Effect of prevention and potentiation of diisopropyl phosphorofluoridate (DFP)-induced delayed neurotoxicity on the mRNA expression of neurofilament subunits in hen central nervous system

2001 ◽  
Vol 79 (2) ◽  
pp. 207-217 ◽  
Author(s):  
Keqin Xie ◽  
Ram P Gupta ◽  
Mohamed B Abou-Donia

Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, which produces mild ataxia in 7–14 days and severe ataxia or paralysis in about 20 days (OPIDN) in hens. Previous studies in this laboratory have shown enhanced temporal expression of neurofilament (NF) subunit mRNAs in the spinal cord (SC) of DFP-treated hens. The main objective of this investigation was to study the effect of DFP administration on NF subunit mRNAs expression, when OPIDN is protected or potentiated by pre-treatment or post-treatment, respectively, with phenylmethylsulfonyl fluoride (PMSF). The hens were sacrificed 1, 5, 10, and 20 days after the last treatment. In contrast with enhanced mRNA expression of NF subunits reported in OPIDN, there was no alteration in the expression of NF subunits in the SC of PMSF-protected hens that did not develop OPIDN. PMSF post-treatment of DFP-treated hens, which enhanced delayed neurotoxicity produced by a low dose of DFP, exhibited decrease in the mRNA expression of NF subunits in SC at all time periods (1–20 days) of observation. The expression of NF subunits was also studied in the degeneration-resistant tissue cerebrum of treated hens. The results from protected hens suggested that temporal enhanced expression of NF subunit mRNAs in DFP-treated hens might be contributing to the development of OPIDN in hens. By contrast, PMSF post-treatment seemed to potentiate OPIDN by a mechanism different from that followed by DFP alone to produce OPIDN.Key words: diisopropyl phosphorofluoridate, phenylmethylsulfonyl fluoride, hen, spinal cord, neurofilament mRNAs.

1995 ◽  
Vol 20 (5) ◽  
pp. 609-617 ◽  
Author(s):  
Feng Yuan PIAO ◽  
Masayoshi KITABATAKE ◽  
Xiu Kui XIE ◽  
Toru YAMAUCHI

2021 ◽  
Author(s):  
Hilal Akalin ◽  
Yakut Erdem ◽  
Nuriye Gokce ◽  
Sevgi Ozmen ◽  
Muhammet Ensar Dogan ◽  
...  

Abstract Background: In this study, expression level analysis of genes associated with Attention Deficit Hyperactivity Disorder (ADHD) (SLC6A3, SLC6A4, SLC1A2, VMAT2, MAOA, COMT, GLYAT, GRM5, DRD4, TPH1, and ADRA2C) by pre-treatment and post-treatment with Atomoxetine and Methylphenidate was investigated. Methods: Forty-three ADHD diagnosed children and 38 healthy children were included to study. Forty-three patients with ADHD were divided into two groups, of which 35 patients used methylphenidate and 8 patients use atomoxetine. Five main study groups were generated: A control group, a group that includes methylphenidate pre-treatment samples, a group includes methylphenidate post-treatment samples, a group that includes atomoxetine pre-treatment samples and a group that includes atomoxetine post-treatment samples. Blood samples (10 ml each) were taken from everyone in study groups into EDTA tubes and RNA isolation was performed. mRNA expression levels of 11 determined candidate genes were showed via reverse transcription quantitative PCR method. Results: The expression levels of SLC6A3 (DAT) of ADHD diagnosed children were significantly higher than the control group, while the mRNA expression levels of SLC6A4, SLC1A2, VMAT2, MAOA, COMT, GLYAT, and TPH1 genes were significantly lower (t- test, p≤0.01).Conclusion: The expression level differences of these genes were determined to be useful as biomarkers in the diagnosis of ADHD. More patient numbers and studies with different groups are needed to fully reveal the relationship between these genes and the disease and its treatment.


2014 ◽  
Vol 84 (3-4) ◽  
pp. 0140-0151 ◽  
Author(s):  
Thilaga Rati Selvaraju ◽  
Huzwah Khaza’ai ◽  
Sharmili Vidyadaran ◽  
Mohd Sokhini Abd Mutalib ◽  
Vasudevan Ramachandran ◽  
...  

Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100 - 300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76 % and 79 % in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2 %, 95.0 %, and 95.6 %, respectively (p < 0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.


1972 ◽  
Vol 69 (1) ◽  
pp. 67-76
Author(s):  
Rolf Plesner

ABSTRACT Twenty-two fertile women were treated cyclically in from 4–30 cycles (mean 15.5) with a total of 341 injections of Deladroxate®, an injectable, long-acting oestrogen-progestogen. The injections were administered on the 8th (7th–9th) day of each cycle. Before treatment, the last pre-treatment cycle was controlled by means of daily recordings of the basal body temperature (BBT), urinary excretion of pregnanediol and total pituitary gonadotrophins at certain intervals, and by endometrial biopsies obtained late in the cycle. The effects of Deladroxate® on ovulation, on pituitary gonadotrophic function, and on the endometrium were controlled by the above mentioned parameters during cycles 1, 3, and 6, and all assessments were repeated after discontinuation of treatment. During treatment, there was a statistically significant fall in gonadotrophin excretion values (as compared with the pre-treatment values), and the fall was found to be gradually progressive during treatment. After discontinuation of treatment, there seemed to be a tendency towards an increase in the excretion values. Suppression of ovulation as determined by means of the pregnanediol excretion during treatment, was effective in nearly all of the treatment cycles checked. The fall in pregnanediol excretion was also gradually progressive during treatment, while there was a slight increase in excretion values in the post-treatment period. During treatment, 79 BBT curves were recorded. Nearly 50 % were monophasic, indicating anovulatory cycles, 17 curves were biphasic, but with the rise in temperature occurring at non-characteristic times in the cycles, 18 curves were classified as thermogenic because of a rise in temperature occurring within 24 hours after the injection, and 5 curves were not assessable. During the first month after discontinuation of treatment, 8 out of 10 recorded curves were monophasic. Out of 53 endometrial biopsies obtained around the 23rd day of the cycle, 31 were of the mixed phase type, but showing a predominance of proliferative patterns, 15 were of the secretory type, and 7 were purely proliferative. Out of 15 biopsies obtained in the post-treatment period, only two were of the mixed phase type, 12 were proliferative and one was purely secretory.


2018 ◽  
Vol 75 (4) ◽  
pp. 44-48
Author(s):  
A. Mukhina ◽  
◽  
I. Boichuk ◽  
L. Zhuravliova ◽  
◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshimi Sugiura ◽  
Fumiki Okamoto ◽  
Tomoya Murakami ◽  
Shohei Morikawa ◽  
Takahiro Hiraoka ◽  
...  

AbstractTo evaluate the effects of intravitreal ranibizumab injection (IVR) on metamorphopsia in patients with branch retinal vein occlusion (BRVO), and to assess the relationship between metamorphopsia and inner retinal microstructure and other factors. Thirty-three treatment-naïve eyes of 33 patients with macular edema caused by BRVO with at least 12 months of follow-up were included. The degree of metamorphopsia was quantified using the M-CHARTS. Retinal microstructure was assessed with spectral-domain optical coherence tomography. Disorganization of the retinal inner layers (DRIL) at the first month after resolution of the macular edema (early DRIL) and at 12 months after treatment (after DRIL) was studied. Central retinal thickness (CRT), and status of the external limiting membrane as well as ellipsoid zone were also evaluated. IVR treatment significantly improved best-corrected visual acuity (BCVA) and CRT, but the mean metamorphopsia score did not improve even after 12 months. Post-treatment metamorphopsia scores showed a significant correlation with pre-treatment metamorphopsia scores (P < 0.005), the extent of early DRIL (P < 0.05) and after DRIL (P < 0.05), and the number of injections (P < 0.05). Multivariate analysis revealed that the post-treatment mean metamorphopsia score was significantly correlated with the pre-treatment mean metamorphopsia score (P < 0.05). IVR treatment significantly improved BCVA and CRT, but not metamorphopsia. Post-treatment metamorphopsia scores were significantly associated with pre-treatment metamorphopsia scores, the extent of DRIL, and the number of injections. Prognostic factor of metamorphopsia was the degree of pre-treatment metamorphopsia.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3256
Author(s):  
Adam Brewczyński ◽  
Beata Jabłońska ◽  
Agnieszka Maria Mazurek ◽  
Jolanta Mrochem-Kwarciak ◽  
Sławomir Mrowiec ◽  
...  

Several immune and hematological parameters are associated with survival in patients with oropharyngeal cancer (OPC). The aim of the study was to analyze selected immune and hematological parameters of patients with HPV-related (HPV+) and HPV-unrelated (HPV-) OPC, before and after radiotherapy/chemoradiotherapy (RT/CRT) and to assess the impact of these parameters on survival. One hundred twenty seven patients with HPV+ and HPV− OPC, treated with RT alone or concurrent chemoradiotherapy (CRT), were included. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (Formalin-Fixed, Paraffin-Embedded) tissue samples and/or extracellular circulating HPV DNA was determined. The pre-treatment and post-treatment laboratory blood parameters were compared in both groups. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and systemic immune inflammation (SII) index were calculated. The impact of these parameters on overall (OS) and disease-free (DFS) survival was analyzed. In HPV+ patients, a high pre-treatment white blood cells (WBC) count (>8.33 /mm3), NLR (>2.13), SII (>448.60) significantly correlated with reduced OS, whereas high NLR (>2.29), SII (>462.58) significantly correlated with reduced DFS. A higher pre-treatment NLR and SII were significant poor prognostic factors for both OS and DFS in the HPV+ group. These associations were not apparent in HPV− patients. There are different pre-treatment and post-treatment immune and hematological prognostic factors for OS and DFS in HPV+ and HPV− patients. The immune ratios could be considered valuable biomarkers for risk stratification and differentiation for HPV− and HPV+ OPC patients.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1685
Author(s):  
Antonino Grassadonia ◽  
Vincenzo Graziano ◽  
Laura Iezzi ◽  
Patrizia Vici ◽  
Maddalena Barba ◽  
...  

The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR: 6.97, 95% CI: 1.65–10.55, p = 0.002) and OS (HR: 7.79, 95% CI: 1.25–15.07, p = 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67 ≥ 14% were also associated with worse DFS (p = 0.016, p = 0.002, and p = 0.001, respectively). In a multivariate analysis, luminal B subtype, post-treatment Ki67 ≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67 ≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.


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