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      The effect of doxycycline on neuron-specific enolase in patients with traumatic brain injury: a randomized controlled trial

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          Abstract

          Objective:

          We aimed to examine the effect of doxycycline on serum levels of neuron-specific enolase (NSE), a marker of neuronal damage in traumatic brain injury (TBI) patients.

          Methods:

          Patients were randomly assigned into two groups ( n = 25 each) to receive either placebo or doxycycline (200 mg daily), with their standard management for 7 days.

          Results:

          NSE serum levels in the doxycycline and control groups on day 3 were 14.66 ± 1.78 versus 18.09 ± 4.38 ng/mL, respectively ( p = 0.008), and on day 7 were 12.3 ± 2.0 versus 16.43 ± 3.85 ng/mL, respectively ( p = 0.003). Glasgow Coma Scale (GCS) on day 7 was 11.90 ± 2.83 versus 9.65 ± 3.44 in the doxycycline and control groups, respectively ( p = 0.031). NSE serum levels and GCS scores were negatively correlated ( r = −0.569, p < 0.001).

          Conclusion:

          Adjunctive early use of doxycycline might be a novel option that halts the ongoing secondary brain injury in patients with moderate to severe TBI. Future larger clinical trials are warranted to confirm these findings.

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          Most cited references46

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          Inflammation and neuroprotection in traumatic brain injury.

          Traumatic brain injury (TBI) is a significant public health concern that affects individuals in all demographics. With increasing interest in the medical and public communities, understanding the inflammatory mechanisms that drive the pathologic and consequent cognitive outcomes can inform future research and clinical decisions for patients with TBI.
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            Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections.

            The entry of anti-infectives into the central nervous system (CNS) depends on the compartment studied, molecular size, electric charge, lipophilicity, plasma protein binding, affinity to active transport systems at the blood-brain/blood-cerebrospinal fluid (CSF) barrier, and host factors such as meningeal inflammation and CSF flow. Since concentrations in microdialysates and abscesses are not frequently available for humans, this review focuses on drug CSF concentrations. The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier. When several equally active compounds are available, a drug which comes close to these physicochemical and pharmacokinetic properties should be preferred. Several anti-infectives (e.g., isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones) reach a CSF-to-serum ratio of the areas under the curves close to 1.0 and, therefore, are extremely valuable for the treatment of CNS infections. In many cases, however, pharmacokinetics have to be balanced against in vitro activity. Direct injection of drugs, which do not readily penetrate into the CNS, into the ventricular or lumbar CSF is indicated when other effective therapeutic options are unavailable.
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              Is Open Access

              Antibiotics, gut microbiota, and Alzheimer’s disease

              Alzheimer’s disease (AD) is a neurodegenerative disease whose various pathophysiological aspects are still being investigated. Recently, it has been hypothesized that AD may be associated with a dysbiosis of microbes in the intestine. In fact, the intestinal flora is able to influence the activity of the brain and cause its dysfunctions. Given the growing interest in this topic, the purpose of this review is to analyze the role of antibiotics in relation to the gut microbiota and AD. In the first part of the review, we briefly review the role of gut microbiota in the brain and the various theories supporting the hypothesis that dysbiosis can be associated with AD pathophysiology. In the second part, we analyze the possible role of antibiotics in these events. Antibiotics are normally used to remove or prevent bacterial colonization in the human body, without targeting specific types of bacteria. As a result, broad-spectrum antibiotics can greatly affect the composition of the gut microbiota, reduce its biodiversity, and delay colonization for a long period after administration. Thus, the action of antibiotics in AD could be wide and even opposite, depending on the type of antibiotic and on the specific role of the microbiome in AD pathogenesis. Alteration of the gut microbiota can induce changes in brain activity, which raise the possibility of therapeutic manipulation of the microbiome in AD and other neurological disorders. This field of research is currently undergoing great development, but therapeutic applications are still far away. Whether a therapeutic manipulation of gut microbiota in AD could be achieved using antibiotics is still not known. The future of antibiotics in AD depends on the research progresses in the role of gut bacteria. We must first understand how and when gut bacteria act to promote AD. Once the role of gut microbiota in AD is well established, one can think to induce modifications of the gut microbiota with the use of pre-, pro-, or antibiotics to produce therapeutic effects.
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                Author and article information

                Contributors
                Journal
                Ther Adv Chronic Dis
                Ther Adv Chronic Dis
                TAJ
                sptaj
                Therapeutic Advances in Chronic Disease
                SAGE Publications (Sage UK: London, England )
                2040-6223
                2040-6231
                23 June 2021
                2021
                : 12
                : 20406223211024362
                Affiliations
                [1-20406223211024362]Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Mansoura University, Mansoura, El-Dakahelia, Egypt
                [2-20406223211024362]Emergency Medicine and Traumatology Department, Faculty of Medicine, Tanta University, Tanta, El-Gharbia, Egypt
                [3-20406223211024362]Clinical Pharmacy and Pharmacy Practice Department - Faculty of Pharmacy, Damanhour University, Elchorniash Street, Damanhour, Elbehairah 31527, Egypt
                Author notes
                Author information
                https://orcid.org/0000-0002-5983-3993
                Article
                10.1177_20406223211024362
                10.1177/20406223211024362
                8246481
                34262678
                38f28276-485f-4631-8a31-baec8bd52158
                © The Author(s), 2021

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 19 February 2021
                : 13 May 2021
                Categories
                Original Research
                Custom metadata
                January-December 2021
                ts1

                brain injury biomarkers,doxycycline,neuron specific enolase,secondary brain injury,traumatic brain injury

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