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tLyp-1: A peptide suitable to target NRP-1 receptor

Larue L, Kenzhebayeva B, Al-Thiabat MG, Jouan-Hureaux V, Mohd-Gazzali A, Wahab HA, et al.

Bioorg Chem, 2023 Jan;130:106200.
PMID: 36332316 DOI: 10.1016/j.bioorg.2022.106200

Targeting vascular endothelial growth factor receptor (VEFGR) and its co-receptor neuropilin-1 (NRP-1) is an interesting vascular strategy. tLyp-1 is a tumor-homing and penetrating peptide of 7 amino acids (CGNKRTR). It is a truncated form of Lyp-1 (CGNKRTRGC), which is known to target NRP-1 receptor, with high affinity and specificity. It is mediated by endocytosis via C-end rule (CendR) internalization pathway. The aim of this study is to evaluate the importance of each amino acid in the tLyp-1 sequence through alanine-scanning (Ala-scan) technique, during which each of the amino acid in the sequence was systematically replaced by alanine to produce 7 different analogues. In silico approach through molecular docking and molecular dynamics are employed to understand the interaction between the peptide and its analogues with the NRP-1 receptor, followed by in vitro ligand binding assay study. The C-terminal Arg is crucial in the interaction of tLyp-1 with NRP-1 receptor. Substituting this residue dramatically reduces the affinity of this peptide which is clearly seen in this study. Lys-4 is also important in the interaction, which is confirmed via the in vitro study and the MM-PBSA analysis. The finding in this study supports the CendR, in which the presence of R/K-XX-R/K motif is essential in the binding of a ligand with NRP-1 receptor. This presented work will serve as a guide in the future work pertaining the development of active targeting agent towards NRP-1 receptor.

Matched MeSH terms: Alanine
Fulltext Use of simple scoring systems for a public health approach in the management of non-alcoholic fatty liver disease patients

Zain SM, Tan HL, Mohamed Z, Chan WK, Mahadeva S, Basu RC, et al.

JGH Open, 2020 Dec;4(6):1155-1161.
PMID: 33319051 DOI: 10.1002/jgh3.12414

Background and Aim: Advanced fibrosis is the most important predictor of liver-related mortality in non-alcoholic fatty liver disease (NAFLD). The aim of this study was to compare the diagnostic performance of noninvasive scoring systems in identifying advanced fibrosis in a Malaysian NAFLD cohort and propose a simplified strategy for the management of NAFLD in a primary care setting.
Methods: We enrolled and reviewed 122 biopsy-proven NAFLD patients. Advanced fibrosis was defined as fibrosis stages 3-4. Noninvasive assessments included aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST-to-platelet ratio index (APRI), AST/ALT ratio, diabetes (BARD) score, fibrosis-4 (FIB-4) score, and NAFLD fibrosis score.
Results: FIB-4 score had the highest area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) of 0.86 and 94.3%, respectively, for the diagnosis of advanced fibrosis. FIB-4 score

Matched MeSH terms: Alanine Transaminase
Fulltext Urinary amino acids profile of vegetarians and non-vegetarians

Chia, Yoke Yin, Ton, So Ha

Malays J Nutr, 2006;12(1):67-78.
MyJurnal

The objective of the study was to quantify and to profile the amino acids content in urine samples. The amino acids content in urine was determined in 162 individuals (62 young non-vegetarians aged 15-45 years, 24 elderly non-vegetarians aged 46-70 years, 40 young vegetarians and 36 elderly vegetarians) by high performance liquid chromatography (HPLC). The most common amino acids detected in the young and elderly individuals on vegetarian and non-vegetarian diets were phenylalanine, threonine, arginine and asparagine, while leucine, aspartic acid and alanine were not found in any urine samples in both groups. Isoleucine was not detected in the urine of vegetarians. The concentrations of the majority of essential amino acids were between 0.10 - 2.00 mgl24hrs except for histidine which had a range of 4.1 - 5.0 mgl24hrs. The concentrations of non-essential amino acids varied. Proline, glycine and tyrosine concentrations were between 0.10 - 1.00 mg/24hrs, while cysteine, glutamine, glutamic acid and cystine concentrations were between 11.0 - 21.0 mg124hrs. Asparagine and hydroxy-proline had a range of 0.10 - 5.00 mg/24hrs, while serine and arginine ranged between 31.0 - 50.0 mg124hrs. Isoleucine and serine were not detected in elderly vegetarians while histidine, glycine, glutamic acid and hydroxy-proline were not detected in elderly non-vegetarians. Isoleucine, glycine and hydroxy proline were detected in young non-vegetarians but not in young vegetarians. The levels of amino acids showed no significant statistical differences between young vegetarians and non-vegetarians as well as between elderly vegetarians and non-vegetarians. Phenylalanine, threonine and trypthophan were commonly detected in the lacto-ovo and lacto vegetarians, while valine, cysteine, arginine and asparagine were commonly detected in vegans. In conclusion, except for isoleucine, general differences were seen in urinary amino acid excretions between vegetarians and non-vegetarians even though the differences were statistically not significant. Therefore lacto-ovo diets could be nutritionally adequate as the nutrients were substituted by dairy or plant products.

Matched MeSH terms: Alanine; Phenylalanine
Treatment of subperiodic Brugia malayi infection with a single dose of ivermectin

Mak JW, Navaratnam V, Grewel JS, Mansor SM, Ambu S

Am J Trop Med Hyg, 1993 Apr;48(4):591-6.
PMID: 8480868

A clinical trial on the efficacy of a single oral dose of ivermectin at 20, 50, 100, and 200 micrograms/kg was carried out in 40 subjects with subperiodic Brugia malayi microfilaremia. There was no significant difference in the clearance of microfilaremia in the four treatment groups, and the lowest geometric mean microfilarial count (GMC) achieved in the 40 subjects was 8.8/ml or 8.3% of the initial count (106.1/ml), at two weeks post-treatment. The GMC started to increase at one month post-treatment and by six months was 22.2% of the initial GMC. Only 27.5%, 23.1%, 15.0%, and 18.9% of subjects were amicrofilaremic at two, four, 12, and 24 weeks post-treatment, respectively. Mild fever in 35% of the subjects was the primary side reaction and was more common in those with microfilarial counts > or = 500/ml (85.7%) than in those with counts < 500/ml (32%). The clearance of B. malayi microfilaremia by ivermectin was less rapid than that reported for Wuchereria bancrofti. The smaller number of side reactions encountered in the present study compared with those reported for bancroftian filariasis is probably related to the lower microfilarial density in the present subjects. Since ivermectin at a single oral dose of 20-200 micrograms/kg can reduce the GMC to less than 10% at two weeks and maintain it below 25% of the initial level even at six months post-treatment, it is recommended that the drug be seriously evaluated for use in the control of brugian filariasis.

Matched MeSH terms: Alanine Transaminase/blood
Transient isotachophoresis-capillary zone electrophoresis with contactless conductivity and ultraviolet detection for the analysis of paralytic shellfish toxins in mussel samples

Abdul Keyon AS, Guijt RM, Bolch CJ, Breadmore MC

J Chromatogr A, 2014 Oct 17;1364:295-302.
PMID: 25223612 DOI: 10.1016/j.chroma.2014.08.074

The accumulation of paralytic shellfish toxins (PSTs) in contaminated shellfish is a serious health risk making early detection important to improve shellfish safety and biotoxin management. Capillary electrophoresis (CE) has been proven as a high resolution separation technique compatible with miniaturization, making it an attractive choice in the development of portable instrumentation for early, on-site detection of PSTs. In this work, capillary zone electrophoresis (CZE) with capacitively coupled contactless conductivity detector (C(4)D) and UV detection were examined with counter-flow transient isotachophoresis (tITP) to improve the sensitivity and deal with the high conductivity sample matrix. The high sodium concentration in the sample was used as the leading ion while l-alanine was used as the terminating electrolyte (TE) and background electrolyte (BGE) in which the toxins were separated. Careful optimization of the injected sample volume and duration of the counter-flow resulted in limit of detections (LODs) ranging from 74.2 to 1020 ng/mL for tITP-CZE-C(4)D and 141 to 461 ng/mL for tITP-CZE-UV, an 8-97 fold reduction compared to conventional CZE. The LODs were adequate for the analysis of PSTs in shellfish samples close to the regulatory limit. Intra-day and inter-day repeatability values (percentage relative standard deviation, n=3) of tITP-CZE-C(4)D and tITP-CZE-UV methods for both migration time and peak height were in the range of 0.82-11% and 0.76-10%, respectively. The developed method was applied to the analysis of a contaminated mussel sample and validated against an Association of Official Analytical Chemists (AOAC)-approved method for PSTs analysis by high performance liquid chromatography (HPLC) with fluorescence detection (FLD) after pre-column oxidation of the sample. The method presented has potential for incorporation in to field-deployable devices for the early detection of PSTs on-site.

Matched MeSH terms: Alanine
Fulltext Transient hyperthyroidism of hyperemesis gravidarum

Tan JYL, Loh KC, Yeo GSH, Chee YC

BJOG, 2002 Jun;109(6):683-8.
PMID: 12118648

OBJECTIVE: To characterise the clinical, biochemical and thyroid antibody profile in women with transient hyperthyroidism of hyperemesis gravidarum.
DESIGN: Prospective observational study.
SETTING: Hospital inpatient gynaecological ward.
POPULATION: Women admitted with hyperemesis gravidarum and found to have hyperthyroidism.
METHODS: Fifty-three women were admitted with hyperemesis gravidarum and were found to have hyperthyroidism. Each woman was examined for clinical signs of thyroid disease and underwent investigations including urea, creatinine, electrolytes, liver function test, thyroid antibody profile and serial thyroid function test until normalisation.
MAIN OUTCOME MEASURES: Gestation at which thyroid function normalised, clinical and thyroid antibody profile and pregnancy outcome (birthweight, gestation at delivery and Apgar score at 5 minutes).
RESULTS: Full data were available for 44 women. Free T4 levels normalised by 15 weeks of gestation in the 39 women with transient hyperthyroidism while TSH remained suppressed until 19 weeks of gestation. None of these women were clinically hyperthyroid. Thyroid antibodies were not found in most of them. Median birthweight in the infants of mothers who experienced weight loss of > 5% of their pre-pregnancy weight was lower compared with those of women who did not (P = 0.093). Five women were diagnosed with Graves' disease based on clinical features and thyroid antibody profile.
CONCLUSIONS: In transient hyperthyroidism of hyperemesis gravidarum, thyroid function normalises by the middle of the second trimester without anti-thyroid treatment. Clinically overt hyperthyroidism and thyroid antibodies are usually absent. Apart from a non-significant trend towards lower birthweights in the infants of mothers who experienced significant weight loss, pregnancy outcome was generally good. Routine assessment of thyroid function is unnecessary for women with hyperemesis gravidarum in the absence of any clinical features of hyperthyroidism.

Matched MeSH terms: Alanine Transaminase/metabolism
Toxicological evaluation of 80% methanol extract of Ludwigia octovalvis (Jacq.) P.H. Raven leaves (Onagraceae) in BALB/c mice

Kadum Yakob H, Manaf Uyub A, Fariza Sulaiman S

J Ethnopharmacol, 2012 Aug 1;142(3):663-8.
PMID: 22705121 DOI: 10.1016/j.jep.2012.05.035

Ludwigia octovalvis (Jacq.) P. H. Raven (Family: Onagraceae), as a traditional Malay herbal medicine,has been used to treat gastrointestinal complaints such as diarrhea and dysentery.

Matched MeSH terms: Alanine Transaminase/blood
Fulltext Toxicity study of Orthosiphon stamineus Benth (Misai Kucing) on Sprague Dawley rats

Chin JH, Abas HH, Sabariah I

Trop Biomed, 2008 Apr;25(1):9-16.
PMID: 18600199

Orthosiphon stamineus Benth (Family: Lamiaceae) or locally known as Misai Kucing has been widely used in Malaysia for treating kidney problems, gout, and diabetes. This study aims to evaluate the possible toxic effect after following fourteen days oral administration of methanol extract of O. stamineus in female Sprague Dawley (SD) rats. Control groups were treated orally with distilled water (vehicle) while the four test groups were treated up to fourteen days with 0.5 g/kg, 1 g/kg, 3 g/kg and 5 g/kg body weight of methanol extract of O. stamineus respectively. Toxicity of the methanol extract of O. stamineus was evaluated by the incident of lethality, side-cage observation and blood serum biochemical parameters. No lethality or adverse toxic signs were seen during the experimental period. A significant decrease in several serum biochemical parameters i.e. AST and ALT and increase in liver weight was observed in young female SD rat after being fed fourteen days with methanol extract of O. stamineus. No delayed toxic effect and lethality was observed in all rats during fourteen days of recovery period. In conclusion, methanol extract of O. stamineus within these range and treatment duration would not cause any severe toxic effects and organ damages in rats.

Matched MeSH terms: Alanine Transaminase/blood
Fulltext Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial

Magosso E, Ansari MA, Gopalan Y, Shuaib IL, Wong JW, Khan NA, et al.

Nutr J, 2013;12(1):166.
PMID: 24373555 DOI: 10.1186/1475-2891-12-166

Nonalcoholic fatty liver disease (NAFLD) is one of the commonest liver disorders. Obesity, insulin resistance, lipid peroxidation and oxidative stress have been identified amongst the possible hits leading to the onset and progression of this disease. Nutritional evaluation of NAFLD patients showed a lower-than-recommended intake of vitamin E. Vitamin E is a family of 8 isoforms, 4 tocopherols and 4 tocotrienols. Alpha-tocopherol has been widely investigated in liver diseases, whereas no previous clinical trial has investigated tocotrienols for NAFLD. Aim of the study was to determine the effects of mixed tocotrienols, in normalising the hepatic echogenic response in hypercholesterolaemic patients with ultrasound-proven NAFLD.

Matched MeSH terms: Alanine Transaminase/blood
Fulltext Tinospora crispa Ameliorates Insulin Resistance Induced by High Fat Diet in Wistar Rats

Abu MN, Samat S, Kamarapani N, Nor Hussein F, Wan Ismail WI, Hassan HF

Evid Based Complement Alternat Med, 2015;2015:985042.
PMID: 25821506 DOI: 10.1155/2015/985042

The antidiabetic properties of Tinospora crispa, a local herb that has been used in traditional Malay medicine and rich in antioxidant, were explored based on obesity-linked insulin resistance condition. Male Wistar rats were randomly divided into four groups, namely, the normal control (NC) which received standard rodent diet, the high fat diet (HFD) which received high fat diet only, the high fat diet treated with T. crispa (HFDTC), and the high fat diet treated with orlistat (HFDO). After sixteen weeks of treatment, blood and organs were harvested for analyses. Results showed that T. crispa significantly (p < 0.05) reduced the body weight (41.14 ± 1.40%), adiposity index serum levels (4.910 ± 0.80%), aspartate aminotransferase (AST: 161 ± 4.71 U/L), alanine aminotransferase (ALT: 100.95 ± 3.10 U/L), total cholesterol (TC: 18.55 ± 0.26 mmol/L), triglycerides (TG: 3.70 ± 0.11 mmol/L), blood glucose (8.50 ± 0.30 mmo/L), resistin (0.74 ± 0.20 ng/mL), and leptin (17.428 ± 1.50 ng/mL) hormones in HFDTC group. The insulin (1.65 ± 0.07 pg/mL) and C-peptide (136.48 pmol/L) hormones were slightly decreased but within normal range. The histological results showed unharmed and intact liver tissues in HFDTC group. As a conclusion, T. crispa ameliorates insulin resistance-associated with obesity in Wistar rats fed with high fat diet.

Matched MeSH terms: Alanine Transaminase
The value of liver function tests in hepatocellular carcinoma

Lopez JB, Balasegaram M, Thambyrajah V, Timor J

Malays J Pathol, 1996 Dec;18(2):95-9.
PMID: 10879229

This study was undertaken to see if liver function tests (LFT) served a worthwhile purpose in the investigation of hepatocellular carcinoma (HCC). Sera from 80 HCC, 76 benign liver disease (BLD) and 152 healthy adult (HA) subjects were assayed for alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase and lactate dehydrogenase, bilirubin and albumin. Cut-off values were determined from the HA. ALP, GGT, AST and albumin were abnormal in about 90% of the HCC. With the exception of bilirubin, the LFT were abnormal more frequently in HCC than in chronic hepatitis and cirrhosis, the conditions which preceed it. Raised ALP in the presence of normal bilirubin was more often a feature of HCC than BLD although this relationship was not statistically significant. It seems unlikely that LFT serve a useful function in HCC.

Matched MeSH terms: Alanine Transaminase/blood
Fulltext The use of remdesivir for the management of patients with moderate-to-severe COVID-19: a systematic review

Thiruchelvam K, Kow CS, Hadi MA, Hasan SS

Expert Rev Anti Infect Ther, 2022 02;20(2):211-229.
PMID: 34192469 DOI: 10.1080/14787210.2021.1949984

OBJECTIVE: We systematically reviewed the evidence of published original research to determine the role of remdesivir in the management of patients with COVID-19 and a moderate-to-severe course of illness.
METHODS: A systematic search of articles was conducted in scientific databases, with the latest update in May 2021. This paper systematically reviewed the clinical evidence available (randomized controlled trials, compassionate use studies, and case reports) on the use of remdesivir for patients with moderate or severe COVID-19.
RESULTS: A total of eleven studies were included: four studies based on compassionate use of remdesivir, three randomized, double-blind, placebo-controlled, multicentre trials, three randomized, open-label, phase III trials, and one case report. Clinical improvement and mortality rates in patients who used remdesivir varied across studies.
CONCLUSION: Given the current evidence, there is insufficient data to confidently recommend the use of remdesivir alone for the treatment of adult hospitalized patients with moderate-to-severe COVID-19. However, remdesivir may be considered along with an anti-inflammatory agent in patients with pneumonia, on oxygen support, provided there is close monitoring of clinical and laboratory parameters and adverse events.

Matched MeSH terms: Alanine/analogs & derivatives*; Alanine/therapeutic use
The protective role of Tropaeolum majus on blood and liver toxicity induced by diethyl maleate in rats

Koriem KM, Arbid MS, El-Gendy NF

Toxicol. Mech. Methods, 2010 Nov;20(9):579-86.
PMID: 20883155 DOI: 10.3109/15376516.2010.518171

The protective role of Tropaelum majus (T.majus) methyl alcohol extract and vitamin E in the case of toxic effect induced by diethyl maleate was evaluated. Forty-two male albino rats were divided into seven groups of six rats each for 15 days. Group 1: normal control group. Group 2: taken daily oral dose of paraffin oil (0.25ml/100g b.wt rat). Group 3: received daily oral dose of vitamin E (100mg/kg b.wt rat). Group 4: taken daily oral dose of 10% of the LD50 of T.majus methyl alcohol extract. Groups 5–7: injected intra-peritoneally with diethyl maleate (5 μl/100g b.wt rat) but groups 6 and 7 received a daily oral dose of either vitamin E or 10% of the LD50 of T.majus methyl alcohol extract 1h prior to diethyl maleate injection. The present results revealed that diethyl maleate induced serum aspartate and alanine aminotransferases enzymes activities decreased in serum, but their activities in the hepatic tissue showed an increase. Glutathione and glucose-6-phosphate dehydrogenase levels showed a decrease, but thiobarbituric acid reactive substances level showed an increase in both serum and liver tissue. Serum and liver proteins decreased in serum and liver tissue. A significant decrease in blood parameters (hemoglobin, hematocrit, as well as red and white blood cells) and serum glucose occurred. Histopathological results showed that diethyl maleate induced a hoop of edema in the hepatic periportal area; while T.majus methyl alcohol extract or vitamin E prior to diethyl maleate injection shift blood and liver toxicity induced by diethyl maleate towards normal values and preserved hepatic lobular architecture. In conclusion, pre-treatment with either T.majus methyl alcohol extract or vitamin E provide protection against blood and liver toxicity induced by diethyl maleate in rats, these results were confirmed by histological examinations.

Matched MeSH terms: Alanine Transaminase/blood
The impact of serum total bilirubin, alanine transaminase and gamma-glutamyl transferase on survival of biliary atresia patients following Kasai procedure

Noor HZ, Noor HZ, Makhmudi A, Gunadi

Med J Malaysia, 2020 05;75(Suppl 1):1-4.
PMID: 32483103

BACKGROUND: Many prognostic factors have been reported for the outcomes of biliary atresia (BA) patients after Kasai procedure, however, it still shows a conflicting result. Our study was to determine the impact of total bilirubin postoperative day-7 and pre-operative ratio (TB7/TB0), gammaglutamyl transferase post-operative day-7 and pre-operative ratio (GGT7/GGT0), and alanine transaminase post-operative day-7 and pre-operative ratio (ALT7/ALT0) on the survival of BA patients following Kasai surgery.
METHODS: We reviewed the medical records of BA patients who underwent Kasai procedure at the Dr. Sardjito Hospital, Indonesia from August 2012 to December 2018. The cut-off values of TB7/TB0, GGT7/GGT0, and ALT7/ALT0 for prediction of patients' survival were determined by receiver operating characteristics (ROC) curves. Log-rank tests were utilised to test the association between cut-off values and overall survival.
RESULTS: In all 46 BA patients (23 males and 23 females) after Kasai procedure were included, consisting of one type 1, 17 type 2A, seven type 2B, and 21 type 3. The cut-off values of TB7/TB0, ALT7/ALT0 and GGT7/GGT0 for overall survival was 0.455 (sensitivity 87.5%, specificity 22.7%, area under curve (AUC) 0.59; 95% Confidence Interval (95%CI): 0.42, 0.75), 0.481 (sensitivity 87.5%, specificity 18.2%, AUC 0.49; 95%CI: 0.31, 0.65), and and 0.31 (sensitivity 79.2%, specificity 9.1%, AUC 0.34; 95%CI: 0.18, 0.50), respectively. However, these cut-off values were not significantly associated with overall survival, with p-values of 0.18, 0.49, and 0.56, respectively.
CONCLUSION: The TB7/TB0, ALT7/ALT0, and GGT7/GGT0 might not predict the overall survival of BA patients after Kasai procedure. Further multicentre studies with a larger sample size is needed to clarify our findings.

Matched MeSH terms: Alanine Transaminase/blood*
The effect of tocotrienol-rich fraction on oxidative liver damage induced by fenitrothion

Putri Ayu Jayusman, Siti Balkis Budin, Putri Ayu Jayusman SBB, Izatus Shima Taib, Ahmad Rohi Ghazali

Sains Malaysiana, 2017;46:1603-1609.

Exposure to organophosphate pesticide including fenitrothion (FNT) has led to many adverse effects on human health.
However, a potent antioxidant like palm oil tocotrienol-rich fraction (TRF) can reduce oxidative damage in various
pathological conditions, could also reduce the adverse effects by FNT. The aim of this study was to evaluate the effect
of TRF on oxidative liver damage in FNT induce hepatotoxicity in experimental rats. A total of 40 male Sprague-Dawley
rats were randomly divided into four groups of 10, namely control, TRF, FNT and TRF+FNT group. TRF (200 mg/kg
body weight) and FNT (20 m/kg body weight) were administered through oral gavage for 28 days. Corn oil which
served as vehicle was given orally to the control group. At the end of the study period, liver and blood was taken for
oxidative damage and biochemical evaluation and histological observation. TRF supplementation prevents oxidative
liver damage by reducing the hepatic malondialdehyde (MDA) and protein carbonyl (PCO) level significantly. Besides,
TRF also restored the endogenous antioxidants particularly reduced glutathione (GSH), glutathione peroxidase (GPx)
and ferric reducing/antioxidant power (FRAP). TRF also prevent liver damage by reducing the liver enzymes, alanine
aminotransferase (ALT) and aspartate aminotransferase (AST). The attenuation of liver damage by TRF was also showed
histologically. In conclusion, TRF supplementation showed a potential in preventing oxidative liver damage in FNTtreated
rats by reducing the oxidative damage and improving the antioxidant status.

Matched MeSH terms: Alanine
Fulltext The combination of mitragynine and morphine prevents the development of morphine tolerance in mice

Fakurazi S, Rahman SA, Hidayat MT, Ithnin H, Moklas MA, Arulselvan P

Molecules, 2013 Jan 04;18(1):666-81.
PMID: 23292329 DOI: 10.3390/molecules18010666

Mitragynine (MG) is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt) combined with morphine (5 mg/kg b.wt) respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05) increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05) in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine.

Matched MeSH terms: Alanine Transaminase/metabolism
Fulltext The Safety Of Capsules Containing Lactic Acid Bacilli

Paraidathathu, Thomas, Lee, S.H.

Ann Dent, 1999;6(1):-.
MyJurnal

The population in Malaysia use various types of health and food supplements. These products are considered safe and are used without any concern for their toxicity. Among the products used as health supplements are products that contain lactic acid bacteria. This project studied the acute and subacute toxicity of a product containing minerals, herbs, vitamins and live lactic acid bacteria, on Sprague- Dawley rats. Acute toxicity was tested 24 hours after a single dose and subacute toxicity was studied 24 hours after 7 days of daily dosing. The parameters that were studied were alanine aminotransferase (AL T,SGPT), aspartate aminotransferase (AST, SGOT), serum urea, ratios of weight of kidney and liver weight to body weight and percentage changes in body weights. The contents of capsules of the product (6, 8 or lO capsules for acute studies and 6, 10 and 12 for subacute studies) were mixed with corn oil and fed orally to rats. Control rats were fed with corn oil alone. In the acute studies, the level of ALT in the rats treated with the contents of the capsule was lower than controls. There were no significant changes in the other parameters of the rats in the treatment groups as compared to controls. There were no significant differences in all the parameters between rats in the treatment groups as compared to controls in the subacute studies. Sprague-Dawley rats fed with high doses of the product did not show signs of toxicity in the parameters that were studied.

Matched MeSH terms: Alanine Transaminase; D-Alanine Transaminase
The Hepatoprotective Effect of Clidemia hirta against Carbon Tetrachloride (CCl4)-Induced Oxidative Stress and Hepatic Damage in Mice

Amzar N, Iqbal M

J Environ Pathol Toxicol Oncol, 2017;36(4):293-307.
PMID: 29431062 DOI: 10.1615/JEnvironPatholToxicolOncol.2017019824

Liver diseases still represents a major health burden worldwide. Moreover, medicinal plants have gained popularity in the treatment of several diseases, including liver disease. Clidemia hirta possesses many medicinal properties for healing several diseases and for health maintenance. However, the hepatoprotective effects and antioxidative potential of C. hirta have not been fully investigated. In the present study, we evaluated the hepatoprotective and antioxidative potential of C. hirta against carbon tetrachloride (CCl4)-induced liver injuries and oxidative damage in a murine model. Various biochemical changes associated with liver damage and oxidative stress were measured. The mice were pretreated for 14 consecutive days with aqueous extract of C. hirta at selected doses (150 mg/kg body weight [b.w.], 300 mg/kg b.w. and 600 mg/kg b.w.) followed by two doses of CCl4 (1.0 mL/kg b.w.) orally on days 14 and 15. All animals were sacrificed 24 hours after the last dose of CCl4 or saline. Blood and liver tissues were taken quickly for biochemical and histopathological studies to assess the derangement in the functioning of liver. The development of oxidative stress was observed through the escalation of hepatic lipid peroxidation, depletion of glutathione, and reduced antioxidant enzymes (glutathione peroxidase, glutathione reductase, catalase, glutathione S-transferase and quinone reductase). Hepatic damage was evaluated by measuring serum transaminase (ALT and AST). In addition, CCl4-induced hepatic damage was further evaluated using histopathological assessments. However, most of these changes were dependently ameliorated by the pretreatment of mice with a C. hirta dose. These results indicate that the hepatoprotective effect of C. hirta might be due to its antioxidant and free-radical scavenging properties.

Matched MeSH terms: Alanine Transaminase/blood
Synthesis of dipeptide benzoylalanylglycine methyl ester and corrosion inhibitor evaluation by tafel equation

Abdurrahman J, Wahyuningrum D, Achmad S, Bundjali B

Sains Malaysiana, 2011;40.

Corrosion is one of the major problems in petroleum mining and processing industry. The pipelines used to transport crude oil from reservoir to the processing installation were made from carbon steel that is susceptible towards corrosion. One of the best methods to prevent corrosion that occurred at the inner parts of carbon steel pipelines is to use organic corrosion inhibitor. One of the potent organic corrosion inhibitors is amino acids derivatives. In this study, dipeptide compound namely benzoylalanylglycine methyl ester and benzoylalanylglycine have been synthesized. The structure elucidation of the products was performed by IR, MS and NMR spectroscopy. The determination of corrosion inhibition activity utilized the Tafel method. The corrosion inhibition efficiency of glycine methyl ester, benzoylalanine, dipeptide benzoylalanylglycine methyl ester and dipeptide benzoylalanylglycine were 63.34%, 35.86%, 68.40% and 27.72%, respectively. These results showed that the formation of dipeptide benzoylalanylglycine methyl ester, derived from carboxylic protected glycine and amine protected alanine, increased the corrosion inhibition activity due to the loss of acidity center in the structure of glicine and L-alanine that would induce the corrosive environment towards carbon steel.

Matched MeSH terms: Alanine
Fulltext Swietenine potentiates the antihyperglycemic and antioxidant activity of Metformin in Streptozotocin induced diabetic rats

Shiming Z, Mak KK, Balijepalli MK, Chakravarthi S, Pichika MR

Biomed Pharmacother, 2021 Jul;139:111576.
PMID: 33862494 DOI: 10.1016/j.biopha.2021.111576

Diabetes mellitus or type-2 diabetes, commonly referred as diabetes, is a metabolic disorder that results in high blood sugar level. Despite the availability of several antidiabetic drugs in the market, they still do not adequately regulate blood sugar levels. Thus, in general people prefer to use herbal supplements/medicines along with antidiabetic drugs to control blood sugar levels. One of such herbal medicine is Swietenia macrophylla seeds. It is widely used in Asia for controlling blood sugar levels. One of the major bioactive compounds, Swietenine, is reported to be responsible for controlling blood glucose levels. However, there were no studies on its efficacy in controlling the blood glucose in diabetic rats. In this study, we evaluated the antihyperglycemic activity of Swietenine and its pharmacodynamic interaction with Metformin in Streptozotocin induced diabetes in rats. The activity of Swietenine was investigated at three different doses: 10, 20 and 40 mg/kg body weight (bw). Metformin (50 mg/kg bw) was used as a standard drug. Swietenine (20 and 40 mg/kg bw) and Metformin (50 mg/kg bw) showed significant effect in reducing the glucose, cholesterol, triglycerides, low-density lipoprotein, urea, creatinine, alanine transaminase, alkaline phosphatase, aspartate transaminase, alanine transaminase, and malondialdehyde level in serum while it had increased the high-density lipoprotein, glutathione, and total antioxidant capacity level. In addition, Swietenine (20 and 40 mg/kg) had shown significant synergistic effect with Metformin. Administration of Swietenine at 10 mg/kg bw neither showed activity nor influenced Metformin's activity. The results from this study confirmed the beneficial effects of Swietenine and its synergistic action with Metformin in controlling the dysregulated serum parameters in Streptozotocin induced diabetes in rats.

Matched MeSH terms: Alanine Transaminase

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