Steroid responsive meningitis-arteritis : a prospective study of potential disease markers, prednisolone treatment, and long-term outcome in 20 dogs (2006 – 2008)

Steroid responsive meningitis-arteritis (SRMA) is a common disease of the dog with no specific ante-mortem diagnostic test and management is complicated by the requirement for prolonged treatment and the potential for relapse. The value of immunosuppressive prednisolone has been established but an optimal regime is not described. The lack of diagnostic and prognostic markers makes management frustrating. This study prospectively evaluates a protocol for the use of a prednisolone monotherapy in the management of SRMA. The utility of conventional and novel protein markers was evaluated by examining their expression at various milestones in the management of SRMA and by comparing this to their expression in other canine inflammatory and non-inflammatory central nervous system (CNS) diseases. This prospective study recruited twenty dogs with a clinical diagnosis of SRMA presenting to the University of Glasgow Small Animal Hospital between May 2006 and May 2008. These patients were enrolled on a strict prednisolone regimen with serum and cerebrospinal fluid samples taken at key points in the management of this disease. The protocol was successful at achieving resolution of clinical signs with no relapse in the follow up period in all 20 dogs. Clinical remission was achieved in all cases within 2 weeks of starting the protocol. When relapse occurred during the treatment schedule (4/20), restarting the treatment schedule led to resolution of the disease. The fact that dogs did not relapse post-treatment in this study is supportive of the value of this protocol in managing SRMA. Overall, the findings detailed in this thesis support the use of an immunosuppressive prednisolone monotherapy in the treatment of canine SRMA. Acute phase proteins are significantly elevated at initial presentation with the remission of clinical signs, induced by immunosuppressive therapy, reducing but not eliminating this increase in serum concentrations. APPs are of particular value in the identification of putative relapse. In contrast, serum and cerebrospinal fluid IgA provides valuable information at diagnosis but a persistent increase throughout the disease limits their value in the monitoring of therapy. This immunoglobulin was found to be also be elevated in the serum and cerebrospinal fluid of other inflammatory and non-inflammatory canine CNS diseases. A robust prognostic marker for SRMA remains elusiv

RECENT ADVANCES INPHARMACOTHERAPY OF ALZHEIMER’S DISEASE

The management of Alzheimer's disease (AD) has been a long-standing challenge and area of interest. Advances in knowledge of the pathogenesis of disease and an increase in disease burden have prompted investigation into innovative therapeutics over the last two decades. Current approved therapies are symptomatic treatments having some effect on cognitive function. Therapies that target β-amyloid (Aβ) have been the focus of efforts to develop a disease modification treatment for AD but these approaches have failed to show any clinical benefit so far. Beyond the 'Aβ hypothesis', there are a number of newer approaches to treat AD. This short review will summarize approved drug therapies, recent clinical trials and new approaches for the treatment of AD

Chagas Disease Diagnostic Applications: Present Knowledge and Future Steps

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a lifelong and debilitating illness of major significance throughout Latin America and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research. The expectation is that these novel biomarkers will provide reliable, reproducible and accurate results irrespective of the genetic background, infecting parasite strain, stage of disease, and clinical-associated features of Chagasic populations. In addition, they should be able to address other still unmet diagnostic needs, including early detection of congenital T. cruzi transmission, rapid assessment of treatment efficiency or failure, indication/prediction of disease progression and direct parasite typification in clinical samples. The lack of access of poor and neglected populations to essential diagnostics also stresses the necessity of developing new methods operational in point-of-care settings. In summary, emergent diagnostic tests integrating these novel and tailored tools should provide a significant impact on the effectiveness of current intervention schemes and on the clinical management of Chagasic patients. In this chapter, we discuss the present knowledge and possible future steps in Chagas disease diagnostic applications, as well as the opportunity provided by recent advances in high-throughput methods for biomarker discovery.Fil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Fernandez Aguero, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentin

Review of pharmacological options for the treatment of Chagas disease

Chagas disease (CD) is a worldwide problem, with over 8 million people infected in both rural and urban areas. CD was first described over a century ago, but only two drugs are currently available for CD treatment: benznidazole (BZN) and nifurtimox (NF). Treating CD-infected patients, especially children and women of reproductive age, is vital in order to prevent long-term sequelae, such as heart and gastrointestinal dysfunction, but this aim is still far from being accomplished. Currently, the strongest data to support benefit–risk considerations come from trials in children. Treatment response biomarkers need further development as serology is being questioned as the best method to assess treatment response. This article is a narrative review on the pharmacology of drugs for CD, particularly BZN and NF. Data on drug biopharmaceutical characteristics, safety and efficacy of both drugs are summarized from a clinical perspective. Current data on alternative compounds under evaluation for CD treatment, and new possible treatment response biomarkers are also discussed. Early diagnosis and treatment of CD, especially in paediatric patients, is vital for an effective and safe use of the available drugs (i.e. BZN and NF). New biomarkers for CD are urgently needed for the diagnosis and evaluation of treatment efficacy, and to guide efforts from academia and pharmaceutical companies to accelerate the process of new drug development

Review of pharmacological options for the treatment of Chagas disease

Chagas disease (CD) is a worldwide problem, with over 8 million people infected in both rural and urban areas. CD was first described over a century ago, but only two drugs are currently available for CD treatment: benznidazole (BZN) and nifurtimox (NF). Treating CD-infected patients, especially children and women of reproductive age, is vital in order to prevent long-term sequelae, such as heart and gastrointestinal dysfunction, but this aim is still far from being accomplished. Currently, the strongest data to support benefit–risk considerations come from trials in children. Treatment response biomarkers need further development as serology is being questioned as the best method to assess treatment response. This article is a narrative review on the pharmacology of drugs for CD, particularly BZN and NF. Data on drug biopharmaceutical characteristics, safety and efficacy of both drugs are summarized from a clinical perspective. Current data on alternative compounds under evaluation for CD treatment, and new possible treatment response biomarkers are also discussed. Early diagnosis and treatment of CD, especially in paediatric patients, is vital for an effective and safe use of the available drugs (i.e. BZN and NF). New biomarkers for CD are urgently needed for the diagnosis and evaluation of treatment efficacy, and to guide efforts from academia and pharmaceutical companies to accelerate the process of new drug development.Fil: Lascano, María Fernanda. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: García Bournissen, Facundo. Public Health Ontario; CanadáFil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentin

Pathogenesis of Encephalitis

Many infectious agents, such as viruses, bacteria, and parasites, can cause inflammation of the central nervous system (CNS). Encephalitis is an inflammation of the brain parenchyma, which may result in a more advanced and serious disease meningoencephalitis. To establish accurate diagnosis and develop effective vaccines and drugs to overcome this disease, it is important to understand and elucidate the mechanism of its pathogenesis. This book, which is divided into four sections, provides comprehensive commentaries on encephalitis. The first section (6 chapters) covers diagnosis and clinical symptoms of encephalitis with some neurological disorders. The second section (5 chapters) reviews some virus infections with the outlines of inflammatory and chemokine responses. The third section (7 chapters) deals with the non-viral causative agents of encephalitis. The last section (4 chapters) discusses the experimental model of encephalitis. The different chapters of this book provide valuable and important information not only to the researchers, but also to the physician and health care workers

Current Perspectives on Viral Disease Outbreaks

The COVID-19 pandemic has reminded the world that infectious diseases are still important. The last 40 years have experienced the emergence of new or resurging viral diseases such as AIDS, ebola, MERS, SARS, Zika, and others. These diseases display diverse epidemiologies ranging from sexual transmission to vector-borne transmission (or both, in the case of Zika). This book provides an overview of recent developments in the detection, monitoring, treatment, and control of several viral diseases that have caused recent epidemics or pandemics

Animal models of listeriosis: a comparative review of the current state of the art and lessons learned

Listeriosis is a leading cause of hospitalization and death due to foodborne illness in the industrialized world. Animal models have played fundamental roles in elucidating the pathophysiology and immunology of listeriosis, and will almost certainly continue to be integral components of the research on listeriosis. Data derived from animal studies helped for example characterize the importance of cell-mediated immunity in controlling infection, allowed evaluation of chemotherapeutic treatments for listeriosis, and contributed to quantitative assessments of the public health risk associated with L. monocytogenes contaminated food commodities. Nonetheless, a number of pivotal questions remain unresolved, including dose-response relationships, which represent essential components of risk assessments. Newly emerging data about species-specific differences have recently raised concern about the validity of most traditional animal models of listeriosis. However, considerable uncertainty about the best choice of animal model remains. Here we review the available data on traditional and potential new animal models to summarize currently recognized strengths and limitations of each model. This knowledge is instrumental for devising future studies and for interpreting current data. We deliberately chose a historical, comparative and cross-disciplinary approach, striving to reveal clues that may help predict the ultimate value of each animal model in spite of incomplete data

Epidemiological Features of Central Nervous System (CNS) Infections in Taiwan and Molecular Investigation of CNS Infections of Unknown Cause

In this thesis, I explore the epidemiological features of CNS infections using a population-based dataset and analyze CSF samples from patients with meningitis or encephalitis of unknown cause using molecular methods. In the second chapter, I review the literature on the epidemiology of meningitis and encephalitis, and current diagnostic approaches, focusing on the strengths and limitations of various diagnostic methods. In the third chapter, I investigate the causes of meningitis and encephalitis using a population-based dataset from the National Health Insurance Research Dataset (NHIRD) from Taiwan, representing the interval from 1996 to 2008. The analysis assesses differences in the disease between known and unknown cause groups in terms of incidence, demographic features, seasonal and geographic distribution. In the fourth chapter, I analyze CSF samples from patients with meningitis or encephalitis of unknown cause using a tiered molecular approach to discover the undetected or novel pathogens; techniques used include MassTag PCR, DNA microarrays and high-throughput pyrosequencing. I conclude the thesis in the fifth chapter, summarizing and highlighting the main results of these studies