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https://www.readbyqxmd.com/read/28933846/inhibition-of-calcium-dependent-protein-kinase-1-cdpk1-by-pyrazolopyrimidine-analogs-decreases-establishment-and-reoccurrence-of-central-nervous-system-disease-by-toxoplasma-gondii
#1
Florentine U Rutaganira, Jennifer Barks, Mary Savari Dhason, Qiuling Wang, Michael Steven Lopez, Shaojun Long, Joshua B Radke, Nathaniel G Jones, Amarendar R Maddirala, James W Janetka, Majida El Bakkouri, Raymond Hui, Kevan M Shokat, L David Sibley
Calcium dependent protein kinase 1 (CDPK1) is an essential enzyme in the opportunistic pathogen Toxoplasma gondii. CDPK1 controls multiple processes that are essential to the intracellular replicative cycle of T. gondii including secretion of adhesins, motility, invasion, and egress. Remarkably, CDPK1 contains a small glycine gatekeeper residue in the ATP binding pocket making it sensitive to ATP-competitive inhibitors with bulky substituents that complement this expanded binding pocket. Here we explored structure-activity relationships of a series of pyrazolopyrimidine inhibitors of CDPK1 with the goals of increasing selectivity over host enzymes, improving anti-parasite potency, and improving metabolic stability...
September 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28933703/longitudinal-study-of-falls-among-hiv-infected-and-uninfected-women-the-role-of-cognition
#2
Anjali Sharma, Donald R Hoover, Qiuhu Shi, Susan Holman, Michael W Plankey, Phyllis C Tien, Kathleen M Weber, Michelle Floris-Moore, Hector H Bolivar, David E Vance, Elizabeth T Golub, Marcia McDonnell Holstad, Michael T Yin
BACKGROUND: Although fracture rates are higher in HIV+ than HIV- women, whether HIV infection increases risk of falls is unclear. We determined the longitudinal occurrence and risk factors for falls in the Women's Interagency HIV Study (WIHS), and explored associations with cognitive complaints. METHODS: Recent (prior 6 months) self-reported falls were collected in 1816 (1250 HIV+; 566 HIV-) women over 24 months. Generalized estimating equation models using stepwise selection determined odds of any fall (vs...
September 21, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28931676/protective-humoral-immunity-in-the-cns-requires-peripheral-cd19-dependent-germinal-center-formation-following-coronavirus-encephalomyelitis
#3
Jeffrey R Atkinson, Cornelia C Bergmann
B cell subsets with phenotypes characteristic of naïve, non-isotype-switched, memory (Bmem), and antibody-secreting cells (ASC) accumulate in various models of central nervous system (CNS) inflammation, including viral encephalomyelitis. During neurotropic coronavirus JHMV infection infiltration of protective ASC occurs after T cell mediated viral control, and is preceded by accumulation of non-isotype switched IgD(+) and IgM(+) B cells. However, the contribution of peripheral activation events in cervical lymph nodes (CLN) in driving humoral immune responses in the infected CNS is poorly defined...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28929959/-in-vitro-effect-of-vancomycin-and-daptomycin-on-biofilm-formation-of-coagulase-negative-staphylococci-strains
#4
Duygu Nilüfer Öcal, İştar Dolapçı, Zeynep Gençtürk, Alper Tekeli
Coagulase-negative staphylococci (CNS) are one of the primer agents of blood stream infections (BSI) and catheter-related bloodstream infections (CR-BSI) which are associated mostly with the usage of central venous catheters and, important causes of morbidity and mortality despite the usage of antibacterial and supportive treatment. It is important to determine the properties of these causative microorganisms in order to make appropriate treatment of such infections. The aims of our study were to evaluate the biofilm formation of coagulase negative staphylococci (CNS) which were causative agents of bloodstream (BSI) and catheter related bloodstream infections (CR-BSI), to determine the minimum inhibitory concentration (MIC) of planktonic forms and minimal biofilm eradication concentration (MBEC) of sessile forms for vancomycin and daptomycin and to evaluate the efficacy of these antibiotics in infections with biofilm-forming isolates in vitro...
July 2017: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28927234/metabolic-profiling-of-central-nervous-system-disease-in-trypanosoma-brucei-rhodesiense-infection
#5
Sabrina D Lamour, Vincent P Alibu, Elaine Holmes, Jeremy M Sternberg
Background: The progression of Human African Trypanosomiasis from the early hemolymphatic stage to the late meningoencephalitic stage is of critical diagnostic importance as it determines the choice of potentially toxic drug regimens. Current diagnostic criteria involving analysis of cerebrospinal fluid (CSF) for parasites and/or pleiocytosis are sensitive, but recent evidence suggests that specificity may be poor. Methods: We used an untargeted global metabolic profiling approach for the discovery of novel candidate stage diagnostic markers in CSF from Trypanosoma brucei rhodesiense patients using 1H nuclear magnetic resonance (NMR) spectroscopy...
September 12, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28919626/addison-s-disease-a-diagnostic-dilemma
#6
S Afroz, S Bain
Adrenal insufficiency is a rare disease, but is life threatening when overlooked. Addison's disease may be an acquired form of adrenal insufficiency due to the destruction or dysfunction of the adrenal cortex. It affects both glucocorticoid and mineralocorticoid function. Main presenting symptoms of Addison's disease such as fatigue, anorexia, vomiting and convulsion often mimics central nervous system (CNS) infections. We describe a case of Addison's disease who was initially misdiagnosed as a case of meningo-encephalitis subsequently renal tubular acidosis and finally Addison's disease...
July 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28919347/invasive-mold-infections-of-the-central-nervous-system-in-patients-with-hematologic-cancer-or-stem-cell-transplantation-2000-2016-uncommon-with-improved-survival-but-still-deadly-often
#7
Minas P Economides, Leomar Y Ballester, Vinodh A Kumar, Ying Jiang, Jeffrey Tarrand, Victor Prieto, Harrys A Torres, Dimitrios P Kontoyiannis
BACKGROUND: Historically considered to have very poor outcome, there is paucity of recent data regarding invasive mold infections (IMIs) of the central nervous system (CNS) in patients with hematologic cancer (HC) or stem cell transplantation (SCT). METHODS: We reviewed the records of HC patients and/or SCT recipients who were diagnosed with CNS IMIs (EORTC/MSG criteria) at MD Anderson Cancer Center (1/1/2000-6/31/2016). Risk factors for survival at day (d) 42 post diagnosis were assessed...
September 14, 2017: Journal of Infection
https://www.readbyqxmd.com/read/28917708/type-2-diabetes-mellitus-balb-c-mice-are-more-susceptible-to-granulomatous-amoebic-encephalitis-immunohistochemical-study
#8
Maritza Omaña-Molina, Raquel Sanchez-Rocha, Dolores Hernandez-Martinez, Miriam Romero Grijalva, Citlaltepetl Salinas-Lara, Miriam Rodriguez-Sosa, Imelda Juarez-Avelar, Lizbeth Salazar-Villatoro, Arturo Gonzalez-Robles, Adolfo Rene Mendez-Cruz, Patricia Aley-Medina, Jesus Espinosa-Villanueva, Ismael Castelan-Ramirez, Jacob Lorenzo-Morales
Granulomatous amoebic encephalitis (GAE) is a chronic, difficult to resolve infection caused by amphizoic amoebae of the genus Acanthamoeba, which in most cases occurs in immunosuppressed persons or with chronic diseases such as diabetes. In this study, we describe the early events of A. culbertsoni infection of GAE in diabetic mice model. Diabetes was induced in male BALB/c mice, with a dose of streptozotocin (130 mg/kg). Healthy and diabetic mice were inoculated via intranasal with 1 × 10(6) trophozoites of A...
September 13, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28913765/treatment-of-theiler-s-virus-induced-demyelinating-disease-with-teriflunomide
#9
Francesca Gilli, Libin Li, Darlene B Royce, Krista D DiSano, Andrew R Pachner
Teriflunomide is an oral therapy approved for the treatment of relapsing remitting multiple sclerosis (MS), showing both anti-inflammatory and antiviral properties. Currently, it is uncertain whether one or both of these properties may explain teriflunomide's beneficial effect in MS. Thus, to learn more about its mechanisms of action, we evaluated the effect of teriflunomide in the Theiler's encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model, which is both a viral infection and an excellent model of the progressive disability of MS...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28913617/fingolimod-induces-neuronal-specific-gene-expression-with-potential-neuroprotective-outcomes-in-maturing-neuronal-progenitor-cells-exposed-to-hiv
#10
Rebeca Geffin, Ricardo Martinez, Alicia de Las Pozas, Biju Issac, Micheline McCarthy
Fingolimod (FTY720), a structural analogue of sphingosine, targets sphingosine-1-phosphate receptor signaling and is currently an immunomodulatory therapy for multiple sclerosis. Fingolimod accesses the central nervous system (CNS) where its active metabolite, fingolimod phosphate (FTY720-P), has pleotropic neuroprotective effects in an inflammatory microenvironment. To investigate potential neuronal-specific mechanisms of fingolimod neuroprotection, we cultured the human neuronal progenitor cell line, hNP1, in differentiation medium supplemented with HIV- or Mock-infected supernatants, with or without FTY720-P...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28913566/adar-rna-editing-in-human-disease-more-to-it-than-meets-the-i
#11
REVIEW
Angela Gallo, Dragana Vukic, David Michalík, Mary A O'Connell, Liam P Keegan
We review the structures and functions of ADARs and their involvements in human diseases. ADAR1 is widely expressed, particularly in the myeloid component of the blood system, and plays a prominent role in promiscuous editing of long dsRNA. Missense mutations that change ADAR1 residues and reduce RNA editing activity cause Aicardi-Goutières Syndrome, a childhood encephalitis and interferonopathy that mimics viral infection and resembles an extreme form of Systemic Lupus Erythmatosus (SLE). In Adar1 mouse mutant models aberrant interferon expression is prevented by eliminating interferon activation signaling from cytoplasmic dsRNA sensors, indicating that unedited cytoplasmic dsRNA drives the immune induction...
September 14, 2017: Human Genetics
https://www.readbyqxmd.com/read/28913358/central-modulation-of-neuroinflammation-by-neuropeptides-and-energy-sensing-hormones-during-obesity
#12
REVIEW
Roger Maldonado-Ruiz, Lizeth Fuentes-Mera, Alberto Camacho
Central nervous system (CNS) senses energy homeostasis by integrating both peripheral and autonomic signals and responding to them by neurotransmitters and neuropeptides release. Although it is previously considered an immunologically privileged organ, we now know that this is not so. Cells belonging to the immune system, such as B and T lymphocytes, can be recruited into the CNS to face damage or infection, in addition to possessing resident immunological cells, called microglia. In this way, positive energy balance during obesity promotes an inflammatory state in the CNS...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28904584/central-nervous-system-inflammatory-myofibroblastic-tumor-masquerading-as-chronic-suppurative-otitis-media
#13
Namit Singhal, Vinay Agarwal, Anu Chawla, Rajiv Tangri
Inflammatory myofibroblastic tumor (IMT) is a rare tumor in the central nervous system (CNS), mostly being extracranial. Approximately 100 sporadic cases have been reported in the literature. The rarity of the tumor, its various histopathological characteristics, and its variable aggressive course render it difficult to diagnose and treat. IMT is generally a histological diagnosis which is rarely suspected preoperatively. It mimics other intracranial tumors such as giant cell tumor, hemangiopericytoma, anaplastic meningioma, plasmacytoma, and lymphoma...
April 2017: Journal of Pediatric Neurosciences
https://www.readbyqxmd.com/read/28903872/prevalence-of-subclinical-mastitis-and-associated-risk-factors-at-cow-and-herd-level-in-dairy-farms-in-north-west-ethiopia
#14
S A Mekonnen, G Koop, S T Melkie, C D Getahun, H Hogeveen, T J G M Lam
Knowledge of mastitis pathogens and their predominance as well as understanding of risk factors are prerequisites to improve udder health in a herd, region or country. In Ethiopia, such information is scarce, despite the fact that mastitis is an important cattle disease in the country. A cross-sectional study that describes prevalence and causative agents of subclinical mastitis (SCM) as well as risk factors at cow and herd level was conducted on 167 dairy farms in North-West Ethiopia. On average, 33% of the quarters and 62% of the cows were California Mastitis Test (CMT) positive, but the within herd quarter level prevalence ranged between 0 and 100%...
September 15, 2017: Preventive Veterinary Medicine
https://www.readbyqxmd.com/read/28895099/neurological-and-multiple-organ-involvement-due-to-paracoccidioides-brasiliensis-and-hiv-co-infection-diagnosed-at-autopsy
#15
Sergio Monteiro de Almeida, Thiago H Roza, Gabriel L O Salvador, João C B França, Luine Rosele Renaud Vidal, Meri Bordignon Nogueira, Lubomira Veronica Oliva, Luis Fernando Bleggi Torres, Lucia Helena de Noronha
Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent systemic mycosis among immunocompetent patients in Latin America; it is rare in immunocompromised patients. The estimated frequency of central nervous system (CNS) involvement in the HIV/PCM population was 2.5%. We report a case of HIV/P. brasiliensis co-infection, with neurological (NPCM) and multiple organ involvement, indicating a diagnosis of AIDS. PCM diagnosis was established during the autopsy. This is the first described case of HIV/P...
September 11, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28895059/central-nervous-system-penetrating-antiretrovirals-impair-energetic-reserve-in-striatal-nerve-terminals
#16
Kelly L Stauch, Katy Emanuel, Benjamin G Lamberty, Brenda Morsey, Howard S Fox
The use of antiretroviral (ARV) drugs with central nervous system (CNS) penetration effectiveness (CPE) may be useful in the treatment of HIV-associated neurocognitive disorder (HAND) as well as targeting a CNS reservoir in strategies to achieve a functional cure for HIV. However, increased cognitive deficits are linked to at least one of these drugs (efavirenz). As mitochondrial dysfunction has been found with a number of ARVs, and as such can affect neuronal function, the objective of this study was to assess the effects of ARV with high CPE for toxicological profiles on presynaptic nerve terminal energy metabolism...
September 11, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28893794/effects-of-hiv-1-tat-and-methamphetamine-on-blood-brain-barrier-integrity-and-function-in-vitro
#17
Sulay Patel, Crystal R Leibrand, Preetha Palasuberniam, Pierre-Olivier Couraud, Babette Weksler, Fay M Jahr, Joseph L McClay, Kurt F Hauser, MaryPeace McRae
Human immunodeficiency (HIV) infection results in neurocognitive deficits in about one half of infected individuals. Despite systemic effectiveness, restricted antiretroviral penetration across the blood-brain barrier (BBB) is a major limitation in fighting CNS-localized infection. Drug abuse exacerbates HIV-induced cognitive and pathologic CNS changes. This study's purpose was to investigate the effects of the HIV-1 protein, Tat, and methamphetamine on factors affecting drug penetration across an in vitro BBB model...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28892964/dengue-haemorrhagic-encephalitis-rare-case-report-with-review-of-literature
#18
Aditya Singh Kutiyal, Chetanya Malik, Gitika Hyanki
Dengue is an endemic arboviral infection prevalent especially in tropical countries including Southern and Southeast Asia. Central Nervous System (CNS) involvement in dengue infection is uncommon. Haemorrhagic encephalitis is a rare presentation in dengue. This is a case of a 58-year-old male who presented with fever, petechial rash and altered sensorium. Dengue serology IgM was reactive and MRI brain was suggestive of haemorrhagic encephalitis. Patient was managed in Intensive Care Unit (ICU) but eventually succumbed to his illness...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28891812/herpes-simplex-virus-1-evasion-of-cd8-t-cell-accumulation-contributes-to-viral-encephalitis
#19
Naoto Koyanagi, Takahiko Imai, Keiko Shindo, Ayuko Sato, Wataru Fujii, Takeshi Ichinohe, Naoki Takemura, Shigeru Kakuta, Satoshi Uematsu, Hiroshi Kiyono, Yuhei Maruzuru, Jun Arii, Akihisa Kato, Yasushi Kawaguchi
Herpes simplex virus-1 (HSV-1) is the most common cause of sporadic viral encephalitis, which can be lethal or result in severe neurological defects even with antiviral therapy. While HSV-1 causes encephalitis in spite of HSV-1-specific humoral and cellular immunity, the mechanism by which HSV-1 evades the immune system in the central nervous system (CNS) remains unknown. Here we describe a strategy by which HSV-1 avoids immune targeting in the CNS. The HSV-1 UL13 kinase promotes evasion of HSV-1-specific CD8+ T cell accumulation in infection sites by downregulating expression of the CD8+ T cell attractant chemokine CXCL9 in the CNS of infected mice, leading to increased HSV-1 mortality due to encephalitis...
September 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28889017/mycoplasmas-brain-invaders
#20
REVIEW
Rubén S Rosales, Roberto Puleio, Guido R Loria, Salvatore Catania, Robin A J Nicholas
Mycoplasmas of humans and animals are usually associated with respiratory, autoimmune, genital and joint diseases. Human mycoplasmas have also been known to affect the brain. Severe central nervous system (CNS) diseases, such as encephalitis, have been linked to Mycoplasma pneumoniae and ureaplasma infections. Less well known is the sheep and goat pathogen, Mycoplasma agalactiae, which has been found in large quantities in the brain where it may be responsible for non-purulent encephalitis as well as ataxia in young animals...
September 5, 2017: Research in Veterinary Science
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