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Nitrogen metabolism and excretion in the aquatic chinese soft-shelled turtle, Pelodiscus sinensis, exposed to a progressive increase in ambient salinity

Lee SM, Wong WP, Hiong KC, Loong AM, Chew SF, Ip YK

J. Exp. Zoolog. Part A Comp. Exp. Biol., 2006 Dec 1;305(12):995-1009.
PMID: 17068799

This study aimed to determine effects of 6-day progressive increase in salinity from 1 per thousand to 15 per thousand on nitrogen metabolism and excretion in the soft-shelled turtle, Pelodiscus sinensis. For turtles exposed to 15 per thousand water on day 6, the plasma osmolality and concentrations of Na+, Cl- and urea increased significantly, which presumably decreased the osmotic loss of water. Simultaneously, there were significant increases in contents of urea, certain free amino acids (FAAs) and water-soluble proteins that were involved in cell volume regulation in various tissues. There was an apparent increase in proteolysis, releasing FAAs as osmolytes. In addition, there might be an increase in catabolism of certain amino acids, producing more ammonia. The excess ammonia was retained as indicated by a significant decrease in the rate of ammonia excretion on day 4 in 15 per thousand water, and a major portion of it was converted to urea. The rate of urea synthesis increased 1.4-fold during the 6-day period, although the capacity of the hepatic ornithine urea cycle remained unchanged. Urea was retained for osmoregulation because there was a significant decrease in urea excretion on day 4. Increased protein degradation and urea synthesis implies greater metabolic demands, and indeed turtles exposed to 15 per thousand water had significantly higher O2 consumption rate than the freshwater (FW) control. When turtles were returned from 15 per thousand water to FW on day 7, there were significant increases in ammonia (probably released through increased amino acid catabolism) and urea excretion, confirming that FAAs and urea were retained for osmoregulatory purposes in brackish water.

Matched MeSH terms: Urea/metabolism
Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): acute and subchronic toxicity studies

Hor SY, Ahmad M, Farsi E, Yam MF, Hashim MA, Lim CP, et al.

Regul Toxicol Pharmacol, 2012 Jun;63(1):106-14.
PMID: 22440551 DOI: 10.1016/j.yrtph.2012.03.006

Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days.

Matched MeSH terms: Urea/blood
Extracellular urease from Arthrobacter creatinolyticus MTCC 5604: scale up, purification and its cytotoxic effect thereof

Rajendran R, Pandi A, Ramchary A, Thiagarajan H, Panneerselvam J, Niraikulam A, et al.

Mol Biol Rep, 2019 Feb;46(1):133-141.
PMID: 30374769 DOI: 10.1007/s11033-018-4453-8

Urease is a potent metalloenzyme with diverse applications. This paper describes the scale up and purification of an extracellular urease from Arthrobacter creatinolyticus MTCC 5604. The urease production was scaled-up in 3.7 L and 20 L fermentor. A maximum activity of 27 and 27.8 U/mL and a productivity of 0.90 and 0.99 U/mL/h were obtained at 30 h and 28 h in 3.7 and 20 L fermentor, respectively. Urease was purified to homogeneity with 49.85-fold purification by gel filtration and anion exchange chromatography with a yield of 36% and a specific activity of 1044.37 U/mg protein. The enzyme showed three protein bands with molecular mass of 72.6, 11.2 and 6.1 kDa on SDS-PAGE and ~ 270 kDa on native PAGE. The cytotoxic effect of urease was assessed in vitro using cancer cell lines (A549 and MG-63) and normal cell line (HEK 293). Urease showed its inhibitory effects on cancer cell lines through the generation of toxic ammonia, which in turn increased the pH of the surrounding medium. This increase in extracellular pH, enhanced the cytotoxic effect of weak base chemotherapeutic drugs, doxorubicin (50 µM) and vinblastine (100 µM) in the presence of urease (5 U/mL) and urea (0-4 mM) significantly.

Matched MeSH terms: Urea/metabolism; Urease/isolation & purification*; Urease/pharmacology*; Urease/physiology
Composition of normal urine in students of the University of Malaya

Chandra N, Bhattathiry EP

Trop Geogr Med, 1967 Dec;19(4):300-3.
PMID: 5585976
Matched MeSH terms: Urea/urine
Fulltext Urea and creatinine detection on nano-laminated gold thin film using Kretschmann-based surface plasmon resonance biosensor

Menon PS, Said FA, Mei GS, Berhanuddin DD, Umar AA, Shaari S, et al.

PLoS One, 2018;13(7):e0201228.
PMID: 30052647 DOI: 10.1371/journal.pone.0201228

This work investigates the surface plasmon resonance (SPR) response of 50-nm thick nano-laminated gold film using Kretschmann-based biosensing for detection of urea and creatinine in solution of various concentrations (non-enzymatic samples). Comparison was made with the presence of urease and creatininase enzymes in the urea and creatinine solutions (enzymatic samples), respectively. Angular interrogation technique was applied using optical wavelengths of 670 nm and 785 nm. The biosensor detects the presence of urea and creatinine at concentrations ranging from 50-800 mM for urea samples and 10-200 mM for creatinine samples. The purpose of studying the enzymatic sample was mainly to enhance the sensitivity of the sensor towards urea and creatinine in the samples. Upon exposure to 670 nm optical wavelength, the sensitivity of 1.4°/M was detected in non-enzymatic urea samples and 4°/M in non-enzymatic creatinine samples. On the other hand, sensor sensitivity as high as 16.2°/M in urea-urease samples and 10°/M in creatinine-creatininase samples was detected. The enhanced sensitivity possibly attributed to the increase in refractive index of analyte sensing layer due to urea-urease and creatinine-creatininase coupling activity. This work has successfully proved the design and demonstrated a proof-of-concept experiment using a low-cost and easy fabrication of Kretschmann based nano-laminated gold film SPR biosensor for detection of urea and creatinine using urease and creatininase enzymes.

Matched MeSH terms: Urea/analysis*; Urease/analysis
Fulltext Effect of corn supplementation on purine derivatives and rumen fermentation in sheep fed PKC and urea-treated rice straw

Saeed OA, Sazili AQ, Akit H, Alimon AR, Samsudin AAB

Trop Anim Health Prod, 2018 Dec;50(8):1859-1864.
PMID: 29948778 DOI: 10.1007/s11250-018-1636-1

This study investigated the effect of different levels of corn supplementation as energy source into palm kernel cake-urea-treated rice straw basal diet on urinary excretion of purine derivatives, nitrogen utilization, rumen fermentation, and rumen microorganism populations. Twenty-seven Dorper lambs were randomly assigned to three treatment groups and kept in individual pens for a 120-day period. The animals were subjected to the dietary treatments as follows: T1: 75.3% PKC + 0% corn, T2: 70.3% PKC + 5% corn, and T3: 65.3% PKC + 10% corn. Hypoxanthine and uric acid excretion level were recorded similarly in lambs supplemented with corn. The microbial N yield and butyrate level was higher in corn-supplemented group, but fecal N excretion, T3 has the lowest level than other groups. Lambs fed T3 had a greater rumen protozoa population while the number of R. flavefaciens was recorded highest in T2. No significant differences were observed for total bacteria, F. succinogenes, R. albus, and methanogen population among all treatment. Based on these results, T3 could be fed to lambs without deleterious effect on the VFA and N balance.

Matched MeSH terms: Urea/metabolism
Optimization of complex fermentation media for glucose oxidase production using statistical approach

Gunny AA, Arbain D, Sithamparam L

Pak J Biol Sci, 2013 Sep 15;16(18):960-4.
PMID: 24502155

Production cost of enzyme is largely determined by the type of the strain and raw material used to propagate the strain. Hence, selection of the strain and raw materials is crucial in enzyme production. For Glucose oxidase (GOx), previous studies showed Aspergillus terreus UniMAP AA-1 offers a better alternative to the existing sources. Thus, a lower production cost could be logically anticipated by growing the strain in a cheaper complex media such as molasses. In this work, sugar cane molasses, supplemented with urea and carbonate salt and a locally isolated strain Aspergillus terreus UniMAP AA-1 were used to produce a crude GOx enzyme in a small scale. A statistical optimization approach namely Response Surface Methodology (RSM) was used to optimize the media components for highest GOx activity. It was found that the highest GOx activity was achieved using a combination of molasses, carbonate salt and urea at concentration 32.51, 4.58 and 0.93% (w/v), respectively. This study provides an alternative optimized media conditions for GOx production using locally available raw materials.

Matched MeSH terms: Urea/metabolism
Fulltext High-dose rabeprazole-amoxicillin dual therapy and rabeprazole triple therapy with amoxicillin and levofloxacin for 2 weeks as first and second line rescue therapies for Helicobacter pylori treatment failures

Goh KL, Manikam J, Qua CS

Aliment Pharmacol Ther, 2012 May;35(9):1097-102.
PMID: 22404486 DOI: 10.1111/j.1365-2036.2012.05054.x

BACKGROUND:
H. pylori eradication failures are difficult to treat and rescue therapies often consist of complex treatment regimens.

AIM:
To determine an effective and practical rescue therapeutic strategy for H. pylori treatment failures using two consecutive regimens: first rescue therapy - rabeprazole 20 mg t.d.s. and amoxicillin 1 g t.d.s. for 2 weeks and for failures a further second rescue therapy - rabeprazole 20 mg b.d., levofloxacin 500 mg b.d., amoxicillin 1 g b.d. for a further 2 weeks.

METHODS:
Consecutive patients who failed the proton pump inhibitor (PPI) 1-week triple therapy were recruited for the study. H. pylori status was determined by a C(13) urea breath test.

RESULTS:
One hundred and forty-nine patients received the first rescue therapy. Seven were not compliant to medication/defaulted follow-up. Eradication success- first rescue therapy: per protocol (PP) analysis-107/142 (75.4%) (95% CI (68.3-82.4%) and intention to treat (ITT) analysis-107/149 (71.8%) 95% CI (64.6-79.0%). Thirty-one of 35 patients who failed the first rescue therapy received the second rescue therapy. All were compliant with medications. Eradication success- PP and ITT was 28/31 (90.3%) 95% CI (74.2-98.0%). The cumulative eradication rate using both rescue therapies: PP analysis- 135/138 (97.8%) 95% CI: (93.8-99.6%), ITT analysis- 135/149 (90.6%) 95% CI: (84.7-94.8%).

CONCLUSIONS:
A 2-week high dose PPI-amoxicillin dual therapy followed by a PPI-amoxicillin-levofloxacin triple therapy were highly successful in achieving eradication in H. pylori treatment failures.

Matched MeSH terms: Urea/metabolism; Urea/pharmacology
Osteonecrosis with renal damage in HIV patients undergoing HAART

Chitra P, Bakthavatsalam B, Palvannan T

Biomed Pharmacother, 2014 Sep;68(7):881-5.
PMID: 25194446 DOI: 10.1016/j.biopha.2014.07.017

Rheumatoid arthritis in HIV patients undergoing HAART is associated with increased risk of side effect. Elevation of uric acid (UA) is important in tissue damage, deposition of crystal in joints leads to the development of rheumatoid arthritis in the HAART complaint group. This study was carried out to investigate the relationship of uric acid, RA factor, ANA, ESR, cystatin C, urea and creatinine in the HAART complaint group. Moreover; the ratio of uric acid/cystatin C, uric acid/urea and uric acid/creatinine were also studied. To analyze the progression of HIV, the immunological parameters were correlated with uric acid. Our result showed a statistically high significant increase in uric acid, RA factor, ANA, ESR, cystatin C, urea and creatinine in the HAART complaint group when compared to HAART non-complaint group, early stage and control. The ratio of uric acid/cystatin C, uric acid/urea, uric acid/creatinine were significantly increased in the HAART complaint group. Statistically significant positive correlation was observed between uric acid and cystatin C, urea, creatinine, absolute CD4 and CD8 count. The increased level of uric acid, RA factor, ANA, ESR, cystatin C and increased ratio of uric acid/cystatin C in the HAART complaint group might conclude the mechanism underlying the increased risk for rheumatoid arthritis in the HAART complaint group which may relate to the combined effects of low-grade inflammation and renal dysfunction.

Study done in India

Matched MeSH terms: Urea/metabolism
Indicators of prolonged hospital stay in hyperemesis gravidarum

Tan PC, Jacob R, Quek KF, Omar SZ

Int J Gynaecol Obstet, 2006 Jun;93(3):246-7.
PMID: 16682037
Matched MeSH terms: Urea/blood
Fulltext Home-based chemically-induced whitening (bleaching) of teeth in adults

Eachempati P, Kumbargere Nagraj S, Kiran Kumar Krishanappa S, Gupta P, Yaylali IE

Cochrane Database Syst Rev, 2018 12 18;12:CD006202.
PMID: 30562408 DOI: 10.1002/14651858.CD006202.pub2

BACKGROUND: With the increased demand for whiter teeth, home-based bleaching products, either dentist-prescribed or over-the-counter products have been exponentially increasing in the past few decades. This is an update of a Cochrane Review first published in 2006.
OBJECTIVES: To evaluate the effects of home-based tooth whitening products with chemical bleaching action, dispensed by a dentist or over-the-counter.
SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 12 June 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library (searched 12 June 2018), MEDLINE Ovid (1946 to 12 June 2018), and Embase Ovid (1980 to 12 June 2018). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (12 June 2018) and the World Health Organization International Clinical Trials Registry Platform (12 June 2018) were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA: We included in our review randomised controlled trials (RCTs) which involved adults who were 18 years and above, and compared dentist-dispensed or over-the-counter tooth whitening (bleaching) products with placebo or other comparable products.Quasi-randomised trials, combination of in-office and home-based treatments, and home-based products having physical removal of stains were excluded.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials. Two pairs of review authors independently extracted data and assessed risk of bias. We estimated risk ratios (RRs) for dichotomous data, and mean differences (MDs) or standardised mean difference (SMD) for continuous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS: We included 71 trials in the review with 26 studies (1398 participants) comparing a bleaching agent to placebo and 51 studies (2382 participants) comparing a bleaching agent to another bleaching agent. Two studies were at low overall risk of bias; two at high overall risk of bias; and the remaining 67 at unclear overall risk of bias.The bleaching agents (carbamide peroxide (CP) gel in tray, hydrogen peroxide (HP) gel in tray, HP strips, CP paint-on gel, HP paint-on gel, sodium hexametaphosphate (SHMP) chewing gum, sodium tripolyphosphate (STPP) chewing gum, and HP mouthwash) at different concentrations with varying application times whitened teeth compared to placebo over a short time period (from 2 weeks to 6 months), however the certainty of the evidence is low to very low.In trials comparing one bleaching agent to another, concentrations, application method and application times, and duration of use varied widely. Most of the comparisons were reported in single trials with small sample sizes and event rates and certainty of the evidence was assessed as low to very low. Therefore the evidence currently available is insufficient to draw reliable conclusions regarding the superiority of home-based bleaching compositions or any particular method of application or concentration or application time or duration of use.Tooth sensitivity and oral irritation were the most common side effects which were more prevalent with higher concentrations of active agents though the effects were mild and transient. Tooth whitening did not have any effect on oral health-related quality of life.
AUTHORS' CONCLUSIONS: We found low to very low-certainty evidence over short time periods to support the effectiveness of home-based chemically-induced bleaching methods compared to placebo for all the outcomes tested.We were unable to draw any conclusions regarding the superiority of home-based bleaching compositions or any particular method of application or concentration or application time or duration of use, as the overall evidence generated was of very low certainty. Well-planned RCTs need to be conducted by standardising methods of application, concentrations, application times, and duration of treatment.

Matched MeSH terms: Urea/therapeutic use
Blood parameters and electroencephalographic responses of goats to slaughter without stunning

Sabow AB, Goh YM, Zulkifli I, Sazili AQ, Kaka U, Kadi MZAA, et al.

Meat Sci, 2016 Nov;121:148-155.
PMID: 27317849 DOI: 10.1016/j.meatsci.2016.05.009

The study compared changes in blood biochemistry, hormonal and electroencephalographic indices associated with possible noxious stimuli following neck cut slaughter in conscious, non-anaesthetized versus minimally-anaesthetized goats. Ten male Boer crossbreed goats were assigned into two groups and subjected to either slaughter conscious without stunning (SWS) or slaughter following minimal anaesthesia (SMA). Hormonal responses and changes in electroencephalographic (EEG) parameters were not influenced by slaughter method. The SWS goats had higher glucose and lactate than did SMA goats. It can be concluded that the noxious stimulus from the neck cut is present in both conscious and minimally anaesthetized goats. The application of slaughter without stunning causes changes in the EEG activities that are consistent with the presence of post slaughter noxious sensory input associated with tissue damage and would be expected to be experienced as pain in goats.

Matched MeSH terms: Urea/blood
Chronotherapeutic effect of fisetin on expression of urea cycle enzymes and inflammatory markers in hyperammonaemic rats

Subramanian P, Jayakumar M, Jayapalan JJ, Hashim OH

Pharmacol Rep, 2014 Dec;66(6):1037-42.
PMID: 25443732 DOI: 10.1016/j.pharep.2014.06.018

BACKGROUND: Elevated blood ammonia leads to hyperammonaemia that affects vital central nervous system (CNS) functions. Fisetin, a naturally occurring flavonoid, exhibits therapeutic benefits, such as anti-cancer, anti-diabetic, anti-oxidant, anti-angiogenic, neuroprotective and neurotrophic effects.
METHODS: In this study, the chronotherapeutic effect of fisetin on ammonium chloride (AC)-induced hyperammonaemic rats was investigated, to ascertain the time point at which the maximum drug effect is achieved. The anti-hyperammonaemic potential of fisetin (50mg/kg b.w. oral) was analysed when administered to AC treated (100mg/kg b.w. i.p.) rats at 06:00, 12:00, 18:00 and 00:00h. Amelioration of pathophysiological conditions by fisetin at different time points was measured by analysing the levels of expression of liver urea cycle enzymes (carbamoyl phosphate synthetase-I (CPS-I), ornithine transcarbamoylase (OTC) and argininosuccinate synthetase (ASS)), nuclear transcription factor kappaB (NF-κB p65), brain glutamine synthetase (GS) and inducible nitric oxide synthase (iNOS) by Western blot analysis.
RESULTS: Fisetin increased the expression of CPS-I, OTC, ASS and GS and decreased iNOS and NF-κB p65 in hyperammonaemic rats. Fisetin administration at 00:00h showed more significant effects on the expression of liver and brain markers, compared with other time points.
CONCLUSIONS: Fisetin could exhibit anti-hyperammonaemic effect owing to its anti-oxidant and cytoprotective influences. The temporal variation in the effect of fisetin could be due to the (i) chronopharmacological, chronopharmacokinetic properties of fisetin and (ii) modulations in the endogenous circadian rhythms of urea cycle enzymes, brain markers, redox enzymes and renal clearance during hyperammonaemia by fisetin. However, future studies in these lines are necessitated.

Matched MeSH terms: Urea/metabolism*
Fulltext Mefenamic Acid induced nephrotoxicity: an animal model

Somchit MN, Sanat F, Hui GE, Wahab SI, Ahmad Z

Adv Pharm Bull, 2014 Dec;4(4):401-4.
PMID: 25436198 DOI: 10.5681/apb.2014.059

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model.
METHODS: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil) or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day). Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN) and creatinine activities were measured.
RESULTS: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine.
CONCLUSION: RESULTS from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

Matched MeSH terms: Blood Urea Nitrogen
Fulltext Helicobacter pylori related dyspepsia: prevalence and treatment outcomes at University Kebangsaan Malaysia-Primary Care Centre

Abdul Aziz AF, Hamzah Z, Tong SF, Nadeson S, Wan Puteh SE

Asia Pac Fam Med, 2009 May 12;8(1):4.
PMID: 19435494 DOI: 10.1186/1447-056X-8-4

BACKGROUND: Optimum management of dyspepsia in primary care is a debatable subject. Testing for Helicobacter pylori (HP) has been recommended in primary care as this strategy will cure most underlying peptic ulcer disease and prevent future gastro duodenal disease.

METHODS: A total of 98 patients completed Modified Glasgow Dyspepsia Severity Score Questionnaire (MGDSSQ) at initial presentation before undergoing the 13Carbon Urea Breath Test (UBT) for HP. Those with positive UBT received Eradication Therapy with oral Omeprazole 20 mg twice daily, Clarithromycin 500 mg daily and Amoxycillin 500 mg twice daily for one week followed by Omeprazole to be completed for another 4 to 6 weeks. Those with negative UBT received empirical treatment with oral Omeprazole 20 mg twice daily for 4 to 6 weeks. Patients were assessed again using the MGDSSQ at the completion of treatment and one month after stopping treatment.

RESULTS: The prevalence of dyspepsia at Universiti Kebangsaan Malaysia-Primary Care Centre was 1.12% (124/11037), out of which 23.5% (23/98) was due to HP. Post treatment assessment in both HP (95.7%, 22/23) and non HP-related dyspepsia (86.7%, 65/75) groups showed complete or almost complete resolution of dyspepsia. Only about 4.3% (1/23) in the HP related dyspepsia and 13.3% (10/75) in the non HP group required endoscopy.

CONCLUSION: The prevalence of dyspepsia due to HP in this primary care centre was 23.5%. Detection of HP related dyspepsia yielded good treatment outcomes (95.7%).

Matched MeSH terms: Urea
Fulltext Solubility enhancement studies on lurasidone hydrochloride using mixed hydrotropy

Madan JR, Pawar KT, Dua K

Int J Pharm Investig, 2015 Apr-Jun;5(2):114-20.
PMID: 25838997 DOI: 10.4103/2230-973X.153390

Low aqueous solubility is a major problem faced during formulation development of new drug molecules. Lurasidone HCl (LRD) is an antipsychotic agent specially used in the treatments of schizophrenia and is a good example of the problems associated with low aqueous solubility. Lurasidone is practically insoluble in water, has poor bioavailability and slow onset of action and therefore cannot be given in emergency clinical situations like schizophrenia. Hence, purpose of this research was to provide a fast dissolving oral dosage form of Lurasidone. This dosage form can provide quick onset of action by using the concept of mixed hydrotropy. Initially, solubility of LRD was determined individually in nicotinamide, sodium citrate, urea and sodium benzoate at concentration of 10, 20, 30 and 40% w/v solutions using purified water as a solvent. Highest solubility was obtained in 40% sodium benzoate solution. In order to decrease the individual hydrotrope concentration mixed hydrotropic agents were used. Highest solubility was obtained in 15:20:5 ratio of Nicotinamide + sodium benzoate + sodium citrate. This optimized combination was utilized in the preparation of solid dispersions by using distilled water as a solvent. Solid dispersions were evaluated for X-ray diffraction, differential scanning calorimetry and Fourier-transform infrared to show no drug-hydrotropes interaction has occurred. This solid dispersion was compressed to form fast dissolving tablets. Dissolution studies of prepared tablets were done using USP Type II apparatus. The batch L3 tablets show 88% cumulative drug release within 14 min and in vitro dispersion time was 32 min. It was concluded that the concept of mixed hydrotropic solid dispersion is novel, safe and cost-effective technique for enhancing the bioavailability of poorly water-soluble drugs. The miraculous enhancement in solubility and bioavailability of Lurasidone is clear indication of the potential of mixed hydrotropy to be used in future for other poorly water-soluble drugs in which low bioavailability is a major concern.

Matched MeSH terms: Urea
Fulltext Polycystic kidney disease concurrent with feline parvovirus and bacterial infections in domestic shorthair cat: a case report

Sim Lam PPL, Reduan MFH, Jasni S, Shaari R, Shaharulnizim N, Nordin ML, et al.

Comp Clin Path, 2020 Sep 28.
PMID: 33013278 DOI: 10.1007/s00580-020-03170-4

Feline polycystic kidney disease (PKD) is an inherited disorder caused by the mutation of PKD1 gene that eventually lead to the development of chronic kidney disease. The latter condition causes hypertension and eventually progress into congestive heart failure. Feline parvovirus (FPV) is a highly contagious and often fatal disease infecting cats and other members of Felidae. An 8-month-old female domestic shorthair cat was presented with complaint of wound dehiscence a day after ovarian hysterectomy procedure. The wound at the suture site appeared necrotic, purulent with foul smell. The cat was found to have diarrhoea during the fixation of suture breakdown and, later, was tested positive with parvovirus infection. Complete blood count revealed anaemia, neutrophilia, lymphopenia and thrombocytosis. Biochemistry profiles showed hypoproteinaemia and elevated of urea and creatinine. The cat was hospitalised, and symptomatic treatments were given. During hospitalisation, the cat showed symptoms of polydipsia and polyuria and found dead 2 days later. Post-mortem findings demonstrated the cat had oral ulceration, thoracic effusion, fibrinopleuropneumonia, pericardial effusion, left ventricular hypertrophy and right ventricular dilation, chronic passive liver congestion, mesenteric lymphadenomegaly, intestinal haemorrhage, adrenomegaly and polycystic kidney. Histopathological evaluation revealed fibrinous pleuropneumonia, pulmonary atelectasis, emphysema and oedema, hypertrophic cardiomyopathy, hepatic necrosis, splenic necrosis, intestinal necrosis, renal necrosis and renal polycystic. Staphylococcus aureus and Escherichia coli were isolated from bronchus swab and intestinal segment, respectively. Polymerase chain reaction (PCR) revealed parvovirus infection. The cat was definitely diagnosed with polycystic kidney disease concurrent with parvoviral and secondary bacterial infections.

Matched MeSH terms: Urea
Effects of the aqueous extracts of rhodamnia cinerea on metabolic indices and sorbitol-related complications in type 2 diabetic rats

Mustapha Umar Imam, Sasikala M. Chinnappan, Maznah Ismail

Sains Malaysiana, 2017;46:589-595.

There is growing interest in the use of plant bioresources for managing type 2 diabetes. In this study, Rhodamnia cinerea, which is used traditionally to manage diseases in Malaysia, was explored for its antidiabetic effects. Type 2 diabetic rats were managed for 4 weeks using aqueous extract of R. cinerea or quercetin. Weights and fasting glucose were measured weekly, while serum lipid profiles, insulin, antioxidant status, urea, creatinine and liver enzymes were assayed at the end. Sorbitol contents, antioxidant capacities and aldose reductase activities of the kidney, lens and sciatic nerve were also assessed. The results showed that the aqueous extract of R. Cinerea mainly contained Myricitrin and it reduced glycemia (p>0.05), lipid profiles (p<0.05), F2-isoprostanes (p<0.05) and overall metabolic condition of type 2 diabetic rats. R. cinerea also attenuated sorbitol contents of the nerve (p<0.05) and kidney (p<0.05), partly through regulating the activity of aldose reductase (p<0.05 for nerve) and sorbitol dehydrogenase (p<0.05 for kidney) in comparison with diabetic untreated group. Quercetin is a known aldose reductase inhibitor and can improve several metabolic indices related to Type 2 diabetes. In this study, the results of R. cinerea were comparable to or better than those of quercetin, suggesting that R. cinerea extract can be a good candidate for managing Type 2 diabetes and its complications related to sorbitol accumulation.

Matched MeSH terms: Urea
Systemic lupus erythematosus in a malay boy

Wan Mohamad WM, Mohd Ashari NS, Wan AbHamid WZ

International Medical Journal (Tokyo), 2017;24(3):295-296.

Objective: We presented a case report, systemic lupus erythematosus (SLE) in a Malay boy. Interestingly, this case occurs in a boy, which is not so common because autoimmune disease usually occurs in female. Design: Case report. Methods: We highlighted a case of a boy with SLE who presented with clinical symptoms suggestive of SLE and fulfilled the criteria for SLE diagnosis. Results: The patient was successfully managed with antihypertensive, intravenous cyclophosphamide and oral prednisolone and respond well to the therapy. Conclusion: Systemic lupus erythematosus is a chronic autoimmune disease which rarely occurs in male. However we reported one such case which fulfilled the criteria for SLE. © 2017 Japan Health Sciences University & Japan International Cultural Exchange Foundation.

Matched MeSH terms: Urea
Fulltext Global serum metabolomics profiling of colorectal cancer

Hashim NAA, Ab-Rahim S, Suddin LS, Saman MSA, Mazlan M

Molecular and clinical oncology, 2019 Jul;11(1):3-14.
PMID: 31289671 DOI: 10.3892/mco.2019.1853

Accurate diagnosis of colorectal cancer (CRC) relies on the use of invasive tools such as colonoscopy and sigmoidoscopy. Non-invasive tools are less sensitive in detecting the disease, particularly in the early stage. A number of researchers have used metabolomics analyses on serum/plasma samples of patients with CRC compared with normal healthy individuals in an effort to identify biomarkers for CRC. The aim of the present review is to compare reported serum metabolomics profiles of CRC and to identify common metabolites affected among these studies. A literature search was performed to include any experimental studies on global metabolomics profile of CRC using serum/plasma samples published up to March 2018. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used to assess the quality of the studies reviewed. In total, nine studies were included. The studies used various analytical platforms and were performed on different populations. A pathway enrichment analysis was performed using the data from all the studies under review. The most affected pathways identified were protein biosynthesis, urea cycle, ammonia recycling, alanine metabolism, glutathione metabolism and citric acid cycle. The metabolomics analysis revealed levels of metabolites of glycolysis, tricarboxylic acid cycle, anaerobic respiration, protein, lipid and glutathione metabolism were significantly different between cancer and control samples. Although the majority of differentiating metabolites identified were different in the different studies, there were several metabolites that were common. These metabolites include pyruvic acid, glucose, lactic acid, malic acid, fumaric acid, 3-hydroxybutyric acid, tryptophan, phenylalanine, tyrosine, creatinine and ornithine. The consistent dysregulation of these metabolites among the different studies suggest the possibility of common diagnostic biomarkers for CRC.

Matched MeSH terms: Urea

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