scholarly journals Effects of a flaxseed mixture and plant oils rich in α-linolenic acid on the adenoma formation in multiple intestinal neoplasia (Min) mice

2005 ◽  
Vol 94 (4) ◽  
pp. 510-518 ◽  
Author(s):  
Seija I. Oikarinen ◽  
Anne-Maria Pajari ◽  
Irma Salminen ◽  
Satu-Maarit Heinonen ◽  
Herman Adlercreutz ◽  
...  
Keyword(s):  
Linolenic Acid ◽  
Median Number ◽  
Control Group ◽  
Inverse Association ◽  
Oil Composition ◽  
Intestinal Neoplasia ◽  
Kinase C ◽  
Tumour Formation ◽  
Intestinal Tumour ◽  
Pkc Ζ

Flaxseed is a dietary source of possible chemopreventive compounds such as lignans and α-linolenic acid (ALA). To study the effects of a flaxseed mixture on adenoma formation in multiple intestinal neoplasia mice, the mice were fed a diet containing 2·7 % flaxseed, 4·5 % fibre and 3·7 % ALA. To elucidate the effect of oils of the mixture we also composed a diet without flaxseed but with the same oil composition. The median number of adenomas in the small intestine was fifty-four for the control group, and thirty-seven (P=0·023) and forty-two (P=0·095) for flaxseed and oil groups, respectively. Compared with controls (1·2 mm), the adenoma size was smaller in the flaxseed (0·9 mm; P=0·002) and oil (1·0 mm; P=0·012) groups. Both diets changed the proportions of n-3 and n-6 fatty acids in the colonic mucosa. Membrane β-catenin and protein kinase C (PKC)-ζ levels were reduced in the adenoma v. mucosa (P<0·05), and an inverse association was found between the membrane PKC-ζ in the mucosa and the adenoma number (r −0·460, P=0·008, n 32). Only the flaxseed diet increased lignan levels in the caecum (P=0·002) and in plasma (P=0·002) but they were not associated with tumour formation. The results suggest that the preventive effect of flaxseed on colon carcinogenesis may be due to the oil part of flaxseed, and the loss of β-catenin and PKC-ζ from the membranes of the mucosal tissue may play a permissive role in intestinal tumour development.

POSSIBILITY TO REDUCE THROMBOCYTOPENIA AFTER CHEMORADIOTHERAPY IN ONCOLOGICAL PATIENTS

2017 ◽  
Vol 63 (3) ◽  
pp. 466-469
Author(s):  
Luiza Korytova ◽  
Aleksey Meshechkin ◽  
Oleg Korytov ◽  
V. Krasnikova
Keyword(s):  
Combined Treatment ◽  
Treated Group ◽  
Median Number ◽  
Blood Analysis ◽  
Control Group ◽  
Level Control ◽  
Normal Range ◽  
Oncological Patients ◽  
Level Increase ◽  
And Control

Objective was to establish efficiency of sodium nucleospermat in correcting thrombocytopenia after chemoradiotherapy in oncological patients. Methods and materials. The study included data on 32 patients that had undergone combined treatment from January till May 2016. After detecting thrombocytopenia patients were randomized into two groups (16 patients in each): treated group, where patients received sodium nucleospermat, and control group, where sodium nucleospermat was not used. Thrombocyte level control was done on 5th, 10th and 15th day after treatment was over. Results and discussion. All 16 patients showed positive dynamics in increasing thrombocyte level after Sodium nucleospermat injection course was finished. This was proven by first (5th day) blood analysis. On average thrombocyte level after sodium nucleospermat treatment has risen to normal, at 161х109/1. Only 3 patients from this group had to pause radiotherapy for 5 days. Control group patients, which did not receive sodium nucleospermat, showed evidence of thrombocyte level recovery by 10th day only. On average thrombocyte level increase was insignificant, and median number was 111*109/l. Low thrombocyte level was main reason to pause radiotherapy for 11 (69%) patients in control group. Conclusion. Sodium nucleospermat allowed raising thrombocyte level to the lower normal range, which surpassed by 40%-50% in control group patients. Use of sodium nucleospermat did not show any cases of allergic reactions, toxicity or complications in oncological patients.

scholarly journals Direct evidence for a key role of protein kinase C in the development of vasospasm after subarachnoid hemorrhage

1992 ◽  
Vol 76 (4) ◽  
pp. 635-639 ◽  
Author(s):  
Shigeru Nishizawa ◽  
Nobukazu Nezu ◽  
Kenichi Uemura
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Direct Evidence ◽  
Control Group ◽  
Content Type ◽  
Kinase C ◽  
Protein Kinase C Activity ◽  
Fine Print

✓ Vascular contraction is induced by the activation of intracellular contractile proteins mediated through signal transduction from the outside to the inside of cells. Protein kinase C plays a crucial role in this signal transduction. It is hypothesized that protein kinase C plays a causative part in the development of vasospasm after subarachnoid hemorrhage (SAH). To verify this directly, the authors measured protein kinase C activity in canine basilar arteries in an SAH model with (γ-32P)adenosine triphosphate and the data were compared to those in a control group. Protein kinase C is translocated to the membrane from the cytosol when it is activated, and the translocation is an index of the activation; thus, protein kinase C activity was measured both in the cytosol and in the membrane fractions. Protein kinase C activity in the membrane in the SAH model was remarkably enhanced compared to that in the control group. The percentage of membrane activity to the total was also significantly greater in the SAH vessels than in the control group, and the percentage of cytosol activity in the SAH group was decreased compared to that in the control arteries. The results indicate that protein kinase C in the vascular smooth muscle was translocated to the membrane from the cytosol and was activated when SAH occurred. It is concluded that this is direct evidence for a key role of protein kinase C in the development of vasospasm.

Anakinra (AKR) prophylaxis (ppx) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) receiving orvacabtagene autoleucel (orva-cel).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2537-2537
Author(s):  
Luciano J. Costa ◽  
Sham Mailankody ◽  
Paul Shaughnessy ◽  
Parameswaran Hari ◽  
Jonathan L. Kaufman ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Phase 1 ◽  
Median Number ◽  
Control Group ◽  
T Cell Therapy ◽  
Disease Response ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

2537 Background: Orva-cel is a B-cell maturation antigen–targeted chimeric antigen receptor (CAR) T cell therapy being evaluated in the phase 1/2 EVOLVE study (NCT03430011) in pts with RRMM who had at least 3 prior lines of therapy (Tx). We previously reported safety and efficacy in the phase 1 study and established the recommended dose (RD) of orva-cel as 600 × 106 CAR+ T cells (Mailankody et al, ASCO 2020). Cytokine release syndrome (CRS), a dominant toxicity of CAR T cell therapy, is mediated in part by IL-1. We explore the role of ppx with AKR, an IL-1 signaling inhibitor, on reducing the incidence of grade (G) ≥2 CRS after orva-cel treatment at the RD. Methods: Fourteen pts were enrolled sequentially for AKR ppx and treated with orva-cel at the RD. The non-AKR ppx control group comprised the remainder of the phase 1 pts receiving orva-cel at the RD (n = 19). The median follow-up (range) was 3.0 mo (1.8–6.2) for the AKR ppx group and 8.8 mo (5.3–12.2) for the non-AKR ppx group. AKR was administered as 100 mg SC the night before orva-cel infusion, 3 h before the infusion (Day 1), and q24 h on Days 2–5. Dosing was increased to q12 h if CRS developed. CRS was graded by Lee (2014) criteria. Tocilizumab (T) and steroids (S) were used per protocol-specified treatment management guidelines. Results: Disease characteristics and outcomes are shown in the table. In AKR ppx and non-AKR ppx groups, median number of prior regimens was 6 and 5, and bridging Tx was used in 57% and 68% of pts, respectively. The total frequency of CRS was similar in the 2 groups, but with less G 2 in the AKR ppx pts; relative risk (95% CI) = 0.54 (0.21, 1.38). No G ≥3 CRS was seen in either group. The incidence of neurological events (NE), G ≥3 infection, and macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH) was similar. T and S use was numerically lower with AKR ppx. Orva-cel expansion kinetics were similar in the 2 groups. All pts had a 2-month efficacy assessment, with ORR in 100% of AKR ppx and 95% of non–AKR ppx pts. Conclusions: In this nonrandomized evaluation of AKR ppx with orva-cel treatment, the incidence of G ≥2 CRS was lower in pts receiving AKR ppx. The use of AKR ppx produced no adverse effect on the incidence of NE, infection, or MAS/HLH, nor on orva-cel expansion or disease response. These results warrant further study of AKR ppx in CAR T cell therapy. Clinical trial information: NCT03430011. [Table: see text]

Protein kinase C-ζ modulates thromboxane A2-mediated apoptosis in adult ventricular myocytes via Akt

2002 ◽  
Vol 282 (1) ◽  
pp. H320-H327 ◽  
Author(s):  
Yukitaka Shizukuda ◽  
Peter M. Buttrick
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cardiac Myocytes ◽  
Ventricular Myocytes ◽  
Kinase Assay ◽  
Dependent Manner ◽  
Adult Rat ◽  
Kinase C ◽  
Adult Cardiac Myocytes ◽  
Pkc Ζ

We hypothesized that thromboxane A2 (TxA2) receptor stimulation directly induces apoptosis in adult cardiac myocytes. To investigate this, we exposed cultured adult rat ventricular myocytes (ARVM) to a TxA2 mimetic [1S-[1α,2α(Z),3β(1E,3S*),4α]]-7-[3-[3-hydroxy-4-(4-iodophenoxy)-1-butenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (I-BOP) for 24 h. Stimulation with I-BOP induced apoptosis in a dose-dependent manner and was completely prevented by a TxA2 receptor antagonist, SQ-29548. We further investigated the role of protein kinase C (PKC) in this process. TxA2 stimulation resulted in membrane translocation of PKC-ζ but not PKC-α, -βII, -δ, and -ε at 3 min and 1 h. The activation of PKC-ζ by I-BOP was confirmed using an immune complex kinase assay. Treatment of ARVM with a cell-permeable PKC-ζ pseudosubstrate peptide (ζ-PS) significantly attenuated apoptosis by I-BOP. In addition, I-BOP treatment decreased baseline Akt activity and its decrease was reversed by treatment with ζ-PS. The inhibition of phosphatidylinositol 3-kinase upstream of Akt by wortmannin or LY-294002 abolished the antiapoptotic effect of ζ-PS. Therefore, our results suggest that the activation of PKC-ζ modulates TxA2 receptor-mediated apoptosis at least, in part, through Akt activity in adult cardiac myocytes.

scholarly journals Relevance of the body mass index in the cognitive status of diabetic patients with different alcohol-drinking patterns

2014 ◽  
Vol 66 (1) ◽  
pp. 347-353
Author(s):  
Serban Lacramioara ◽  
Cristina Toarba ◽  
Simona Hogas ◽  
A. Covic ◽  
A. Ciobica ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Alcohol Consumption ◽  
Alcohol Drinking ◽  
The Body ◽  
Control Group ◽  
Diabetic Patients ◽  
Inverse Association ◽  
Drinking Patterns ◽  
Alcohol Drinking Patterns ◽  
The Relationship

Nowadays the general relevance of alcohol consumption in diabetes is extremely controversial. There are recent reports that alcohol consumption could result in a decreased incidence of diabetes, as well as other studies demonstrating a positive association between alcohol consumption and type 2 diabetes; there are also reports arguing for an inverse association between the two or for no correlation at all. The different results obtained in these studies could be explained by the existence of several confounders that could influence the outcome of the aforementioned studies. In this paper, we studied the possible relevance of BMI as a confounder in the relationship between alcohol consumption in diabetes and cognitive function, by analyzing the correlations between BMI values in diabetic patients with different alcohol drinking patterns and the subdomains from some main psychometric tests, such as MMSE (Mini-Mental State Examination) and MOCA (Montreal Cognitive Assessment). Our results provide evidence for BMI as a possible confounder of the relationship between alcohol consumption in diabetes and cognitive function. We found a significant increase (p<0.0001) in BMI values in patients with diabetes compared to our control group. Most importantly, significant correlations between BMI parameters in alcohol-consuming diabetic patients and most of the subdomains for psychometric testing.

scholarly journals Effect of hydration with oral water on nonstress test in a hospital, Turkey: a randomized controlled trial

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Yeter Şener ◽  
Hüseyin Aksoy ◽  
Mürüvvet Başer
Keyword(s):  
Pregnant Women ◽  
Controlled Trial ◽  
Stress Test ◽  
Intervention Group ◽  
Median Number ◽  
Control Group ◽  
Normal Range ◽  
Content Type ◽  
Randomized Controlled ◽  
Study Intervention

PurposeThe aim of this study was to assess the effect of hydration with oral water on non-stress test (NST).Design/methodology/approachThe study was conducted as single-blinded and randomized controlled. Healthy and outpatient 32- to 40-week pregnant women who were aged 19 and older were included in the study. Intervention group pregnant women (n = 66) drank 500 ccs of water before the NST, and no attempt was made to the control group (n = 66). The NST parameters of the groups with fetal heart rate (FHR), variability, acceleration, deceleration, reactivity and nonreactivity were evaluated.FindingsBoth groups were found to be similar in terms of their descriptive characteristics and variables related to pregnancy (p > 0.05). The median FHR was 130.0 in the intervention group, 140.0 in the control group (p < 0.001), and the median number of the acceleration was 6.0 in the intervention group and 4.0 in the control group (p < 0.001). In terms of the median number of decelerations, the groups were similar (p > 0.05).Originality/valueIt was found that hydration with oral water had an effect on NST parameters of FHR and the number of accelerations. However, it was observed that the FHR was within the normal range in both groups. It was thought that it tended to increase the number of accelerations.

scholarly journals Essential role of protein kinase C ζ in transducing a motility signal induced by superoxide and a chemotactic peptide, fMLP

2007 ◽  
Vol 176 (7) ◽  
pp. 1049-1060 ◽  
Author(s):  
Kageaki Kuribayashi ◽  
Kiminori Nakamura ◽  
Maki Tanaka ◽  
Tsutomu Sato ◽  
Junji Kato ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Morphological Changes ◽  
Specific Inhibitor ◽  
Squamous Carcinoma ◽  
Inflammatory Cells ◽  
Dominant Negative ◽  
Chemotactic Peptide ◽  
Kinase C ◽  
Pkc Ζ

Under various pathological conditions, including infection, malignancy, and autoimmune diseases, tissues are incessantly exposed to reactive oxygen species produced by infiltrating inflammatory cells. We show augmentation of motility associated with morphological changes of human squamous carcinoma SASH1 cells, human peripheral monocytes (hPMs), and murine macrophage-like cell line J774.1 by superoxide stimulation. We also disclose that motility of hPMs and J774.1 induced by a chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine [fMLP]) was inhibited by superoxide dismutase or N-acetylcystein, indicating stimulation of motility by superoxide generated by fMLP stimulation. In these cells, protein kinase C (PKC) ζ was activated to phosphorylate RhoGDI-1, which liberated RhoGTPases, leading to their activation. These events were inhibited by dominant-negative PKCζ in SASH1 cells, myristoylated PKCζ peptides in hPMs and J774.1, or a specific inhibitor of RhoGTPase in SASH1, hPMs, and J774.1. These results suggest a new approach for manipulation of inflammation as well as tumor cell invasion by targeting this novel signaling pathway.

Ethanol sensitizes NF-κB activation in pancreatic acinar cells through effects on protein kinase C-ε

2006 ◽  
Vol 291 (3) ◽  
pp. G432-G438 ◽  
Author(s):  
Akihiko Satoh ◽  
Anna S. Gukovskaya ◽  
Joseph R. Reeve ◽  
Tooru Shimosegawa ◽  
Stephen J. Pandol
Keyword(s):  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
High Dose ◽  
Pancreatic Acini ◽  
Kinase C ◽  
Pkc Isoforms ◽  
Ethanol Abuse ◽  
Pkc Ζ ◽  
Sensitizing Effect

Although ethanol abuse is the most common cause of pancreatitis, the mechanism of alcohol's effect on the pancreas is not well understood. Previously, we demonstrated that in vitro ethanol treatment of pancreatic acinar cells augmented the CCK-8-induced activation of NF-κB, a key signaling system involved in the inflammatory response of pancreatitis. In the present study, we determine the role for individual PKC isoforms in the sensitizing effect of ethanol on NF-κB activation. Dispersed rat pancreatic acini were treated with and without ethanol and then stimulated with CCK-8; 100 nM CCK-8 caused both NF-κB and PKC-δ, -ε, and -ζ activation, whereas 0.1 nM CCK-8 did not increase PKC-ε, PKC-ζ, or NF-κB activity. CCK-8 (0.1 nM) did activate PKC-δ. PKC-ε activator alone did not cause NF-κB activation; however, together with 0.1 nM CCK-8, it caused NF-κB activation. Ethanol activated PKC-ε without affecting other PKC isoforms or NF-κB activity. Of note, stimulation of acini with ethanol and 0.1 nM CCK-8 resulted in the activation of PKC-δ, PKC-ε, and NF-κB. The NF-κB activation to 0.1 nM CCK-8 in ethanol-pretreated acini was inhibited by both PKC-δ inhibitor and PKC-ε inhibitor. Taken together, these results demonstrate the different modes of activation of PKC isoforms and NF-κB in acini stimulated with ethanol, high-dose CCK-8, and low-dose CCK-8, and furthermore suggest that activation of both PKC-ε and -δ is required for NF-κB activation. These results suggest that ethanol enhances the CCK-8-induced NF-κB activation at least in part through its effects on PKC-ε.

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