scholarly journals Apoptosis of blood leukocytes in case of chronic brain ischemia

Author(s):  
Roksolana Nasalyk ◽  
Svitlana Shkrobot ◽  
Nataliia Sokhor ◽  
Khrystyna Duve ◽  
Bohdan Nasalyk

The aim of our study was to study leukocyte apoptosis and to establish its relationship with changes of cognitive function in patients with chronic brain ischemia (CBI) and hydrocephalus (HC). A comprehensive examination of 110 patients with CBI and HC was performed. Indicators of apoptosis, mitochondrial dysfunction, intracellular oxidative stress were studied by cytofluorimetric method. Significantly higher indicators of ANV+-, PI+-, APK+- and Mito+-cells in the presence of HC. In the group of men, the inverse correlation between the content of AnV+-cells and the result of the MoCA-test — r = –0.42; p = 0.006, in women — r = –0.51; p = 0.005. A significant relationship was found between the content of APK+- and ANV+- cells (r = 0.67, p = 0.003) and between the number of APK+- and PI+-cells (r = 0.73, p = 0.002) in patients aged 60—74. In patients with dementia progression, a moderate relationship was found between the level of cognitive functioning and the proportion of cells in the early stage (ANV+-cells) (r = –0.50; p = 0.026) and late (PI+-cells) (r = –0.30; p = 0.041) apoptosis. In the group of patients with mild and moderate cognitive deficits, correlations between the MoCA scale result and the content of ANV+-cells were recorded at the level of moderate — (r = –0.37; p = 0.040) and PI+-cells at the level of weak (r = –0.24; p = 0.049). Significantly (p < 0.05) higher content of leukocytes in the stage of apoptosis and necrosis and leukocytes with increased content of intracellular APK and with reduced mitochondrial potential compared to patients without HC was found in patients with CBI with HC. There is a significant difference between the values of indicators in middle-aged and elderly patients and indicators of patients older 74 years. The progression of neurological and cognitive deficits was accompanied by an increase of the production of ANV+-, APK+- and Mito+-cells. The highest proportion of ANV+- and PI+-cells was detected in the presence of a combination of dementia, extrapyramidal syndrome and gait apraxia in patients with CBI with HC.

Fitoterapia ◽  
2019 ◽  
Vol 2 (2) ◽  
pp. 44-45
Author(s):  
L. V. Andriyuk ◽  
◽  
A. V. Yermolaieva ◽  
N. V. Matsko ◽  
O. V. Grabous ◽  
...  

2021 ◽  
Vol 39 (2) ◽  
pp. 107-115
Author(s):  
Paul J. Bröckelmann ◽  
Horst Müller ◽  
Teresa Guhl ◽  
Karolin Behringer ◽  
Michael Fuchs ◽  
...  

PURPOSE We evaluated disease and treatment characteristics of patients with relapse after risk-adapted first-line treatment of early-stage, favorable, classic Hodgkin lymphoma (ES-HL). We compared second-line therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) or conventional chemotherapy (CTx). METHODS We analyzed patients with relapse after ES-HL treated within the German Hodgkin Study Group HD10+HD13 trials. We compared, by Cox proportional hazards regression, progression-free survival (PFS) after relapse (second PFS) treated with either ASCT or CTx and performed sensitivity analyses with overall survival (OS) from relapse and Kaplan-Meier statistics. RESULTS A total of 174 patients’ disease relapsed after treatment in the HD10 (n = 53) and HD13 (n = 121) trials. Relapse mostly occurred > 12 months after first diagnosis, predominantly with stage I-II disease. Of 172 patients with known second-line therapy, 85 received CTx (49%); 70, ASCT (41%); 11, radiotherapy only (6%); and 4, palliative single agent therapies (2%). CTx was predominantly bleomycin, etoposide, doxorubicin cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [68%]), followed by the combination regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (19%), or other regimens (13%). Patients aged > 60 years at relapse had shorter second PFS (hazard ratio [HR], 3.0; P = .0029) and were mostly treated with CTx (n = 33 of 49; 67%) and rarely with ASCT (n = 8; 16%). After adjustment for age and a disadvantage of ASCT after the more historic HD10 trial, we did not observe a significant difference in the efficacy of CTx versus ASCT for second PFS (HR, 0.7; 95% CI, 0.3 to 1.6; P = .39). In patients in the HD13 trial who were aged ≤ 60 years, the 2-year, second PFS rate was 94.0% with CTx (95% CI, 85.7% to 100%) versus 83.3% with ASCT (95% CI, 71.8% to 94.8%). Additional sensitivity analyses including OS confirmed these observations. CONCLUSION After contemporary treatment of ES-HL, relapse mostly occurred > 12 months after first diagnosis. Polychemotherapy regimens such as BEACOPP are frequently administered and may constitute a reasonable treatment option for selected patients with relapse after ES-HL.


2020 ◽  
Vol 17 ◽  
pp. 00256
Author(s):  
Murat Baimishev ◽  
Sergey Eremin ◽  
Kirill Plemyashov ◽  
Hamidulla Baimishev ◽  
Igor Konopeltsev ◽  
...  

The purpose of the research is to determine the etiopathogenesis of reproductive dysfunction in highly productive cows. For this, one group of cows was formed on the principle of paranalogs in the amount of 37 animals inseminated in the first sexual hunt after calving, followed by taking blood samples from them using the Monovet system, considering the duration of pregnancy. During the start-up period, blood was taken 1–4 days before calving and on the first day after calving. A total of 253 blood samples were examined. Subsequently, depending on the effectiveness of insemination, animals were divided into two groups. The first group included inseminated cows after the first insemination (20 animals), the second group included 17 unfertilized cows after the first insemination. Subsequently, blood was taken from animals considering the course of childbirth and the postpartum period. Blood counts were studied according to generally accepted methods using certified equipment. The study found that at an early stage of pregnancy, cows have a significant difference in lipid metabolism and in their peroxidation, in the state of antioxidant systems compared to unstable animals. In the process of pregnancy development in cows, there is a decrease in the level of total lipids and their class, and the accumulation of products of transoxidation of lipids is reduced. In animals with retention of the placenta, a low lipid metabolism and a higher level of peroxidation were established already in the dry period. After calving, this difference increases. The obtained data can be used to develop an algorithm for the prevention of postpartum complications in cows by using substances with antioxidant properties.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1417
Author(s):  
Binafsha M. Syed ◽  
Andrew R. Green ◽  
Emad A. Rakha ◽  
David A.L. Morgan ◽  
Ian O. Ellis ◽  
...  

As age advances, breast cancer (BC) tends to change its biological characteristics. This study aimed to explore the natural progression of such changes. The study included 2383 women with clinically T0-2N0-1M0 BC, managed by primary surgery and optimal adjuvant therapy in a dedicated BC facility. Tissue micro-arrays were constructed from their surgical specimens and indirect immunohistochemistry was used for analysis of a large panel (n = 16) of relevant biomarkers. There were significant changes in the pattern of expression of biomarkers related to luminal (oestrogen receptor (ER), progesterone receptors (PgR), human epidermal growth factor receptor (HER-2), E-cadherin, MUC1, bcl2 CK7/8, CK18 and bcl2) and basal (CK5/6, CK14, p53 and Ki67) phenotypes, lymph node stage, histological grade and pathological size when decade-wise comparison was made (p < 0.05). The ages of 40 years and 70 years appeared to be the milestones marking a change of the pattern. There were significantly higher metastasis free and breast cancer specific survival rates among older women with ER positive tumours while there was no significant difference in the ER negative group according to age. Biological characteristics of BC show a pattern of change with advancing age, where 40 years and 70 years appear as important milestones. The pattern suggests <40 years as the phase with aggressive phenotypes, >70 years as the less aggressive phase and 40–70 years being the transitional phase.


2020 ◽  
Vol 18 (6) ◽  
pp. 648-657
Author(s):  
Karen E. Steinhauser ◽  
Karen M. Stechuchak ◽  
Katherine Ramos ◽  
Joseph Winger ◽  
James A. Tulsky ◽  
...  

AbstractObjectiveCompare the efficacy of two interventions addressing emotional and existential well-being in early life-limiting illness.MethodPrimary trial analysis (n = 135) included patients with advanced cancer, congestive heart failure, or end-stage renal disease; Arm 1 received the Outlook intervention, addressing issues of life completion and preparation, and Arm 2 received relaxation meditation (RM). Primary outcomes at five weeks (primary endpoint) and seven weeks (secondary): completion and preparation (QUAL-E); secondary outcomes: anxiety (POMS) quality of life (FACT-G) and spiritual well-being (FACIT-Sp) subscales of faith, meaning, and peace.ResultsAverage age was 62; 56% were post-high school-educated, 54% were married, 52% white, 44% female, and 70% had a cancer diagnosis. At baseline, participants demonstrated low levels of anxiety (<5 on POMS subscale) and depression (<10 on CESD) relative to population norms. Results of the primary analysis revealed no significant differences in mean Preparation by treatment arm at five weeks (14.4 Outlook vs. 14.8 RM; between-group difference −0.4 [95% CI, −1.6, 0.8], p = 0.49) or seven weeks (15.2 vs.15.4; between-group difference −0.2 [95% CI, −1.5, 1.0], p = 0.73). There were also no significant differences in mean Life Completion by treatment arm between five weeks (26.6 Outlook vs. 26.3 RM; between-group difference 0.2 [95% CI, −1.2, 1.7], p = 0.76) or seven weeks (26.5 vs. 27.5; between-group difference −1.0 [95% CI, −2.7, 0.7], p = 0.23). Compared to RM, Outlook participants did not have significant differences over time in the secondary outcomes of overall quality of life, anxiety, depression, FACT-G subscales, and FACIT-Sp subscales.DiscussionIn early-stage life-limiting illness, Outlook did not demonstrate a significant difference in primary or secondary outcomes relative to RM. Results underscore the importance of pre-screening for distress. Qualitatively, Outlook participants were able to express suppressed emotions, place illness context, reflect on adaptations, and strengthen identity. Screening for distress and identifying specified measures of distress, beyond anxiety and depression, is essential in our ability to adequately assess the multi-dimensional mechanisms that decrease existential suffering.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Annarita Perillo ◽  
Valeria Landoni ◽  
Alessia Farneti ◽  
Giuseppe Sanguineti

Abstract Purpose The purpose of this study is to evaluate inter- and intra-fraction organ motion as well as to quantify clinical target volume (CTV) to planning target volume (PTV) margins to be adopted in the stereotactic treatment of early stage glottic cancer. Methods and materials Stereotactic body radiotherapy (SBRT) to 36 Gy in 3 fractions was administered to 23 patients with early glottic cancer T1N0M0. Patients were irradiated with a volumetric intensity modulated arc technique delivered with 6 MV FFF energy. Each patient underwent a pre-treatment cone beam computed tomography (CBCT) to correct the setup based on the thyroid cartilage position. Imaging was repeated if displacement exceeded 2 mm in any direction. CBCT imaging was also performed after each treatment arc as well as at the end of the delivery. Swallowing was allowed only during the beam-off time between arcs. CBCT images were reviewed to evaluate inter- and intra-fraction organ motion. The relationships between selected treatment characteristics, both beam-on and delivery times as well as organ motion were investigated. Results For the population systematic (Ʃ) and random (σ) inter-fraction errors were 0.9, 1.3 and 0.6 mm and 1.1, 1.3 and 0.7 mm in the left-right (X), cranio-caudal (Y) and antero-posterior (Z) directions, respectively. From the analysis of CBCT images acquired after treatment, systematic (Ʃ) and random (σ) intra-fraction errors resulted 0.7, 1.6 and 0.7 mm and 1.0, 1.5 and 0.6 mm in the X, Y and Z directions, respectively. Margins calculated from the intra-fraction errors were 2.4, 5.1 and 2.2 mm in the X, Y and Z directions respectively. A statistically significant difference was found for the displacement in the Z direction between patients irradiated with > 2 arcs versus ≤ 2 arcs, (MW test, p = 0.038). When analyzing mean data from CBCT images for the whole treatment, a significant correlation was found between the time of delivery and the three dimensional displacement vector (r = 0.489, p = 0.055), the displacement in the Y direction (r = 0.553, p = 0.026) and the subsequent margins to be adopted (r = 0.626, p = 0.009). Finally, displacements and the subsequent margins to be adopted in Y direction were significantly greater for treatments with more than 2 arcs (MW test p = 0.037 and p = 0.019, respectively). Conclusions In the setting of controlled swallowing during treatment delivery, intra-fraction motion still needs to be taken into account when planning with estimated CTV to PTV margins of 3, 5 and 3 mm in the X, Y and Z directions, respectively. Selected treatments may require additional margins.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maher Kurdi ◽  
Badrah Alghamdi ◽  
Nadeem Shafique Butt ◽  
Saleh Baeesa

Abstract Background Tumour associated macrophages (TAMs) and tumour infiltrating lymphocytes (TILs) are considered dominant cells in glioblastoma microenvironment. Aim The purpose of this study was to assess the expression of CD204+ M2-polarized TAMs in glioblastomas and their relationship with CD4+TILs, Iba+microglia, and IDH1 mutation. We also exploreed the prognostic value of these markers on the recurrence-free interval (RFI). Methods The expressions of CD204+TAMs, CD4+TILs, and Iba1+microglia were quantitively assessed in 45 glioblastomas using immunohistochemistry. Kaplan–Meier analysis and Cox hazards were used to examine the relationship between these factors. Results CD204+TAMs were highly expressed in 32 tumours (71%) and the remaining 13 tumours (29%) had reduced expression. CD4+TILs were highly expressed in 10 cases (22%) and 35 cases (77.8%) had low expression. There was an inverse correlation between CD204+TAMs and CD4+TILs, in which 85% of tumours had a high expression of CD204+TAMs and a low expression of CD4+TILs. Nevertheless, there was no significant difference in IDH1 mutation status between the two groups (p = 0.779). There was a significant difference in Iba1+microglial activation between IDH1mutant and IDH1wildtype groups (p = 0.031). For cases with a high expression of CD204+TAMs and a low expression of CD4+TILs, there was a significant difference in RFI after treatment with chemoradiotherapy or radiotherapy (p = 0.030). Conclusion Glioblastoma with a dense CD204+TAMs and few CD4+TILs is associated with IDH1wildtype. These findings suggest that TAMs masks tumour cell and suppress T-cell tumoricidal functions via immunomodulatory mechanisms. Blockade of the CD204-TAM receptor may prevent this mechanism and allow the evolution of TILs.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Liangxiao Bao ◽  
Shengwei Rong ◽  
Zhanjun Shi ◽  
Jian Wang ◽  
Yang Zhang

Abstract Background Femoral posterior condylar offset (PCO) and posterior tibial slope (PTS) are important for postoperative range of motion after total knee arthroplasty (TKA). However, normative data of PCO and PTS and the correlation between them among healthy populations remain to be elucidated. The purpose of this study was to determine PCO and PTS in normal knees, and to identify the correlation between them. Methods Eighty healthy volunteers were recruited. CT scans were performed followed by three-dimensional reconstruction. PCO and PTS were measured and analyzed, as well as the correlation between them. Results PTS averaged 6.78° and 6.11°, on the medial and lateral side respectively (P = 0.002). Medial PCO was greater than lateral (29.2 vs. 23.8 mm, P <  0.001). Both medial and lateral PCO of male were larger than female. On the contrary, male medial PTS was smaller than female, while there was no significant difference of lateral PTS between genders. There was an inverse correlation between medial PCO and PTS, but not lateral. Conclusions Significant differences exhibited between medial and lateral compartments, genders, and among individuals. An inverse correlation exists between PCO and PTS in the medial compartment. These results improve our understanding of the morphology and biomechanics of normal knees, and subsequently for optimising prosthetic design and surgical techniques.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 282.1-282
Author(s):  
R. Flood ◽  
C. Kirby ◽  
Y. Alammari ◽  
D. Kane ◽  
R. Mullan

Background:Emerging evidence that the joints of asymptomatic hyperuricaemic individuals contain monosodium urate (MSU) deposits and that alternative presentations of foot pain occur in hyperuricaemia suggests that preclinical phases may occur prior to a first episodic gout attack. (1) This case–control study evaluates urate deposition in hyperuricaemic individuals not fulfilling the current gout classification criteria, as well as a potential therapeutic role for urate lowering therapy (ULT).Objectives:To investigate whether ULT reduces non-episodic foot pain in patients who fail to meet ACR/EULAR 2015 gout classification criteria.Methods:Following informed consent, hyperuricaemic individuals with persistent, non-episodic foot pain (n=53) not fulfilling ACR/EULAR 2015 gout classification criteria, were compared with asymptomatic hyperuricaemic controls (n=18). Ultrasound (US) of bilateral first metatarsophalangeal (MTP) joints and features of MSU deposition including double contour (DC) sign, tophus and juxta-articular erosion were recorded. Cases only were treated with febuxostat or allopurinol daily for 6 months. Serum urate, 24-hour and 7-day visual analogue score (VAS) 0–100 mm pain scales and the Manchester Foot Pain and Disability Index (MFPDI) were recorded before treatment and after 3 and 6 months. MTP Ultrasound was repeated after a minimum of 6 months on treatment.Results:53 hyperuricaemic individuals with persistent, non-episodic foot pain not meeting the ACR/EULAR 2015 gout classification criteria were recruited. At baseline MTP US DC sign, erosion and tophus occurred in 62.5%, 20.8% and 49% of cases, respectively. No US features of gout occurred in controls. No significant difference was seen in baseline serum urate between cases (481±14 mg/dL) versus controls (437±14; p=NS). Serum urate in cases fell at 3 months (325±25; p<0.01) and 6 months (248±19; p<0.01). For cases, baseline 24-hour pain VAS (46±3.9) reduced at 3 months (32±4.1; p<0.05) and 6 months (21±5.2; p<0.05) of ULT. The 7-day pain VAS (59±3.9) decreased at 3 months (35±4.5; p<0.05) and 6 months (30±5.3; P<0.05). MFPDI (17±1.4) decreased at 3 month (13±1.8; p=<0.05) and 6 months (11±2.2; p=<0.05). When cases were grouped according to the presence (N=33) or absence (N=18) of DC sign on baseline US, no differences were observed for baseline pain scores. Following ULT however, 24-hour pain VAS were significantly lower in DC positive patients at 3 months (22±4.48 DC positive vs 42±6.14 DC negative; p<0.05) and 6 months (12.±5.4 vs 33±8.4; p<0.05). The 7-day pain VAS were significantly lower in DC positive patients at 3 months (23±4.6 vs 47±6.6; p<0.05) and MFDPI were significantly lower in DC positive patients at 3 months (10±1.9 DC positive vs 19±2.9 DC negative; p<0.05).Conclusion:These findings indicate that persistent, non-episodic foot pain in hyperuricaemia is both associated with US features of MSU deposition and is responsive to ULT. Symptomatic hyperuricaemia occurring prior to episodic gout therefore represents an earlier or alternative disease presentation. Changes to the ACR/ EULAR classification criteria to include non-episodic foot pain in the presence of US features of gout may increase the sensitivity of disease classification at an early stage, leading to improved future treatment strategies and long-term outcomes.References:[1]Stewart S, Dalbeth N, Vandal AC, Rome K. Characteristics of the first metatarsophalangeal joint in gout and asymptomatic hyperuricaemia: A cross-sectional observational study. J Foot Ankle Res. 2015;8(1):1–8.Disclosure of Interests:None declared


Sign in / Sign up

Export Citation Format

Share Document