Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma

High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8+ cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs. [18F]FHBG imaging was safe and enabled the longitudinal imaging of T cells stably transfected with a PET reporter gene in patients. Further optimization of this imaging approach for monitoring in vivo cell trafficking should greatly benefit various cell-based therapies for cancer

Anti-ganglioside antibodies-mediated leptospiral meningomyeloencephalopolyneuritis

A case of leptospirosis complicated with meningo-myelo-encephalo-polyneuritis and nephrotic syndrome is presented. Anti-ganglioside antibodies were detected for the first time in a patient with neurological complications of leptospirosis. Possible pathogenic mechanisms and treatment options of these rare manifestations are discussed

Nephropathy in leptospirosis

Renal involvement is common in leptospirosis. Bacterial invasion, inflammatory process, haemodynamic alterations and direct toxicity of bacterial products are thought to be responsible for the development of nephropathy. Pathologically, all renal structures are involved. Interstitial nephritis is the basic lesion, and is observed even in patients without clinical renal manifestations. Tubular necrosis is the important pathological counterpart of acute renal failure. The clinical spectrum of renal manifestations includes mild urinary sediment change, hypokalemia, tubular dysfunction, decreased response to fluid load and acute renal failure (ARF). ARF reflects the severity of leptospirosis, is catabolic and is commonly associated with cholestatic jaundice. Severe renal failure may be complicated by multiple organ involvement. Renal failure with hyperbilirubinemia represents a severe form of renal dysfunction with oligo-anuria and prolonged clinical course. Mild renal failure is usually anicteric and non-oliguric and without complication. Besides antibiotic treatment, early and frequent dialysis is life saving. ARF with major organ failure has unfavorable outcome. Plasmapheresis and continuous venovenous hemofiltration improve hemodynamics and are beneficial for the patients with acute renal failure and multiorgan involvement. Recovery of renal function is usually complete in most patients

Nephropathy in leptospirosis

Renal involvement is common in leptospirosis. Bacterial invasion, inflammatory process, haemodynamic alterations and direct toxicity of bacterial products are thought to be responsible for the development of nephropathy. Pathologically, all renal structures are involved. Interstitial nephritis is the basic lesion, and is observed even in patients without clinical renal manifestations. Tubular necrosis is the important pathological counterpart of acute renal failure. The clinical spectrum of renal manifestations includes mild urinary sediment change, hypokalemia, tubular dysfunction, decreased response to fluid load and acute renal failure (ARF). ARF reflects the severity of leptospirosis, is catabolic and is commonly associated with cholestatic jaundice. Severe renal failure may be complicated by multiple organ involvement. Renal failure with hyperbilirubinemia represents a severe form of renal dysfunction with oligo-anuria and prolonged clinical course. Mild renal failure is usually anicteric and non-oliguric and without complication. Besides antibiotic treatment, early and frequent dialysis is life saving. ARF with major organ failure has unfavorable outcome. Plasmapheresis and continuous venovenous hemofiltration improve hemodynamics and are beneficial for the patients with acute renal failure and multiorgan involvement. Recovery of renal function is usually complete in most patients

Symposium- Nephropathy in leptospirosis

Renal involvement is common in leptospirosis. Bacterial invasion, inflammatory process, haemodynamic alterations and direct toxicity of bacterial products are thought to be responsible for the development of nephropathy. Pathologically, all renal structures are involved. Interstitial nephritis is the basic lesion, and is observed even in patients without clinical renal manifestations. Tubular necrosis is the important pathological counterpart of acute renal failure. The clinical spectrum of renal manifestations includes mild urinary sediment change, hypokalemia, tubular dysfunction, decreased response to fluid load and acute renal failure (ARF). ARF reflects the severity of leptospirosis, is catabolic and is commonly associated with cholestatic jaundice. Severe renal failure may be complicated by multiple organ involvement. Renal failure with hyperbilirubinemia represents a severe form of renal dysfunction with oligo-anuria and prolonged clinical course. Mild renal failure is usually anicteric and non-oliguric and without complication. Besides antibiotic treatment, early and frequent dialysis is life saving. ARF with major organ failure has unfavorable outcome. Plasmapheresis and continuous venovenous hemofiltration improve hemodynamics and are beneficial for the patients with acute renal failure and multiorgan involvement. Recovery of renal function is usually complete in most patients

Exosome-Derived Mediators as Potential Biomarkers for Cardiovascular Diseases: A Network Approach

Cardiovascular diseases (CVDs) are widely recognized as the leading cause of mortality worldwide. Despite the advances in clinical management over the past decades, the underlying pathological mechanisms remain largely unknown. Exosomes have drawn the attention of researchers for their relevance in intercellular communication under both physiological and pathological conditions. These vesicles are suggested as complementary prospective biomarkers of CVDs; however, the role of exosomes in CVDs is still not fully elucidated. Here, we performed a literature search on exosomal biogenesis, characteristics, and functions, as well as the different available exosomal isolation techniques. Moreover, aiming to give new insights into the interaction between exosomes and CVDs, network analysis on the role of exosome-derived mediators in coronary artery disease (CAD) and heart failure (HF) was also performed to incorporate the different sources of information. The upregulated exosomal miRNAs miR-133a, miR-208a, miR-1, miR-499-5p, and miR-30a were described for the early diagnosis of acute myocardial infarction, while the exosome-derived miR-192, miR-194, miR-146a, and miR-92b-5p were considered as potential biomarkers for HF development. In CAD patients, upregulated exosomal proteins, including fibrinogen beta/gamma chain, inter-alpha-trypsin inhibitor heavy chain, and alpha-1 antichymotrypsin, were assessed as putative protein biomarkers. From downregulated proteins in CAD patients, albumin, clusterin, and vitamin D-binding protein were considered relevant to assess prognosis. The Vesiclepedia database included miR-133a of exosomal origin upregulated in patients with CAD and the exosomal miR-192, miR-194, and miR-146a upregulated in patients with HF. Additionally, Vesiclepedia included 5 upregulated and 13 downregulated exosomal proteins in patients in CAD. The non-included miRNAs and proteins have not yet been identified in exosomes and can be proposed for further research. This report highlights the need for further studies focusing on the identification and validation of miRNAs and proteins of exosomal origin as biomarkers of CAD and HF, which will enable, using exosomal biomarkers, the guiding of diagnosis/prognosis in CVDs

Exosome-Derived Mediators as Potential Biomarkers for Cardiovascular Diseases: A Network Approach

Cardiovascular diseases (CVDs) are widely recognized as the leading cause of mortality worldwide. Despite the advances in clinical management over the past decades, the underlying pathological mechanisms remain largely unknown. Exosomes have drawn the attention of researchers for their relevance in intercellular communication under both physiological and pathological conditions. These vesicles are suggested as complementary prospective biomarkers of CVDs; however, the role of exosomes in CVDs is still not fully elucidated. Here, we performed a literature search on exosomal biogenesis, characteristics, and functions, as well as the different available exosomal isolation techniques. Moreover, aiming to give new insights into the interaction between exosomes and CVDs, network analysis on the role of exosome-derived mediators in coronary artery disease (CAD) and heart failure (HF) was also performed to incorporate the different sources of information. The upregulated exosomal miRNAs miR-133a, miR-208a, miR-1, miR-499-5p, and miR-30a were described for the early diagnosis of acute myocardial infarction, while the exosome-derived miR-192, miR-194, miR-146a, and miR-92b-5p were considered as potential biomarkers for HF development. In CAD patients, upregulated exosomal proteins, including fibrinogen beta/gamma chain, inter-alpha-trypsin inhibitor heavy chain, and alpha-1 antichymotrypsin, were assessed as putative protein biomarkers. From downregulated proteins in CAD patients, albumin, clusterin, and vitamin D-binding protein were considered relevant to assess prognosis. The Vesiclepedia database included miR-133a of exosomal origin upregulated in patients with CAD and the exosomal miR-192, miR-194, and miR-146a upregulated in patients with HF. Additionally, Vesiclepedia included 5 upregulated and 13 downregulated exosomal proteins in patients in CAD. The non-included miRNAs and proteins have not yet been identified in exosomes and can be proposed for further research. This report highlights the need for further studies focusing on the identification and validation of miRNAs and proteins of exosomal origin as biomarkers of CAD and HF, which will enable, using exosomal biomarkers, the guiding of diagnosis/prognosis in CVDs.</jats:p