Multi-stakeholder Engagement for the Sustainable Development Goals: Introduction to the Special Issue.

The world is not on track to achieve Agenda 2030-the approach chosen in 2015 by all UN member states to engage multiple stakeholders for the common goal of sustainable development. The creation of the 17 Sustainable Development Goals (SDGs) arguably offered a new take on sustainable development by adopting hybrid and principle-based governance approaches, where public, private, not for profit and knowledge-institutions were invited to engage around achieving common medium-term targets. Cross-sector partnerships and multi-stakeholder engagement for sustainability have consequently taken shape. But the call for collaboration has also come with fundamental challenges to meaningful engagement strategies-when private enterprises try to establish elaborate multi-stakeholder configurations. How can the purpose of businesses be mitigated through multi-stakeholder principle-based partnerships to effectively serve the purpose of a common sustainability agenda? In selecting nine scholarly contributions, this special issue aims at advancing this discourse. To stimulate further progress in business studies, this introductory essay, furthermore, identifies three pathways for research on multi-stakeholder engagement processes in support of the Decade of Action along three coupling lines: multi-sector alignment (relational coupling), operational perception alignment (cognitive coupling) and goal and strategic alignment (material coupling).

Site of origin of nasal polyps: relevance to pathogenesis and management.

The site of origin of sino-nasal polyps was documented in 113 consecutive patients undergoing functional endoscopic sinus surgery (FESS). These patients were assigned pre-operatively to 4 clinical groups according to the out-patient recorded endoscopic appearance of their nasal cavities; chronic rhinosinusitis without polyps (CRSS) n=35, grade 1 polyps n=28, grade 2 polyps n=30 and grade 3 polyps n=20. In the group of patients diagnosed with polyps pre-operatively, 97.4% had polyps originating in the anterior ethmoid complex, of which 89.7% had polyps originating in the anterior ethmoidal cells and over 60% had polyps specifically originating from each of the following sites: the uncinate or infundibulum, the posterior ethmoid sinus, the frontal recess and the face of the bulla ethmoidalis. In the group diagnosed pre-operatively as CRSS without polyps, polyps were found in 60% of patients within the sinuses during surgery. In summary, our findings suggest that polyps originate from the middle meatus, and may be found at surgery when undetectable at pre-operative endoscopy.

Development of the diabetes knowledge (DKN) scales: forms DKNA, DKNB, and DKNC.

The Diabetes Knowledge Assessment (DKN) scales were developed to meet a specific need for rapid and reliable knowledge assessment in diabetic patients. Item format and item selection from an initial pool of 89 items were determined by pilot-testing over 300 diabetic subjects. Reliability analysis of the resulting 40 multiple-choice items, with a further sample of 56 subjects, gave a Cronbach's alpha coefficient of 0.92. Parallel forms DKNA, DKNB, and DKNC, each of 15 items selected from the parent set, had alpha coefficients above 0.82 and correlated 0.90 with each other. A full clinical trial, using DKNA, DKNB, and DKNC in randomized order of presentation, was conducted with 219 subjects attending a 2-day diabetes education program. Overall DKN scores improved from 7.6 (51%) to 11.3 (75%). Analysis of variance confirmed that DKNA, DKNB, and DKNC were equivalent forms at pretest. Mean posttest scores on DKNB were lower than the other scales (P less than 0.001), but variances were equivalent for all three. A specific local change in the education program format was found to account for this discrepancy in the DKNB posttest mean. In situations where comprehensive assessment of diabetes knowledge would be time-consuming and unnecessary, these results indicate that rapid and reliable assessment is possible with a scale of only 15 validated items. The development of parallel forms of the scale extends the range of retesting possibilities for diagnosis and research.

Somatogenic receptors of rat liver: regulation by insulin.

Somatogenic (i.e. GH) receptors have been studied on liver microsomal membranes from male and female rats. Tracer bovine GH was displaced from its binding sites by GHs of various species, but was displaced only weakly by PRLs. Specific bovine GH binding was 3.5-fold higher to female rat liver membranes than to membranes from males. Streptozotocin-induced diabetes significantly reduced binding, by 80% in females and 50% in males, while insulin therapy to normalize weight gain reversed the decrease in binding. Competitive binding curves were consistent with two independent classes of binding site: low affinity sites with K equal to 0.5 nm-1 in both sexes, and high affinity sites with K equal to 12.1 nm-1 in males and 21.4 nm-1 in females (P less than 0.001). The addition of excess ovine PRL caused a substantial loss of high affinity binding with little loss in the low affinity region, suggesting a weak somatogenic role for ovine PRL. In diabetic animals, low affinity sites were unchanged from normal, while high affinity sites were decreased in number, with no change in affinity, and restored on insulin therapy. Serum immunoreactive rat GH levels were the same in normal and diabetic, male and female animals. These studies suggest that the apparent hepatic resistance to GH seen in diabetes when liver somatomedin release is low despite normal serum GH might be explained by the loss of GH receptors in this condition.

Autocrine regulation of milk secretion.

Mammary development and the rate of milk secretion are regulated by frequency and completeness of milk removal. This regulation occurs through chemical feedback inhibition by a milk constituent. Novel, immunologically related milk proteins able to perform this function have been isolated from caprine, bovine and human milk, based on their ability to inhibit milk constituent synthesis in mammary tissue and cell cultures, and to decrease temporarily milk secretion when added to milk stored in the mammary gland. Inhibition is concentration-dependent, suggesting that milk accumulation and removal is accompanied by cyclical changes in inhibitor accretion and depletion in milk. Feedback inhibition is an autocrine mechanism: the caprine inhibitor, termed FIL (feedback inhibitor of lactation) is synthesized by mammary epithelial cells in primary culture. Inhibition is by reversible blockade of the secretory pathway, an effect which, by down-regulating cell-surface hormone receptors, has longer-term consequences on epithelial cell differentiation. Treatment of goat mammary epithelial cell cultures with caprine FIL initially decreased milk protein secretion and subsequently reduced milk protein messenger RNA abundance. Thus the actions of a single milk constituent can bring about both the effect of milking frequency on milk secretion rate and a sequential modulation of cellular differentiation which acts to sustain the secretory response. Long-term regulation, through changes in galactopoietic hormone receptors, also provides an efficient mechanism for integrating acute intramammary regulation of lactation with strategic endocrine control of mammary tissue development.

High-affinity receptor for insulin-like growth factor II in rat liver: properties and regulation in vivo.

Receptors for insulin-like growth factor II (IGF-II) have been identified in many tissue types and have been shown to differ widely in their specificities and affinities. We have characterized the IGF-II receptor in rat liver microsomal membranes, both in the intact membrane and in a solubilized extract. Binding was time- and temperature-dependent and was unaffected by changes in pH in the range 6-9. Half-maximal displacement was obtained with 0.33 ng IGF-II/ml standard, and Scatchard analysis showed a class of receptors with an affinity for IGF-II of 1.33 +/- 0.36 X 10(10) litres/mol which increased threefold in the presence of Ca (1 mmol/l) to 3.74 +/- 0.89 X 10(10) litres/mol. There was also a threefold decrease in the rate of dissociation in the presence of Ca. Cross-reactivity with IGF-I was less than 1% and there was no cross-reactivity with insulin. Infusion of rat GH or prolactin for 1 week, at the rate of 175-200 micrograms/day, into female rats had no effect on IGF-II binding in control animals, but rat GH infusion caused a 60% increase (P less than 0.001) in binding in hypophysectomized rats by increasing the number of receptors. These studies demonstrate that rat liver microsomal membranes contain a highly specific, high-affinity receptor for IGF-II which may be under partial GH control.

Production of insulin-like growth factor-II by human fetal pancreas in culture.

Insulin-like growth factor-II (IGF-II) is a polypeptide hormone thought to be involved in fetal development because of its wide distribution in fetal tissues and its presence in the fetal circulation. We have developed a highly sensitive radioreceptor assay for IGF-II using rat liver microsomal membranes and have used this assay to test for the presence of IGF-II in the human fetal pancreas and the release of IGF-II by the human fetal pancreas in organ culture. IGF-II was present in extracts of pancreatic tissue (0.056 +/- 0.012 pmol/mg tissue, n = 5) and was released in culture at the rate of 0.027-0.134 pmol/mg tissue per day with release being maintained for at least 3 weeks in culture. The rate of release was not affected by the gestational age of the fetus over 14 to 20 weeks but was significantly related to the rate of insulin release (r = 0.712, P less than 0.001, n = 34). Chronic exposure to 12-0-tetradecanoylphorbol-13-acetate (TPA), which inhibits insulin release in the human fetal pancreas, caused an 85% drop in IGF-II production, which was reversed when TPA was removed. These studies demonstrate that IGF-II is produced by the human fetal pancreas in a pattern similar to that of insulin. We suggest that control of IGF-II release, like that of insulin, may involve protein-kinase C and that IGF-II may have a paracrine or autocrine role in the development of fetal pancreatic function.

In vivo and in vitro suppression by leptin of glucose-stimulated insulin hypersecretion in high glucose-fed rats.

OBJECTIVES: Chronic feeding to rats of high glycaemic index (GI) diets results in the hypersecretion of insulin in response to an i.v. glucose load. The first aim of this study was to see if this exaggerated insulin response was accompanied by a hypersensitivity to glucose stimulation in isolated islets in vitro. The second aim was to see if the adipocyte factor, leptin, was able to alter insulin secretion in this model both in vivo and in vitro. DESIGN AND METHODS: Rats were fed for 6 weeks either a high GI diet in which the carbohydrate component was mostly glucose (GLUC diet) or a low GI diet containing mostly amylose (AMOSE diet). Rats then underwent an i.v. glucose tolerance test (ivGTT) (1g/kg) with and without a prior infusion of leptin (133 microg/kg perh). Islets were then isolated from these rats and basal and glucose-stimulated insulin secretion (GSIS) measured in both the absence and presence (100ng/ml) of leptin. RESULTS AND CONCLUSIONS: Peak insulin response during the ivGTT was 3-fold greater in GLUC rats (P<0.001). Leptin had no effect on AMOSE rat insulin response but lowered the GLUC rat response to AMOSE rat levels. In vitro, basal insulin secretion was 4-fold greater in GLUC rats (P<0.05). At 20mmol/l glucose, there was no further increase in insulin secretion in GLUC rats but a 2-fold increase in AMOSE rats. Leptin had no effect on basal insulin secretion or GSIS in AMOSE rats but reduced basal insulin secretion and GSIS in GLUC rats. These results show insulin hypersecretion in high GI-fed rats may be reduced by leptin.

The effect of fasting on liver receptors for prolactin and growth hormone.

The effects of 3 day fasting on liver prolactin and growth hormone receptors have been investigated in male and female rats. Fasting caused a significant fall in serum immunoreactive insulin (67% decrease), while receptor-reactive somatomedin fell 82% when measured in whole serum and by 72% when measured in serum fractions following gel chromatography at low pH. Tracer ovine prolactin binding to liver microsomal membranes was reduced by 55% on fasting in females, but unchanged in males. Tracer bovine growth hormone binding fell significantly in both sexes. Analysis of competitive binding curves showed the decrease binding to be due to a loss of prolactin receptors in females, and of high affinity (but not low affinity) growth hormone receptors in males and females. Significant correlations were seen between serum insulin and tracer prolactin (females) and growth hormone (males and females) binding to liver membranes. Correlations between serum insulin and liver high affinity growth hormone binding sites were particularly significant (r = 0.899 in females, r = 0.910 in males). It is proposed that the hypoinsulinemia of fasting causes a loss of high affinity growth hormone receptors in the liver, which could result in a relative hepatic resistance to growth hormone and a decreased hepatic generation of somatomedin.

Changes in rat liver prolactin binding sites in diabetes are sex dependent.

The effect of streptozotocin-induced diabetes (100 mg/kg) on lactogenic binding sites, measured by iodinated ovine prolactin (PRL) binding, has been studied in liver microsomal membranes from males and female rats. In females, specific binding was reduced in diabetes from 13% to 4.5% of total tracer, while in males specific binding increased from 0.5% to 2.5%. Similar results were obtained using iodinated human growth hormone as tracer, through overall binding was higher. Scatchard plots of binding curves in females showed that changes in binding were due to changes in receptor concentration, while affinity remained unchanged at 2 X 10(9) M-1. In diabetes, serum PRL and estradiol levels fell by 60% in males but showed no significant change in females, and could therefore not account for receptor changes. In contrast, mean testosterone levels fell in diabetic males from 9.0 to 3.9 nM, and rose in diabetic females from 2.1 to 5.8 nM. Estrogen treatment of male rats caused a marked induction of binding in nondiabetic animals, and a change from the male to the female response to diabetes. Testosterone treatment of nondiabetic females suppressed binding, although not to the male levels, and diabetes caused further suppression. These results are consistent with a role for testosterone in regulating PRL receptors in experimental diabetes, but suggest that other hormonal influences are also involved.

Cellular uptake of taurine by lactating porcine mammary tissue.

Milk taurine plays a critical role in neonatal development. Taurine uptake in lactating sow mammary tissue has not been characterized previously. The kinetic properties, ion dependence and substrate specificity of taurine uptake were characterized in mammary tissue collected from lactating sows at slaughter. Tissue explants were incubated in an isosmotic physiologic buffer with [3H]taurine tracer to measure taurine uptake. Taurine uptake was dependent upon the presence of extracellular sodium and chloride ions, which is consistent with the co-transport of sodium and chloride with taurine. Uptake was not dependent upon ion exchange mechanisms or upon furosemide-sensitive ion co-transport. Taurine uptake was saturable and exhibited an apparent Km of 20 microM and a V(max) of 386 micromol/kg cell water/30 min. Substrate specificity studies indicated a strong interaction of beta-amino acids with the taurine transport system. Taurine transport in lactating sow mammary tissue is therefore a high affinity, sodium-dependent mechanism specific for beta-amino acids, and is analogous to sodium-dependent taurine uptake in other tissues. The high affinity and high specificity of the taurine uptake system allows for concentration of taurine within the mammary cell and is ultimately responsible for provision of taurine required for neonatal development.

Lysine uptake by mammary gland tissue from lactating sows.

Kinetic properties and substrate specificity of the lysine transport system in porcine mammary gland were studied using mammary tissue explants from nine lactating sows. Sodium dependence of lysine uptake was determined by replacing sodium in the medium with choline. Kinetic parameters of lysine uptake were determined using lysine concentrations from 5 microM to 5.12 mM. Competition of lysine uptake by other amino acids was determined using the cationic amino acids, arginine and ornithine, and using other essential amino acids. Transport of lysine was time-dependent and was unaffected by replacing sodium with choline. Lysine uptake occurred by a transport mechanism with a Km of approximately 1.4 mM and a Vmax of 7.9 mmol x kg cell water(-1) x 30 min(-1). Lysine uptake was inhibited by arginine and ornithine and by high concentrations of L-alanine, L-methionine, L-leucine, cycloleucine, and D-lysine, but not by 2-(methylamino)-isobutyric acid. This transport mechanism is the primary system responsible for uptake of cationic amino acids in lactating sow mammary tissue. The relatively high Km, compared with physiological blood concentrations of lysine, indicates that the kinetic properties of the lysine transport system should not be limiting to milk protein synthesis. Transmembrane transport of lysine by lactating sow mammary tissue should be a direct function of plasma concentrations. However, interactions of other amino acids with the uptake system may affect lysine uptake.

Cellular uptake of valine by lactating porcine mammary tissue.

The cellular uptake of branched-chain amino acids in mammary tissue is important for understanding their role in milk synthesis in the sow. This study characterized the kinetic properties and substrate specificity of the valine uptake system in the porcine mammary gland. Mammary tissue was collected from lactating sows at slaughter and tissue explants were incubated in media containing isosmotic salt and amino acids of interest, plus [3H]valine tracer. Valine uptake was time-dependent and was dependent on the presence of sodium, as indicated by a reduction in uptake when sodium in the medium was replaced by choline. The valine transport system in porcine mammary tissue had a Km of 0.64 mM, a Vmax of 1.84 mmol-kg cell water(-1) 30 min(-l), and a Kd (diffusion constant) of 1.16 L x kg cell water(-1) x 30 min(-1). Valine uptake was inhibited by leucine and alpha-aminoisobutyric acid and by high concentrations of L-alanine, L-lysine, cycloleucine, L-glutamine, and L-methionine, but not by 2-(methyl-amino)-isobutyric acid. This transport system is the primary system responsible for uptake of valine, and probably other branched-chain amino acids, in lactating sow mammary tissue. Physiological concentrations of valine in the blood are below the Km of the specific valine transport system and well below the diffusion uptake capabilities. The kinetic parameters of this valine transport system should not be limiting to valine uptake for milk protein synthesis. However, competition of valine uptake with branched-chain amino acids, as well as with other amino acids, may affect valine uptake in lactating tissue.

Medullary thyroid carcinoma: a rare presentation as a hypervascular tumour.

Sporadic medullary thyroid carcinoma (MTC) usually presents with a thyroid mass, cervical lymphadenopathy or other local cervical symptoms. Often the diagnosis is unsuspected pre-operatively. We report a unique case of a mixed follicular medullary thyroid carcinoma presenting as a tumour with extreme vascularity. The management of hypervascular thyroid tumours is discussed together with current controversies regarding persistent hypercalcitoninaemia.

Leptin secretion is related to glucose-derived lipogenesis in isolated adipocytes.

OBJECTIVE: Leptin secretion in rats is regulated acutely by nutritional state. Insulin plays an important role in this acute nutritional regulation both directly and indirectly through effects on glucose metabolism. The aim of this study was to investigate if the fasting-induced suppression of leptin secretion was reversed by incubation under conditions mimicking nutritional repletion. DESIGN: Leptin secretion and glucose metabolism were measured following incubation with glucose and insulin in adipocytes isolated from fed and fasted rats. RESULTS: Leptin secretion was stimulated by incubation with glucose and insulin in adipocytes isolated from fed but not from fasted rats as was glucose flux through oxidative and lipogenic pathways. Ob expression and intracellular leptin content were decreased in adipocytes isolated from fasted rats throughout the whole incubation period. Suppression of glucose metabolism with cytochalasin B was accompanied by suppression of leptin secretion. The amount of leptin secretion correlated with the glucose incorporated into lipid under insulin-stimulated conditions. CONCLUSIONS: It is proposed that glucose incorporation into lipid, at least during insulin-stimulated conditions, reflects the metabolic status of the adipocyte and may be a more important regulator of leptin production and secretion than circulating glucose or insulin levels.

Insulin determines leptin responses during a glucose challenge in fed and fasted rats.

OBJECTIVE: Leptin secretion has been shown to respond acutely to changes in blood glucose and insulin. Nutritional state also has a marked effect on both the level of circulating leptin protein and leptin gene expression. The aim of this study was to assess whether the prior nutritional state altered the leptin secretory response to an acute glucose challenge, and to determine potential mechanisms. DESIGN: Male fed or fasted rats (200-250 g) were administered a single intravenous glucose bolus (1, 4 or 7 g/kg). The serum leptin, glucose, insulin and free fatty acid responses were studied over the following 5 h. The level of leptin gene expression and leptin protein was then determined in the epididymal fat pads, and in fed and fasted untreated rats for basal comparison. RESULTS: Leptin secretion in response to glucose was suppressed in fasted rats following all glucose doses. The total leptin response was correlated with the total insulin response in all conditions (r = 0.85) and with the glucose response in fed rats (r = 0.69). Both leptin gene expression and leptin protein content were lower in basal fasted rats. Leptin gene expression and leptin protein content still remained lower 5 h following a glucose bolus but there was partial reversal of the effects of fasting following the 7 g/kg glucose dose. CONCLUSIONS: Leptin secretion in response to an intravenous glucose bolus was determined by the insulin response and was significantly suppressed in fasted compared to fed rats. In addition to differences in the total insulin response of the animals, lower leptin responses may be facilitated by lower levels of both leptin gene mRNA and pre-existing leptin protein in epididymal adipose tissue of fasted rats.