Concurrent Treatment with Denileukin Diftitox (DD) To Deplete T-Regulatory Cells Enhances Rebound Lymphocytosis and Eosinophilia in Patients Treated with High-Dose IL-2 (HDIL-2) for Metastatic Renal Cell Cancer (MRCC).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1729-1729
Author(s):  
Adi Gidron ◽  
John Eklund ◽  
Brenda Martone ◽  
Alfred W. Rademaker ◽  
Charles Goolsby ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Statistical Significance ◽  
Cell Cancer ◽  
Peak Level ◽  
High Dose ◽  
Maximal Increase ◽  
Group A ◽  
Group B ◽  
Group D

Abstract Background: CD4+CD25+hi T cells (Treg) play a suppressive role in immune regulation. DD is an IL-2 receptor specific cytotoxin. We postulated depletion of Treg with DD may enhance immune effector cell populations after HDIL-2 treatment, including rebound lymphocytosis and also eosinophilia which has been reported to be involved in immune response to neoplasm (Mattes J Exp Med 197: 387, 2003). Methods: In this pilot study, 12 pts (8 male, median age 58 yrs) with MRCC were tx with HDIL-2 and DD in different schedules to determine safety and effect on immune response as manifested by changes in Treg, peak lymphocyte, and eosinophil counts. Pts were treated with IL-2 600,000 IU/kg Q8H on days (d) 1–5 and 15–19. Three (group A) and 4 (group B) pts were given 6 and 9ug/kg daily on d8–10 respectively, while 5 (group C) pts received 9ug/kg of DD on d −4 to −2. Nine (group D) pts with metastatic melanoma who received HDIL-2 as above but without DD were included as controls. Flow cytometry was done on days −4, 1,8,10,15,22 for group C and on days 1,8,10,15,22 for groups B, and D. CBC was obtained concurrent or within 24 hours of flow cytometry. Group A pts were evaluated for safety only and were excluded from analysis. Results: Prior to enrollment, all pts had undergone nephrectomy and four patients received interferon-alpha. One pt from group B withdrew from study and was not included in analysis. Administration of DD resulted in a median decline of 25% in Treg number (not significant). DD given before HDIL-2 was associated with a greater increase in Treg post HDIL-2. In Group C there was an increase of rebound median Treg count of 0.88k/ul compared with 0.060k/ul in group B (p=0.025). Absolute lymphocytosis was higher in the combined group getting DD compared to control (median maximal increase of 7.6 vs 4.7 k/ul, respectively) although the difference did not reach statistical significance. However, group C pts had a greater increase in absolute lymphocytosis than did group B pts in which absolute lymphocytosis actually decreased (median increase 10.6 vs. median decrease 0.4 k/ul, p=0.025). A higher peak level of eosinophilia was noted in groups B and C compared with group D (mean increase of 10.5 vs. 4.0 k/ul p=0.2). Group C had a greater peak eosinophilia than group B (11.2 vs 2.2 k/ul p=0.053) Toxicity was manageable and consistent with those seen with HDIL-2. Median HDIL-2 dose given was 21 (range, 14–28). No clinical responses were observed. Of 11 pts included in the analysis 1 pt from group A expired 68 weeks after enrollment. All remaining patients are alive. Survival from enrollment ranges from 11 to 93 weeks. Conclusion: Overall, the combination of DD and HDIL-2 results in a stimulatory effect as manifested by increased rebound lymphocytosis and eosinophilia compared to HDIL-2 alone. Administration of DD in conjunction with HDIL-2 was associated with a rebound in Treg that may be schedule and dose dependent. The results suggest an enhanced immune stimulatory effect as manifested by lymphocytosis and peak eosinophilia in group C. However, this stimulatory effect also extends to Treg that may prove detrimental clinically. Further exploration of these effects in immunotherapy naïve patients would be beneficial.

Treg depletion with denileukin difititox (DD) enhances lymphocytosis and eosinphilia in patients treated with high-dose IL-2 (HDIL-2) for metastatic renal cell cancer (MRCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14627-14627
Author(s):  
A. Gidron ◽  
J. Eklund ◽  
B. Mortone ◽  
A. W. Rademaker ◽  
C. Goolsby ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
T Cells ◽  
Cell Cancer ◽  
Peak Level ◽  
Absolute Number ◽  
High Dose ◽  
Immune Effector ◽  
Treg Depletion ◽  
Group A

14627 Background: CD4+CD25+ T cells (Treg) play a suppressive role in immune regulation. DD is an IL-2 receptor specific cytotoxin. We postulated depletion of Treg with DD may enhance immune effector cell populations during HDIL-2 tx, including eosinophilia which was reported to be involved in immune response to neoplasm (Mattes et al. J Exp Med 197: 387, 2003). Methods: Seven pts (5 male, median age 58 yrs) with MRCC were tx’d with HDIL-2 and DD in different schedules to determine safety and effect on immune response as manifested by changes in Treg, lymphocyte, and peak eosinophil counts. Pts were tx’d with IL-2 600,000 IU/kg Q8H on days (d) 1–5 and 15–19. Three (group A) and 2 (group B) pts were given 6 and 9 ug/kg daily on d 8–10 respectively, while 2 (group C) pts received 9 ug/kg of DD on d -4- -2. Four (group D) pts with metastatic melanoma who received HDIL-2 as above but without DD were included as controls. Flow cytometry was done on days -4, 1,8,10,15 for group C and on days 1, 8, 10, 15, 22 for groups A, B, and D. CBC was obtained within 24 hours of flow cytometry. Results: After DD Treg increased in group A (mean change in absolute T-reg count of 16%) and decreased in groups B and C (34.5 and 20% respectively) compared to baseline. Group C trended toward a greater lymphocytosis at day 8 compared to all other groups (mean increase of 8.6 vs. 3.3 K/ul p = 0.059). A higher peak level of eosinophilia was noted in group C compared with groups A, B and D combined (mean increase of 9.9 vs. 3.0 k/ul p = 0.03). Group C demonstrated a higher mean % change in absolute number of CD8+ T-cells between onset of therapy and Day 8 compared to groups A, B, D combined (increase of 1095% vs. 496% respectively, p = 0.35). Toxicity was similar to that expected with HDIL-2. Conclusions: Administration of DD in conjunction with HDIL-2 was associated with a decrease in Treg that may be schedule and dose dependent. The results suggest an enhanced immune stimulatory effect as manifested by lymphocytosis and peak eosinophilia and CD8+ T-cells in group C. Despite small pt numbers, results suggest that pre-treatment with DD may confer an advantage. It is too early to know if laboratory results correlate to clinical benefit. [Table: see text]

scholarly journals EFEK PEMBERIAN ANABOLIK ANDROGENIK STEROID INJEKSI DOSIS RENDAH DAN TINGGI TERHADAP GAMBARAN HISTOPATOLOGI HATI DAN OTOT RANGKA TIKUS WISTAR (Rattus Novergicus)

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Pamela K. Sari ◽  
Poppy M. Lintong ◽  
Lily L. Loho
Keyword(s):  
Protein Synthesis ◽  
Wistar Rats ◽  
Low Dose ◽  
Anabolic Steroids ◽  
Inflammatory Cells ◽  
High Dose ◽  
Group A ◽  
Androgenic Anabolic Steroids ◽  
Group B ◽  
Group D

Abstract: Androgenic-anabolic steroids (AAS) are synthetic derivatives of the male hormone endogenous testosterone that stimulates anabolic (protein synthesis) and androgenic effects (masculinization). Long-term usage of AAS can result in liver damage. However, physiological concentrations of testosterone can stimulate protein synthesis which lead to an increase in muscle size, body mass, and endurance. This study aimed to determine the histopathology of liver and skeletal muscles of wistar rats that were given low dose and high dose injection of AAS. Subjects were 21 wistar rats divided into 7 groups. Group A was given standard pellets for 56 days (negative control), terminated on days 29,43, and 57. Group B was treated with low-dose AAS injection and standard pellets for 28 days, terminated on day 29. Group C was treated with low-dose AAS injection and standard pellets for 42 days, terminated on day 43. Group D was treated with low-dose AAS injection and standard pellets for 56 days, terminated on day 57. Group E was treated with high-dose AAS injection and standard pellets for 28 days, terminated on day 29. Group F was treated with high-dose AAS injection and standard pellets for 42 days, terminated on day 43. Group G was treated with high-dose AAS injection and standard pellets for 56 days, terminated on day 57. The results showed that the histopathology of liver and muscles in group A was still normal. In group B, the architecture of liver was still normal with a few inflammatory cells around the Kiernan triangle while in muscle the ratio of myofibril diameter was 1.28:1. In group C and group D, there were widening of the hepatic artery, bile duct, and portal vein containing blood fibrin, and inflammatory cells around the Kiernan triangle. The ratio of myofibril diameter was 1.43:1 in group C and 2.14:1 in group D. In group E, F and G, there were micro-vesicular fatty cells in the peripheral part of the liver meanwhile the myofibril diameter ratio of the muscles in group E was 1.43:1, group F 2.1:1, and group G 2.28:1. Conclusion: Administration of AAS injection of low dose and high dose for less than 4 weeks could result in inflammation, dilation of the portal vein, hepatic artery and bile duct meanwhile administration of AAS for over 4 weeks could ressult in focal fatty liver (steatosis). The administration of AAS injection of low dose and high dose for 4,6 and 8 weeks reslutid in enlargement of skeletal muscle (muscle hypertrophy).Keywords: androgenic-anabolic steroids, liver, skeletal muscleAbstrak: Anabolik Androgenik Steroid (AAS) adalah derivat sintetis dari hormon sex testosteron endogen pria, yang merangsang efek anabolik (sintesis protein) dan androgenik (maskulinisasi). Penggunaan AAS jangka panjang dapat mengakibatkan terjadinya kerusakan hati namun secara fisiologi testosteron dapat menstimulasi sintesis protein sehinggaberdampak pada peningkatan ukuran otot, massa tubuh dan ketahanan tubuh. Penelitian ini bertujuan untuk mengetahui gambaran histopatologi hati dan otot rangka wistar yang diberikan AAS injeksi dosis rendah dan dosis tinggi. Subjek penelitian 21 ekor wistar yang dibagi menjadi 7 kelompok. Kelompok A diberi pelet standar selama 56 hari (kontrol negatif), terminasi pada hari ke-29, 43, dan 57. Kelompok B diberi perlakuan AAS injeksi dosis rendah dan pelet standar selama 28 hari, terminasi hari ke-29. Kelompok C diberi AAS injeksi dosis rendah dan pelet standar selama 42 hari, terminasi hari ke-43. Kelompok D diberi AAS injeksi dosis rendah dan pelet standar selama 56 hari, terminasi hari ke-57. Kelompok E diberi perlakuan AAS injeksi dosis tinggi dan diberi pelet standar selama 28 hari, terminasi hari ke-29. Kelompok F diberi perlakuan AAS injeksi dosis tinggi dan diberi pelet standar selama 42 hari, terminasi hari ke-43. Kelompok G diberi perlakuan AAS injeksi dosis tinggi dan diberi pelet standar selama 56 hari, terminasi hari ke-57. Hasil penelitian menunjukkan pada kelompok A didapatkan gambaran histopatologi hati normal sedangkan pada otot tidak terdapat perubahan. Pada kelompok B didapatkan arsitektur hati masih normal dengan sedikit sel radang disekitar segitiga Kiernan sedangkan pada otot terlihat diameter miofibril ratio 1,28:1. Pada kelompok C dan D terlihat pelebaran arteri hepatika, duktus biliaris, dan vena porta yang berisi fibrin darah, serta sel-sel radang di sekitar segitiga Kiernan. Pada kelompok C diameter miofibril ratio 1,43;1 dan pada kelompok D 2,14:1. Pada kelompok E, F dan G terdapat sel-sel perlemakan mikrovesikuler di perifer sedangkan pada otot diameter miofibril ratio kelompok E 1,43:1, kelompok F 2,1:1, dan kelompok G 2,28:1. Simpulan: Pada pemberian AAS injeksi dosis rendah dan dosis tinggi kurang dari 4 minggu terjadi peradangan hati, pelebaran vena porta, arteri hepatika dan duktus biliaris sedangkan lebih dari 4 minggu terdapat perlemakan (steatosis) fokal hati. Pemberian AAS injeksi dosis rendah dan tinggi dalam waktu 4,6 dan 8 minggu menunjukkan pembesaran otot rangka (hipertrofi otot).Kata kunci: AAS, hati, otot rangka

Prognostic Impact of Clinico-Pathological Parameters on the Outcome of Multiple Myeloma Patients: A Single-Center Analysis on 143 Consecutive Patients Treated with Standard Versus Intensive Chemotherapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5436-5436
Author(s):  
Truc Ngo ◽  
Martina Kleber ◽  
Barbara Deschler ◽  
Gabriele Ihorst ◽  
Monika Engelhardt
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Statistical Significance ◽  
Performance Status ◽  
Stage Ii ◽  
Treatment Modalities ◽  
High Dose ◽  
Prognostic Impact ◽  
Group A ◽  
Group B

Abstract Multiple myeloma (MM) remains an incurable disease, with significant variation in the response and survival even with current treatment modalities, such as high-dose chemotherapy (CTx) and autologous stem cell transplantation (auto-SCT), novel drugs and intensive supportives. Hence, prognostic parameters that help to predict the benefit of different therapeutics are of utmost importance to be defined further. The objective of this analysis was to determine whether treatment selection and response are markedly influenced by specific clinico-pathological parameters and how these effect overall survival (OS). Of 143 consecutive MM patients (pts) receiving either standard therapy (Std-CTx, group A, n=79) or auto-SCT (group B, n=64) at our center between 1997–2003, gender, age, MM-type, -stage, number of CTx lines, LDH,β 2-MG and bone marrow (BM) infiltration were evaluated on response and survival in uni- and multivariate analyses and hazard ratios (HR) were determined. To further pay tribute to pts’ average age, as MM is primarily a disease of the elderly, special attention was paid to the influence of the performance status (Karnofsky Index=KI) and number of concurrent diagnoses (CD). Pts in groups A and B were comparable in terms of gender distribution, MM type, CD and LDH-level. However, group A as compared to B pts were older (65 vs. 56 yrs), had received more radiation (26 vs. 19%) and showed higher β2-MG (5 vs. 2.3g/L; respectively). Moreover, pts in group B as compared to A had more advanced disease (Durie and Salmon [D&S] stage II/III: 92 vs. 65%), a higher BM-infiltration (40 vs. 30%), and were treated later in their disease course. In group A pts, HR were increased for β2-MG>3, D&S stage II/III, stage B disease, CD>1, LDH>200U/L and age >60y, and HR decreased for females and KI>80%, reaching significance for β2-MG, D&S stage II/III, stage B disease, CD and KI. Although these HR were also observed for group B pts, none of these prognostic factors reached statistical significance. Multivariate analysis on all pts identified β2-MG >3mg/L and age >60y as independent prognostic factors, with HRs of 3.6 (95% CI 1.6–8.1) and 2.1 (CI 0.9–5.0), respectively. Of note, current CR/PR rates for group A and B pts are 4 vs. 20%, and at last follow-up (6/2006) median OS from treatment initiation is 49.5% vs. 61.4%, respectively. Our data show that an elevated β2-MG, D&S stage II/III, stage B disease, more than 1 CD and reduced performance status before therapy, negatively influence response and OS in Std-group pts, whereas these do not significantly impact HR in auto-SCT pts. We conclude that MM pts benefit from auto-SCT independently of prognostic factors which, however, do impact outcome with Std-CTx alone. Since randomized trials have repetitively shown response and survival with auto-SCT to be superior to Std-CTx, we propose that pts with the above prognostic factors should be carefully evaluated for intensive therapies, as this analysis accentuates that auto-SCT is the treatment of choice for eligible MM pts.

scholarly journals Evaluation of complements serum level (C3 and C4) in pregnant women with history of toxoplasmosis

2011 ◽  
Vol 5 (2) ◽  
pp. 12-16
Author(s):  
Dunya F. Salloom ◽  
Harith S. AL-Warid ◽  
Ali H. Abbas
Keyword(s):  
Immune Response ◽  
Serum Level ◽  
Pregnant Women ◽  
Normal Pregnancy ◽  
Igm Antibodies ◽  
History Of ◽  
Group A ◽  
Group B ◽  
Group D

C3 and C4 serum level were evaluated in 30 pregnant women which divided into groups: Group A16 (53.3%) (Pregnant women with history of abortion and positive anti toxoplasma IgM antibodies), Group B10 (33%) (Normal pregnancy women with no history of abortion or Toxoplasmosis.), Group C6 (20%) (Pregnant women with history of two abortion and positive anti toxoplasma IgM), group D 10 (33.3%) (Pregnant women with history of only one abortion and positive anti- toxoplasma IgM), group E 4 (13.3%) (Pregnant women with history of only one abortion and negative anti-toxoplasma IgM). The results showed that highest level of both C3 and C4 in women with positive anti toxplasma IgM and history of one or two abortion/abortions while the lowest level of these two complements were in women with negative anti toxplasma IgM even they had one abortion or no abortion. There is significant differences in concentration of C3 ( 189.7 ± 20.3 mg/dl ) and C4 ( 59.3 ± 7.5 mg/dl ) in group A and C3 ( 189.6 ± 17.7 mg/dl ) and C4 ( 63.08 ± 4.7 mg/dl) when compared with group B and E, and the result showed statistical differences in C4 concentration between group C and D at P< 0.05. We conclude that complement was play role in immune response of pregnant women especially against toxoplasmosis that cause abortion to these women.

CD33/CD10 Ratios in the Blast Region Evaluated by Flow Cytometry Predicts the Response of Chronic Myelogeneous Leukemia to Imatinib.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2595-2595
Author(s):  
Satoko Oka ◽  
Masaki Mori
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Healthy Volunteers ◽  
Peripheral Blood ◽  
Chronic Myelogeneous Leukemia ◽  
Group A ◽  
One Year ◽  
Group B ◽  
Group D

Abstract Abstract 2595 Poster Board II-571 Background: The prediction of the response of chronic myelogeneous leukemia (CML) to imatinib is clinically important. However, no reliable markers are known. Methods: From January 2005 to April 2007, 32 patients with newly diagnosed CML were treated at our hospital. The diagnosis was made based on the existence of the Philadelphia chromosome. A routine bone marrow aspiration was performed to evaluate bone marrow smears, karyotypes, phenotypes, and bcr/abl message levels before the start of imatinib. Phenotypic analysis was conducted using three-color flow cytometry as follows: bone marrow mononuclear cells were stained with fluorescein isothiocyanate-conjugated monoclonal antibody, phycoerythrin-conjugated monoclonal antibody, and peridinin chlorophyll protein-conjugated CD45. A gate was set to identify blasts characterized by intermediate CD45 expression and low side-scatter properties. Phenotypes of the cells in the blast region were analyzed using a flow cytometer (FACSCalibur; BD Biosciences, San Jose, CA, USA). As a control, bone marrow samples were obtained from 8 healthy volunteers and 35 patients with refractory anemia of myelodysplastic syndrome (MDS-RA). Results: All patients were diagnosed as having CML in the chronic phase and given imatinib alone. According to the response after one year of treatment with imatinib, patients showing and not showing a complete cytogenetic response were designated as group A (26 patients) and group B (6 patients), respectively. There were no significant differences between the two groups in terms of the age, peripheral blood cell counts, peripheral blood blast percentages, peripheral blood basophil percentages, bone marrow cell differentials, bone marrow blast percentages, additional chromosomal abnormalities, Sokal's score, Hasford's score, and spleen size before the start of imatinib. The mean imatinib dose per day was higher in group A (349 mg) than in group B (284.4 mg); however, the results were not significant (p=0.051). Group B showed higher percentages of myeloid cells in the blast region than group A, while the former showed lower percentages of B lymphoid cells in the blast region than the latter. CD33/CD10, CD33/CD19, CD13/CD10, and CD13/CD19 ratios in the blast region in group B were significantly higher than in group A: 56.6 vs. 6.0 (p<0.01), 34.5 vs. 6.0 (p<0.01), 33.1 vs. 7.7 (p<0.01), and 23.8 vs. 4.9 (p<0.05), respectively. There were no differences between the two groups regarding the percentage of CD34+ and CD117+ cells. Similar results were obtained, when patients were evaluated after six months of treatment with imatinib. After the six-month imatinib treatment, patients were divided into two groups: one group (group C) showed undetectable bcr/abl messages (17 patients), and the other (group D) showed detectable bcr/abl messages (6 patients). There were no significant differences between the two groups in terms of imatinib dose per day and other clinical data. CD33/CD10, CD33/CD19, CD13/CD10, and CD13/CD19 ratios in the blast region in the group D and in the group C were 11.6 vs. 6.4 (p=0.05), 10.5 vs. 6.1 (p<0.05), 13.9 vs. 8.1 (p<0.05), and 9.4 vs. 5.7 (p<0.05), respectively. CD33/CD10, CD33/CD19, CD13/CD10, and CD13/CD19 ratios in the blast region in the MDS-RA patients and healthy volunteers were 3.2 vs. 0.7, 3.2 vs. 0.5, 2.5 vs. 0.6, and 3.0 vs. 0.6, respectively. Conclusion: An increase in CD33/CD10 ratios in the blast region in CML before the start of imatinib is associated with resistance to the drug. A cut-off value of 30 for CD33/CD10 ratios in the blast region in CML at diagnosis is useful for predicting the response of CML to imatinib after one year of treatment with the drug. Disclosures: No relevant conflicts of interest to declare.

Flow Cytometric Analysis of Lymphocyte Subsets in Migraine Patients During and Outside of an Acute Headache Attack

Cephalalgia ◽  
1998 ◽  
Vol 18 (4) ◽  
pp. 197-201 ◽  
Author(s):  
AD Mosnaim ◽  
H Kulaga ◽  
AJ Adams ◽  
ME Wolf ◽  
J Puente ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Statistical Significance ◽  
Flow Cytometric Analysis ◽  
Immunological Parameters ◽  
Total N ◽  
Immune Parameters ◽  
Flow Cytometric ◽  
Group A ◽  
Group B ◽  
Group D

We have conducted flow cytometric studies of two subsets of lymphocyte markers in groups of migraineurs during ( n = 12; group B) and outside ( n = 10; group C) of a migraine without aura attack (total n = 22; group A), including a group of patients tested in both of these phases ( n = 5; group D), and compared these results with those obtained from a population of age-comparable, sex- and race-matched healthy volunteers ( n = 12; group E). Comparison of the first set of lymphocytes (CD3+CD16+56+, CD3-CD16+56+, CD3-CD19+, CD3+CD19+, and CD3+HLA-DR+) between the patients in group A and the controls (group E) showed differences, reflecting greater group A percentages of CD3+CD16+CD56+ and CD3-CD19+ lymphocytes. Furthermore, these differences reached statistical significance only for the CD3+CD16+CD56+ lymphocytes, and then solely for the patients in group C (Scheffe's test, p< 0.05). Paired analysis of the above lymphocyte markers for subjects in group D failed to show significant differences between patients when they were having and not having a migraine attack, raising the possibility that results from a larger study could show meaningful increases in percentages of CD3+CD16+CD56+ lymphocytes as one of the immune parameters useful for differentiating migraineurs from controls. Comparison of a second set of lymphocyte markers (CD19+CD5+, CD20+CD72-, CD20-CD72+, CD20+CD72+) among either the different groups of patients or between the patients and controls failed, however, to show statistically significant differences, emphasizing the apparent specificity of the findings described above for CD3+CD16+CD56+ lymphocytes. Our results, albeit of a preliminary nature, suggest the occurrence of significant, differential changes in lymphocyte subset immunophenotyping between groups of pain-free migraineurs and patients during an acute migraine episode or controls. Corroboration of these findings may prove useful in clinical laboratory practice to identify changes in immunological parameters specifically associated with migraineurs, and help towards a better understanding of the etiology and pathophysiology of this condition.

scholarly journals Morphological and Biochemical Effects of Aqueous Extract of Moringa oleifera Leaf on Cobalt Chloride-Induced Cerebral Damage in Adult Wistar Rats

2021 ◽  
pp. 46-57
Author(s):  
A. J. Ajibade ◽  
A. E. Okeleye ◽  
I. A. Ogunmola
Keyword(s):  
Cerebral Cortex ◽  
Wistar Rats ◽  
Moringa Oleifera ◽  
Cobalt Chloride ◽  
High Dose ◽  
Male Wistar Rats ◽  
Group A ◽  
Group B ◽  
Group D ◽  
The Brain

Cobalt induces hypoxia in the brain which leads to oxygen deprivation resulting in cognitive disturbance and decreased motor control. This study evaluated the effect of Moringa oleifera extract on the cobalt chloride-induced cerebral cortex of adult male wistar rats.  40 male wistar rats weighing (90 ± 120g) were used for the study and they were divided into 5 groups with each group containing 8 rats. Group A served as control which received distilled water, Group B was treated orally with Cobalt chloride at dose 45 mg/kg, Group C received cobalt chloride 45 mg/kg + low dose of Moringa oleifera extract 250 mg/kg for 52 days, Group D treated with cobalt chloride 45 mg/kg + high dose of Moringa oleifera extract 500 mg/kg and Group E treated with 500 mg/kg Moringa oleifera extract only and rats were sacrificed on the 53rd day by cervical dislocation. The brain of each rat was removed and weighed before half was fixed in formol calcium for histological analysis and the second half was used for oxidative stress parameters. The mean body weight of the wistar rats in group C and E increased significantly (P <0.05) while it decreased significantly (P <0.05) in group D. The biochemical analysis shows a significant increase (P<0.05) in the level of MDA in group B and a significant decrease (P<0.05) in group E. additionally, NO level shows a significant increase (P<0.05) in group B compared with control. SDH activity decreased significantly in group C, D, and E. Microscopic examination of the cerebral cortex in group B, C and D showed degenerative changes compared with normal histological features in A and E. The study concluded that cobalt chloride induced cerebral cortical damage while administration of Moringa oleifera extract attenuated the toxic effect of cobalt chloride in wistar rats.

scholarly journals Effect of combined application of Zylexis and a vaccine against FHV-1 and FCV on selected immune response parameters in cats

2020 ◽  
Vol 76 (08) ◽  
pp. 6443-2020
Author(s):  
OLIWIER TEODOROWSKI ◽  
BARBARA MAJER-DZIEDZIC ◽  
MARCIN KALINOWSKI ◽  
STANISŁAW WINIARCZYK ◽  
ŁUKASZ ADASZEK
Keyword(s):  
Immune Response ◽  
Cellular Response ◽  
Immunological Parameters ◽  
Combined Application ◽  
Combined Administration ◽  
Group A ◽  
Haptoglobin Level ◽  
Group B ◽  
Almost All ◽  
Group D

The aim of the study was to evaluate the immune response in cats after the administration of Zylexis (group A), a vaccine against FHV-1 and FCV infections (group B), and a combination of the vaccine and Zylexis (group D). The evaluated parameters included the total number of leukocytes and lymphocytes in peripheral blood, the number of CD4 and CD8 lymphocytes, the ratio of CD4 to CD8 (CD4/CD8) and the concentration of antiFCV and anti-FHV-1 antibodies in the serum of the subjects, as well as the bacteriolytic activity of lysozyme and the haptoglobin level. Significantly higher values of almost all these parameters were recorded in cats receiving a combination of the immunostimulator and the vaccine during the whole study period compared to cats receiving only the immunostimulator or only the vaccine. Additionally, the increase in immunological parameters in animals from this group was positively correlated with the concentration of anti-FHV-1 and anti-FCV antibodies. This may indicate a stimulated humoral as well as cellular response. Neither Zylexis nor the vaccine alone induced as strong an immune response as the combined administration of the vaccine with the immunostimulator. This indicates that it may be advisable to combine vaccines against FHV-1 and FCV with immunostimulators to increase immunity against FHV-1 and FCV. Further studies of the influence of combined administration of vaccines and different immunomodulating preparations on the parameters of specific and non-specific immune responses in cats are necessary.

scholarly journals Effect of Acupoint Catgut Embedding on Intestinal Flora in Rats with Ovariectomized Osteoporosis

2021 ◽  
Vol 46 (4) ◽  
pp. 307-318
Author(s):  
Na Shi ◽  
Chu-Qiong Zhang ◽  
Long Han ◽  
Gang Ouyang
Keyword(s):  
Pathogenic Bacteria ◽  
Statistical Significance ◽  
Intestinal Flora ◽  
Valeric Acid ◽  
Mineral Density ◽  
Treatment Of Osteoporosis ◽  
Prevention And Treatment ◽  
Group A ◽  
Group B ◽  
Group D

Objectives: By observing the effect of acupoint catgut embedding on the intestinal flora of ovariectomized osteoporotic rats, the correlation between the regulation of intestinal flora and the prevention and treatment of osteoporosis was discussed preliminarily. Methods: By observing the effect of acupoint catgut embedding on the intestinal flora of ovariectomized osteoporotic rats, the correlation between the regulation of intestinal flora and the prevention and treatment of osteoporosis was discussed preliminarily. Result: Compared with Group A and Group B, bone mineral density (BMD) of femur and tibia in Group C decreased significantly (p<0.05), indicating successful modeling. Compared with Group C, BMD of femur and tibia in Group D was significantly increased (p<0.05). Compared with Group A and Group B, content of serum estrogens, calcium, and PTHrP in Group C were significantly decreased (p<0.05 or p<0.01). Content of serum estrogen, calcium, and PTHrP in Group D were significantly higher than those in Group C (p<0.05 or p<0.01). Compared with Group A and Group B, the abundance of mollicutes, actinobacteria, acidobacteria, chloroflexi and fusobacteria in group C was significantly increased. The abundance of probiotics in Group D such as lactobacillales, (lactobacillaceae, lactobacillus), bacillales, and streptococcus was significantly higher than that in Group C (p<0.05). The content of SCFAs such as acetic acid, butyric acid, iso-valeric acid, valeric acid and caproic acid in Group D were significantly higher than those in Group C, with statistical significance (p<0.05). Conclusions: Acupoint catgut embedding can effectively improve BMD, increase content of estrogen, calcium, PTHrP and SCFAs. Furthermore, embedding can also improve the abundance of probiotics and reduce the abundance of pathogenic bacteria. The changes of intestinal flora were correlated with the changes of estrogen and calcium, which may be one of the mechanisms of acupoint catgut embedding in the prevention and treatment of osteoporosis.

Clinical significance of prophylactic intrathecal chemotherapy in the treatment of glioblastoma multiforme

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13022-e13022
Author(s):  
T. Iuchi ◽  
K. Hatano ◽  
T. Sakaida ◽  
S. Hirono
Keyword(s):  
Clinical Significance ◽  
Local Control ◽  
Progression Free Survival ◽  
Intrathecal Administration ◽  
High Dose ◽  
Free Survival ◽  
Local Progression ◽  
Group A ◽  
Group B ◽  
Group D

e13022 Backgrounds: We previously have reported that hypo-fractionated high-dose irradiation (HdI; 68Gy/8F) showed excellent local control but no effect on prevention of cerebrospinal fluid dissemination (CSFd), resulted in limited efficacy on patients’ survival in glioblastoma (GBM). The aim of present analysis is to evaluate the clinical significance of prophylactic intrathecal administration of thiotepa (iT) in the treatment of GBM patients. Methods: Histologically confirmed GBMs without CSFd at diagnosis were enrolled. Patients were classified into four groups owing to the post-surgical treatment strategy as follows: Group A patients (n = 65) were treated by conventional radiotherapy (cRT; 60Gy/30F) alone; Group B patients (n = 17) were by cRT concurrent witn iT; Group C patients (n = 28) were by HdI alone; Group D patients (n = 30) were by HdI concurrent with iT. In Group B and D, Ommaya reservoir was placed into the lateral ventricle and 10mg of thiotepa was administrated weekly after surgery for five times. The local progression-free survival (PFS), CSFd-free survival (CFS), and overall survival (OS) were compared in these four groups. Results: Group C and D patients showed significantly longer PFS than Group A and B (p < 0.0001), suggesting the clinical significance of HdI for local control of this tumor. On the other hand, CFS in Group B and D was significantly longer than that in Group A and C (p = 0.049), demonstrating the effect of iT for prevention of CSFd. However, significant improvement of OS on the conventional treatment (Group A, median OS: 12.3 months) was observed only in Group D (median OS: 30.2 months, p = 0.002) and not in Group B or C (24 months, p = 0.135, and 14.9 months, p = 0.481 respectively). Conclusions: These data indicated that both of local control and prevention of CSFd were required for better survival of patients with GBM, and iT concurrent with HdI may be one of the treatments that fill these requirements. No significant financial relationships to disclose.

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