Electrochemical Preparation of Poly(3,4-Ethylenedioxythiophene) Layers on Gold Microelectrodes for Uric Acid-Sensing Applications

Two different methods for the synthesis of poly(3,4-ethylenedioxythiophene) (PEDOT) on gold electrodes are described, using electropolymerization of ...

The University of Auckland

Intestinal ischaemia is implicated in the pathogenesis of severe acute pancreatitis, a disorder characterized by acinar necrosis. To study the relationship between pancreatic and intestinal microvascular perfusion during 40 min of intestinal ischaemia and 30 min of reperfusion in rodents with acute pancreatitis, a model utilizing laser Doppler flowmetry was developed. It is reported here together with practical solutions for (1) a modified method of vessel cannulation; (2) a novel method for the temperature-controlled optical coupling between laser Doppler probes and rodent tissues, and (3) a simple technique of inducing intestinal ischaemia-reperfusion while continuously monitoring the microvascular perfusion in both pancreas and intestine. The utility of the model is demonstrated in a pilot study that showed that the pancreatic perfusion fell acutely to 58% (p = 0.029) of baseline during the intestinal reperfusion phase. This reduced perfusion continued for 30 min despite recovery of both the intestinal perfusion and the mean arterial blood pressure to baseline levels.

A method using laser Doppler flowmetry to study intestinal and pancreatic perfusion during an acute intestinal ischaemic injury in rats with pancreatitis.

The etiology of pancreatic cancer remains elusive. Identification of high-risk groups may enable targeted study to identify new markers and risk factors.

Ethnic disparity of pancreatic cancer in New Zealand.

Insufficient maternal protein intake has been postulated to cause impaired fuel metabolism and diabetes mellitus in adult mammalian progeny, but the mechanism remains unclear.

Impaired insulin secretion in perfused pancreases isolated from offspring of female rats fed a low protein whey-based diet.

There is no consistency between the individual studies in the literature on whether organ failure (OF) or infected pancreatic necrosis (IPN) is the main determinant of severity in acute pancreatitis. We aimed to statistically aggregate the available data and determine the pooled influence of OF and IPN on mortality in patients with acute pancreatitis.

Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis.

Nasojejunal tube feeding is a standard of care in patients with predicted severe acute pancreatitis (AP) and several recent trials suggested that nasogastric tube feeding (NGT) is as safe and efficient as nasojejunal tube feeding in these patients. The aim was to investigate whether NGT presents any benefit to patients with mild to moderate AP.

Early nasogastric tube feeding versus nil per os in mild to moderate acute pancreatitis: a randomized controlled trial.

Diabetes mellitus (DM) is common in the general population and it poses a heavy burden to society in the form of long-term disability, healthcare use and costs. The pancreas is a key player in glucose homeostasis, but the occurrence of newly diagnosed DM after acute pancreatitis (AP), the most frequent disease of the pancreas, has never been assessed systematically. The aim of this study was to conduct a systematic literature review to determine the prevalence and time course of DM and related conditions after the first attack of AP as well as the impact of covariates.

Newly diagnosed diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis.

Extra-pancreatic infectious complications in acute pancreatitis increase morbidity, but their incidence and association with infected pancreatic necrosis is unknown. Half of bacterial cultures of pancreatic necrosis are of non-enteric origin, raising the possibility of other sources of infection. The aim of this systematic review was to assess the incidence of extra-pancreatic infectious complications in acute pancreatitis, their timing, and relation to severity of pancreatitis and mortality.

A systematic review of the extra-pancreatic infectious complications in acute pancreatitis.

Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P < 0.0001) at concentrations that only moderately impaired function of control hearts. To our knowledge, this is the first report describing the acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease.

Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

Cyclic voltammetry (CV) and high performance liquid chromatography (HPLC), were compared to quantify uric acid and antioxidant reducing agents in 36 milk samples. The enzymes uricase and ascorbate oxidase were used to remove uric and ascorbic acids and showed that the peaks obtained by CV and HPLC did not contain contributions from other unknown compounds. The levels of uric acid obtained by CV compared well to those determined using HPLC, with only a few exceptions, and the average difference was around 6%. CV measurements were made using the main anodic peak seen at approximately 330 mV (Ag/AgCl), while a later oxidation peak at approximately 650 mV can be associated with further reducing agents present in milk. The electrochemical method was quicker to apply than HPLC that included a pre-treatment step, and provides an inexpensive and simple method for the reliable analysis of uric acid in milk.

Application of cyclic voltammetry to analyse uric acid and reducing agents in commercial milks.

The intestinal lymphatic system transports fluid, immune cells, dietary lipids, and highly lipophilic drugs from the intestine to the systemic circulation. These transport functions are important to health and when dysregulated contribute to pathology. This has generated significant interest in approaches to deliver drugs to the lymphatics. Most of the current understanding of intestinal lymph flow, and lymphatic lipid and drug transport rates, comes from  studies and  animal studies. In contrast, intestinal lymphatic transport studies in human subjects have been limited. Recently, three surgical patients had cannulation of the thoracic lymph duct for collection of lymph before and during a stepwise increase in enteral feed rate. We compared these data to studies where we previously enterally administered controlled quantities of lipid and the lipophilic drug halofantrine to mice, rats and dogs and collected lymph and blood (plasma). The collected lymph was analyzed to compare lymph flow rate, triglyceride (TG) and drug transport rates, and plasma was analyzed for drug concentrations, as a function of enteral lipid dose across species. Lymph flow rate, TG and drug transport increased with lipid administration in all species tested, and scaled allometrically according to the equation A = M  where A is the lymph transport parameter, M is animal body mass,  is constant and  is the allometric exponent. For lymph flow rate and TG transport, the allometric exponents were 0.84-0.94 and 0.80-0.96, respectively. Accordingly, weight normalized lymph flow and TG mass transport were generally lower in larger compared to smaller species. In comparison, mass transport of drug via lymph increased in a greater than proportional manner with species body mass with an exponent of ∼1.3. The supra-proportional increase in lymphatic drug transport with species body mass appeared to be due to increased partitioning of drug into lymph rather than blood following absorption. Overall, this study proposes that intestinal lymphatic flow, and lymphatic lipid and drug transport in humans is most similar to species with higher body mass such as dogs and underestimated by studies in rodents. Notably, lymph flow and lipid transport in humans can be predicted from animal data via allometric scaling suggesting the potential for similar relationships with drug transport.

Anthony R. J. Phillips

School of Biological Sciences,
Surgical and Translational Research Center

The University of Auckland

Electrochemical Preparation of Poly(3,4-Ethylenedioxythiophene) Layers on Gold Microelectrodes for Uric Acid-Sensing Applications

Anthony R. J. Phillips

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}School of Biological Sciences,Surgical and Translational Research Center

The University of Auckland

Electrochemical Preparation of Poly(3,4-Ethylenedioxythiophene) Layers on Gold Microelectrodes for Uric Acid-Sensing Applications

School of Biological Sciences,
Surgical and Translational Research Center