Effects of mulberry extract on the liver pathology and serum biochemical parameters in carmustine administrated rats

BACKGROUND: Carmustine is a chemotherapeutic agent that is mainly used in the treatment of glioblastoma and can cause toxic effects on various organs, including the liver. The white mulberry extract has anti-apoptotic and anti-oxidant effects. OBJECTIVE: The study aimed at investigating the effects of the dried white mulberry extract on the pathology, apoptosis, and oxidative stress in the liver, as well as the levels of serum adenosine deaminase, glutathione peroxidase, superoxide dismutase, ceruloplasmin, paraoxonase, and malondialdehyde in carmustine-administrated rats. METHODS: Forty-two rats divided into six groups were used in this study. BCNU was administrated intraperitoneally (IP) (5 mg/kg body weight (BW)/week) for 10 weeks to the BCNU and BCNU-DWME groups. DWME was administered (600 mg/kg-BW by oral gavage) daily for 10 weeks to the DWME and BCNU-DWME groups. After the experimental procedure, histopathological, immunohistochemical, and biochemical analyses were performed. RESULTS: Carmustine caused biliary hyperplasia at a dose of 5 mg/kg. However, the mulberry extract was not effective in alleviating this pathology. Furthermore, the administration of carmustine induced apoptosis in hepatocytes, and the mulberry extract had an anti-apoptotic effect. Carmustine increased the 8-OHdG activity in the liver, and dried mulberry extract ameliorated this activity. Although there was no significant difference in the serum oxidative stress parameters between the groups, carmustine significantly increased the adenosine deaminase activity during the recovery period, while mulberry extracts partially ameliorated these effects in the recovery period. CONCLUSIONS: Dried white mulberry extract has anti-apoptotic and anti-oxidative effects against carmustine-induced toxicity.

Changes of adenosine deaminase activity in serum and saliva around parturition in sows with and without postpartum dysgalactia syndrome

Background Postpartum dysgalactia syndrome (PDS) is associated with a significantly higher activation of the inflammatory and stress response at parturition than in the healthy sow. Therefore, reliable and possibly non-invasive biomarkers for substantial increases of inflammation are searched to support the PDS diagnosis. This report studies the possible changes of the inflammatory marker enzyme adenosine deaminase (ADA) in serum and saliva of 38 PDS positive sows (PDS+) and 38 healthy sows (PDS-). Sampling was performed every 24 h from 60 h before to 36 h after parturition. Isoenzyme 1 (ADA1) and isoenzyme 2 (ADA2), as well as total ADA (tADA), were measured and their statistical association with several serum and saliva biomarkers of inflammation and stress was investigated. Results Compared to a baseline (60 to 36h prepartum), salivary activities of ADA1, ADA2 and tADA increased significantly over time in both PDS+ and PDS- sows, reaching their peaks after parturition. In serum from PDS- sows, no changes were observed over time in either ADA1, ADA2 or tADA. In PDS+ sows, serum ADA2 activity decreased temporarily after parturition followed by a significant increase compared to baseline. ADA1, ADA2 and tADA were all significantly associated with several inflammatory biomarkers and ADA1 in serum was associated with serum cortisol. Although serum activity was higher in PDS+ than in PDS- sows, the differences were not statistically significant. Further, no difference was noted between the groups in the analyses of saliva. Conclusions Salivary ADA1 and ADA2 increased in all sows after parturition, potentially as a response to the postpartum inflammation. However, no difference in the activity of ADA1, ADA2 and tADA were found between PDS+ and PDS- sows indicating inability to diagnose PDS under the conditions described in this report.

Serum Biomarker Profile Including CCL1, CXCL10, VEGF, and Adenosine Deaminase Activity Distinguishes Active From Remotely Acquired Latent Tuberculosis

IntroductionThere is an urgent medical need to differentiate active tuberculosis (ATB) from latent tuberculosis infection (LTBI) and prevent undertreatment and overtreatment. The aim of this study was to identify biomarker profiles that may support the differentiation between ATB and LTBI and to validate these signatures.Materials and MethodsThe discovery cohort included adult individuals classified in four groups: ATB (n = 20), LTBI without prophylaxis (untreated LTBI; n = 20), LTBI after completion of prophylaxis (treated LTBI; n = 20), and healthy controls (HC; n = 20). Their sera were analyzed for 40 cytokines/chemokines and activity of adenosine deaminase (ADA) isozymes. A prediction model was designed to differentiate ATB from untreated LTBI using sparse partial least squares (sPLS) and logistic regression analyses. Serum samples of two independent cohorts (national and international) were used for validation.ResultssPLS regression analyses identified C-C motif chemokine ligand 1 (CCL1), C-reactive protein (CRP), C-X-C motif chemokine ligand 10 (CXCL10), and vascular endothelial growth factor (VEGF) as the most discriminating biomarkers. These markers and ADA(2) activity were significantly increased in ATB compared to untreated LTBI (p ≤ 0.007). Combining CCL1, CXCL10, VEGF, and ADA2 activity yielded a sensitivity and specificity of 95% and 90%, respectively, in differentiating ATB from untreated LTBI. These findings were confirmed in the validation cohort including remotely acquired untreated LTBI participants.ConclusionThe biomarker signature of CCL1, CXCL10, VEGF, and ADA2 activity provides a promising tool for differentiating patients with ATB from non-treated LTBI individuals.

ADENOSINE DEAMINASE LEVEL IN DRUG RESISTANT TUBERCULOSIS

Tuberculosis (TB) remains one of the health problems in Nigeria and worldwide. Adenosine Deaminase acts in proliferation and differentiation of lymphocyte, especially T lymphocyte. It also acts in maturation of monocytes transforming them to macrophage. Adenosine Deaminase is a significant indicator of active cellular immunity. Adenosine Deaminase has been proposed to be a useful surrogate marker for TB because it can be detected in body fluids such as pleural, pericardial and peritoneal fluid. This study aimed to determine the relationship between Adenosine Deaminase and drug Resistant Tuberculosis (DR-TB) among patients attending Tuberculosis Clinic in Government Chest Hospital, Jericho, Oyo State, Nigeria. Methodology: A prospective case-control study involving thirty (30) Multi-Drug Resistance Tuberculosis patients and thirty (30) apparently healthy participants in Tuberculosis Clinic in Government Chest Clinic Hospital, Jericho, Oyo State, Nigeria. Theparticipants socio-demographic data was obtained using questionnaire. Sputum samples were collected from each patient from the two groups of participants in leak proof screw capped specimen containers. About 5 mL of venous blood sample was collected from the antecubital fossa of the study participants into vacutainer plain tubes. Sputum samples collected were analysed for Mycobacterium tuberculosis using Gene Xpert. Blood sample collected was analyzed for Adenosine Deaminase using ELISA method. The prevalence of MDR-TB was 0.18%, majority of MDR-TB were within age of 15-30 years with mean age 36.30±13.40 years with female having 63.3% and male 36.7%. Among MDR-TB, the mean±SD Adenosine Deaminase activity was 37.67±15.25 IU/L and among Healthy controls, the mean±SD of Adenosine Deaminase was 12.26±5.11 IU/L. There was significance increased in ADA activity among MDR-TB participants when compared to Healthy controls at p-value<0.05 (p=0.001). ADA level of 18 IU/L cut off point has a sensitivity of 90.0%, specificity of 87.0% and diagnostic accuracy of 88.0%. In conclusion, there was moderately high prevalence of MDR-TB among the study participants. There was increased in ADA levels among MDR-TB. High sensitivity and specificity of ADA activity was observed among MDR-TB. This might be a useful alternative test to diagnose and rule out drug resistance tuberculosis.

Adenosine-regulated mechanisms in the pathogenesis of ventilation disorders in patients with pulmonary tuberculosis

Uncovering involvement of the purinergic system in the pathogenesis of ventilation disorders (VD) may provide additional information about the pathophysiological mechanisms leading to the development of VD in pulmonary tuberculosis (PT). The aim was to identify a relationship between the parameters of adenosine metabolism, inflammatory response and altered ventilation metabolism in PT patients. Materials and methods. Obstructive and mixed PT patients were assigned to subgroups with/without VD for assessing adenosine deaminase activity (ADA-1, 2) in serum, mononuclear cells, neutrophils; ecto-5’-nucleotidase (ecto-5’-NT); CD26 (dipeptidyl peptidase-4, DPP-4), phagocyte oxidative burst measured by NO generation. Results. PT patients showed decreased ADA-1 and CD26 (DPP-4), but increased ADA-2. Elevated intracellular adenosine concentration was found in mononuclear cells in patients lacking VD, whereas patients with mixed and obstructive VD — had it in neutrophils. Mononuclear cells of patients with PT lacking VD as well as with obstructive VD type had decreased NO3– concentration. Neutrophil hyperactivity was recorded in all groups of PT patients. Patients with PT lacking VD as well as with mixed VD type showed that the parameters of external respiration were associated with activity of extra-/intracellular ADA, whereas obstructive VD was caused by excessive formation of serum adenosine. Changes in respiratory function in PT were associated with decreased level of serum NO radicals, impaired nitrogen-dependent bactericidal phagocyte activity, and overproduced neutrophil oxygen radicals. Conclusion. Purinergic regulation is involved in regulating inflammatory and compensatory processes in PT patients as well as impaired ventilation efficiency. The most severe respiratory disorders observed in PT patients with mixed VD type are associated with the most prominent changes in nucleotidase activity, particularly ecto-ADA-2 and DPP-4/CD26.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy in Children: A Retrospective Study

Objective: To describe the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy in children.Method: Data from 11 pediatric patients with autoimmune GFAP astrocytopathywas retrospectively analyzed.Results: All of the patients showed encephalitis and meningoencephalitis or meningoencephalomyelitis with or without myelitis, include fever (45.4%), headaches (27.3%), dizziness (18.2%), drowsiness (18.2%) and mental disorders (18.2%). Cerebrospinal fluid (CSF) were detected in all patients. The white cell counts (WBC) (90.9%), lactic dehydrogenase levels (72.7%), protein level (36.4%), and adenosine deaminase activity (ADA) level (27.3%) were elevated, and the CSF glucose levels (72.7%) were slightly reduced. Nine patients (90%) were found to have brain abnormalities, of which five (50.0%) patients had abnormal symmetrical laminar patterns or line patterns hyperintensity lesions on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images in the basal ganglia, hypothalamus, subcortical white matter and periventricular white matter. The linear radial enhancement pattern of the cerebral white matter was only seen in two patients, the most common being abnormal enhancement of leptomeninges (50%). Five patients had longitudinally extensive spinal cord lesions.Conclusion: The findings of pediatric patients with autoimmune GFAP astrocytopathy is different from the previous reports.

Function of Serum Adenosine Deaminase as an Indicator of Immune Status in HIV Patients treated with Combination Antiretroviral Therapy

Acquired immunodeficiency syndrome (AIDS) is one of the greatest public health and social problems threatening the human race. The trend of annual AIDS deaths is showing a steady decline since the implementation of the free Anti-Retroviral Therapy (ART) program in India (2004). HIV infection is characterized by replication of virus by abnormal non specific immune activation and persistent inflammation. Adenosine deaminase (ADA) has a cytokine-like co-stimulatory role in T cell proliferation which is independent of catalytic activity. Therefore, we decided to study the role of ADA as an indicator of immune status in HIV patients treated with combination antiretroviral therapy (cART). Adenosine deaminase activity (ADA) in HIV patients was estimated before and after 3 months interval of antiretroviral therapy (ART) up to 9 months. The study included 150 HIV positive patients between age group of 20-50 years from ICTC (Integrated Counseling and Testing Centre) and ART centre. Venous blood samples were collected in plain bulb to estimate serum ADA activity before and after 3 months interval upto 9 months of ART. Serum ADA activity was estimated using colorimetric method of Giusti and Galanti. Activity of serum ADA was significantly raised before and after 3 months interval of ART with decrease in CD4 cell count. After 6 months, increased ADA activity started declining and comes to near normal after 9 months of ART (p<0.001). Elevated serum adenosine deaminase activity in HIV patients is an indicator of T-cell activation. Serum ADA activity along with other markers can be used as a prognostic marker to monitor response to antiretroviral therapy and immunocompetence in HIV patients.

Long-term Outcomes after Gene Therapy for Adenosine Deaminase Severe Combined Immune Deficiency (ADA SCID)

Patients lacking functional adenosine deaminase activity suffer from severe combined immunodeficiency (ADA SCID), which can be treated with ADA enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT), or autologous HSCT with gene-corrected cells (gene therapy-GT). A cohort of 10 ADA SCID patients, aged 3 months to 15 years, underwent GT in a Phase II clinical trial between 2009 and 2012. Autologous bone marrow CD34+ cells were transduced ex vivo with the MND-ADA gamma-retroviral vector (gRV) and infused following busulfan reduced intensity conditioning. These patients were monitored in a long-term follow-up protocol over 8-11 years. Nine of ten patients have sufficient immune reconstitution to protect against serious infections, and have not needed to resume ERT or proceed to secondary allogeneic HSCT. ERT was restarted 6 months after GT in the oldest patient who had no evidence of benefit from GT. Four of nine evaluable patients with the highest gene marking and B cell numbers remain off immunoglobulin replacement therapy and responded to vaccines. There were broad ranges of responses in normalization of ADA enzyme activity and adenine metabolites in blood cells, and levels of cellular and humoral immune reconstitution. Outcomes were generally better in younger patients and those receiving higher doses of gene-marked CD34+ cells. No patient experienced a leukoproliferative event after GT, despite persisting prominent clones with vector integrations adjacent to proto-oncogenes. These long-term findings demonstrate enduring efficacy of GT for ADA SCID, but risks of genotoxicity with gRVs. (Clinicaltrials.gov #NCT00794508)