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Blood brain barrier and antibiotic

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https://www.readbyqxmd.com/read/29137682/cefepime-induced-neurotoxicity-a-systematic-review
#1
Lauren E Payne, David J Gagnon, Richard R Riker, David B Seder, Elizabeth K Glisic, Jane G Morris, Gilles L Fraser
BACKGROUND: Cefepime is a widely used antibiotic with neurotoxicity attributed to its ability to cross the blood-brain barrier and exhibit concentration-dependent ϒ-aminobutyric acid (GABA) antagonism. Neurotoxic symptoms include depressed consciousness, encephalopathy, aphasia, myoclonus, seizures, and coma. Data suggest that up to 15% of ICU patients treated with cefepime may experience these adverse effects. Risk factors include renal dysfunction, excessive dosing, preexisting brain injury, and elevated serum cefepime concentrations...
November 14, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29064811/-the-risk-of-epileptic-seizures-during-antibiotic-therapy
#2
Ewa Czapińska-Ciepiela
Numerous antibiotics may trigger epileptic seizures or status epilepticus by decreasing inhibitory transmission in the brain, thus lowering the seizure threshold. The most potent seizurogenic effect is exerted by penicillins, cephalosporins, fluorochinolons and carbapenems. Predisposing factors that facilitate development of epileptic seizures in the course of antibiotic therapy comprise all conditions accompanied by damage to the blood-brain barrier (including cerebral trauma and encephalitis), a high dose of an antibiotic or lack of adequate dose adjustment in patients with renal failure...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28884751/tuberculous-meningitis
#3
REVIEW
Robert J Wilkinson, Ursula Rohlwink, Usha Kant Misra, Reinout van Crevel, Nguyen Thi Hoang Mai, Kelly E Dooley, Maxine Caws, Anthony Figaji, Rada Savic, Regan Solomons, Guy E Thwaites
Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis (TBM), for which more than 100,000 new cases are estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Study of TBM pathogenesis is hampered by a lack of experimental models that recapitulate all the features of the human disease. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation...
October 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28843822/clofazimine-protects-against-mycobacterium-tuberculosis-dissemination-in-the-cns-following-an-aerosol-challenge-in-a-murine-model
#4
Sooraj Baijnath, Chivonne Moodley, Bongani Ngcobo, Sanil D Singh, Hendrik G Kruger, Per I Arvidsson, Tricia Naicker, Alexander Pym, Thavendran Govender
BACKGROUND: Tuberculosis (TB) has been the scourge of the human race for many decades, claiming countless number of lives along the way. This is further complicated by the ability of Mycobacterium tuberculosis (M.tb) to infect extra-pulmonary sites, more specifically the brain. These forms of TB are difficult to treat due to the problems associated with drug delivery across the blood brain barrier (BBB). Linezolid (LZD and clofazimine (CFZ) are two of the more promising anti-TB antibiotics in recent times...
August 23, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28763689/investigation-of-novel-pharmacological-chaperones-for-gaucher-disease
#5
Buge Yilmazer, Z Begum Yagci, Emre Bakar, Burcu Ozden, Kutlu Ulgen, Elif Ozkirimli
Beta-Glucocerebrosidase (GBA) is a lysosomal protein that is responsible for the hydrolysis of glycosylceramide into glucose and ceramide. Mutations in GBA lead to the accumulation of glycosylceramide in the lysosome causing an enlargement of the spleen and the liver and skeletal deformations. This disease is called Gaucher Disease. Enzyme replacement therapies and substrate reduction methods that are used to treat Gaucher Disease fail when the disease is neuropathic because they fail to pass the blood brain barrier...
July 20, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28759731/antibiotic-drug-piperacillin-induces-neuron-cell-death-through-mitochondrial-dysfunction-and-oxidative-damage
#6
Shan Jiang, Tong Li, Xiao Zhou, Wenjun Qin, Zijun Wang, Yi Liao
Although nerve damage/toxicity has been shown to be one of the side effects in patients given prolonged antibiotic treatment, the mechanisms of the action of antibiotics on neuron cells are not clear. In this work, we investigated the toxicity of piperacillin (an antibiotic that can penetrate blood-brain barrier) on neuron cells and its underlying mechanisms. We show that clinically relevant doses of piperacillin induce apoptosis in SH-SY5Y and human primary neuron cells through activating caspase 3 activity and decreasing Mcl-1 and Bcl-2 levels...
July 31, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28515075/pigr-and-pecam-1-bind-to-pneumococcal-adhesins-rrga-and-pspc-mediating-bacterial-brain-invasion
#7
Federico Iovino, Joo-Yeon Engelen-Lee, Matthijs Brouwer, Diederik van de Beek, Arie van der Ende, Merche Valls Seron, Peter Mellroth, Sandra Muschiol, Jan Bergstrand, Jerker Widengren, Birgitta Henriques-Normark
Streptococcus pneumoniae is the main cause of bacterial meningitis, a life-threating disease with a high case fatality rate despite treatment with antibiotics. Pneumococci cause meningitis by invading the blood and penetrating the blood-brain barrier (BBB). Using stimulated emission depletion (STED) super-resolution microscopy of brain biopsies from patients who died of pneumococcal meningitis, we observe that pneumococci colocalize with the two BBB endothelial receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1)...
June 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28450902/role-of-neural-barriers-in-the-pathogenesis-and-outcome-of-streptococcus-pneumoniae-meningitis
#8
Ofer Prager, Alon Friedman, Yaffa Mizrachi Nebenzahl
Bacterial meningitis is an inflammatory disease of the meninges of the central nervous system (CNS). Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitidis, and Haemophilus influenzae are the major bacterial pathogens causing meningitis with S. pneumoniae being responsible for two thirds of meningitis cases in the developed world. To reach the CNS following nasopharyngeal colonization and bacteraemia, the bacteria traverse from the circulation across the blood brain barrier (BBB) and choroid plexus...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28450047/signaling-pathways-regulating-blood-tissue-barriers-lesson-from-the-testis
#9
REVIEW
Qing Wen, Elizabeth I Tang, Ying Gao, Tito T Jesus, Darren S Chu, Will M Lee, Chris K C Wong, Yi-Xun Liu, Xiang Xiao, Bruno Silvestrini, C Yan Cheng
Signaling pathways that regulate blood-tissue barriers are important for studying the biology of various blood-tissue barriers. This information, if deciphered and better understood, will provide better therapeutic management of diseases particularly in organs that are sealed by the corresponding blood-tissue barriers from systemic circulation, such as the brain and the testis. These barriers block the access of antibiotics and/or chemotherapeutical agents across the corresponding barriers. Studies in the last decade using the blood-testis barrier (BTB) in rats have demonstrated the presence of several signaling pathways that are crucial to modulate BTB function...
April 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28442909/tat-functionalized-liposomes-for-the-treatment-of-meningitis-an-in-vitro-study
#10
Caterina Bartomeu Garcia, Di Shi, Thomas J Webster
Bacterial meningitis has become a global concern, because of the emergence of antibiotic-resistant bacteria. It has been demonstrated that liposomes can enter bacteria, thus providing a possible treatment for numerous infections, including meningitis. Fusogenic liposomes are pH-sensitive with a high capacity to fuse with the bacteria membrane and promote intracellular drug release. Moreover, this ability can be improved by using cell-penetrating peptides (such as Tat47-57, which is a peptide derived from the Tat protein of HIV)...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28375200/low-dose-penicillin-in-early-life-induces-long-term-changes-in-murine-gut-microbiota-brain-cytokines-and-behavior
#11
Sophie Leclercq, Firoz M Mian, Andrew M Stanisz, Laure B Bindels, Emmanuel Cambier, Hila Ben-Amram, Omry Koren, Paul Forsythe, John Bienenstock
There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice...
April 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28372330/the-gut-microbiota-and-alzheimer-s-disease
#12
Chunmei Jiang, Guangning Li, Pengru Huang, Zhou Liu, Bin Zhao
The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also central nervous system disorders such as Alzheimer's disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-β peptides (Aβ). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28287461/alkoxy-and-enediyne-derivatives-containing-1-4-benzoquinone-subunits-synthesis-and-antitumor-activity
#13
Monika Kadela-Tomanek, Ewa Bębenek, Elwira Chrobak, Małgorzata Latocha, Stanisław Boryczka
The compounds produced by a living organism are most commonly as medicinal agents and starting materials for the preparation of new semi-synthetic derivatives. One of the largest groups of natural compounds consists of products containing a 1,4-benzoquinone subunit. This fragment occurs in three enediyne antibiotics, dynemicin A, deoxydynemicin A, and uncilamicin, which exhibit high biological activity. A series of alkoxy derivatives containing 1,4-naphthoquinone, 5,8-quinolinedione, and 2-methyl-5,8-quinolinedione moieties was synthesized...
March 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28270812/borrelia-burgdorferi-keeps-moving-and-carries-on-a-review-of-borrelial-dissemination-and-invasion
#14
REVIEW
Jenny A Hyde
Borrelia burgdorferi is the etiological agent of Lyme disease, a multisystemic, multistage, inflammatory infection resulting in patients experiencing cardiac, neurological, and arthritic complications when not treated with antibiotics shortly after exposure. The spirochetal bacterium transmits through the Ixodes vector colonizing the dermis of a mammalian host prior to hematogenous dissemination and invasion of distal tissues all the while combating the immune response as it traverses through its pathogenic lifecycle...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28192085/influence-of-peptide-transporter-2-pept2-on-the-distribution-of-cefadroxil-in-mouse-brain-a-microdialysis-study
#15
Xiaomei Chen, Richard F Keep, Yan Liang, Hao-Jie Zhu, Margareta Hammarlund-Udenaes, Yongjun Hu, David E Smith
Peptide transporter 2 (PEPT2) is a high-affinity low-capacity transporter belonging to the proton-coupled oligopeptide transporter family. Although many aspects of PEPT2 structure-function are known, including its localization in choroid plexus and neurons, its regional activity in brain, especially extracellular fluid (ECF), is uncertain. In this study, the pharmacokinetics and regional brain distribution of cefadroxil, a β-lactam antibiotic and PEPT2 substrate, were investigated in wildtype and Pept2 null mice using in vivo intracerebral microdialysis...
May 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28036021/monitoring-the-response-of-hyperbilirubinemia-in-the-mouse-brain-by-in-vivo-bioluminescence-imaging
#16
Isabella Manni, Giuliana Di Rocco, Salvatore Fusco, Lucia Leone, Saviana Antonella Barbati, Carmine Maria Carapella, Claudio Grassi, Giulia Piaggio, Gabriele Toietta
Increased levels of unconjugated bilirubin are neurotoxic, but the mechanism leading to neurological damage has not been completely elucidated. Innovative strategies of investigation are needed to more precisely define this pathological process. By longitudinal in vivo bioluminescence imaging, we noninvasively visualized the brain response to hyperbilirubinemia in the MITO-Luc mouse, in which light emission is restricted to the regions of active cell proliferation. We assessed that acute hyperbilirubinemia promotes bioluminescence in the brain region, indicating an increment in the cell proliferation rate...
December 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28034813/is-first-line-vancomycin-still-the-best-option-to-treat-staphylococcus-health-care-associated-meningitis
#17
Roman Mounier, David Lobo, Anne Hulin, Biba Nebbad, Fabrice Cook, Gilles Dhonneur
BACKGROUND: Cerebrospinal fluid (CSF) penetration of vancomycin through the blood-brain barrier is poor but important inflammation improved it. Hence, vancomycin is recommended for the treatment of community meningitis. However, what about mild inflammatory health care-associated meningitis? The aim of this study was to evaluate the impact of vancomycin diffusion on CSF in Staphylococcus epidermidis health care-associated meningitis. CASE DESCRIPTION: This was a retrospective study of all consecutive patients with S...
March 2017: World Neurosurgery
https://www.readbyqxmd.com/read/27774592/rifampicin-attenuates-experimental-autoimmune-encephalomyelitis-by-inhibiting-pathogenic-th17-cells-responses
#18
Ke Ma, Xi Chen, Jia-Cheng Chen, Ying Wang, Xi-Meng Zhang, Fan Huang, Jun-Jiong Zheng, Xiong Chen, Wei Yu, Ke-Ling Cheng, Yan-Qing Feng, Huai-Yu Gu
Rifampicin, a broad-spectrum antibiotic, has neuroprotective, immunosuppressive, and anti-inflammatory properties. However, the effect of rifampicin on autoimmune disorders of the nervous system is not clear. In this study, we investigated whether rifampicin was beneficial to myelin oligodendrocyte glycoprotein peptide (MOG33-35 )-induced female C57BL/6 experimental autoimmune encephalomyelitis (EAE) mice, the well-established animal model of multiple sclerosis. Rifampicin treatment (daily from the first day after EAE immunization) remarkably attenuated clinical signs and loss of body weight, which are associated with suppression of inflammatory infiltration and demyelination in spinal cords of EAE mice...
December 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27711202/sphingosine-1-phosphate-activation-of-egfr-as-a-novel-target-for-meningitic-escherichia-coli-penetration-of-the-blood-brain-barrier
#19
Xiangru Wang, Ravi Maruvada, Andrew J Morris, Jun O Liu, Michael J Wolfgang, Dong Jae Baek, Robert Bittman, Kwang Sik Kim
Central nervous system (CNS) infection continues to be an important cause of mortality and morbidity, necessitating new approaches for investigating its pathogenesis, prevention and therapy. Escherichia coli is the most common Gram-negative bacillary organism causing meningitis, which develops following penetration of the blood-brain barrier (BBB). By chemical library screening, we identified epidermal growth factor receptor (EGFR) as a contributor to E. coli invasion of the BBB in vitro. Here, we obtained the direct evidence that CNS-infecting E...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27680224/a-case-of-cefepime-encephalopathy-being-difficult-to-distinguish-from-non-convulsive-status-epilepticus-during-the-treatment-of-bacterial-meningitis
#20
REVIEW
Yusuke Toda, Mineo Yamazaki, Tomohiro Ota, Yosuke Fujisawa, Kazumi Kimura
A 64-year-old man with fever, appetite loss, and pain in the back of the neck visited our hospital. We diagnosed him as having bacterial meningitis because of pleocytosis of the cerebrospinal fluid, and started treatment with antibiotics. Multiple cerebral infarcts were found on brain MRI. We suspected that the origin of the bacterial meningitis was infective endocarditis, and administered Cefepime and Gentamicin according to the guidelines for treatment of infective endocarditis. Three days later, he became drowsy and had myoclonus and flapping of the extremities...
October 28, 2016: Rinshō Shinkeigaku, Clinical Neurology
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