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Blood brain barrier and antibiotic

Paolo Ruzza, Rosa Maria Vitale, Rohanah Hussain, Alessia Montini, Claudia Honisch, Alice Pozzebon, Charlotte S Hughes, Barbara Biondi, Pietro Amodeo, GianPietro Sechi, Giuliano Siligardi
BACKGROUND: Lysozyme is a widely distributed enzyme present in a variety of tissue and body fluids. Human and hen egg white lysozyme are used as validated model to study protein folding and stability and to understand protein misfolding and aggregation. We recently found that ceftriaxone, a β-lactam antibiotic able to overcome the blood-brain barrier, successfully eliminated the cellular toxic effects of misfolded proteins as Glial Fibrillary Acidic Protein and α-synuclein. To further understand the anti-amyloidogenic properties of ceftriaxone, we studied its activity towards lysozyme aggregation with the aim to investigate a possible chaperone-like activity of this molecule...
March 7, 2018: Biochimica et Biophysica Acta
Wei Guo, Shao-Chun Guo, Min Li, Li-Hong Li, Yan Qu
Background: Acinetobacter baumannii nosocomial ventriculitis/meningitis, especially those due to drug-resistant strains, has substantially increased over recent years. However, limited therapeutic options exist for the Acinetobacter baumannii ventriculitis/meningitis because of the poor penetration rate of most antibiotics through the blood-brain barrier. Case presentation: A 57-year-old male patient developed ventriculitis from an extensively drug-resistant strain of Acinetobacter baumannii after the decompressive craniectomy for severe traumatic brain injury...
2018: Antimicrobial Resistance and Infection Control
J M Cabrera-Maqueda, L Fuentes Rumí, G Valero López, A E Baidez Guerrero, E García Molina, J Díaz Pérez, E García-Vázquez
Central nervous system (CNS) infections caused by pathogens with a reduced sensitivity to drugs are a therapeutic challenge. Transport of fluid and solutes is tightly controlled within CNS, where vasculature exhibits a blood-brain barrier (BBB).The entry of drugs, including antibiotics, into the cerebro-spinal fluid (CSF) is governed by molecular size, lipophilicity, plasma protein binding and their affinity to transport systems at the BBB. The ratio of the AUCCSF (Area under the curve in CSF)/AUCS (Area under the curve in serum) is the most accurate parameter to characterize drug penetration into the CSF...
January 31, 2018: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
Aitak Farzi, Esther E Fröhlich, Peter Holzer
The microbial ecosystem that inhabits the gastrointestinal tract of all mammals-the gut microbiota-has been in a symbiotic relationship with its hosts over many millennia. Thanks to modern technology, the myriad of functions that are controlled or modulated by the gut microbiota are beginning to unfold. One of the systems that is emerging to closely interact with the gut microbiota is the body's major neuroendocrine system that controls various body processes in response to stress, the hypothalamic-pituitary-adrenal (HPA) axis...
January 27, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Mariana Teixeira da Trindade, Hérida Regina Nunes Salgado
Ceftriaxone sodium is a third-generation semi-synthetic antibiotic belonging to the class of cephalosporins. Is administered only by parenteral route and has the ability to cross the blood-brain barrier. It has bactericidal action; its main activity is related to the Gram-negative bacteria, being also able to act against Gram-negative bacilli resistant to the first- and second-generation cephalosporins. The present study presents a survey of the characteristics, properties and analytical methods used for the determination of ceftriaxone sodium, for the gathering of data searches were carried out in scientific articles in the world literature, as well as in the official compendia...
January 29, 2018: Critical Reviews in Analytical Chemistry
Claire Gendrin, Sean Merillat, Jay Vornhagen, Michelle Coleman, Blair Armistead, Lisa Ngo, Anjali Aggarwal, Phoenicia Quach, Jacob Berrigan, Lakshmi Rajagopal
Group B Streptococcus (GBS) are encapsulated, β-hemolytic bacteria that are a common cause of infections in human newborns and certain adults. Two virulence factors important for GBS virulence are the sialic acid capsular polysaccharide that promotes immune evasion and the hemolytic pigment that induces host cell cytotoxcity. These virulence factors are often oppositely regulated by the CovR/CovS two-component system. Clinical GBS strains exhibiting hyperhemolysis and low capsule due to pathoadaptive covR/S mutations have been isolated from patients...
January 2, 2018: Journal of Infectious Diseases
Sergio B Socias, Florencia Gonzalez-Lizarraga, Cesar L Avila, Cecilia Vera, Leonardo Acuña, Julia E Sepulveda-Diaz, Elaine Del-Bel, Rita Raisman-Vozari, Rosana N Chehin
Neurodegenerative diseases are chronic and progressive disorders that affect specific regions of the brain, causing gradual disability and suffering that results in a complete inability of patients to perform daily functions. Amyloid aggregation of specific proteins is the most common biological event that is responsible for neuronal death and neurodegeneration in various neurodegenerative diseases. Therapeutic agents capable of interfering with the abnormal aggregation are required, but traditional drug discovery has fallen short...
December 11, 2017: Progress in Neurobiology
Anne K Braczynski, Marc A Brockmann, Torben Scholz, Jan-Philipp Bach, Jörg B Schulz, Simone C Tauber
BACKGROUND: Anterior sacral meningoceles are rare, and usually occur with other malformations of the posterior lower spine. While these are more frequently reported in pediatric cohorts, we report a case in an elderly woman. CASE PRESENTATION: We report on a 71 year-old woman with a recently diagnosed colorectal adenocarcinoma who presented with a severe bacterial meningitis. The cerebrospinal fluid cell count revealed a pleocytosis of 80,000 cells/μl and a severe disturbance of the blood-brain-barrier...
December 8, 2017: BMC Neurology
Liyuan Zhang, Ping Huang, Hui Chen, Wen Tan, Jiawei Lu, Wei Liu, Jingdong Wang, Shuyu Zhang, Wei Zhu, Jianping Cao, Ye Tian, Hongying Yang
Due to an increasing concern about radiation-induced cognitive deficits for brain tumor patients receiving radiation therapy, developing and evaluating countermeasures has become inevitable. Our previous study has found that minocycline, a clinical available antibiotics that can easily cross the blood brain barrier, mitigates radiation-induced long-term memory loss in rats, accompanied by decreased hippocampal neuron apoptosis. Thus, in the present study, we report an unknown mechanism underlying the neuroprotective effect of minocycline...
November 27, 2017: Scientific Reports
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
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
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
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
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
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
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
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
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...
January 2018: Biochimica et Biophysica Acta
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
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
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