Hepatoprotective effect of trypsin/chymotrypsin against olanzapine-induced non-alcoholic steatohepatitis in rats

2021 ◽  
pp. 1-9
Author(s):  
Ghada S. Mahmoud ◽  
Ghada Hosny ◽  
Sally A. Sayed
Keyword(s):  
Hepatic Steatosis ◽  
Atypical Antipsychotics ◽  
Memory Function ◽  
Serum Levels ◽  
Drug Adherence ◽  
Ki67 Expression ◽  
Activity Unit ◽  
Before And After ◽  
Alpha 1 Antitrypsin ◽  
Hepatocyte Necrosis

Metabolic side effects of atypical antipsychotics are an important cause of deterioration of cognitive function and failure of drug adherence. The antifatty effect trypsin/chymotrypsin (T/C) and their mechanisms of action remain unclear. To investigate possible therapeutic effect of T/C in rat model of chronic olanzapine (OLZ) – induced hepatic steatosis. Twenty rats were divided into two groups: control (C), given distilled water, and O, given 1 mg/kg of OLZ orally daily for 7 weeks. Then, both groups were given T/C 3 enzyme activity unit (EAU)/kg orally as an add-on treatment daily for the next 5 weeks and were named T/C or T/C+O groups. Rat performance in radial arm water maze was tested twice before and after T/C treatment. We measured liver enzymes, alpha-1 antitrypsin, albumin, total protein, direct and total bilirubin, inflammatory cytokines, and lipoprotein serum levels. Liver samples were collected for histopathology and Ki67 expression. The T/C add-on caused significant reduction in OLZ-induced elevation of alanine transaminase (ALT; P < 0.01), aspartate transaminase (AST; P < 0.001), alkaline phosphatase (ALP; P < 0.05), total cholesterol (Tc; P < 0.01), low-density lipoproteins (LDL-c; P < 0.05), steatosis score (P < 0.001), hepatocyte necrosis (P < 0.01), and significantly increased Ki67 expression (P < 0.01). The T/C add-on to OLZ provided protection against hepatic steatosis, elevated enzymes, and disturbed lipid profile and increased Ki67 without disturbing memory function.

POSTOPERATIVE COMPLIANCE OF BARIATRIC SURGERY PATIENTS REGARDING THE ASSESSMENT OF SERUM LEPTIN LEVELS AND INSULIN RESISTANCE

2019 ◽  
Vol 49 (1/2019) ◽  
Keyword(s):  
Insulin Resistance ◽  
Bariatric Surgery ◽  
Serum Levels ◽  
Medical Laboratory ◽  
Leptin Resistance ◽  
Obese Patients ◽  
Laboratory Assessment ◽  
Serum Leptin ◽  
Before And After ◽  
Bariatric Patients

Background and aims: Overweight and obese patients who undergo bariatric surgery require a rigorous clinical and paraclinical assessment both before and after the surgery at 3, 6, and 12 months.The present study aims the assessment of serum leptin levels and insulin resistance status in compliant bariatric patients to scheduled medical laboratory assessment at 6 months after surgery. Material and Method: The study included 109 eligible patients selected for bariatric surgery, 48 of whom attended the scheduled visit at 6 months after the surgery. Laboratory assessing regarded the insulin resistance by determining before meal the serum levels of leptin, glucose and insulin, as well as HOMA 1 and HOMA 2 indexes. Results: Patients who underwent bariatric treatment experienced a significant decrease in insulin resistance status. A higher percentage in the preoperative group was recorded in women, feature which was also recorded in the postoperative group that attended the scheduled visit at 6 months after surgery. Age is also an important factor that significantly influences the behavioral adherence to postoperative visits. Conclusions: Insulin resistance status improved significantly in 6 months after bariatric surgery among the fully compliant patients. The percentage of attendance at scheduled visits is higher among women, and decreases with age. Keywords: obesity surgery, leptin resistance, insulin resistance, HOMA index, compliance

A pilot study on the effect of ulipristal acetate on myoma angiogenesis, measured by 2D ultrasound and VEGF serum levels

2020 ◽  
pp. 19-29
Author(s):  
Patricia Diaz Ortega ◽  
Manuel García Manero
Keyword(s):  
Pilot Study ◽  
Power Doppler ◽  
Uterine Fibroids ◽  
Premenopausal Women ◽  
Serum Levels ◽  
Ulipristal Acetate ◽  
Before And After ◽  
Angiogenesis Process ◽  
2D Ultrasound ◽  
Average Size

Introduction: Symptomatic uterine fibroids can cause symptoms that can be disabling. There are many treatments, including ulipristal acetate, whose role in reducing symptoms and decreasing the size of the fibroid is well known. With this preliminary study, we also try to evaluate the correlation between myoma vascularization measured by ultrasound (Power Doppler 2D) and serum VEGF levels, before and after treatment with ulipristal acetate; in patients diagnosed with symptomatic uterine fibroids. Materials and Methods: A preliminary, prospective observational pilot study was designed. Twenty-four premenopausal women, diagnosed with symptomatic uterine fibroids, were included and all of them completed the study. Four cycles of ulipristal acetate were administered according to the dose and indications specified in the data sheet. In order to assess the influence of this treatment on the angiogenesis process of the fibroids, measurements of VEGF serum levels were made and their vascularization was assessed by means of 2D power doppler ultrasound; at the beginning and the end of treatment. In addition, several determinations of the same parameters were made throughout the successive visits. Endpoints were defined as the decrease in VEGF levels from previous levels, the decrease in myoma vascularization on ultrasound, and the reduction in myoma size. Result: 24 patients who met the inclusion criteria were enrolled (n=24). The average size of myomas was reduced from 45,08 ? 24,02mm to 29?16,96mm after treatment. The average VEGF serum level significantly decreased after the first treatment cycle (from 147,17 ? 153,51 pg/ml to 102,04 ? 186,08pg/ml). Vascularization of myomas after treatment with ulipristal acetate was analyzed, and a significantly decrease was achieved in 83,3% of cases. Conclusion: There is a correlation between myoma vascularization and treatment with Ulipristal acetate. SPRMs may provide effective treatment for women with symptomatic fibroids by two ways: supports selective progesterone receptor modulators and reduced angiogenesis. Keywords: Angiogenesis; Ulipristal Acetate; Uterine fibroids; VEGF

Immunosuppression medication adherence after allogeneic hematopoietic stem cell transplant: Impact of a specialized clinical pharmacy program

2021 ◽  
pp. 107815522110001
Author(s):  
Florent Charra ◽  
Michael Philippe ◽  
Chloé Herledan ◽  
Anne-Gaëlle Caffin ◽  
Virginie Larbre ◽  
...  
Keyword(s):  
Clinical Pharmacy ◽  
Hematopoietic Stem Cell Transplant ◽  
Acute Gvhd ◽  
Intervention Group ◽  
Serum Levels ◽  
Control Group ◽  
Cell Transplant ◽  
Drug Adherence ◽  
Hematopoietic Stem ◽  
Discharge Prescription

This study aims to evaluate the impact of implementing a specialized clinical pharmacy program in patients with allogeneic hematopoietic stem cell transplant (HSCT) on their adherence to the immunosuppression treatment after discharge. A prospective open interventional design using a retrospective control group was used. The intervention was based on pharmaceutical consultations: the first was performed the day before discharge of HSCT unit and the next consultations during day-care follow-up (weeks 2 and 4 after discharge). Proactive medication reconciliation was implemented with a complete list of medications before the discharge prescription. The discharge prescription summarized on a personalized drug schedule was explained to the patient. The importance of optimal adherence and the potential problems related to self-medication were explained to the patient. Immunosuppression drug adherence was assessed by a direct method using serum levels of calcineurin inhibitors. The potential impact on acute GvHD, and infection was investigated. Twenty-six patients were included in the specialized clinical pharmacy program and 35 patients were in the control group. Seventy-nine pharmaceutical consultations were conducted in the intervention group, lasting a mean 25 min and 16 min for the first and following consultations, respectively. Serum levels in the therapeutic target range were higher in the intervention group (61.5% versus 53.0%, p = 0.07), with greater intra-individual variation (p = 0.005). There was no significant intergroup difference in acute GvHD (53.8% versus 50.3%, p = 0.85) or infection (26.9 versus 22.8%, p = 0.72). The implementation of a specialized clinical pharmacy program for patients who have received allogeneic HSCT seems to be beneficial for immunosuppression drug adherence; this now needs to be confirmed in a multicenter study involving a larger number of patients.

scholarly journals A prospective, observational clinical trial on the impact of COVID-19-related national lockdown on thyroid hormone in young males

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giulia Brigante ◽  
Giorgia Spaggiari ◽  
Barbara Rossi ◽  
Antonio Granata ◽  
Manuela Simoni ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Serum Levels ◽  
Stressful Event ◽  
Italian Population ◽  
Reference Ranges ◽  
Endocrine Regulation ◽  
Before And After ◽  
Hpt Axis ◽  
The Impact

AbstractTrying to manage the dramatic coronavirus disease 2019 (COVID-19) infection spread, many countries imposed national lockdown, radically changing the routinely life of humans worldwide. We hypothesized that both the pandemic per se and the consequent socio-psychological sequelae could constitute stressors for Italian population, potentially affecting the endocrine system. This study was designed to describe the effect of lockdown-related stress on the hypothalamic-pituitary-thyroid (HPT) axis in a cohort of young men. A prospective, observational clinical trial was carried out, including patients attending the male infertility outpatient clinic before and after the national lockdown for COVID-19 pandemic. The study provided a baseline visit performed before and a follow-up visit after the lockdown in 2020. During the follow-up visit, hormonal measurements, lifestyle habits and work management were recorded. Thirty-one male subjects were enrolled (mean age: 31.6 ± 6.0 years). TSH significantly decreased after lockdown (p = 0.015), whereas no significant changes were observed in the testosterone, luteinising hormone, follicle-stimulating hormone, estradiol and prolactin serum levels. No patient showed TSH serum levels above or below reference ranges, neither before nor after lockdown. Interestingly, TSH variation after lockdown was dependent on the working habit change during lockdown (p = 0.042). We described for the first time a TSH reduction after a stressful event in a prospective way, evaluating the HPT axis in the same population, before and after the national lockdown. This result reinforces the possible interconnection between psychological consequences of a stressful event and the endocrine regulation.

scholarly journals Clinical significance of circulating tumor cell related markers in patients with epithelial ovarian cancer before and after adjuvant chemotherapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meysam Yousefi ◽  
Sara Rajaie ◽  
Vahideh Keyvani ◽  
Somayeh Bolandi ◽  
Malihe Hasanzadeh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Clinical Significance ◽  
Therapy Response ◽  
Serum Levels ◽  
Circulating Tumor Cell ◽  
Tumor Stage ◽  
Disease Stage ◽  
Before And After

AbstractCirculating tumor cells (CTCs) have recently been considered as new prognostic and diagnostic markers for various human cancers; however, their significance in epithelial ovarian cancer (EOC) remains to be elucidated. In this study, using quantitative real-time PCR, we evaluated the expression of EPCAM, MUC1, CEA, HE4 and CA125 mRNAs, as putative markers of CTCs, in the blood of 51 EOC patients before and/or after adjuvant chemotherapy. Our results demonstrated that, before chemotherapy, the expression of EPCAM, MUC1, CEA and HE4 mRNAs were correlated to each other. CEA expression was correlated with tumor stage (r = 0.594, p = 0.000) before chemotherapy, whereas its expression after chemotherapy was correlated with serum levels of CA125 antigen (r = 0.658, p = 0.000). HE4 mRNA showed the highest sensitivity both before and after chemotherapy (82.98% and 85.19%, respectively) and the persistence of this marker after chemotherapy was associated with advanced disease stage. The expression of CA125 mRNA had negative correlation with the other markers and with tumor stage and therapy response (evaluated by the measurement of serum CA125 antigen). Collectively, our results indicated a better clinical significance of tumor-specific markers (CEA and HE4 mRNAs) compared to epithelial-specific markers (EPCAM and MUC1 mRNAs).

scholarly journals AB0042 CYTOKINE NETWORK ELUCIDATED BY THE QUANTIFICATION OF MULTIPLE CYTOKINES IN THE SERUM SEQUENTIALLY SAMPLED FROM RA PATIENTS WHO WERE TREATED WITH BIOLOGIC DMARDS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1323.2-1324
Author(s):  
K. Sato ◽  
S. Mamada ◽  
C. Hayashi ◽  
T. Nagashima ◽  
S. Minota
Keyword(s):  
Bone Erosion ◽  
Feedback System ◽  
Serum Levels ◽  
Type I Interferons ◽  
Type I ◽  
Serum Samples ◽  
Cytokine Network ◽  
Biologic Dmards ◽  
Type I Ifns ◽  
Before And After

Background:Biologic disease modifying anti-rheumatic drugs (DMARDs) have demonstrated that proinflammatory cytokines such as interleukin (IL-) 6 and tumor necrosis factor (TNF) play important roles in the pathogenesis of rheumatoid arthritis (RA). Other cytokines, such as type I interferons (IFNs), are also implicated in its pathogenesis (ref 1). However, the complete picture of the cytokine network involved in RA remains to be elucidated.Objectives:By quantifying sets of cytokines in the serum of RA patients before and after treatment with various biologic DMARDs, we sought to determine the effects of drugs on (A) type I IFNs, (B) soluble IL-6 receptors, and (C) other cytokines.Methods:52 patients with RA were treated with various biologic DMARDs (tocilizumab (TOC): 16, abatacept (ABT): 15, and TNF inhibitors (TNFi): 21). Serum samples were obtained (1) before, (2) approximately 4 weeks after (3) and approximately 12 weeks after the initiation of treatment. A suspension bead-array system was used for analysis; Bio-Plex Human Cytokine 17-plex Assay kits and Express Custom Panels (Bio-Rad), including IFN-β, IFN-α2, soluble IL-6 receptor α (sIL6Rα) and gp130 were used.Results:(1) As expected, the disease activity score 28-joiny count (DAS28) using the erythrocyte sedimentation rate (ESR) significantly decreased in all three groups (TOC, ABT and TNFi) by 12 weeks.(2) IFN-α2 was barely detected in the serum samples. IFN-β seemed to increase slightly in the ABT group, but the increase was not statistically significant.(3) The levels of sIL6Rα did not change substantially. Those of gp130 decreased slightly but significantly in the TOC group by 12 weeks.(4) The levels of IL-6 decreased significantly in the ABT group by 12 weeks. Those in the TNFi group decreased significantly at 4 weeks but not 12 weeks (Fig. 1A).(5) The levels of IL-7 decreased significantly only in the TOC group (Fig. 1B).Conclusion:(1) The biologic DMARDs tested in this study did not significantly affect the serum levels of type I IFNs in this study.(2) The decrease in gp130 in the TOC group may imply that gp130 is induced by IL-6, although whether this level of decrease has physiological significance is open to question.(3) Serum IL-6 was significantly decreased in the TNFi group at 4 weeks but not 12 weeks. TNF has been reported to induce IL-6 (ref 2), but negative feedback loop(s) may be present. Such a feedback system might make the discontinuation of TNFi difficult, even if patients are in remission.(4) IL-7 may be a target of IL-6. A higher level of IL-7 has been reported to be present in the joints of RA patients compared with osteoarthrosis and it is a cytokine implicated in the differentiation of osteoclasts (ref 3). This may partly explain the effect of TOC on preventing bone erosion in RA.References:[1]Ann Rheum Dis. 2007; 66: 1008–14[2]Rheumatology 2007; 46: 920-6[3]Rheumatology 2008; 47: 753-9Acknowledgments:We thank all the members of the Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University. We are also grateful to the patients involved in this study.Disclosure of Interests:Kojiro Sato Grant/research support from: Abbie, Pfizer, Chugai, Astellas, Mitsubishi-Tanabe, Ono, Takeda, Sachiko Mamada: None declared, Chiyomi Hayashi: None declared, Takao Nagashima: None declared, Seiji Minota: None declared

Antitumor effects of Auraptene in 4T1 tumor‐bearing Balb/c mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mohammad Reza. Shiran ◽  
Davar Amani ◽  
Abolghasem Ajami ◽  
Mahshad Jalalpourroodsari ◽  
Maghsoud Khalizadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Tumor Volume ◽  
Serum Levels ◽  
Ki 67 ◽  
Tumor Bearing ◽  
Paraffin Oil ◽  
Anti Cancer ◽  
Before And After ◽  
Ifn Γ

Abstract Objectives Breast cancer is a common malignant tumor in women with limited treatment options and multiple side effects. Today, the anti-cancer properties of natural compounds have attracted widespread attention from researchers worldwide. Methods In this study, we treated 4T1 tumor-bearing Balb/c mice with intraperitoneal injection of Auraptene, paraffin oil, and saline as two control groups. Body weight and tumor volume were measured before and after treatment. Hematoxylin and eosin (H & E) staining and immunohistochemistry of Ki-67 were used as markers of proliferation. In addition, ELISA assays were performed to assess serum IFN-γ and IL-4 levels. Results There was no significant change in body weight in all animal groups before and after treatment. 10 days after the last treatment, Auraptene showed its anti-cancer effect, which was confirmed by the smaller tumor volume and H & E staining. In addition, Ki-67 expression levels were significantly reduced in tumor samples from the Auraptene-treated group compared to the paraffin oil and saline-treated groups. In addition, in tumor-bearing and normal mice receiving Auraptene treatment, IL-4 serum production levels were reduced, while serum levels of IFN-γ were significantly up-regulated in tumor-bearing mice after Auraptene treatment. Conclusions In the case of inhibition of tumor volume and Ki-67 proliferation markers, Auraptene can effectively inhibit tumor growth in breast cancer animal models. In addition, it might increases Th1 and CD8 + T cell responses after reducing IL-4 serum levels and IFN-γ upregulation, respectively. However, further research is needed to clarify its mechanism of action.

scholarly journals Continuous elevation of procalcitonin in cirrhosis combined with hepatic carcinoma: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Juan Lu ◽  
Chun-lei Chen ◽  
Jian-di Jin ◽  
Jun Chen ◽  
Cheng-bo Yu
Keyword(s):  
Liver Disease ◽  
Bacterial Infection ◽  
Severe Infection ◽  
Serum Levels ◽  
Decompensated Cirrhosis ◽  
Hepatic Carcinoma ◽  
Multiple Loci ◽  
Before And After ◽  
Severe Cirrhosis ◽  
End Stage

Abstract Background Serum levels of procalcitonin (PCT) are considered a useful biomarker for the diagnosis of bacterial infection or inflammation. There are few reports of high PCT levels in end-stage liver disease regardless of bacterial infection. Here, we present a case of extremely high PCT levels (> 100 ng/mL) in a patient with severe cirrhosis combined with hepatic carcinoma. Case presentation A 65-year-old man developed end-stage cirrhosis with hepatic carcinoma. Radiographic imaging showed a massive hepatocellular carcinoma with multiple loci lack of indications of resection. Hence, transcatheter hepatic arterial chemoembolization was performed three times over a period of 4 months. Before and after interventional therapies, the biochemistry laboratory results were only slightly abnormal except for persistently high PCT concentrations (> 100 ng/mL), irrespective of the evidence for bacterial infection or sepsis. Conclusions This case suggests that continuously high levels of PCT (> 100 ng/mL) may be present in advanced liver disease, particularly in complex situations such as decompensated cirrhosis and liver cancer, in the absence of severe infection or sepsis. This knowledge could expand the significance of PCT in liver disease.

scholarly journals Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Conti Fabrizio ◽  
Ceccarelli Fulvia ◽  
Perricone Carlo ◽  
Massaro Laura ◽  
Marocchi Elisa ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Laboratory ◽  
Renal Involvement ◽  
Serum Levels ◽  
Activity Measurement ◽  
Systemic Lupus ◽  
Before And After ◽  
Dsdna Antibodies

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status.Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM).Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.;P=0.001). Serositis resulted significantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.;P<0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA − (21.8%,P=0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P=0.7).Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.

Cyclosporine increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system

2008 ◽  
Vol 294 (3) ◽  
pp. R811-R818 ◽  
Author(s):  
Chao-Hung Wang ◽  
Wen-Jin Cherng ◽  
Ning-I Yang ◽  
Chia-Ming Hsu ◽  
Chi-Hsiao Yeh ◽  
...  
Keyword(s):  
Critical Role ◽  
Serum Levels ◽  
Blood Levels ◽  
Short Term ◽  
Endothelial Progenitor ◽  
Beneficial Effects ◽  
Dpp Iv ◽  
Before And After ◽  
Cell Mobilization

Cyclosporin A (CsA) improves the success rate of transplantation. The CD26/dipeptidylpeptidase IV (DPP IV) system plays a critical role in mobilizing endothelial progenitor cells (EPCs) from bone marrow. This study investigated whether CsA manipulates CD26/DPP IV activity and increases EPC mobilization. C57BL/6 mice were divided into control and CsA-treated groups. Before and after hindlimb ischemia was induced, circulating EPC number and serum levels of different cytokines were measured. Compared with the controls, CsA treatment significantly increased the blood levels of stroma-derived factor-1α and stem cell factor after ischemic stress ( P < 0.001). The CsA group displayed a significant increase in the number of circulating EPCs (sca-1+KDR+ and c-kit+CD31+ EPCs, both P < 0.05). In vivo, CsA caused a significant increase in the numbers of EPCs incorporated into the Matrigel and ischemic limbs ( P < 0.05). In the peripheral blood, CsA significantly decreased CD26+ cell numbers and attenuated the plasma CD26/DPP IV activity ( P < 0.001). Furthermore, short-term CsA treatment significantly improved the perfusion of ischemic limbs and decreased the spontaneous digital amputation rate. In summary, CsA manipulates the mobilization of EPCs into the circulation via the CD26/DPP IV system. Short-term CsA treatment has beneficial effects on angiogenesis of ischemic tissues.

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