scholarly journals Altered levels of interleukins and neurotrophic growth factors in mood disorders and suicidality: an analysis from periphery to central nervous system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bharathi S. Gadad ◽  
Javier Vargas-Medrano ◽  
Enrique Ivan Ramos ◽  
Katherine Najera ◽  
Matthew Fagan ◽  
...  

AbstractInterleukins and neurotrophins levels are altered in the periphery of patients with major depression and suicidal behavior, however it is not clear if similar abnormalities occur in the central nervous system. Our objective was to examine the association of IL-6, IL-1β, BDNF, and GDNF levels between postmortem plasma, cerebrospinal fluid (CSF), and brain tissue in a heterogeneous diagnostic subject groups including normal controls, mood disorders only, mood disorders with AUD/SUD (alcohol abuse disorder, substance abuse disorder), and AUD/SUD without mood disorders. To address these questions we collected postmortem plasma (n = 29), CSF (n = 28), and brain (BA10) (n = 57) samples from individuals with mood disorder, mood disorder with AUD/SUD, AUD/SUD and normal controls. These samples were analyzed using a multiplex based luminex assay with a customized 4-plex cytokine/interleukins- IL-6, IL-1β, BDNF, and GDNF human acute phase based on xMAP technology platform. Protein levels were determined using a Luminex 200 instrument equipped with Xponent-analyzing software. We observed IL-6 (p = 2.1e-07), and GDNF (p = 0.046) were significantly correlated between brain and CSF. In addition, IL-6 (p = 0.031), were significantly correlated between brain and plasma. Overall diagnostic group analysis showed a significant difference with brain GDNF, p = 0.0106. Pairwise comparisons showed that GDNF level is—39.9 ± 12 pg/ml, p = 0.0106, was significantly higher than in the brains derived from mood disorders compared to normal controls, —23.8 ± 5.5 pg/ml, p = 0.034. Brain BDNF was higher in suicide (p = 0.0023), males compared to females (p = 0.017), and psychiatric medication treated vs. non-treated (p = 0.005) individuals. Overall, we demonstrate that blood IL-6, GDNF and BDNF could be informative peripheral biomarkers of brain biology associated with mood disorders, substance disorders, and suicide.

2019 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Dini Kesuma

Synthesis of the 4-chlorobenzoylthiourea compound was carried out by acylating thiourea with 4-chlorobenzoyl chloride. The 4-chlorobenzoylthiourea compound  will increase the lipophilic and the electronic properties other than the lead compounds of benzoylthiourea in order to, by expectation, raise the central nervous system depressant as well. The lipophilic would affect the ability of the compounds in penetrating biological membranes, which is highly dependent on the solubility of the drug within lipid/water. Log P is the most common method used in determining the parameter value. This experiment was to mix two dissolvents (octanol and water) which are immissible. The both levels of the compounds were carefully observed by a spectrophotometer UV-Vis. From the test, the result of log P value of the 4-chlorobenzoylthiourea compound was 2.32, while the theoretical log P value of the compounds, by using the π Hansch-Fujita method is 1.62 and the f Rekker-Mannhold method is 2.225. Consequently, the result of the test shows that there is a significant difference between the progress experiment and both theoretical log P methods. Moreover, in the test of the central nervous system depressant through the potentiation test to thiopental using mice indicates that the 4-chlorobenzoylthiourea compound have potentiation effects to thiopental compared to the lead compounds of benzoylthiourea.


MedAlliance ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 14-24

The clinic and diagnostics of tuberculosis meningitis (TM) in 926 patients treated in St. Petersburg hospitals in 1965–1994 (group 1) and in 1995–2018 (group 2) is presented. The TM clinic is demonstrated to be determined by the form of tuberculosis and its characteristic generalization nature in the presence of repeated waves of bacteremia and allergic vasculitis of greater or lesser severity. There is clinical peculiarity of TM in primary pulmonary tuberculosis and its early large-focal and late miliar generalization, as well as in hematogenous tuberculosis. In patients of the 1st and 2nd groups the TM clinic shows in some respects a noticeable similarity, in others — a significant difference. Despite the typical symptoms, early diagnosis of TM took place in less than 20% of patients. Clinical examples illustrating the unusual development of TM, contrasting with its usual course, are given. A number of objective and subjective factors contributing to the adverse evolution of TM and its lethal outcome are discussed. These include the peculiarity of modern tuberculosis, especially when associated with HIV infection, as well as medical errors associated with ignorance of the pathogenesis of tuberculosis and failure to comply with the minimum examination for tuberculosis.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Florian Scheichel ◽  
Franz Marhold ◽  
Daniel Pinggera ◽  
Barbara Kiesel ◽  
Tobias Rossmann ◽  
...  

Abstract Background Corticosteroid therapy (CST) prior to biopsy may hinder histopathological diagnosis in primary central nervous system lymphoma (PCNSL). Therefore, preoperative CST in patients with suspected PCNSL should be avoided if clinically possible. The aim of this study was thus to analyze the difference in the rate of diagnostic surgeries in PCNSL patients with and without preoperative CST. Methods A multicenter retrospective study including all immunocompetent patients diagnosed with PCNSL between 1/2004 and 9/2018 at four neurosurgical centers in Austria was conducted and the results were compared to literature. Results A total of 143 patients were included in this study. All patients showed visible contrast enhancement on preoperative MRI. There was no statistically significant difference in the rate of diagnostic surgeries with and without preoperative CST with 97.1% (68/70) and 97.3% (71/73), respectively (p = 1.0). Tapering and pause of CST did not influence the diagnostic rate. Including our study, there are 788 PCNSL patients described in literature with an odds ratio for inconclusive surgeries after CST of 3.3 (CI 1.7–6.4). Conclusions Preoperative CST should be avoided as it seems to diminish the diagnostic rate of biopsy in PCNSL patients. Yet, if CST has been administered preoperatively and there is still a contrast enhancing lesion to target for biopsy, surgeons should try to keep the diagnostic delay to a minimum as the likelihood for acquiring diagnostic tissue seems sufficiently high.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Canyang Zhan ◽  
Lihua Chen ◽  
Lingling Hu

Abstract Background Neonatal meningitis is a severe infectious disease of the central nervous system with high morbidity and mortality. Ureaplasma parvum is extremely rare in neonatal central nervous system infection. Case presentation We herein report a case of U. parvum meningitis in a full-term neonate who presented with fever and seizure complicated with subdural hematoma. After hematoma evacuation, the seizure disappeared, though the fever remained. Cerebrospinal fluid (CSF) analysis showed inflammation with CSF pleocytosis (1135–1319 leukocytes/μl, mainly lymphocytes), elevated CSF protein levels (1.36–2.259 g/l) and decreased CSF glucose (0.45–1.21 mmol/l). However, no bacterial or viral pathogens in either CSF or blood were detected by routine culture or serology. Additionally, PCR for enteroviruses and herpes simplex virus was negative. Furthermore, the CSF findings did not improve with empirical antibiotics, and the baby experienced repeated fever. Thus, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the infection. U. parvum was identified by mNGS in CSF samples and confirmed by culture incubation on mycoplasma identification medium. The patient’s condition improved after treatment with erythromycin for approximately 5 weeks. Conclusions Considering the difficulty of etiological diagnosis in neonatal U. parvum meningitis, mNGS might offer a new strategy for diagnosing neurological infections.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21534-e21534
Author(s):  
Achuta Kumar Guddati ◽  
Takefumi Komiya ◽  
Picon Hector ◽  
Allan N. Krutchik ◽  
Gagan Kumar

e21534 Background: Patients with melanoma frequently develop central nervous system metastases. Oligometastatic disease is often treated either by surgical resection or by stereotactic radiotherapy. This study investigates the trends and clinical outcomes of patients with melanoma who have undergone surgical procedures on the central nervous system during their hospitalization. Methods: A retrospective cohort study was performed based on admissions of adult patients who underwent craniectomy/surgical resection for metastatic melanoma from 2002 -2014 using the Nationwide Inpatient Sample database. The primary outcome measure was all-cause in-hospital mortality. Secondary outcomes included length of hospital stay(LOS) and discharge disposition (home/home with health care and skilled nursing facilities/long term acute care (SNF/LTAC)). Factors associated with in-hospital mortality were examined by multivariable logistic regression. We adjusted for patient and hospital characteristics, payer, and comorbid conditions. We also examined trends of mortality for the study years. P was kept at 0.05. Results: There were an estimated 5972 discharges of patients with melanoma undergoing craniectomy/surgical resection during the study period. Patients undergoing surgical interventions were typically males (69%) and whites (79%). 98% of procedures were performed at teaching hospitals. Unadjusted all-cause in-hospital mortality was 3.1%. There was no significant difference in mortality over 13 years. Age, gender, and race were not associated with increased in-hospital mortality. Median LOS was 5 days (IQR 3-9 days). LOS was longer in elderly and those with higher Charlson co-morbid index. Of the survivors, 76% were discharged to home or with home healthcare while 24% were discharged to SNF/LTAC. Patients with age > 65 (OR 2.9; 95%CI 2.2-3.9, p < 0.001) and those with higher Charlson co-morbid index (OR 1.2; 95%CI 1.1-1.3) had higher odds for being discharged to SNF/LTAC. Conclusions: Patients who undergo craniectomy/surgical resection for melanoma have a low in-hospital mortality rate. One quarter of patients are discharged to SNF/LTAC.


2020 ◽  
Vol 7 ◽  
Author(s):  
Timur Koca ◽  
Aylin Fidan Korcum ◽  
Yasemin Şengün ◽  
Melek Gamze Aksu ◽  
Mine Genç

Aim: In this study, we aimed to evaluate the overall and progression-free survival, the radiotherapy process and the early and late adverse effects in patients who underwent radiotherapy (RT) for primary nervous system lymphoma in our clinic.Method: Between January 2010 and September 2019, 16 patients who received radiotherapy due to primary central nervous system lymphoma in our clinic were examined according to their statistically significant differences in terms of survival and side effects.Results: The median disease-free survival of the patients was 6 months, and the median overall survival was 12.5 months. 18.75% of the patients could not receive chemotherapy but only radiotherapy. Radiotherapy doses were range from 2600 to 5000 cGy. When patients were evaluated in terms of radiotherapy dose, field size and chemotherapy, no statistically significant difference in overall survival was detected. Cognitive disorders were observed as the most common late side effects while the most common acute side effects in patients were headaches.Conclusion: In the treatment of primary central nervous system lymphoma, changes in radiotherapy portals and radiotherapy doses can be predicted in patients who received high-dose methotrexate chemotherapy or not. Furthermore, it has been considered that more comprehensive studies are needed to increase the success of treatment and provide standardization in treatment, especially in patients with elderly and comorbid diseases.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yingying Zhu ◽  
Xiaohui Gong ◽  
Zhiling Li ◽  
Danni Wang ◽  
Chongbing Yan

Objective: The aim of the study was to observe the clinical efficacy and safety of intravenous and oral sequential treatment with voriconazole for Candida central nervous system (CNS) infection in premature infants.Methods: The study included retrospective analysis of the clinical data of six premature infants with Candida CNS infection admitted to the neonatology department in Shanghai Children’s Hospital between November 2016 and November 2019. By reviewing the characteristics of voriconazole based on the literature, it showed that infants without gastrointestinal dysfunction could be effectively treated by intravenous and oral sequential therapy with voriconazole (both 7 mg/kg/dose, every 12 h). Clinical manifestations, the time required for the cerebrospinal fluid (CSF), blood culture, nonspecific infection markers such as platelets and C-reactive protein (CRP) to turn normal, and drug-related side effects were observed and recorded in the process of treatment. All data were statistically analyzed by T test and Mann–Whitney U test.Results: A total of six premature infants were diagnosed with Candida CNS infection, two cases were diagnosed by a positive CSF culture and four cases were clinically diagnosed. Blood culture was positive for Candida in five cases. Among the 6 patients, 4 cases were Candida albicans and 2 cases were Candida parapsilosis. All the six cases were cured. After 3–5 days of treatment, symptoms such as lethargy, apnea, and feeding intolerance were improved and disappeared; a repeated blood culture turned negative in 3–7 days; CSF returned to normal in 15 ± 9 days on an average. Brain abscess, meningeal inflammation, and other infectious lesions were cleared on cranial magnetic resonance imaging (MRI) after treatment. The average total course of voriconazole was 61 ± 29 days, and the average oral treatment was 28 ± 15 days. No Candida recurrence was found during the treatment, and no drug-related side effects such as skin rash, liver and kidney function impairment, or visual abnormalities were found. The white blood cells, CSF glucose/plasma glucose ratio, and protein in CSF were significantly improved after the treatment (p &lt; 0.05). No statistically significant difference was identified in the liver and kidney function indexes (p &gt; 0.05).Conclusion: Voriconazole is a relatively safe and effective alternative treatment for Candida CNS infection in preterm infants. No severe drug-related side effects were detected.


2012 ◽  
Vol 27 (11) ◽  
pp. 1408-1425 ◽  
Author(s):  
Gulay Alper

Acute disseminated encephalomyelitis is an immune-mediated inflammatory and demyelinating disorder of the central nervous system, commonly preceded by an infection. It principally involves the white matter tracts of the cerebral hemispheres, brainstem, optic nerves, and spinal cord. Acute disseminated encephalomyelitis mainly affects children. Clinically, patients present with multifocal neurologic abnormalities reflecting the widespread involvement in central nervous system. Cerebrospinal fluid may be normal or may show a mild pleocytosis with or without elevated protein levels. Magnetic resonance image (MRI) shows multiple demyelinating lesions. The diagnosis of acute disseminated encephalomyelitis requires both multifocal involvement and encephalopathy by consensus criteria. Acute disseminated encephalomyelitis typically has a monophasic course with a favorable prognosis. Multiphasic forms have been reported, resulting in diagnostic difficulties in distinguishing these cases from multiple sclerosis. In addition, many inflammatory disorders may have a similar presentation with frequent occurrence of encephalopathy and should be considered in the differential diagnosis of acute disseminated encephalomyelitis.


2021 ◽  
Vol 21 ◽  
Author(s):  
Minyong Peng ◽  
Shan Li ◽  
Hui Xiang ◽  
Wen Huang ◽  
Weiling Mao ◽  
...  

<P>Background: Little is known about the efficacy of programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitors in patients with central nervous system (CNS) metastases. <P> Objective: Assess the difference in efficacy of PD-1 or PD-L1 inhibitors in patients with and without CNS metastases. <P> Methods: From inception to March 2020, PubMed and Embase were searched for randomized controlled trials (RCTs) about PD-1 or PD-L1 inhibitors. Only trails with available hazard ratios (HRs) for overall survival (OS) of patients with and without CNS metastases simultaneously would be included. Overall survival hazard ratios and their 95% confidence interval (CI) were calculated, and the efficacy difference between these two groups was assessed in the meantime. <P> Results: 4988 patients (559 patients with CNS metastases and 4429 patients without CNS metastases) from 8 RCTs were included. In patients with CNS metastases, the pooled HR was 0.76 (95%CI, 0.62 to 0.93), while in patients without CNS metastases, the pooled HR was 0.74 (95%CI, 0.68 to 0.79). There was no significant difference in efficacy between these two groups (Χ=0.06 P=0.80). <P> Conclusion: With no significant heterogeneity observed between patients with or without CNS metastases, patients with CNS metastases should not be excluded from PD-1 or PD-L1 blockade therapy. Future research should permit more patients with CNS metastases to engage in PD-1 or PD-L1 blockade therapy and explore the safety of PD-1 or PD-L1 inhibitors in patients with CNS metastases.</P>


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