Systemic and Local Cytokine Profile in Biliary Atresia

Purpose Systemic and local immune environments in human biliary atresia (BA) were analyzed. Methods Plasma concentrations of 19 inflammatory components in 16 preoperative BA patients (median age, 51 days), 13 normal controls (NCs) (44 days), and 15 cholestatic controls (CC) (23 days) were measured using flow cytometry, and compared according to post-Kasai outcomes in BA patients. Hepatic mRNA levels of representative helper T (Th) cell cytokines and forkhead box protein 3 (FoxP3) quantified by real-time reverse transcription polymerase chain reaction were compared between BA and non-BA. Results No significant differences were observed between BA and control in serum Th1, Th2, or macrophage markers, while soluble cellular adhesion molecule (CAM) levels were significantly higher in BA (p < 0.0001 for NC; p = 0.0003 for CC). No statistically significant difference was discovered between BA with favorable and unfavorable prognosis. Hepatic mRNA levels of interferon-gamma or interleukin-4 showed no significant differences between BA and non-BA, while FoxP3 was significantly higher in BA (p = 0.01). Conclusions A skewed bias toward specific Th-oriented immunity was not demonstrated in either the systemic or local environment in the early stage of human BA, with patient prognoses not necessarily revealed by preoperative plasma inflammatory component levels. CAM and regulatory T cell roles and functions warrant further investigation.

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Identification a potential therapeutic target in castrate resistance prostate cancer by using microarray

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v9ispl1.1416 ◽

2018 ◽

Vol 9 (SPL1) ◽

Author(s):

Massar Ibrahim Shekhan

Keyword(s):

Prostate Cancer ◽

Cell Line ◽

Lncap Cell ◽

Early Stage ◽

Cancer Cell Line ◽

Mrna Levels ◽

Line Model ◽

Cell Line Model ◽

Number Of Patients ◽

Significant Difference

The androgen receptor (AR) has a crucial role in the proliferation and progression of prostate cancer. anti-androgen therapy is used in the early stage of the disease and the patients respond well,howevera significant number of patients eventually will develop resistance,entering a castrate-resistant state,with very poor prognosis,which is a major clinical challenge at the moment. Enzalutamide,have shown potential in the treatment of CRPC patients,but response is just 50% and the development of resistance to these are challenging clinic. This study aims to investigate the whole genomic expression of LNCaP prostate cancer cell line model,compared to resistant to Enzalutamide model. TROP-2 demonstrates high expression in Enzalutamide resistant cells in our gene microarray,which mightsuggest TROP-2 may serve as a biomarker of resistance. The preliminary data reveal an increase in expression of TROP-2 in the LNCaP-Enz-R cell line model,compared with parental LNCaP cell,at both the protein and mRNA levels. siRNA againstTROP-2 led a decreases in a proliferation and cell cycle progression of the LNCaP-Enz-R cell line,whereas no significant difference was noticed in the parental,androgen sensitive LNCaP cell line. In addition,Knockdown of TROP-2 decrease migration of LNCaP-Enz-R cell line significantly,while no effect was observed in parental LNCaP cell

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PROGNOSTIC VALUE OF PRO-ADM BIOMARKER IN PATIENTS WITH COVID-19.

Working Paper of Public Health ◽

10.4081/wpph.2021.9312 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Nashua Daidone ◽

Tiziana Callegari ◽

Elia Ranzato

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Prognostic Value ◽

Early Stage ◽

Plasma Concentrations ◽

Risk Of Mortality ◽

Single Center Study ◽

Significant Difference ◽

Short Term Mortality ◽

Automated Instrument

This study was performed at the analytical laboratory of the Hospital SS. Antonio e Biagio e Cesare Arrigo" Hospital in Alessandria (AL) in the period March-June 2020. This is an observational, prospective, single-center study carried out on a cohort of patients diagnosed with ARDS secondary to SARS-CoV2 infection admitted in the first wave of the pandemic at the Sub-Intensive Care Unit of the Hospital of Alessandria. OBJECTIVE The aim of this study was to assess plasma concentrations of the regional mean proadrenomedullin biomarker (MR-proADM) at the time of patient access to the Emergency Department and subsequently 1, 3 and 5 days after admission, to verify its prognostic value in terms of short-term mortality. The second objective of the study was to compare this biomarker with other commonly used biomarkers such as PCR and Procalcitonin, to evaluate the effectiveness of MR-proADM in risk stratification in these patients. METHODOLOGY Samples used in this study were collected in a tube containing the anticoagulant EDTA, and measurements were performed using a fully automated instrument: the Kryptor Compact Plus. RESULTS Among the various Biomarkers assayed only MR-proADM and LDH concentrations were significantly higher in deceased patients than in surviving patients while no statistically significant difference was observed for PCR PCT concentrations. Increasing levels of MRproADM between the second and fifth day of admission to the intensive care unit represent the key to determining mortality risk. CONCLUSIONS Mr-proADM was found to be a more effective biomarker than other commonly used biomarkers (PCR, WBC, Procalcitonin) in identifying Covid-19 patients with poor prognosis at an early stage. This study allowed clinicians to routinely include the assay of this biomarker, useful in the stratification of these patients and in predicting a higher or lower risk of mortality, in the second wave of the epidemic.

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High Levels of Adhesion Molecules Are Associated with Impaired Endothelium-dependent Vasodilation in Patients with Peripheral Arterial Disease

Thrombosis and Haemostasis ◽

10.1055/s-0037-1612905 ◽

2001 ◽

Vol 85 (01) ◽

pp. 63-66 ◽

Cited By ~ 57

Author(s):

Vincenzo Martone ◽

Tiziana de Cristofaro ◽

Salvatore Corrado ◽

Antonio Silvestro ◽

Anna Maria Di Donato ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Adhesion Molecules ◽

Adhesion Molecule ◽

Close Association ◽

Plasma Concentrations ◽

Arterial Disease ◽

Cellular Adhesion ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Cellular Adhesion Molecule

SummarySoluble intercellular adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (sVCAM-1) were measured alongside flow-mediated vasodilation (FMD) in 34 patients with intermittent claudication and 14 control subjects. Patients with plasma sICAM-1 >253 ng/mL (median value) showed lower FMD than those with sICAM-1 <253 ng/mL (5.6 ± 1.8% vs 9.6 ± 4.2%, p <0.01). Similarly, in the 17 patients with plasma sVCAM-1 >414 ng/mL, FMD was lower than in the remaining 17 patients (6.1 ± 1.9% vs 9.2 ± 4.5%, p <0.05). Additionally, when endothelial dysfunction was defined as FMD ≤5.5%, patients with FMD below this value had higher plasma concentrations of sICAM-1 and sVCAM-1 than those with FMD >5.5%. Therefore, our findings indicate a close association between elevated plasma levels of adhesion molecules and endothelial dysfunction. As impaired endothelial function is one of the first steps in atherogenesis, our findings have clinical relevance since they serve as the basis for further evaluation of sICAM-1 and sVCAM-1 as potential plasma markers for progression of atherosclerosis in a population at high risk.

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Endothelial Activation and Immune Thrombocytopenia: An Engagement Waiting for Consolidation

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211054514 ◽

2021 ◽

Vol 27 ◽

pp. 107602962110545

Author(s):

Alaa Efat ◽

Sabry Shoeib ◽

Aida Nazir ◽

Essam Abdelmohsen ◽

Ashraf Dawod ◽

...

Keyword(s):

Immune Thrombocytopenia ◽

Complete Blood Count ◽

Serum Levels ◽

Endothelial Activation ◽

Cellular Adhesion ◽

Coagulation System ◽

Enzyme Linked Immunosorbent Assay ◽

Cellular Adhesion Molecule ◽

Significant Difference ◽

Patients At Risk

Immune thrombocytopenia (ITP) appears to be a heterogeneous disease. In some patients, autoimmunity may be associated with an inflammatory process, and in other patients, low platelets may interfere with other aspects of the coagulation system. Either may predispose to thrombosis or bleeding. Further investigation of the interactions of platelets, with inflammatory cytokines and endothelial biomarkers, may help us to better understand the disease, and to recognize those patients at risk of bleeding, or conversely thrombosis. The aim of this work is to estimate von Willebrand factor (vWF) and vascular cellular adhesion molecule (V-CAM) serum levels in adult immune thrombocytopenic patients (ITP) and to decipher their possible clinical correlates. Eighty adults (≥ 18 years) were enrolled in the study; naive newly diagnosed 40 patients with primary ITP (according to the ASH 2019) and 40 sex and age-matched healthy controls, all groups are subjected for complete blood count (CBC), liver, and renal function tests, ESR, CRP, V-CAM, and VWF-Ag by enzyme-linked immunosorbent assay (ELISA). There was a highly statistically significant difference between case and control as regards to the mean level of VWF-Ag and V-CAM. vWF and V-CAM could serve as biomarkers for endothelial alterations and should be investigated as a predictor of thrombocytopenic bleeding and tailor patient management accordingly.

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Comparative Plasma Heparin Levels after Subcutaneous Sodium and Calcium Heparin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648673 ◽

1978 ◽

Vol 40 (02) ◽

pp. 397-406 ◽

Cited By ~ 8

Author(s):

Joyce Low ◽

J C Biggs

Keyword(s):

Peak Plasma ◽

Plasma Concentrations ◽

Factor Xa ◽

Normal Subjects ◽

Sodium Salts ◽

Sodium Heparin ◽

Significant Difference ◽

Heparin Plasma ◽

Calcium Heparin ◽

Plasma Heparin

SummaryComparative plasma heparin levels were measured in normal subjects injected subcutaneously with 5,000 units of the sodium and calcium salts of heparin. Plasma heparin levels were measured up to 7 hr post-injection by an anti-factor Xa assay (Denson and Bonnar 1973). Preliminary studies indicated that heparin levels were reproducible in subjects who received two injections of the same heparin. Peak plasma concentrations (Cmax) and the time at which peak concentration was reached (Tmax) varied greatly from subject to subject. In one group of subjects (15) two commonly used heparins, a sodium heparin (Evans) and a calcium heparin (Choay) were compared. Peak heparin concentrations were not significantly different. However the Tmax for the sodium heparin (1.5 hr) was significantly earlier than the Tmax for the calcium heparin (3 hr) and this was not due to a difference in the volume of the two heparin injections. No significant difference could be detected in the plasma clearance rate and the molecular weight distribution of the two heparins.In two other groups of subjects, sodium and calcium preparations from two manufacturers were compared. In general, the sodium salts gave rise to significantly higher plasma concentrations, which could be interpreted as a greater bioavailability of sodium salts. These results indicate that the salt of the heparin can influence the plasma concentration achieved after subcutaneous injection.

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Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

Current Drug Metabolism ◽

10.2174/1389200221666200218121050 ◽

2020 ◽

Vol 21 (2) ◽

pp. 126-131

Author(s):

Bhuvanachandra Pasupuleti ◽

Vamshikrishna Gone ◽

Ravali Baddam ◽

Raj Kumar Venisetty ◽

Om Prakash Prasad

Keyword(s):

Plasma Concentration ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Plasma Concentrations ◽

Control Group ◽

Drug Concentrations ◽

Significant Difference ◽

Post Hoc ◽

Hydrolysis Of ◽

Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

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Relapse After Early-Stage, Favorable Hodgkin Lymphoma: Disease Characteristics and Outcomes With Conventional or High-Dose Chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.20.00947 ◽

2021 ◽

Vol 39 (2) ◽

pp. 107-115

Author(s):

Paul J. Bröckelmann ◽

Horst Müller ◽

Teresa Guhl ◽

Karolin Behringer ◽

Michael Fuchs ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Early Stage ◽

High Dose Chemotherapy ◽

Sensitivity Analyses ◽

High Dose ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy ◽

Significant Difference ◽

First Diagnosis

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.

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The effect of metabolism on the course of labor and the postpartum period in highly productive cows

BIO Web of Conferences ◽

10.1051/bioconf/20201700256 ◽

2020 ◽

Vol 17 ◽

pp. 00256

Author(s):

Murat Baimishev ◽

Sergey Eremin ◽

Kirill Plemyashov ◽

Hamidulla Baimishev ◽

Igor Konopeltsev ◽

...

Keyword(s):

Lipid Metabolism ◽

Postpartum Period ◽

Early Stage ◽

Antioxidant Properties ◽

Antioxidant Systems ◽

Dry Period ◽

Blood Samples ◽

Start Up ◽

Significant Difference ◽

Duration Of Pregnancy

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.

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Intranasal administration of the chemotherapeutic perillyl alcohol results in selective delivery to the cerebrospinal fluid in rats

Scientific Reports ◽

10.1038/s41598-021-85293-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Geetika Nehra ◽

Shannon Andrews ◽

Joan Rettig ◽

Michael N. Gould ◽

Jill D. Haag ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Brain Tumors ◽

Nasal Mucosa ◽

Brain Cancer ◽

Intranasal Administration ◽

High Performance ◽

Early Stage ◽

Plasma Concentrations ◽

Perillyl Alcohol ◽

Systemic Absorption

AbstractPerillyl alcohol (POH) has been extensively studied for the treatment of peripheral and primary brain tumors. The intranasal route of administration has been preferred for dosing POH in early-stage clinical trials associated with promising outcomes in primary brain cancer. However, it is unclear how intranasal POH targets brain tumors in these patients. Multiple studies indicate that intranasally applied large molecules may enter the brain and cerebrospinal fluid (CSF) through direct olfactory and trigeminal nerve-associated pathways originating in the nasal mucosa that bypass the blood–brain barrier. It is unknown whether POH, a small molecule subject to extensive nasal metabolism and systemic absorption, may also undergo direct transport to brain or CSF from the nasal mucosa. Here, we compared CSF and plasma concentrations of POH and its metabolite, perillic acid (PA), following intranasal or intravascular POH application. Samples were collected over 70 min and assayed by high-performance liquid chromatography. Intranasal administration resulted in tenfold higher CSF-to-plasma ratios for POH and tenfold higher CSF levels for PA compared to equal dose intravascular administration. Our preclinical results demonstrate POH undergoes direct transport from the nasal mucosa to the CSF, a finding with potential significance for its efficacy as an intranasal chemotherapeutic for brain cancer.

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Age-Related Biology of Early-Stage Operable Breast Cancer and Its Impact on Clinical Outcome

Cancers ◽

10.3390/cancers13061417 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1417

Author(s):

Binafsha M. Syed ◽

Andrew R. Green ◽

Emad A. Rakha ◽

David A.L. Morgan ◽

Ian O. Ellis ◽

...

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Histological Grade ◽

Survival Rates ◽

Growth Factor Receptor ◽

Progesterone Receptors ◽

Biological Characteristics ◽

Cancer Specific Survival ◽

Age Related ◽

Significant Difference

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.

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