Red flags for the early detection of spinal infection in back pain patients

© 2019 The Author(s). Background: Red flags are signs and symptoms that are possible indicators of serious spinal pathology. There is limited evidence or guidance on how red flags should be used in practice. Due to the lack of robust evidence for many red flags their use has been questioned. The aim was to conduct a systematic review specifically reporting on studies that evaluated the diagnostic accuracy of red flags for Spinal Infection in patients with low back pain. Methods: Searches were carried out to identify the literature from inception to March 2019. The databases searched were Medline, CINHAL Plus, Web of Science, Embase, Cochrane, Pedro, OpenGrey and Grey Literature Report. Two reviewers screened article texts, one reviewer extracted data and details of each study, a second reviewer independently checked a random sample of the data extracted. Results: Forty papers met the eligibility criteria. A total of 2224 cases of spinal infection were identified, of which 1385 (62%) were men and 773 (38%) were women mean age of 55 (± 8) years. In total there were 46 items, 23 determinants and 23 clinical features. Spinal pain (72%) and fever (55%) were the most common clinical features, Diabetes (18%) and IV drug use (9%) were the most occurring determinants. MRI was the most used radiological test and Staphylococcus aureus (27%), Mycobacterium tuberculosis (12%) were the most common microorganisms detected in cases. Conclusion: The current evidence surrounding red flags for spinal infection remains small, it was not possible to assess the diagnostic accuracy of red flags for spinal infection, as such, a descriptive review reporting the characteristics of those presenting with spinal infection was carried out. In our review, spinal infection was common in those who had conditions associated with immunosuppression. Additionally, the most frequently reported clinical feature was the classic triad of spinal pain, fever and neurological dysfunction. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Spinal infection: state of the art and management algorithm

Spinal infection is a rare pathology although a concerning rising incidence has been observed in recent years. This increase might reflect a progressively more susceptible population but also the availability of increased diagnostic accuracy. Yet, even with improved diagnosis tools and procedures, the delay in diagnosis remains an important issue. This review aims to highlight the importance of a methodological attitude towards accurate and prompt diagnosis using an algorithm to aid on spinal infection management. METHODS: Appropriate literature on spinal infection was selected using databases from the US National Library of Medicine and the National Institutes of Health. RESULTS: Literature reveals that histopathological analysis of infected tissues is a paramount for diagnosis and must be performed routinely. Antibiotic therapy is transversal to both conservative and surgical approaches and must be initiated after etiological diagnosis. Indications for surgical treatment include neurological deficits or sepsis, spine instability and/or deformity, presence of epidural abscess and upon failure of conservative treatment. CONCLUSIONS: A methodological assessment could lead to diagnosis effectiveness of spinal infection. Towards this, we present a management algorithm based on literature findings

Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a devastating and fatal motor neuron disease. Diagnosis typically occurs in the fifth decade of life and the disease progresses rapidly leading to death within ~ 2–5 years of symptomatic onset. There is no cure, and the few available treatments offer only a modest extension in patient survival. A protein central to ALS is the nuclear RNA/DNA-binding protein, TDP-43. In > 95% of ALS patients, TDP-43 is cleared from the nucleus and forms phosphorylated protein aggregates in the cytoplasm of affected neurons and glia. We recently defined that poly(ADP-ribose) (PAR) activity regulates TDP-43-associated toxicity. PAR is a posttranslational modification that is attached to target proteins by PAR polymerases (PARPs). PARP-1 and PARP-2 are the major enzymes that are active in the nucleus. Here, we uncovered that the motor neurons of the ALS spinal cord were associated with elevated nuclear PAR, suggesting elevated PARP activity. Veliparib, a small-molecule inhibitor of nuclear PARP-1/2, mitigated the formation of cytoplasmic TDP-43 aggregates in mammalian cells. In primary spinal-cord cultures from rat, Veliparib also inhibited TDP-43-associated neuronal death. These studies uncover that PAR activity is misregulated in the ALS spinal cord, and a small-molecular inhibitor of PARP-1/2 activity may have therapeutic potential in the treatment of ALS and related disorders associated with abnormal TDP-43 homeostasis

Does varicocele repair improve conventional semen parameters? A meta-analytic study of before-after data

Purpose The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. Materials and Methods The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). Results Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129–0.278; p<0.001; I2=83.62%, Egger’s p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474–1.706; p<0.001; I2=97.86%, Egger’s p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526–2.121; p<0.001; I2=97.88%, Egger’s p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318–1.968; p<0.001; I2=98.65%, Egger’s p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%–2.153%; p<0.001; I2=98.97%, Egger’s p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%–1.759%; p<0.001; l2=97.98%, Egger’s p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%–1.211%; p<0.001; I2=97.87%, Egger’s p=0.1864. Conclusions The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele. Keywords Controlled before-after studies; Infertility, male; Meta-analysis; Varicocel

Effect of ?-glutamylcysteine ethylester on the levels of c-fos mRNA expression, glutathione and reactive oxygen species formation in kainic acid excitotoxicity

PubMed ID: 20663035Objectives The aim of this study was to investigate the effect of ?-glutamylcysteine ethylester (GCEE), a precursor of glutathione biosynthesis, on the levels of glutathione, formation of reactive oxygen species and c-fos mRNA expression in rat hippocampus and cortex in kainic acid-induced excitotoxicity. Methods Sprague-Dawley rats were used and divided into four groups: control, kainic acid (10 mg/kg), GCEE (10 mg/kg) and kainic acid (10 mg/kg) + GCEE (10 mg/kg). Kainic acid and GCEE were administered to the rats intraperitoneally. The levels of glutathione and the expressions of c-fos mRNA in hippocampus and cortex tissues were determined using spectrophotometric and reverse transcription followed real-time PCR methods, respectively. Formation of reactive oxygen species was determined using dichlorofluorescin fluorescence in brain synaptosomes treated with kainic acid or GCEE in vitro. Key findings Kainic acid treatment significiantly upregulated the expression of c-fos mRNA in the hippocampus and cortex when compared to the control group. GCEE treatment significantly decreased the levels of c-fos mRNA in the cortex when compared to the kainic acid-treated group. GCEE treatment against kainic acid significantly increased the levels of glutathione in the cortex and hippocampus, and decreased the levels of formation of reactive oxygen species when compared to kainic acid-treated synaptosomes. Conclusions The increased levels of glutathione and the reduced levels of reactive oxygen species formation lead us to conclude that GCEE may be beneficial as a potential antioxidant against neurodegenerative processes where excitotoxicity is involved. © 2010 The Authors. Journal compilation

Neuroprotection by mefenamic acid against d-serine: Involvement of oxidative stress, inflammation and apoptosis

PubMed ID: 22369458Mefenamic acid, a non-steroidal antiinflammatory drug (NSAID), directly and dose-dependently exhibits neuroprotective activity. In our study, we investigated the effects of mefenamic acid against d-serine on oxidative stress in the hippocampus, cortex and cerebellum of rats. Furthermore, the potential inflammatory and apoptotic effects of d-serine and potential protective effect of mefenamic acid were determined at mRNA and protein levels of TNF-?, IL-1ß, Bcl-2 and Bax. We found that d-serine significantly increased oxidative stress, levels of inflammation-and apoptosis-related molecules in a region specific manner. Mefenamic acid treatment provided significant protection against the elevation of lipid peroxidation, protein oxidation, levels of TNF-?, IL-1ß and Bax. As a conclusion, we suggest that d-serine, as a potential neurodegenerative agent, may have a pivotal role in the regulation of oxidative stress, inflammation and apoptosis; and NSAIDs, such as mefenamic acid, may assist other therapeutics in treating disorders where d-serine-induced neurotoxic mechanisms are involved in. © 2012 Informa UK, Ltd.Scientific Research Foundation of Beijing Normal University: 09/ ECZ/019This study was supported by the Ege University Scientific Research Foundation (Project No: 09/ ECZ/019). G.A and E.T. acknowledge a scholarship for postgraduate students obtained from Turkish Scientific and Technological Council (TUBITAK). The authors also acknowledge the Pharmaceutical Sciences Research Centre (FABAL) of Ege University, Faculty of Pharmacy for equipmental support including membrane visualisation for protein analysis. -

Effect of mefenamic acid on some of the base excision repair enzymes against D-serine-induced neurotoxicity [D-serin ile indüklenen nörotoksisitede mefenamik asit’in baz eksizyon tamir enzimleri üzerine etkisi]

N-methyl-D-aspartate receptor (NMDAR) overactivation leads to free radical production, protein degradation, lipid peroxidation and DNA damage. Recently, nonsteroidal antiinflammatory drugs (NSAIDs) are suggested to be good candidates for the treatment of neurological insults. In this study, we aimed to evaluate the effect of mefenamic acid on 8-OHdG levels, the expression of poly(ADP ribose) polymerase-1 (PARP-1) and base excision repair (BER) enzymes; 8-oxoguanine DNA glycosylase 1 (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1) against D-serine. Adult Sprague-Dawley rats were divided into four groups: (i) the control (n=6); (ii) D-serine (n=6); (iii) Mefenamic acid (n=6); (iv) D-serine+Mefenamic acid (n=6). Rats were decapitated 6 hours after the injections. The mRNA and protein expression levels were determined by real-time PCR and western blot techniques, respectively. D-serine increased APE1 mRNA, PARP-1 mRNA and 8-OHdG levels. APE1 and PARP-1 genes were significantly upregulated by mefenamic acid. Protein expression profiles were also consistent with mRNA levels. However neither mRNA nor protein levels of OGG1 were affected by D-serine or mefenamic acid. Our results suggest that NMDA/D-serine signaling triggers DNA repair mechanisms and oxidative DNA damage simultaneously. We may conclude that mefenamic acid have a potential neuroprotective effect and assist to repair NMDAR-mediated DNA damage via modulating DNA repair mechanisms. © 2016, Turkish Pharmacists Association. All rights reserved

Nicotinamide treatment reduces the levels of oxidative stress, apoptosis, and PARP-1 activity in Aß(1-42)-induced rat model of Alzheimer's disease

PubMed ID: 24151909The underlying mechanisms of Alzheimer's Disease (AD) are still unclear. It is suggested that poly(ADP-ribose) polymerase-1 (PARP-1) overactivation can cause neuroinflammation and cell death. In this study we searched the effects of nicotinamide (NA), endogenous PARP-1 inhibitor, on oxidative stress, apoptosis, and the regulation of PARP-1 and nuclear factor kappa B (NF-?B) in amyloid beta peptide (1-42) (Aß(1-42))-induced neurodegeneration. Sprague-Dawley rats were divided into four groups as control, Aß(1-42), Aß(1-42) + NA(100 and 500 mg/kg). All groups were stereotaxically injected bilaterally into the hippocampus with Aß(1-42) or saline. After surgery NA administrations were made intraperitoneally (ip) for 7 days. In order to investigate the effects of Aß(1-42) and NA, protein carbonyls, lipid peroxidation, reactive oxygen species (ROS) production, glutathione (GSH) levels, activities of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), mitochondrial function, mRNA and protein levels of PARP-1, NF-?B, p53, Bax, and Bcl-2 were measured in specific brain regions such as cortex and hippocampus. Aß(1-42) treatment only increased the oxidative stress parameters and caused decline in antioxidant enzyme activities, mitochondrial function, and GSH levels. Also, overexpression of PARP-1, NF-?B, p53, Bax, and the decreased levels of Bcl-2 were observed in Aß(1-42)-treated group. NA treatments against Aß(1-42)-upregulated Bcl-2 and downregulated PARP-1, NF-?B, p53, and Bax levels. NA treatments also decreased the oxidative stress parameters and elevated antioxidant enzyme activities, GSH levels, and mitochondrial function against Aß(1-42) treatment. These data suggest that NA may have a therapeutic potential in neurodegenerative processes due to the decreased levels of oxidative stress, apoptosis, and PARP-1 activity. © 2013 Informa UK, Ltd.Foundation for the National Institutes of Health Scientific Research Foundation of Beijing Normal University: 10/ECZ/011Male Sprague – Dawley rats (200 – 250 g) were used for present study. Animals were obtained from the Experimental Research Center of Ege University and maintained on a 12:12 h light – dark cycle and given continuous access to food and water. All procedures were approved by the Utilization Committee of Ege University (Ref. No: 2010-35) and confirmed by the National Institutes of Health Guide for the Care and Use of Laboratory Animals. All efforts were made to minimize animal suffering and to reduce the number of animals used. -- The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper. This study was supported by the Ege University Scientific Research Foundation (Project No: 10/ECZ/011). E.T. acknowledged a scholarship for postgraduate students obtained from Turkish Scientific and Technological Council (TUBITAK). The authors also acknowledged the Pharmaceutical Sciences Research Centre (FABAL) of Ege University, Faculty of Pharmacy for equipmental support in the determination of protein expressions. -