Phorbol ester (TPA) potentiates noradrenaline and acetylcholine-evoked amylase secretion in the rat pancreas

AbstractThe effect of the phorbol ester 12-O-tetradeconyl-phorbol-13-acetate (TPA) on noradrenaline (NA) and acetylcholine (ACh)-evoked amylase secretion in isolated segments of rat pancreas was investigated. TPA alone evoked a relatively small increase in amylase output. However, when combined with either noradrenaline or ACh, the phorbol ester markedly enhanced the secretagogue-induced amylase secretion. These effects were dose related. TPA also enhanced the amylase secretion evoked by either the Ca2+ ionophore A23187 or dibutyryl cyclic AMP. This potentiation by TPA of noradrenaline, ACh, Ca2+ ionophore A23187 and dibutyryl cyclic AMP-evoked amylase output may suggest the existence of a third pathway controlling enzyme secretion in the pancreas

A theoretical analysis of secondary structural characteristics of anticancer peptides

Here, cluster analysis showed that a database of 158 peptides formed 21 clusters based on net positive charge, hydrophobicity and amphiphilicity. In general these clusters showed similar median toxicities (p = 0.176) against eukaryotic cell lines and no single combination of these properties was found optimal for efficacy. The database contained 14 peptides, which showed selectivity for tumour cell lines only (ACPCT), 123 peptides with general toxicity to eukaryotic cells (ACPGT) and 21 inactive peptides (ACPI). Hydrophobic arc size analysis showed that there was no significant difference across the datasets. Even though there was no correlation there was no correlation observed, peptides with wide hydrophobic arcs (> 270°) appeared less toxic. Extended hydrophobic moment plot analysis predicted that over 50% of ACPCT and ACPGT peptides would be surface active, which led to the suggestion that amphiphilicity is a key driver of the membrane interactions for these peptides but probably plays a role in their efficacy rather than their selectivity. This analysis also predicted that only 14% of ACPCT peptides compared to 45% of ACPGT peptides were candidates for tilted peptide formation. This implies that those peptides with non-specific activity may have a tendency towards the utilisation of membrane disruptive structures such as tilt peptides which led to the suggestion that the absence of this structure may support cancer cell selectivity. However, these analyses predicted that ACPI peptides, which possess no anticancer activity, would also form surface active and tilted a-helices, clearly showing that other factors are involved in determining the efficacy and selectivity of ACPs

Correlation of random urine protein creatinine (P-C) ratio with 24-hour urine protein and P-C ratio, based on physical activity: a pilot study

Quantification of proteinuria is usually predicated upon 24-hour urine collection. Multiple factors influence urine collection and the rate of protein and creatinine excretion. Urine collection is often incomplete, and therefore creatinine and protein excretion rates are underestimated. A random urine protein-creatinine (P-C) ratio has been shown over the years to be a reliable alternative to the 24-hour collection for detection and follow up of proteinuria. However, urine protein excretion may be influenced by physical activity. We studied 48 patients with proteinuria and varying levels of physical activity to determine the correlation between the measures of urine protein excretion. The correlation coefficient (r) between 24-hour urine total protein and random urine P-C ratio was 0.75 (P < 0.01) in the overall study population, but varied according to the level of proteinuria and physical activity in a stratified analysis: r = 0.99 (P < 0.001) and r = 0.95 (P < 0.01) in bedridden patients; r = 0.44 (P = not significant [NS]) and r = 0.54 (P = NS) in semiactive patients; and r = 0.44 (P = NS) and r = 0.58 (P < 0.05) in active patients with nephrotic- (>3500 mg/day) and non-nephrotic (<3500 mg/day) range proteinuria, respectively. The correlation appeared to be stronger between random urine and 24-hour urine P-C ratio for the overall study population (r = 0.84; P < 0.001), and when stratified according to the level of proteinuria and physical activity: r = 0.99 (P < 0.001) and r = 0.92 (P < 0.01) in bedridden patients; r = 0.61 (P = NS) and r = 0.54 (P = NS) in semiactive patients; and r = 0.64 (P < 0.02) and r = 0.52 (P < 0.05) in active patients with nephrotic and non-nephrotic range proteinuria, respectively. We conclude that the random urine P-C ratio is a reliable and practical way of estimating and following proteinuria, but its precision and accuracy may be affected by the level of patient physical activity

How to deliver an effective course: A student\u27s perspective

Certain course features, such as engaging delivery, can benefit student learning. This essay presents one student’s opinion of what made for an effective introductory psychology course. The student provides his perspective on various features of the recently completed psychology course and how those elements supported his learning. The elements he identified included various ongoing knowledge checks, test reviews, tests, in-class engagement, personalized touchpoints, scaffolding, and student feedback. For each, the course instructor explains the pedagogical underpinnings of her choices. Faculty may find a student’s perspective on courses valuable as they consider their pedagogical decisions in terms of course design and delivery

Phytochemical Analysis and Anti-diabetic Potential of Annona muricata L., Persea americana Mill. and Montrichardia arborescens L. Schott Utilized by the Residents of Pakuri (St. Cuthbert’s Mission) in Guyana

Aim: This study was designed to assess the utilization of plants with anti-diabetic properties and to conduct preliminary phytochemical analysis and moreover, to assess the anti-diabetic potential of selected plants used to treat and manage Type 2 diabetes mellitus (T2DM) among the residents of Pakuri (St. Cuthbert’s Mission) in Guyana. Methodology: The leaves of sour sop (Annona muricata L.), pear (Persea americana Mill.) and Mocou-Mocou (Montrichardia arborescens L. Schott) underwent phytochemical testing and -amylase Inhibition testing to determine their anti-diabetic properties. Results: This study showed that the leaves of pear, sour sop and mocou mocou contained different chemical constituents including alkaloids, flavonoids, saponins and tannins but the absence of amino acids (proteins), carbohydrates and glycosides. The x-amylase inhibitory studies performed demonstrated that the extracts of A. muricata in ethanol and chloroform had significant inhibitory potential. Conclusion: Considering the promising potential of phytochemicals and the anti-diabetic activity of these species of plant extracts in anti-diabetic drug development, in vivo experiments and clinical trials are required for efficacy and safety evaluation. Also, the anti-diabetic phytochemicals may be used in combination with existing orthodox drugs, thereby, reducing the dose of synthetic anti-diabetic drugs, which will help in addressing the toxicity and cost-related issues in chronic use during the management of diabetes mellitus (DM)

Pathogenesis of Painful Diabetic Neuropathy

The prevalence of diabetes is rising globally and, as a result, its associated complications are also rising. Painful diabetic neuropathy (PDN) is a well-known complication of diabetes and the most common cause of all neuropathic pain. About one-third of all diabetes patients suffer from PDN. It has a huge effect on a person’s daily life, both physically and mentally. Despite huge advances in diabetes and neurology, the exact mechanism of pain causation in PDN is still not clear. The origin of pain could be in the peripheral nerves of the central nervous system. In this review, we discuss various possible mechanisms of the pathogenesis of pain in PDN. We discuss the role of hyperglycaemia in altering the physiology of peripheral nerves. We also describe central mechanisms of pain

Diagnosis and Treatment of a Typical Painful Neuropathy Due to "Insulin Neuritis" in Patients with Diabetes

Diabetes is very common and its global prevalence is rising day by day. As a result we are seeing more complications related to diabetes. In order to prevent micro vascular and macro vascular complications such as retinopathy, nephropathy, erectile dysfunction, neuropathy, myocardial infarction and stroke health care professionals are keen to have better glycaemic control. When dealing with newly diagnosed or poorly controlled diabetes patients are encouraged to bring down glycated haemoglobin (HbA1c). Diabetic painful neuropathy (DPN) is one of the well-known complications associated with long- term poor glycaemic control. However, on the other hand rapid control of high blood sugar can precipitate painful neuropathy known as “insulin neuritis”. The rapid tight glycaemic control with either insulin or oral hypoglycaemic agents on poorly controlled diabetic patients cause flux of blood glucose and metabolic shift resulting in structural changes at nerve endings (endoneural blood vessels) which resemble the retinopathy changes in retina. It causes steal effect and hypoxia in the nerves and hence precipitates neuropathic pain. It lasts for about 6 months and responds well to standard treatment of painful neuropathy. Health professionals need to be aware of this condition and consider gentle glycaemic control when aiming for Target HbA1c. This review outlines the disease, the symptoms, the types and treatment

Evidence for the involvement of intracellular cyclic 3', 5' - nucleotides in regulating miocardial contractility

An investigation was made into one aspect of the molecular control of cardiac contractility, namely, the putative role of the two endogenous cyclic 3',5'-nucleotides, adenosine cyclic 3',5' monophosphate (cyclic AMP) and guanosine cyclic 3',5' monophosphate (cyclic GMP) in regulating the capacity of the heart to produce force. It began as a study of a poorly understood but well documented effect of exogenous adenosine 5'-triphosphate (ATP) on the electrical and mechanical properties of the isolated frog ventricle. In common with several related purine and pyrimidine nucleotides, treatment of the ventricle with ATP elicits a characteristic triphasic response which is not blocked by either atropine or propranolol. Preliminary experiments with ATP led to the hypothesis that it exerts a dual effect on the heart. The two effects were attributed tentatively to the induction of elevated levels of intracellular cyclic AMP and cyclic GMP respectively. Indirect evidence for the involvement of cyclic nucleotides in mediating the ATP-induced response comes from studies with agents which are known to influence cyclic 3',5'-nucleotide metabolism on the form of the ATP-induced response. Measurements of endogenous cyclic 3',5'-nucleotides during the development of the hypodynamic state is associated by a gradual decline in intracellular cyclic AMP and a progressive increase in cyclic GMP. This gradual loss in contractility is also accompanied by the release of prostaglandins E1 and E2 and one or more prostaglandin-related substances into the perfusate. Subsequent experiments with exogenous ATP elicits profound changes in cyclic 3',5'-nucleotides. Both cyclic AMP and cyclic GMP are affected as had been postulated. A third series of experiments with the -agonist isoprenaline (isoproterenol) was undertaken to investigate the generality of the relationship between intracellular cyclic nucleotide levels and contractility, and this produced similar results. The most significant feature to emerge from the results was the finding that in all three responses, which on the face of it appear to be physiologically distinct and quite unrelated, changes in the ratio of intracellular cyclic AMP / cyclic GMP almost exactly parallel the observed changes in contractile force. This observation has led to the formulation of a hypothesis which postulates that both endogenous cyclic 3',5'-nucleotides are integral components of an intracellular control mechanism which is responsible for regulating the contractility of the amphibian ventricle