Start Of Ingestion Research Articles

Case Series Of Selenium Toxicity From A Nutritional Supplement

Introduction. Selenium is an essential trace element, but can be toxic in excess. In May 2008, US FDA reported 201 individuals with adverse reactions to liquid nutritional supplements containing excess selenium and chromium resulting in the largest epidemic of selenosis in the history of the United States. Objective. To describe the clinical features, biomonitoring data of selenium levels, and the estimated total dose of selenium ingestions of nine patients with selenium toxicity who presented after use of a liquid dietary supplement with a formulation error. Methods. A retrospective observational case series was performed on nine patients presenting to our medical toxicology clinic between March 2008 and May 2008 with symptoms of selenosis after consuming a nutritional supplement. Institutional IRB approval was obtained for this case series. Results. Supplement testing revealed almost 200 times the reported amount of selenium. There were 5 males and 4 females and their ages ranged from 15 to 57 years (median 46 years, mean 44.2 years). The mean estimated cumulative dose of selenium ingested in our patients was 1.3 gram over a mean period of 37.5 days (10–60 days). In each case, the symptoms of selenium toxicity manifested within 1 week from the start of ingestion. Initial symptoms included alopecia, dystrophic fingernail changes, GI symptoms, and memory difficulties. The initial whole blood selenium concentrations ranged from 150 to 732 mcg/L (reference mean range 123–193 mcg/L) at an average of 27 days post cessation of the formula. The urinary selenium concentrations ranged from 41 to 220 mcg/g Creat (reference < 25 mcg/g Creatinine). None of the patients required more than supportive care for symptoms and none required hospitalization. Conclusion. Selenium is an essential element, which can result in significant toxicity if ingested in large amounts.

Influence of honey versus sucrose on satiety and postprandial metabolism in healthy subjects

We recently demonstrated that rats consuming a honey‐based diet gained less body weight and fat and ate less food versus rats consuming a sucrose‐based diet. The objectives of this study were to assess the effects of honey compared to sucrose on satiety and plasma concentrations of glucose, insulin and ghrelin in healthy humans. Thirteen healthy (BMI: 23.2±3.3) participants (6 men, 7 women) aged 21‐40 y fasted overnight (10 hours) then consumed isocaloric beverages (240 kcal) sweetened with sucrose, clover honey, or glucose in a randomized, crossover design where glucose served as a control. Fingerprick blood samples were collected and satiety ratings were assessed prior to beverage consumption and 15, 30, 45, 60, 90 and 120 minutes following the start of ingestion. Plasma was analyzed for concentrations of glucose, insulin and ghrelin, and area under the curve (AUC) or over the curve was calculated for all variables. Satiety was not different between sucrose and honey. Lower (p&lt;0.05) AUCs for plasma glucose were detected for honey (‐35±28%) and sucrose (‐27±29%) relative to glucose consumption. No differences in insulin or ghrelin responses were detected among groups. Honey promoted a potentially healthier response than glucose but not sucrose with regard to postprandial glucose metabolism, but no differences in the satiating effects of the sweeteners were detected.Supported by the American Heart Association.

Experimental swainsonine poisoning in goats ingesting Ipomoea sericophylla and Ipomoea riedelii (Convolvulaceae)

Ipomoea sericophylla and Ipomoea riedelii cause a glycoprotein storage disease in goats. This paper reports the experimental poisoning in goats by dried I. sericophylla and I. riedelii containing 0.05% and 0.01% swainsonine, respectively. Three groups with four animals each were used. Group 1 received daily doses of 2g/kg body weight (bw) of dried I. sericophylla (150mg of swainsonine/kg). Goats from this group had clinical signs 36-38 days after the start of ingestion. Group 2 received dried I. riedelii daily doses of 2g/kg of I. riedelii (30mg of swainsonine/kg) for 70 days. No clinical signs were observed, therefore the swainsonine dose was increased to 60mg/kg for another 70 days. Goats from Group 2 had clinical signs 26-65 days after increase in swainsonine dose to 60mg/kg. Group 3 was used as control. In these experiments the minimum toxic dose was 60mg/kg which represents 0.0004% of the dry matter in goats ingesting 1.5% bw of the dry matter. For goats ingesting 2%-2.5% bw of dry matter this dose would be 0.00024%-0.0003% of the dry matter. After the end of the experiment two goats were euthanized and another six were observed for recovery of clinical signs. Four goats that continued to consume swainsonine containing plant for 39-89 days after the first clinical signs had non reversible signs, while two goats that ingested the plant for only 15 and 20 days after the first clinical signs recovered completely. These and previous results indicate that irreversible lesions due to neuronal loss occur in goats that continue to ingest the plants for about 30 days after the first clinical signs. Clinical signs and histological lesions were similar to those reported previously for goats poisoned by swainsonine containing plants. No significant alterations were found in packed cell volume, red and white blood cell counts, hemoglobin and mean corpuscular hemoglobin concentrations, mean corpuscular volume, and serum levels of glucose, total protein, and albumin, and the serum activities of gamma glutamyl transferase and aspartate aminotransferase. Swainsonine concentration of 0.05% in I. sericophylla and 0.01% in I. riedelii are different from samples of these plants used in previous experiments, which contained 0.14% and 0.5% swainsonine, respectively, demonstrating a wide variation in the toxicity of different samples.

Blood flow is an important determinant of forearm glucose uptake following a mixed meal.

Insulin-mediated vasodilation has been suggested to be of importance for glucose uptake during normoglycemic hyperinsulinemia. If this also is valid after an ordinary mixed meal remains to be evaluated. Forearm blood flow (FBF) and forearm glucose uptake change (evaluated by venous occlusion plethysmography) and glucose arteriovenous differences were evaluated over 120 minutes in 10 healthy volunteers following an ordinary mixed meal (700-900 kcal, 34% of energy from fat). Fasting arterial glucose level was 4.9+/-0.9 mmol/l, and the maximum glucose level was reached 30 minutes after the start of ingestion (6.6+/-0.8 mmol/l, p<0.0001). Plasma insulin levels were increased four-fold. FBF increased rapidly within 20 minutes after the start of ingestion and reached its maximum after 50 minutes (94% higher than baseline level, p<0.01). After 2 hours FBF was still substantially elevated (75% above baseline level, p<0.01). Forearm glucose uptake increased fivefold already after 20 minutes ( p<0.01). During the 2 hours, the increase in FBF contributed to 41% of the forearm glucose uptake ( p<0.05). The present study showed that the increase in FBF seen after an ordinary mixed meal is important for the change in forearm glucose uptake. These results support the view that modulation of limb blood flow is a determinant of glucose uptake.

Timing of Postprandial Dyspeptic Symptoms and Transpyloric Passage of Gastric Contents

Background: Patients with functional dyspepsia often experience early satiety and discomfort after a meal. The role of early gastric emptying in symptom generation is not known. Our aim was to relate timing of symptoms and early postprandial emptying in functional dyspepsia. Methods: Twelve patients with functional dyspepsia were investigated during 3 min of fasting, during 3 min of ingesting 500 ml of a meat soup, and during the first 10 min postprandially by means of duplex sonography. Results: Gastric emptying commenced on average 52 sec after the start of ingestion. Transpyloric movements of gastric contents unrelated to peristalsis (that is, alternating transpyloric emptying and reflux within a common chamber created by the terminal antrum, the pylorus, and the duodenal bulb) appeared before peristaltic-related emptying, which commenced after on average 116 sec. In all patients epigastric, meal-related discomfort was experienced after the commencement of transpyloric emptying, on average after 143 sec. A negative correlation was found between intensity of fullness and duration of presymptomatic transpyloric movements of gastric contents (that is, the duodenal `tasting' period). Conclusions: The early occurrence of meal-related symptoms suggests that gastric distension is the main factor in symptom generation. However, the onset of symptoms after the commencement of gastric emptying suggests that intestinal tasting receptors are involved in symptom generation. The inverse relationship between the duration of the tasting period and symptom intensity suggests that the time allowed for duodenal tasting might be too short in patients with FD.

Identification of vagal preganglionics that mediate cephalic phase insulin response

To define the vagal circuitry mediating the cephalic phase insulin response (CPIR), this reflex was measured in conscious, freely moving rats that had previously undergone selective abdominal vagotomies that spared different columnar subpopulations of dorsal motor nucleus of the vagus (dmnX) neurons. The CPIR was defined as an increase of plasma insulin from basal at 2 min after the start of ingestion. The CPIR measured in peripheral blood after chow ingestion was reliable and significant (P less than 0.05) in rats with all branches intact, +24.9 +/- 5.1 microU/ml (+130% increase from basal); rats with only the two gastric branches and the hepatic branch intact, +27.0 +/- 3.5 microU/ml (+153%); and rats with only the hepatic branch intact, +13.5 +/- 4.8 microU/ml (+188%). No significant response occurred in animals with only the two celiac branches intact, +1.8 +/- 1.8 microU/ml (+15%) or in those with none of the branches intact, +3.9 +/- 3.3 microU/ml (+21%). The CPIRs measured in portal vein blood were generally larger but showed the same pattern across groups. Plasma glucose measurements of portal vein blood indicated that with chow ingestion no significant absorption had occurred by 2 min, whereas with either milk or glucose intake absorption did occur. Subsequent bilateral electrical cervical vagal stimulation-induced insulin and glucagon responses in the same animals under anesthesia showed the same branch dependency. It is concluded that the CPIR is mediated by the two gastric and the hepatic branches but not the two celiac vagal branches. The perikarya of the preganglionics innervating the pancreatic B-cells are contained within a large pool occupying the two medial columns of the dmnX.

Effects of pancreas transplantation on insulin secretion in the rat during ingestion of varying glucose loads.

Following alloxan induced diabetes in rats, transplantation of neonatal pancreases under the kidney capsule was successfully carried out. The insulin response to oral ingestion of 150 and 750 mg of glucose was studied. The responses in controls and in rats 40 days after transplantation demonstrated a load-dependent increment of plasma insulin responses which was not related to the similar glucose responses. In control rats a part of the insulin response had occurred at 1 min, i.e. 2 min before the rise in blood glucose. After transplantation in the absence of this nervously triggered response, blood glucose rose faster than in control rats from 3 to 5 min after start of ingestion (p less than 0.01). In non-transplanted rats regenerating a part of their original pancreas within one week, glucose intolerance was seen 10 min after glucose ingestion, probably due to the lack of adequate secondary phase release. This study shows that maintenance of a normal glucose tolerance curve to glucose ingestion depends on at least two factors. First, an anticipatory nervously triggered insulin secretion. Second, a load dependent humoral potentiation of glucose stimulated insulin release.