Direct comparison of the effects of liraglutide and dulaglutide on the dynamics of scales and markers of hepatic fibrosis

Objective. Comparison of the effects of liraglutide and dulaglutide on the dynamics of scales and markers of hepatic fibrosis.Materials and methods. 35 patients with NAFLD were included in the study and received liraglutide 1.8 mg or dulaglutide 1.5 mg once daily for 6 months.Results. Body weight and glycated hemoglobin (HbA1C) decreased significantly and comparable after 6 months of treatment in both groups. Serum aspartate aminotransferase (AST) levels decreased only in the dulaglutide group. The decrease in the AST level in the dulaglutide group was from 31.9 ± 26.8 to 30.8 ± 10.6 U / L (p = 0.04). The dynamics of the risk of fibrosis reached statistical significance only when assessed on the FIB-4 scale in the liraglutide group when comparing the baseline values and values after 6 months of treatment — 1.18 ± 0.51 and 0.97 ± 0.40, respectively (p = 0.022). In the dulaglutide group, there was also an insignificant positive dynamics of 1.31 ± 0.53 and 1.11 ± 0.23 (p = 0.865), which can be explained by the minimal severity of changes at baseline.Conclusions. The study demonstrated comparable effects of liraglutide and dulaglutide on metabolic parameters and, at the same time, the advantage of liraglutide in influencing the dynamics of the risk of fibrosis, assessed on the FIB-4 scale. To unequivocally confirm the benefits of liraglutide in the treatment of patients with NAFLD, randomized prospective comparative studies of various aGPP1 on large samples of patients with different stages of NAFLD are needed.

Download Full-text

Effect of Terminalia Chebula (Haritaki) on Serum Aspartate Aminotransferase, Alanine Aminotransferase in Paracetemol induced liver damage in Wister Albino Rats

Journal of Bangladesh Society of Physiologist ◽

10.3329/jbsp.v10i1.24609 ◽

2015 ◽

Vol 10 (1) ◽

pp. 1-5

Author(s):

Tania Yeasmin ◽

Qazi Shamima Akhter ◽

Syeda Tasfia Siddika ◽

Fayeza Karim

Keyword(s):

Body Weight ◽

Liver Function ◽

Liver Damage ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Basal Diet ◽

Base Line ◽

Terminalia Chebula ◽

Serum Aspartate Aminotransferase ◽

Bonferroni Test

Background: Liver plays a major role in detoxification and excretion of many endogenous and exogenous compounds. Any injury may lead to severe liver damage and impairment of liver function. Harbal plants such as Terminalia chebula (Haritaki) may have free radical scavenging activity thereby can be used for the prevention and treatment of liver damage.Objective: To observe the effect of Terminalia chebula on paracetamol induced changes of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in Wister albino rats.Methods: This experimental study was carried out in the Department of Physiology, Dhaka Medical College, Dhaka from January to December 2013. Total 44 rats with age 90 to 120 days, weighing between 150 to 200 gm were selected. After acclimatization for 14 days, they were divided into base line control (BC, n=11), paracetamol treated control (PC, n=11),Terminalia chebula pretreated and paracetamol treated (TCP-PCT n=11) and paracetamol pretreated and Terminalia chebula treated group (PCP-TCT, n=11). All groups received basal diet for 21 consecutive days. In addition to basal diet, rats of BC received propylene glycol (2ml/kg body weight, orally) and PC received single dose of paracetamol suspension (750mg/kg body weight, orally) on 21st day. Rats of TCP-PCT received Terminalia chebula extract (200 mg/kg body weight, orally) for 21 consecutive days and paracetamol suspension (750mg/kg body weight, orally) on 21st day. Again, rats of PCP-TCT received paracetamol suspension (750mg/kg body weight, orally) on the 1st day and Terminalia chebula extract (200 mg/kg body weight orally) for 21 consecutive days. All rats were sacrificed on 22nd day and then blood samples were collected. For assessment of liver function serum AST and ALT levels were estimated by using standard laboratory kits. The statistical analysis was done by one way ANOVA and post hoc Bonferroni test as applicable.Results: The mean serum AST and ALT levels were significantly (p<0.001) higher in PC in comparison to those of BC. Serum AST and ALT levels of all experimental groups were significantly (P<0.001) lower than PC group. Conclusion: From the results of this study, it may be concluded that Terminalia chebula may have some hepatoprotective effects in paracetamol induced liver damage in rats.Bangladesh Soc Physiol. 2015, June; 10(1): 1-5

Download Full-text

Crocin attenuates cisplatin-induced liver injury in the mice

Human & Experimental Toxicology ◽

10.1177/0960327113511475 ◽

2013 ◽

Vol 33 (8) ◽

pp. 855-862 ◽

Cited By ~ 30

Author(s):

Y Sun ◽

J Yang ◽

L-Z Wang ◽

L-R Sun ◽

Q Dong

Keyword(s):

Oxidative Stress ◽

Body Weight ◽

Caspase 3 ◽

Antitumor Agents ◽

Mitogen Activated Protein Kinase ◽

Protective Effects ◽

Once Daily ◽

Liver Histopathology ◽

Mitogen Activated Protein ◽

Serum Aspartate Aminotransferase

Cisplatin (CDDP) is one of the most frequently used antitumor agents, but its application is significantly limited by its hepatotoxicity. In the present study, we investigated the effects of crocin against CDDP-induced oxidative stress and apoptosis in the liver of Kunming mice. Crocin was administered to the mice once daily for 7 consecutive days at the doses of 6.25 and 12.5 mg/kg body weight orally. On day 1, a single intraperitoneal injection of CDDP was given at the dose of 10 mg/kg body weight. Crocin treatment significantly improved CDDP-induced hepatic damage as indicated by serum aspartate aminotransferase and alanine aminotransferase levels. Crocin relieved CDDP-induced oxidative stress by reducing malondialdehyde level and recovering the levels of glutathione and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. In addition, liver histopathology indicated that crocin alleviated CDDP-induced focal necrosis. Immunohistochemical staining and Western blot analysis showed that crocin significantly decreased the levels of phospho-p38 mitogen-activated protein kinase (MAPK), tumor protein 53 (p53), and cleaved caspase-3. Taken together, our data suggest that crocin provides protective effects against CDDP-induced hepatoxicity by attenuating oxidative stress and inhibiting the activation of p38 MAPK, p53, and caspase-3.

Download Full-text

Toxicological Interactions of Cassia Senna and Nerium oleander in the Diet of Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x02000521 ◽

2002 ◽

Vol 30 (04) ◽

pp. 579-587 ◽

Cited By ~ 4

Author(s):

M. A. Al-Yahya ◽

A. H. Al-Farham ◽

S. E. I. Adam

Keyword(s):

Alkaline Phosphatase ◽

Body Weight ◽

Total Protein ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Wistar Rats ◽

Feed Utilization ◽

Nerium Oleander ◽

Serum Aspartate Aminotransferase ◽

Male Wistar Rats

The toxic effects of diet containing 10% of C. senna L. fruits or 10% of N. oleander L. leaves or their 1 : 1 mixture (5%+5%) on male Wistar rats treated for 6 weeks were investigated. Diarrhea was a prominent sign of C. senna L. toxicosis. In both phytotoxicities, there were decreases in body weight gains, inefficiency of feed utilization, dullness and enterohepatonephropathy. These findings accompanied by leukopenia and anemia were correlated with alterations of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and concentrations of total protein, albumin, urea and other serum constituents. In both phytotoxicities, the ability of the liver to excrete bilirubin remained unchanged. Feeding the mixture of C. senna L. fruits and N. oleander L. leaves caused more serious effects and death of rats. The implications of these findings are discussed.

Download Full-text

Elevated serum aspartate aminotransferase levels concomitant with normal alanine aminotransferase levels in older low body weight people: Preliminary findings from a community-based epidemiological study

10.1101/528034 ◽

2019 ◽

Cited By ~ 1

Author(s):

Michi Shibata ◽

Kei Nakajima

Keyword(s):

Body Weight ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Elevated Serum ◽

Serum Levels ◽

Cross Sectional Study ◽

Healthy Population ◽

Gamma Glutamyl Transpeptidase ◽

Cross Sectional ◽

Serum Aspartate Aminotransferase

AbstractBackgroundSerum enzyme levels, including hepatic transaminase, are unknown in older people with low body weight (LBW), who can easily experience sarcopenia. Therefore, we addressed preliminarily this issue in a cross-sectional study of an apparently healthy population.MethodsWe investigated the relationship of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and total bilirubin levels with body mass index (BMI) and age in 79,623 subjects aged 20–80 years who underwent an annual checkup.ResultsSerum levels of AST, ALP, and LDH levels were significantly higher in older (≥50 years) non-obese subjects compared with younger (< 50 years) corresponding subjects. Serum AST levels were significantly higher in older LBW subjects (BMI≤18.9 kg/m2) than in those with a reference BMI of 20.9–22.9 kg/m2. Serum AST levels showed a J-shaped curve against BMI, whereas ALT and GGT levels showed a linear relationship, regardless of age.ConclusionElevated serum AST levels concomitant with normal ALT levels, which might reflect systemic damage of skeletal muscle, may be prevalent in older LBW people. Further studies need to determine whether such a condition is equivalent to the etiology of sarcopenia.

Download Full-text

Single and repeated testing of growth hormone secretory capacity in hypopituitarism using growth hormone releasing factor

Acta Endocrinologica ◽

10.1530/acta.0.112s118 ◽

1986 ◽

Vol 113 (4_Suppl) ◽

pp. S118-S122 ◽

Cited By ~ 3

Author(s):

O. BUTENANDT ◽

M. EMMLINGER ◽

H. DOERR

Keyword(s):

Growth Hormone ◽

Body Weight ◽

Pituitary Gland ◽

Bolus Injection ◽

Hormone Deficiency ◽

Test Results ◽

Repeated Testing ◽

Plasma Growth Hormone ◽

Once Daily ◽

Secretory Capacity

Abstract 38 patients with proven growth hormone deficiency (GHD) and 19 children with familial short stature received an iv GRF-bolus injection of 1 ug/kg body weight. Whereas in all control children plasma growth hormone rose significantly (mean of maximal values 36 ng/ml), only 7 out of 38 patients with GHD reached peak values of 8 ng/ml or more. GRF-priming by 1 ug GRF/kg BW given once daily s.c. for 5 days in 19 patients improved the response of the pituitary gland in 11. Thus, following the first GRF test, only 21 % of patients demonstrated function of the pituitary gland whereas 45 % did so when all test results are combined. To evaluate the pituitary function in patients with GHD correctly, GRF tests following a GRF priming period seems to be necessary to reactivate atrophic somatotropic cells of the pituitary gland.

Download Full-text

Effect of Oral Gavage Dosing Regimens in Female Tg rasH2 Transgenic Mice

Toxicologic Pathology ◽

10.1080/01926230490457567 ◽

2004 ◽

Vol 32 (4) ◽

pp. 413-417 ◽

Cited By ~ 1

Author(s):

Daniel Morton ◽

Rani S. Sellers ◽

Sylvia M. Furst ◽

Kristen D. Hawley ◽

Jeffrey R. May

Keyword(s):

Body Weight ◽

Incidental Finding ◽

Sodium Dodecyl ◽

Control Group ◽

Oral Gavage ◽

Once Daily ◽

Dosing Regimens ◽

Rash2 Mice ◽

Daily Water ◽

Cortical Architecture

Female Tg rasH2 (CB6F1/Jic-TgrasH2@Tac) mice were administered water once daily, water twice daily with 8 or 12 hours between doses, 1% sodium dodecyl sulfate in water (1% SDS) once daily, or 1% SDS twice daily with 12 hours between doses by oral gavage at volumes of 10 ml/kg/day for 28 or 29 consecutive days. A control group of mice received no treatment and no sham manipulation. There were no significant differences in body weight or food consumption between treated groups and untreated control mice. Mean weights of spleens, livers, and thymuses were lower than control values in most groups of mice subjected to gavage. Focal or multifocal loss of thymic cortical architecture was observed in 13 of 50 mice distributed among all groups (including naïve controls), however only in one instance was this finding suggestive of a precursor to neoplasia. This study demonstrated that Tg rasH2 mice can tolerate once or twice daily gavage dosing with water or vehicle containing 1% SDS. Loss of thymic cortical architecture was a common incidental finding in female Tg rasH2 mice.

Download Full-text

Two-Segment Foot Model for the Biomechanical Analysis of Squat

Journal of Healthcare Engineering ◽

10.1155/2017/9652948 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11

Author(s):

E. Panero ◽

L. Gastaldi ◽

W. Rapp

Keyword(s):

Body Weight ◽

Inverse Dynamics ◽

Statistical Significance ◽

Lower Limbs ◽

Biomechanical Analysis ◽

Wide Range ◽

Foot Model ◽

Partial Body ◽

The One ◽

Midtarsal Joint

Squat exercise is acquiring interest in many fields, due to its benefits in improving health and its biomechanical similarities to a wide range of sport motions and the recruitment of many body segments in a single maneuver. Several researches had examined considerable biomechanical aspects of lower limbs during squat, but not without limitations. The main goal of this study focuses on the analysis of the foot contribution during a partial body weight squat, using a two-segment foot model that considers separately the forefoot and the hindfoot. The forefoot and hindfoot are articulated by the midtarsal joint. Five subjects performed a series of three trials, and results were averaged. Joint kinematics and dynamics were obtained using motion capture system, two force plates closed together, and inverse dynamics techniques. The midtarsal joint reached a dorsiflexion peak of 4°. Different strategies between subjects revealed 4° supination and 2.5° pronation of the forefoot. Vertical GRF showed 20% of body weight concentrated on the forefoot and 30% on the hindfoot. The percentages varied during motion, with a peak of 40% on the hindfoot and correspondently 10% on the forefoot, while the traditional model depicted the unique constant 50% value. Ankle peak of plantarflexion moment, power absorption, and power generation was consistent with values estimated by the one-segment model, without statistical significance.

Download Full-text

Abstract MP56: Nitric Oxide-Therapy but Not Remote Ischemic Conditioning is Cerebroprotective in Stroke: A Study in Mouse Model of Endothelial Dysfunction and Hypertension

Stroke ◽

10.1161/str.52.suppl_1.mp56 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Syed M Zaidi ◽

Md Nasrul Hoda ◽

Farid Ahmed ◽

Heba Alkhatabi ◽

Muhammed H Al Qahtani

Keyword(s):

Nitric Oxide ◽

Endothelial Dysfunction ◽

Statistical Significance ◽

Intravenous Thrombolysis ◽

Once Daily ◽

Remote Ischemic Conditioning ◽

Ischemic Conditioning ◽

Stroke Models ◽

Endogenous Protection ◽

Endothelial Nitric Oxide

Background: Remote Ischemic Conditioning (RIC) was found effective in stroke models, likely via increased endothelial nitric oxide (NO); yet RIC failed to improve clinical outcomes ( NCT02342522 ; NCT02189928 ). We anticipated that comorbidities neutralize the benefits of RIC in stroke. Hypothesis: NO-therapy but not RIC is vasculoprotective in hypertensive stroke. Methods: Aged (18±1-mo old) S100A1-hets mutant (S100A +/- ) and wild-type (WT) mice were used. As needed, mice were treated with RIC, s-nitrosoglutathione (GSNO) reductase inhibitor (GRI; 5 mg/kg nebulized once daily for 2-wks), GSNO (100-ug/kg; nebulized once daily at 2h post-TES), and/or intravenous thrombolysis (IVT; 10mg/kg at 4h post-TES). Stroke and outcome measures were performed as mentioned below. Statistical significance was determined at P &lt 0.05. Results: S100A +/- compared to WT-type mice showed significantly higher mean arterial pressure (MAP) and lower plasma-NO, supporting a hypertensive phenotype with endothelial dysfunction in S100A +/- mice. In photothrombotic stroke (PTS), RIC significantly improved cerebral blood flow (CBF), behavior and reduced infarction in WT but not in S100A +/- mice at 48h. GRI in S100A +/- mice enhanced plasma NO, improved behavior and CBF, and reduced infarction significantly as compared to vehicle-treated S100A +/- at 48h post-PTS. RIC with GRI did not produce additive protection in S100A +/- mice at 48h post-PTS, demonstrating that the preservation of NO-pool with GRI protects against stroke, but RIC is not effective to enhance this endogenous protection in hypertensive mice. Moreover, GSNO nebulization but not RIC enhanced PbtO 2 , reduced BBB-leakage and brain hemoglobin (Hb)-content at 24h after thromboembolic stroke with and without IVT. Conclusions: NO-therapies but not RIC is effective in hypertensive stroke. RIC- and NO- therapies need further validation in comorbid stroke before embarking on the clinical trial.

Download Full-text

Serum Aspartate Aminotransferase Level and Previous Histopathological Findings Enable Reduction of Protocol Liver Biopsies after Liver Transplantation for Hepatitis C

Canadian Journal of Gastroenterology ◽

10.1155/2013/904636 ◽

2013 ◽

Vol 27 (3) ◽

pp. 131-136 ◽

Cited By ~ 1

Author(s):

Tomohiro Tanaka ◽

George Therapondos ◽

Nazia Selzner ◽

Eberhard L Renner ◽

Leslie B Lilly

Keyword(s):

Liver Transplantation ◽

Hepatitis C ◽

Antiviral Therapy ◽

Aspartate Aminotransferase ◽

Aminotransferase Level ◽

Fibrosis Stage ◽

Protocol Biopsy ◽

Serum Aspartate Aminotransferase ◽

Histological Activity ◽

Liver Biopsies

BACKGROUND: Hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) worldwide. Recurrent hepatitis C following LT is universal, and significant fibrosis (SF, Metavir fibrosis stage ≥2) apparent on protocol biopsy typically prompts antiviral therapy.OBJECTIVE: To determine the optimal timing of protocol liver biopsies in this setting.METHODS: A total of 151 patients who underwent LT related to HCV infection between July 2004 and December 2009 were analyzed retrospectively. Data regarding protocol liver biopsies at six, 12 and 24 months post-LT, conventional laboratory parameters and demographic information were obtained.RESULTS: The 151 patients included in the present study had significantly lower serum aspartate aminotransferase (AST) levels than the four patients who progressed to receive antiviral treatment for SF before six months post-LT (P<0.001). AST level, but not alanine aminotransferase level, histological activity or fibrosis stage at the six-month biopsy was independently associated with the progression to SF at 12 months (P<0.05). However, AST level, histological activity and fibrosis stage at the 12-month biopsy emerged as independent parameters associated with progression to SF at 24 months (P<0.05).CONCLUSION: The protocol liver biopsy at six months could be eliminated, especially in patients who consistently exhibit low AST levels. Histological activity, the presence or absence of fibrosis, and AST values at the 12-month biopsy may lead to the decision to defer the protocol biopsy at 24 months or result in earlier introduction of antiviral therapy.

Download Full-text

Lack of Neuropathological Changes in Rats Administered Tedizolid Phosphate for Nine Months

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03950-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 475-481 ◽

Cited By ~ 12

Author(s):

Michael J. Schlosser ◽

Hiromi Hosako ◽

Ann Radovsky ◽

Mark T. Butt ◽

Dragomir Draganov ◽

...

Keyword(s):

Body Weight ◽

Optic Nerve ◽

Body Weight Gain ◽

Maximum Tolerated Dose ◽

High Dose ◽

Once Daily ◽

Clinical Observations ◽

Activity Measures ◽

Dose Levels ◽

Neurobehavioral Effects

ABSTRACTTedizolid, a novel oxazolidinone antibacterial, was administered to Long Evans rats by oral gavage once daily for up to 9 months at doses near the maximum tolerated dose (MTD) to evaluate for potential neurotoxicity. Mean plasma exposures of tedizolid at the low-, medium-, and high-dose levels (7.5, 15, and 30 mg/kg of body weight/day for males; 2.5, 5, and 10 mg/kg/day for females) were similar between males and females and were 1.8-, 3.9-, and 8.0-fold greater than exposures in patients at the therapeutic dose (200 mg once daily). Evaluated endpoints included survival, clinical observations, body weight, and food consumption. At 1, 3, 6, and 9 months, ophthalmic examinations, functional observational batteries, and locomotor activity measures were conducted, brain weights/sizes were recorded, and perfusion-fixed tissues were collected from 12 rats/sex/group/time point. A detailed morphological assessment was conducted on brain, eyes, optic nerve/tract, spinal cord, peripheral nerves (includes sciatic, sural, tibial, peroneal, trigeminal), and skeletal muscle. At the end of 9 months, less body weight gain was seen in high-dose males (−6.7%) and females (−5.8%) compared with that seen in controls. There were no tedizolid-related adverse neurobehavioral effects or tedizolid-related histopathologic changes in the central/peripheral nervous systems, including the optic nerve. Results of this study indicate that tedizolid was not neurotoxic when administered long term to pigmented rats at doses near the MTD, which were up to 8-fold higher than the human therapeutic exposure.

Download Full-text