gênero Plasmodium. Apresenta a taxonomia, agente etiológico, ciclo de vida, sintomas, diagnóstico e tratamento da doença, bem como sua epidemiologia e medidas de controle. A malária é endêmica em regiões tropicais e subtropicais e causa milhões de casos e mortes por ano, principalmente entre crianças na África.
Apresentação do Trabalho de Conclusão de Curso sobre um plano de educação em saúde na região da Subprefeitura de Parelheiros, realizada no seminário de apresentação dos TCCs das primeiras turmas (2011) do Curso Técnico em Vigilância em Saúde, na Escola Municipal Regionalizada - Sul, em março de 2014. Por Alexsandro Alves de Oliveira
Fernando Dantas do Carmo e Reginaldo dos Anjos Pereira, alunos do curso.
A malária é causada por protozoários do gênero Plasmodium transmitidos pela picada de mosquitos fêmeas Anopheles infectados. Os sintomas incluem febre, calafrios e sudorese periódicos, podendo evoluir para formas graves e até morte se não tratada. O diagnóstico é feito por exame de sangue para identificar os parasitas.
O documento fornece informações sobre a malária, definindo-a como uma doença infecciosa causada por protozoários do gênero Plasmodium transmitidos por mosquitos Anopheles. Detalha os sintomas, ciclo de vida do parasita, formas de prevenção e diagnóstico, incluindo a gota espessa como método padrão no Brasil.
O documento discute a malária, incluindo sua etiologia, transmissão, agente causador (Plasmodium), ciclo de vida, epidemiologia e recomendações de prevenção. A doença afeta principalmente regiões tropicais e subtropicais, sendo transmitida pela picada do mosquito fêmea Anopheles infectado. Sintomas incluem febre alta, calafrios e dores musculares.
Este documento descreve a malária, uma doença causada por parasitas do gênero Plasmodium transmitida por mosquitos. Detalha as quatro espécies de Plasmodium que infectam humanos, seus sintomas e gravidade. Também explica o ciclo de vida do parasita no corpo humano e no mosquito, assim como fatores de transmissão e esforços para desenvolver uma vacina.
Malaria is caused by parasites of the Plasmodium type, which are transmitted via the bites of infected Anopheles mosquitoes. The parasites multiply in the liver and then infect red blood cells. Symptoms of malaria include fever, chills, and flu-like illness. Malaria most commonly occurs in subtropical and tropical areas of Africa, Asia, and South America. While the disease can be treated with antimalarial drugs, prevention through mosquito bite avoidance and antimalarial prophylaxis is most effective.
Joseph Eron, M.D., of University of North Carolina at Chapel Hill, presents "The State of the Art in HIV Cure Research – Hope or Hype: What Does It Mean for Patients" at AIDS Clinical Rounds
This document summarizes a presentation on insurability and survival of people living with HIV and other chronic diseases like diabetes. It discusses:
1) Comparing mortality of HIV-infected South Africans initiating antiretroviral therapy to those initiating diabetes treatment and a control group to assess insurability.
2) HIV disease progression improved greatly with long-term antiretroviral therapy but long-term mortality remains uncertain.
3) Type 2 diabetes requires similar lifelong treatment to HIV and its control is associated with better outcomes, making it a relevant comparison.
4) Preliminary results show HIV mortality decreases with longer time on treatment and higher original CD4 count, but excess mortality remains compared to other groups
Understanding Hiv Diagnostics And Lab Testsarthur_smith
The document discusses the importance of lab tests in managing HIV disease. It provides an overview of common diagnostic tests used including:
- CD4 count and viral load to monitor immune system and response to treatment. CD4 count helps determine when to start/switch treatment.
- Resistance tests before starting treatment or if viral load increases, to identify drugs virus has become resistant to.
- New tests under investigation like tropism tests help identify if co-receptor antagonists may benefit a patient.
D1 Highly Active Antiretroviral Treatment (HAART) DHHS Guidelines 2009 DuffusDSHS
The document discusses guidelines for initiating highly active antiretroviral treatment (HAART) based on CD4 count and viral load. Guidelines from 1998-2009 increasingly recommended treating HIV at higher CD4 counts and without a specific viral load threshold. Studies show the magnitude of CD4 increase is greatest when starting HAART at low counts, but normalization is more likely the earlier therapy begins. A CD4 count below 350 cells/mm3 increases the risk of cardiovascular and other non-AIDS complications.
This document summarizes a presentation on immune activation in treated HIV infection. The presentation discusses how immune activation persists even during antiretroviral therapy (ART), contributing to increased risk of age-related diseases. It reviews evidence that microbial translocation, co-infections like CMV, and tryptophan catabolism via the kynurenine pathway may drive residual immune activation and inflammation during ART. Interventions like earlier ART initiation, statins, aspirin, exercise, and anti-CMV therapy may help reduce inflammation, but more research is still needed.
Fast-track the end of AIDS in the EU - practical evidence-based interventions.
Presentation by: Jens Lundgren, CHIP
In a two-day meeting under the auspices of the Maltese Presidency of the Council of the European Union (30-31 January 2017), HIV experts from across the European Union discussed how to reverse this trend and how to prepare Europe to achieve the set target of ending AIDS by 2030.
Non-Hodgkin's lymphoma accounts for approximately 4% of cancer cases in the United States. The document discusses several subtypes of lymphoma including diffuse large B-cell lymphoma and follicular lymphoma. Rituximab is an anti-CD20 monoclonal antibody approved for the treatment of certain lymphoma subtypes. Combination chemotherapy regimens including rituximab such as R-CHOP have improved survival rates compared to chemotherapy alone for diffuse large B-cell lymphoma. Follicular lymphoma is typically indolent but incurable with conventional therapies, and treatment may include radiation, chemotherapy, immunotherapy with rituximab, or stem cell transplantation.
Dr. Patrick Hwu presents the latest information on immunotherapies for melanoma at the MRF's Patient Symposium at MD Anderson Cancer Center on January 31, 2015.
1) A phase 3 trial compared nivolumab to everolimus in advanced renal cell carcinoma patients who had received 1-2 prior anti-angiogenic therapies. Nivolumab demonstrated significantly longer overall survival compared to everolimus, with median overall survival of 25 months versus 19.6 months.
2) Nivolumab had a higher objective response rate compared to everolimus (25% vs 5%) and longer median duration of response.
3) The overall survival benefit of nivolumab was consistent across patient subgroups and was independent of PD-L1 expression levels.
The document summarizes a randomized trial comparing a public health approach to a standard clinical approach for delivering antiretroviral therapy in Cameroon. The trial aims to compare the increase in CD4 cell count and other outcomes between the two approaches. It describes the standard clinical approach as relying on biological exams and physicians, while the public health approach uses simplified criteria and involves other personnel like nurses. The trial design involves randomizing patients across 9 rural hospitals to receive antiretrovirals through either approach and following outcomes over 24 months. Baseline characteristics of the 459 enrolled patients are provided. Survival and treatment change outcomes over time are shown graphically. The discussion covers feasibility challenges and capacity building efforts, as well as relevance for
Preventing TB infection in HIV-infected
individuals living in medium and high TB endemic
settings
February 5, 2016
Jeffrey D. Jenks, MD, MPH
UCSD HIV & Global Health Rounds
Sub-Optimal Recovery of CD4 Cells in HIV Treated Patients: Research ProposalNelson Vergel
This lecture made by HIV research advocates shows how a subset of people living with HIV that are on antiretroviral treatment do not have full recovery of their CD4 cells even after years of having undetectable HIV viral load. These patients are called Immunological Non-Responders (INR). This presentation made to the FDA shows how potential therapies for INR can be studied using patient quality of life outcomes. The FDA agreed that this proposal by activists was a valid and feasible one for companies to use for developing studies that could get these immune-boosting therapies to be approved.
Perrotti A.P. From empiric therapy to guide lines of silent and aggressive li...Gianfranco Tammaro
This document summarizes treatment approaches for non-Hodgkin lymphomas over time:
1. Prior to 1997, treatment included surgery, watchful waiting for indolent lymphomas, radiotherapy for stage I disease, and polychemotherapy. Chemotherapy regimens like CHOP became the standard.
2. After 1997, immunotherapy was introduced with monoclonal antibodies like rituximab, improving response rates and survival. Rituximab combined with chemotherapy became the standard first-line treatment for B-cell lymphomas.
3. Recent studies are exploring new drug combinations, such as lenalidomide and rituximab for untreated indolent lymphomas, which achieved high response rates
This document summarizes findings from the HPTN 052 clinical trial which showed that early initiation of antiretroviral therapy (ART) in HIV-infected individuals significantly reduces sexual transmission of HIV to their uninfected partners. The trial involved 1,750 serodiscordant couples across nine countries. Couples were randomized to either receive ART immediately if CD4 count was 350-550 cells/μL or defer ART until CD4 dropped below 250 cells/μL. Results showed a 96% reduction in risk of HIV transmission in the immediate ART arm compared to the deferred ART arm. Early ART was also found to be very cost-effective over a lifetime in South Africa and India based on individual and public health benefits
The document discusses Clostridium difficile infection (CDI) and its environmental impact. It finds that C. difficile is commonly found in environmental settings like homes, public areas, stores and restaurants. Over 60% of public area samples, 36.9% of home samples, and 17.8-20.8% of retail samples tested positive for C. difficile. The ribotypes found in environmental samples matched those found in clinical isolates, suggesting environmental transmission may contribute to CDI acquisition. A comparison to European studies found similar prevalence of environmental C. difficile in parks, public transit and other public areas. This highlights the potential for widespread environmental exposure to C. difficile.
The document discusses the pathophysiology of AIDS, autoimmune diseases, and hypersensitivity reactions. It provides details on the diagnosis, pathogenesis, and treatment of AIDS, describing how HIV infects and destroys CD4 cells, leading to immunosuppression. Mechanisms of several autoimmune diseases like Graves' disease and rheumatoid arthritis are examined, focusing on how lymphocytes fail to recognize the body's own cells and tissues, resulting in autoimmune responses.
Harder-to-treat and more lethal tubercle bacilli continue to emerge across the globe, especially in the African region. Together with HIV, these infectious killers continue to have profound effects on the productive workforce in different countries. The deck is a brief overview of developments in disease management and research, with an emphasis on medications and vaccines.
Similar to Dr. Celso Ferreira Ramos Filho: "Cura funcional do HIV". (20)
O médico Paulo Roberto Benchimol Barbosa apresenta o tema Morte Súbita: do diagnóstico à prevenção em sessão na ANM, no dia 17/10/2013 e falou sobre casos marcantes, aspectos relacionadas a epidemiologia, sintomas e prevenção.
O documento discute as diferentes opções para treinamento em cirurgia, incluindo operações em animais, cadáveres humanos e simuladores. Destaca os simuladores como uma opção ética para treinar procedimentos cirúrgicos complexos sem riscos a pacientes.
O documento discute a hepatite C, incluindo sua história natural, prevalência, diagnóstico e tratamento. Aborda novos medicamentos antivirais em desenvolvimento que podem revolucionar o tratamento da hepatite C.
O documento discute a fragilidade do idoso, osteoporose e suas interações celulares. Aborda a sarcopenia, perda óssea, fatores de risco genéticos e de estilo de vida para osteoporose. Também apresenta dados epidemiológicos sobre osteoporose no Brasil e tratamentos para melhorar a massa muscular e óssea em idosos.
Nesta conferência para a ANM, o oncogeneticista Dr. José Claudio Casali explica didaticamente o que é a genética e como ela pode ajudar no tratamento e na prevenção personalizados dos cânceres.
O documento descreve a evolução do tratamento da hiperplasia prostática ao longo dos séculos, comparando os resultados de diferentes técnicas cirúrgicas. No século XXI, as novas perspectivas incluem o uso do laser, como o Greenlight, que tem proporcionado bons resultados com internamentos mais curtos e poucas complicações. O documento também discute detalhes técnicos do procedimento laser e resultados de estudos comparando o Greenlight à ressecção transuretral da próstata.
O documento discute as mais recentes evidências sobre fibrilação atrial, incluindo: 1) a epidemiologia crescente da fibrilação atrial; 2) os novos anticoagulantes orais que evitam a necessidade de monitorização; 3) técnicas avançadas de ablação por cateter como o isolamento da veia pulmonar para tratamento da fibrilação atrial.
O documento discute o abortamento espontâneo recorrente de causa imunitária e como a imunoterapia com linfócitos paternos pode ajudar. A gravidez representa um desafio ao sistema imune materno que deve tolerar os aloantígenos paternos. Uma resposta imune inadequada pode levar ao abortamento. A imunoterapia visa induzir uma resposta de células T do tipo Th2, protegendo o feto.
O documento discute as estratégias de tratamento para pacientes com doença coronariana e carotídea concomitante. Há três abordagens tradicionais: endarterectomia carotídea seguida de cirurgia de revascularização miocárdica, os procedimentos combinados ou a cirurgia miocárdica seguida da endarterectomia. Recomenda-se tratar o território sintomático primeiro e procedimentos combinados apenas em casos específicos devido ao maior risco de complicações. Uma abordagem ideal permanece controversa sem estudos
O professor, pediatra e acadêmico Aderbal Sabrá abordou nesta conferência alguns fatores que predispõe a alergia alimentar, formas de diagnóstico e tratamentos mais usuais.
Médico brasileiro e radicado no Canadá, Tirone David é novo membro Honorário Estrangeiro da Academia Nacional de Medicina. Em sua palestra de posse, falou sobre criatividade na medicina e em outros campos do saber.
Na área de medicina, David relatou sua experiência própria de como usou a criatividade para solucionar casos críticos na sala de cirurgia – culminando em descobertas que revolucionaram a cirurgia cardíaca em todo o mundo. Leia a matéria sobre a apresentação em: http://www.anm.org.br/conteudo_view.asp?id=1299
O documento descreve os avanços na neurocirurgia, incluindo a especialização em subáreas e grupos multidisciplinares, melhorias nos equipamentos de estereotaxia e ressonância magnética intraoperatória, e novas técnicas como neuroendoscopia e estimulação cerebral profunda.
Nesta apresentação, a professora da UFRJ e Acadêmica, Patrícia Rocco, traz resultados de seu grupo de pesquisa nas investigações do uso de células-tronco em doenças respiratórias. Leia a matéria sobre a palestra em: http://www.anm.org.br/conteudo_view.asp?id=1275
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
3. Pallela et al. JAIDS 2006
Redução da Mortalidade Coincide com
Expansão do Uso de TARV
4. Estimativas mundiais para crianças e adultos 2011
Pessoas com vivendo com HIV 34,0 milhões [31,4 –35.9]
Novas infecções pelo HIV em 2011 2,5 milhões [2,2 –2,8 ]
Óbitos devidos ao HIV em 2011 1,7 milhões [1,5 million–1,9 ]
FONTES: OMS e UNAIDS
5. Total: 34,0 milhões [31,4 milhões – 35,9 milhões]
Western &
Central Europe
900 000
[830 000 – 1.0 million]
Middle East & North Africa
300 000
[250 000 – 360 000]
Sub-Saharan Africa
23.5 million
[22.1 million – 24.8 million]
Eastern Europe
& Central Asia
1.4 million
[1.1 million – 1.8 million]
South & South-East Asia
4.0 million
[3.1 million – 5.2 million]
Oceania
53 000
[47 000 – 60 000]
North America
1.4 million
[1.1 million – 2.0 million]
Latin America
1.4 million
[1.1 million – 1.7 million]
East Asia
830 000
[590 000 – 1.2 million]
Caribbean
230 000
[200 000 – 250 000]
Prevalência bruta estimada do HIV (adultos e crianças) 2011
FONTE: OMS e UNAIDS
6. Incidência bruta estimada do HIV (adultos e crianças) 2011
Western &
Central Europe
30 000
[21 000 – 40 000]
Middle East & North Africa
37 000
[29 000 – 46 000]
Sub-Saharan Africa
1.8 million
[1.6 million – 2.0 million]
Eastern Europe
& Central Asia
140 000
[91 000 – 210 000]
South & South-East Asia
280 000
[170 000 – 460 000]
Oceania
2900
[2200 – 3800]
North America
51 000
[19 000 – 120 000]
Latin America
83 000
[51 000 – 140 000]
East Asia
89 000
[44 000 – 170 000]
Caribbean
13 000
[9600 – 16 000]
Total: 2.5 million [2.2 million – 2.8 million]
FONTE: OMS e UNAIDS
7. Novas infecções pelo HIV e mortes relacionadas à aidsPeople
Novas infecções pelo HIV
Mortes relacionadas à Aids
0
500 000
1 000 000
1 500 000
2 000 000
2 500 000
3 000 000
3 500 000
4 000 000
4 500 000
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Pico mundial de incidência em 1997
FONTES: OMS e UNAIDS
8. Prevalência bruta do HIVmillions
People living with HIV
0
5
10
15
20
25
30
35
40
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
FONTES: OMS e UNAIDS
9. Número de pessoas recebendo tratamento em países de baixa e média renda,
2002 – 2011
FONTES: OMS e UNAIDS
12. Adaptado de clinicaloptions.com/hiv
New Classes of Antiretrovirals
Inibidores de entrada celular do HIV
Fusão
vírus-célula
gp41
gp120
Alça V3
Ligação
à CD4
CD4
Membrana
celular
Ligação
ao co-
receptor
CCR5/CXCR4
(R5/X4)
Antagonistas do CCR5
Maraviroque
Enfuvirtida
TNX-355
Antagonistas
do CXCR4
Figura adaptada de Doms R, et al. Genes Dev. 2000;14:2677-2688.
13. clinicaloptions.com/hiv
HIV Entry and Tropism
Tropismo Viral
Tropismo = qual correceptor o HIV usa para entrar em
uma célula CD4+
ExpressÃo de CCR5 e/ou CXCR4 em uma célula
determina se ela pode ser infectada por vírus R5 e/ou X4
– Vírus R5 usa apenas o correceptor CCR5
– Vírus X4 usa apenas o correceptor CXCR4
Vírus com tropismo duplo podem usar ambos
Populações virais mistas: tanto R5 quanto X4
14. clinicaloptions.com/hiv
HIV Entry and Tropism
CCR5 wild type CCR5 32
2 normal copies 1 copy of 32 2 copies of 32
wt/wt wt/ 32 32/ 32
Standard
disease
progression
Delayed
disease
progression
“Resistant” to
HIV infection
Normal Heterozygous Homozygous
CCR5 original e mutação CCR5 32
Liu R, et al. Cell. 1996;86:367-367. Samson M, et al. Nature. 1996;382:722-725. Dean M, et al. Science.
1996;273:1856-1862. Huang Y, et al. Nat Med.1996;2:1240-1243. Michael NL, et al. Nat Med.
1997;3:1160-1162. Eugen-Olsen J, et al. AIDS. 1997;11:305-310.
15. clinicaloptions.com/hiv
HIV Entry and Tropism
Pacientes homozigotos ou
heterozigotos para CCR5 32
Homozigotos
– ~ 1% da etnia branca[1]
– Sem moléculas CCR5 na superfície de células CD4+ [2,3]
– Resistentes a vírus R5
– Suscetíveis aos vírus X4
– Função imune relativamente normal
Heterozigotos
– 10% a 15% da etnia branca [1]
– Menos moléculas CCR5 na superfície celular[4]
– Função imune normal[2]
1. McNicholl JM, et al. Emerg Infect Dis. 1997;3:261-271. 2. Liu R, et al. Cell. 1996;86:367-367. 3. Samson
M, et al. Nature. 1996;382:722-725. 4. Wu L, et al. J Exp Med. 1997;185:1681-1691.
16. clinicaloptions.com/hiv
HIV Entry and Tropism
Rheumatoid arthritis 32/wt: milder course
Kidney transplantation 32/ 32: improved transplant survival
Disseminated sclerosis 32/wt: delayed onset, less relapse
HIV-1 32/ 32: resistance to infection
32/wt: delayed disease progression
Hepatitis C Data controversial
Atopic asthma Data controversial
Multiple sclerosis 32/ 32: predisposition?
Sarcoidosis 32/wt: increased disease manifestation rate and
activity
Lupus erythematosus 32/wt: increased disease severity
West Nile virus 32/ 32: increased susceptibility to disease
Ahlenstiel G, et al. J Antimicrob Chemother. 2004;53:895-898.
CCR5 32: Impacto potencial sobre
outras doenças
18. Paciente de Berlim (2009)
• Branco, 40 anos, HIV-1 diagnosticado > 10 anos
– CCR5 +/Δ32
• EFV/TDF/FTC há 4 anos
– CD4+ 415 células/mm3
– CV indetectável
• Leucemia mieloide aguda
– 2 ciclos de QT de indução + consolidação
– Hepatotoxicidade, insuficiência renal
• Suspensão do tratamento ARV
CV = 6,9 milhões cópias/mm3
Hütter et al. NEJM 2009. 360:692
19. Paciente de Berlim (2009)
• Reinício ARV, CV indetectável em 3 meses
• Após 7 meses, recaída da LMA
• Transplante alogênico de células-tronco periféricas
– Compatibilidade HLA
– Doador homozigoto para CCR5Δ32
• Recaída após 332 dias
• Novo transplante, mesmo doador
– Citarabina + gemtuzumabe + irradiação total
Hütter et al. NEJM 2009. 360:692
20. Paciente de Berlim (2009)
• Vírus CCR5-trópico
– 2,9% CXCR4 ou tropismo duplo
• Quimerismo completo Δ32/Δ32 após 2 meses
• Diminuição de AC anti polimerase e cápside
• Manutenção de AC anti Gp 120 e Gp 41
Hütter et al. NEJM 2009. 360:692
24. Conclusões (2009)
• “Enquanto a carga viral estiver indetectável, o
paciente não necessitará de terapia
antirretroviral”
• “O resultado demonstra a importância do
receptor CCR5 na persistência da infecção
pelo HIV-1”
Hütter et al. NEJM 2009. 360:692
25.
26.
27.
28. Paciente de Berlim (2011)
• Houve recuperação da população T CD4+,
inclusive células de memória ativadas
• Houve repopulação do tecido linfoide
intestinal
• Não houve redução na disponibilidade de
CXCR4 na membrana celular
• Células CD4+ permanecem suscetíveis a vírus
CCR5-trópicos
Allers et al. Blood 2011. 117:2791
29. Paciente de Berlim (2011)
• HIV não foi detectado em diversos tecidos e
populações celulares
– Plasma e LCR
– Cérebro e mucosa intestinal
– Células mononucleares periféricas e medulares
• Houve redução continuada dos níveis de
anticorpos específicos
– Permanecem apenas AC contra ENV
Allers et al. Blood 2011. 117:2791
30. Paciente de Berlim (2012)
International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies
31. Long-Term Reduction in Peripheral Blood
HIV-1 Reservoirs Following Reduced-
Intensity Allogeneic Stem Cell
Transplantation in Two HIV-Infected
Individuals
Timothy J. Henrich1,2, Gaia Sciaranghella3, Jonathan Z. Li1,2, Sebastien
Gallien4, Vincent Ho5,2, Ann S. LaCasce5,2, and Daniel R. Kuritzkes1,2
1Brigham and Women's Hospital, Boston, MA; 2Harvard Medical School, Boston, MA; 3Ragon Institute of
MGH, MIT, and Harvard, Boston, MA; 4 Hopital Saint-Louis, Paris, France;
5Dana-Farber Cancer Institute, Boston, MA.
Your logo
19th International AIDS Conference 2012 (Washington)
abstract no. THAA0101
32. Background
• One reported “functional cure” of HIV-1 infection: myeloablative
allogeneic HSCT from a homozygous ccr5Δ32 donor1,2
• Several factors may have contributed to functional cure
including pre-transplant myeloablative chemotherapy, GVHD,
full engraftment of CCR5- donor cells
• Cytotoxic chemotherapy alone insufficient to eliminate
reservoirs as HIV-1 DNA persists after autologous HSCT3,4
• The long-term effects of allogeneic HSCT using CCR5+ stem
cells have not been studied in detail
1Hutter et al. 2009; 2Allers et al. 2010;
3Simonelli et al. 2010; 4Cillo et al. 2011;
33. Study Aims
Study Aims:
Examine long-term changes in the peripheral HIV-1 reservoir
following allogeneic HSCT in the setting of cART
Explore HIV-1 coreceptor usage, PBMC coreceptor
expression and HIV-specific antibody responses pre- and
post-HSCT
Patients:
2 HIV-1 infected patients on combination ART who underwent
reduced-intensity conditioning (RIC) allogeneic HSCT
RIC = non-myeloablative chemotherapy, no total body
irradiation or anti-thymocyte globulin
34. Methods
Studied stored blood samples collected pre- and post-HSCT and
prospectively collected samples (5 time points)
1) Quantified proviral HIV-1 DNA from peripheral blood mononuclear
cells (PBMCs) and purified CD4+ T cells by real-time PCR
2) Quantified 2-LTR circles from PBMC episomal DNA
3) Quantified plasma viremia by a single-copy assay
4) Viral outgrowth assays using ~107 patient-derived CD4+ T cells and
CD8 T cell-depleted lymphoblasts from an HIV-negative donor
5) CCR5 genotyping/flow cytometric quantification of CCR5
expression on CD3+ T lymphocytes
6) Genotypic and phenotypic determination of HIV-1 coreceptor usage
7) Quantified HIV-1-specific Ab levels & avidity
35. Study Patients
Patient A:
Male with perinatally acquired HIV-1 on long-term ART
2006: Stage IV Hodgkin disease standard treatment
Disease recurrence salvage therapy
2007: Autologous HSCT
2008: Relapse RIC partially mismatched unrelated-donor HSCT
cART: TDF/FTC/EFV 3-4 years pre-HSCT with undetectable VL
Clinical course post-allogeneic HSCT
36. Study Patients
Patient B:
Male with sexually acquired HIV-1 in mid-1980’s
2003: Large B-cell lymphoma chemotherapy and cART started
2006: New stage IV Hodgkin lymphoma
Disease recurrence salvage therapy
2007: Autologous HSCT
2010: MDS (Tx-related) RIC matched related-donor HSCT
cART: TDF/FTC/RAL peri-transplant with undetectable VL
Clinical course post-allogeneic HSCT
38. Patient B
DLI= donor lymphocyte infusion
0 100 200 300 400 500 600 700
0
100
200
300
HIV-1DNA
(copies/106PBMC)
0 100 200 300 400 500 600 700
0
200
400
600
800
1000
Days after HSCT
CD4+TCells
(permm3)
VL
(clinical lab)
VL
(SCA)
<1.8
TN
D
TN
D
<48
100% donor
granulocyte chimerism
DLI
<0.5
<1.8
<1.8
<1.8
Viral outgrowth assay
negative day +652
No 2-LTRs
detected
39. CCR5 / Coreceptor Usage
• Both patients heterozygous for ccr5Δ32 mutation
• PBMC homozygous wild-type for CCR5 after engraftment
• Percentage of CCR5-expressing lymphocytes nearly doubled
after full donor engraftment in Patient A (sufficient sample)
• Full-length HIV-1 env amplified from proviral DNA at pre- and
1st post-HSCT PBMC samples (later timepoints negative)
• V3-loop genotyping predicted CCR5 usage pre- and post-HSCT
• R5 phenotype confirmed by tropism assay of pseudotyped viruses
expressing PBMC-derived env
40. Anti-HIV Ab Quantification
0 200 400 600 800 1000 1200
0
1
2
3
4
5
6
7
8
9
10
11
Subject A
Subject B
Day Post-HSCT
HIV-1AbLevel(S/C)
0 200 400 600 800 1000 1200
0
1
2
3
4
Subject A
Subject B
Day Post-HSCT
LAg-AvidityODn
• HIV-specific Ab detected by VITROS assay pre- & post-HSCT
• Decrease in Ab levels post-HSCT from diluted and undiluted
plasma
• Similar decrease in antigen avidity by limiting-antigen assay
Limited Sensitivity VITROS Assay Limiting-Antigen Avidity Assay
Patient A
Patient B
41. Summary & Conclusions
• Allogeneic HSCT with RIC in the setting of suppressive ART led
to a substantial and sustained reduction in the HIV-1 reservoir
in PBMC
- Reduction in proviral HIV-1 DNA correlated temporally with full
donor engraftment
• Engraftment of susceptible donor cells without infection adds
supportive evidence that HIV-1 replication is fully suppressed
by effective cART
• Declining HIV-specific Ab levels/avidity provide further evidence
for minimal persistence of HIV-1 antigen
• Tissue sampling and analytic treatment interruption are
necessary to fully assess the extent of HIV-1 reservoir
reduction after allogeneic HSCT
44. Em geral, apenas um
vírion inicia a infecção
• Em 80% das infecções
em heterossexuais
•Em 60% das infecções
em homossexuais
•Em 40% das infecções
em UDI
Cohen, NEJM 2011
46. Cura Funcional do HIV em Criança Após
Início Muito Precoce de Tratamento
• Criança nascida de mãe HIV+ (subtipo B) sem tratamento
• Parto vaginal, 35 semanas
• Infecção materna detectada no trabalho de parto (EIA & WB)
• Infecção do RN confirmada por PCR (DNA e RNA), 2 amostras
2º dia de vida
• CV plasmática detectável aos 7, 12 e 20 dias de vida
• CV plasmática indetectável (< 20 cópias/ml) no 29 dia de vida
• CV plasmática indetectável em 16 mensurações até 26 meses
de vida
Persaud D, et al. CROI 2013.(Atlanta) Abstract 48LB
47. • Tratamento:
– ZDV/3TC + NVP (doses plenas) a partir da 31ª
hora, por 7 dias
– ZDV/3TC + LPV/RTV de 7 dias a 18 meses
• CV plasmática (HIV-1 RNA) indetectável no 30º dia (30
e 31 horas pós-nascimento)
• Mãe interrompeu tratamento da criança aos 18 meses
Persaud D, et al. CROI 2013.(Atlanta) Abstract 48LB
Cura Funcional do HIV em Criança Após
Início Muito Precoce de Tratamento
48. • CV inicial 19.812 cópias/ml
– CV indetectável aos 30 dias
– CV permaneceu indetectável até > 80 dias
• Avaliações aos 24 e 26 meses de vida
– Ausência de anticorpos específicos
– Sem detecção de vírus em co-cultura
– Níveis de RNA e DNA do HIV indetectáveis por métodos
usuais
• Aos 24 meses: CV (RNA) 1 cópia/ml; pesquisa de DNA 37
cópias/milhão de PBMC
• Aos 26 meses: pesquisa de DNA = 4 cópias/milhão de PMBC
Persaud D, et al. CROI 2013.(Atlanta) Abstract 48LB
Cura Funcional do HIV em Criança Após
Início Muito Precoce de Tratamento
50. Figure 1. Multiphasic viral decline after potent treatment.
Rong L, Perelson AS (2009) Modeling Latently Infected Cell Activation: Viral and Latent Reservoir Persistence, and Viral Blips in
HIV-infected Patients on Potent Therapy. PLoS Comput Biol 5(10): e1000533. doi:10.1371/journal.pcbi.1000533
http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000533
51. Figure 2. Schematic representation of the model with latently infected cell activation (Eq. (4)).
Rong L, Perelson AS (2009) Modeling Latently Infected Cell Activation: Viral and Latent Reservoir Persistence, and Viral Blips in
HIV-infected Patients on Potent Therapy. PLoS Comput Biol 5(10): e1000533. doi:10.1371/journal.pcbi.1000533
http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000533