Detection of Paraquat in Oral Fluid, Plasma, and Urine by Capillary Electrophoresis for Diagnosis of Acute Poisoning

FAPESP

Determination of epinephrine in urine using multi-walled carbon nanotube modified with cobalt phthalocyanine in a paraffin composite electrode

This paper describes the development, electrochemical characterization and utilization of a cobalt phthalocyanine (CoPc), modified multi-walled carbon nanotube (MWCNT), and paraffin composite electrode for the quantitative determination of epinephrine (EP) in human urine samples. The electrochemical profile of the proposed composite electrode was analyzed by differential pulse voltammetry (DPV) that showed a shift of the oxidation peak potential of EP at 175 mV to less positive value, compared with a paraffin/graphite composite electrode without CoPc. DPV experiments in PBS at pH 6.0 were performed to determine EP without any previous step of extraction, clean-up, and derivatization, in the range from 1.33 to 5.50 mu mol L(-1), with a detection limit of 15.6 nmol L(-1) (2.86) of EP in electrolyte prepared with purified water. The lifetime of the proposed sensors was at least over 1000 determinations with 1.7 and 3.1 repeatability and reproducibility relative standard deviations, respectively. Human urine samples without any purification step were successfully analyzed under the standard addition method using paraffin/MWCNT/CoPc composite electrode. (C) 2010 Elsevier B.V. All rights reserved.

Cloning and mRNA expression of guanylin, uroguanylin, and guanylyl cyclase C in the Spinifex hopping mouse, Notomys alexis

Guanylin and uroguanylin are peptides that activate guanylyl cyclase C (GC-C) receptors in the intestine and kidney, which causes an increase in the excretion of salt and water. The Spinifex hopping mouse, Notomys alexis, is a desert rodent that can survive for extended periods without free access to water and it was hypothesised that to conserve water, the expression of guanylin, uroguanylin, and GC-C would be down-regulated to reduce the excretion of water in urine and faeces. Accordingly, this study examined the expression of guanylin, uroguanylin, and GC-C mRNA in Notomys under normal (access to water) and water-deprived conditions. Initially, guanylin and uroguanylin cDNAs encoding the full open reading frame were cloned and sequenced. A PCR analysis showed guanylin and uroguanylin mRNA expression in the small intestine, caecum, proximal and distal colon, heart, and kidney. In addition, a partial GC-C cDNA was obtained and GC-C mRNA expression was demonstrated in the proximal and distal colon, but not the kidney. Subsequently, a semi-quantitative PCR method showed that water deprivation in Notomys caused a significant increase in guanylin and uroguanylin mRNA expression in the distal colon, and in guanylin and GC-C mRNA expression in the proximal colon. No significant difference in guanylin and uroguanylin mRNA expression was observed in the kidney. The results of this study indicate that there is, in fact, an up-regulation of the colonic guanylin system in Notomys after 7 days of water deprivation.

The effect of water deprivation on signalling molecules that utilise cGMP in the Spinifex Hopping Mouse Notomys alexis

In mammals the natriuretic and guanylin peptides influence renal and intestinal fluid content and electrolyte transport by binding to and activating guanylyl cyclase (GC) receptors that in turn stimulate production of the intracellular second messenger guanosine 3':5'-cyclic monophospate
(cGMP). However, the role of natriuretic and guanylin peptides in desert mammals is not understood. The spinifex hopping-mouse (Notomys alexis), has a suite of behavioural and physiological mechanisms that permits survival for extended periods without access to free water. Because signalling molecules that generate cGMP are known to promote water excretion, it was predicted that natriuretic and guanylin peptide synthesis would be down regulated in water-deprived N. alexis, and thus reduce the amount of water lost in the urine and faeces. However, in the kidney ANP and GC-A mRNA levels were increased in water-deprived mice, but CNP and GC-B mRNA levels were decreased. Water deprivation increased guanylin and uroguanylin mRNA expression in the distal colon, but it remained unchanged in the kidney and proximal colon. The expression of GC-C mRNA increased in the proximal colon but not in the distal colon. This study shows that water deprivation differentially affects the expression of regulatory molecules that stimulate cGMP producti

Pharmacokinetics of recombinant human endostatin in rats

The pharmacokinetics of recombinant human endostatin (rh-Endo) has not been established in the rat, although this species of animal is commonly used in the pharmacological studies of rh-Endo. This study aimed to investigate the pharmacokinetics, tissue distribution, and excretion of rh-Endo in rats. 125I-radiolabeled rh-Endo was administered to healthy rats by intravenous (i.v) bolus injection at 1.5, 4.5 and 13.5 mg/kg. The maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) of rh-Endo increased proportionally with the increase of the dosage. There were no significant differences in total body clearance (CL) and elimination half-life (t1/2beta) of rh-Endo among the three dosages used. A 93.5% and 2.2% of the radioactivity was recovered in the urine and feces, respectively, in bile-duct intact rats; whereas only 0.1% of the total radioactivity was excreted into the bile in bile-duct cannulated rats. rh-Endo was rapidly and widely distributed in the liver, kidneys, spleen and lungs. Furthermore, a significant allometric relationship between CL, but not volume of distribution (Vd) and t1/2beta of rh-Endo, and the body weight was observed across mouse, rat and monkey, with the predicted values in humans significantly lower than those observed in cancer patients. rh-Endo exhibited a linear pharmacokinetics in rats and it is mainly excreted through the urine.

Effect of a low sodium DASH diet, including red meat on blood pressure in post-menopausal women

Background – The DASH type dietary pattern which consists of high fruit, vegetable and dairy products and low saturated fat, is “base-producing” but restricts red meat with no clear justification.
Objective – To compare the BP-lowering effect of Vitality diet (VD), a moderately low sodium, “base” producing modified DASH diet, containing 6 serves/week of lean red meat to a “ high carbohydrate, low fat diet (HCLF diet), with a higher dietary acid load in post-menopausal women.
Design – Ninety-five hypertensive post-menopausal women (46 VD and 49 HCLF) completed a 14-wk randomised parallel study. Home BP was measured daily. Repeat 24-h dietary records and 24-h urine samples were collected fortnightly. Dietary acid load, expressed as potential renal acid load (PRAL), was calculated from nutrient intakes.
Outcomes – During the intervention, the VD group had an average daily consumption of 85 g cooked red meat. They had a mean (± SEM) reduction of 38 ± 7 mmol/d in urinary sodium excretion (P <0.0001), and a 7 ± 4 mmol/d increase in urinary potassium (P = 0.0681), with an estimated 23.1± 2.3 mEq/d lower PRAL than the HCLF group (P <0.0001). The fall in systolic pressure in the VD group tended to be greater by 3 ± 2 mmHg (P = 0.08) than the fall in systolic pressure seen with the HCLF diet. A greater BP-lowering effect of VD was observed among those taking anti-hypertensive medication (n = 17) with a greater 5.5 ± 2.7 mm Hg (P = 0.0518) reduction of systolic BP and greater reduction in diastolic BP by 3.6 ± 1.7 mm Hg (P = 0.0388) compared to the HCLF diet. However, no relationship between BP and PRAL was observed.
Conclusions – A low sodium DASH type dietary pattern with the inclusion of lean red meat was effective in reducing BP in post-menopausal women, particularly in those taking anti-hypertensive medication. This dietary pattern could be recommended for this group who are at increased risk of cardiovascular disease.
This study was funded by Meat & Livestock Australia.

Method design and validation for the determination of uranium levels in human urine using high-resolution alpha spectrometry

Quantification of uranium in human urine is a valuable technique for assessing occupational and public exposure to uranium. A reliable method has been developed and validated in the ARPANSA Radiochemistry Laboratory by means of standard radiochemical separation and purification techniques and measurement using high-resolution alpha spectrometry. This method can be used to evaluate the levels of naturally occurring ²³⁴U, ²³⁵U and ²³⁸U in urine. Method design and validation is the process of defining an analytical requirement, and then confirming that the method under consideration has performance capabilities consistent with what the application requires. The method was designed to measure levels down to 2 mBq/day of total uranium, corresponding to approximately 1/100th of the annual committed effective dose of 20 mSv. Validation tests were developed to assess selectivity, accuracy, recovery and quantification of uncertainty. The radiochemical recovery of this method was measured using ²³²U tracer. The typical minimum detectable concentration for total uranium for 24-h urine samples is approximately 0.6 mBq/day or 0.019 μg/day.

Relationship of heart failure patients' knowledge, perceived barriers, and attitudes regarding low-sodium diet recommendations to adherence.

The purposes of this study were to describe heart failure patient perceptions regarding instructions received for following a low-sodium diet and the benefits, barriers, and ease and frequency of following the diet. A total of 246 patients with heart failure referred from academic medical centers in the United States and Australia participated in the study. A subset of 145 patients provided 24-hour urine samples for sodium excretion assessment. While most (80%) patients reported receiving recommendations to follow a low-sodium diet, their recall of specific instructions was poor. Although the majority (75%) reported following a low-sodium diet most or all of the time, 24-hour urine sodium excretion indicated that only 25% of patients were adherent. Patients who reported being more adherent, however, had lower urine sodium excretion levels. Attitudes regarding difficulty in and perceived benefits of following the diet were not related to sodium excretion. Data on attitudes and barriers provided guidance for strategies to improve adherence.

Renal responses to angiotensin II in conscious dogs : effects of aspirin and indomethacin

1. Angiotensin II was infused into the renal artery of unanaesthetized dogs at 0.4 and 2.0 ng/kg per min for 40 min each.

2. Indomethacin (3 mg/kg, and 1 mg/kg per h infusion i.v.) accentuated the angiotensin II-induced falls in glomerular filtration rate, renal blood flow and urine flow rate. Indomethacin did not alter the effects of angiotensin II on Na+ or K+ excretions.

3. Aspirin (35 mg/kg p.o. 2.5 h and 0.5 h prior to experiment) did not significantly change the renal effects of angiotensin II.

4. Both aspirin and indomethacin accentuated renal vasoconstriction during briefer (5 min) angiotensin II infusion.

5. Thus indomethacin and aspirin had markedly different effects on the actions of angiotensin II in the kidney. This suggests that at least one of these drugs has actions which affect angiotensin II-mediated vasoconstriction other than via cyclooxygenase inhibition.