Consumer attitudes on cough and cold: US (ACHOO) survey results.

OBJECTIVE: The Attitudes of Consumers Toward Health, Cough, and Cold (ACHOO) survey was developed to better inform health care providers on the natural history and impact of common cold and cough, and related consumer experience and behaviors. RESEARCH DESIGN AND METHODS: Randomly selected US Internet/mobile device users were invited to participate in an online survey (N = 3333) in October 2012. Response quotas modeled upon 2010 US Census data ensured a demographically representative sample. To reduce potential bias from the quota design, 75% of the completed surveys were randomly selected as the primary analysis pool. MAIN OUTCOME MEASURES: Survey questions assessed participant demographics, frequency and duration of cough/cold symptoms, impact of symptoms on daily life, treatment preferences, and knowledge about cough/cold pathophysiology. RESULTS: In the past year, 84.6% of respondents had experienced at least one cold. Colds typically started with sore/scratchy throat (39.2%), nasal congestion (9.8%), and runny nose (9.3%) and lasted 3-7 days. Cough, the most common cold symptom (73.1%), had a delayed onset (typically 1-5 days after cold onset) and a long duration (>6 days in 35.2%). Nasal congestion and cough were the most bothersome symptoms. Many respondents waited until symptoms were 'bad enough' (42.6%) or multiple symptoms were present (20.2%) before using nonprescription medications. Drivers of choice included effectiveness in relieving symptoms, safety, and past experience. Respondents rarely consulted clinicians regarding treatment, and more than three-quarters had never received instructions from a clinician on how to choose a nonprescription cough/cold medication. Misperceptions regarding etiology and treatment of the common cold were prevalent. The main limitation is potential recall bias, since respondents had to recall cough/cold episodes over the prior year. CONCLUSIONS: The ACHOO survey confirms that cold is a common, bothersome experience and that there are gaps in consumers' knowledge of pathophysiology and appropriate management of cough/cold.

Changes in ryanodine receptor-mediated calcium release during skeletal muscle differentiation. II. Resolution of a caffeine-ryanodine paradox.

Our previous study demonstrated a disparity of action between two established pharmacological modulators of the same calcium (Ca2+) release channel, the ryanodine receptor (RyR). Specifically, we observed that caffeine sensitivity was elicited at earlier stages of development than that of ryanodine. In the present study, we offer a hypothesis to resolve this paradox. We provide evidence that ryanodine acts as a pure uncompetitive inhibitor of Ca2+ transport, with respect to Ca2+ itself. This explains why little ryanodine inhibition was observed at low Ca2+ concentrations, while maximal ryanodine inhibition was observed at saturating Ca2+ concentrations. In order to exclude the possibility of nonspecific ryanodine actions as an alternative explanation, we established the phenomenon of capacitative calcium entry (CCE) for L6 cells. Since it is known that CCE is inversely correlated with [Ca2+] of the ER/SR lumen, the extent of CCE is therefore an indirect measure of Ca2+ concentration within the SR. We also demonstrated the functional pathway for Ca2+ entry. Employing pharmacological inhibitors, we found that a T-type plasma membrane channel was predominant in the myoblasts, while an L-type channel was predominant in the adult myotubes. Our data using these inhibitors made nonspecific ryanodine actions an unlikely explanation of the disparity in action between ryanodine and caffeine. Moreover, we found no evidence that inositol trisphosphate, a proposed regulator of CCE for other cells, could influence CCE in L6 cells. We conclude that the disparity between caffeine and ryanodine can be explained by Ca2+ dependence of ryanodine action. This study may also offer an explanation of other studies showing unclear actions of ryanodine binding and action.

Proabsorptive action of gum arabic: regulation of nitric oxide metabolism in the basolateral potassium channel of the small intestine.

BACKGROUND: Gum arabic, a high-molecular-weight natural polysaccharide, has been shown to have proabsorptive properties in animal models of gastrointestinal disease that involve nitric oxide (NO). Gum arabic may indirectly regulate NO metabolism by creating an outward NO gradient, thus altering other intracellular NO-dependent mechanisms such as gating of the potassium (K+) channel. This hypothesis was further investigated using the K+ channel blocker, glybenclamide. METHODS: Following intraperitoneal injection of 4.5 mg/kg glybenclamide or saline, the jejunum of anesthetized rats was perfused with a standard oral rehydration solution in the presence or absence of 2.5 g/L gum arabic, as well as 1 mmol/L l-arginine to enhance NO production. Sodium, net water, and glucose absorption and unidirectional water movement were determined. RESULTS: Gum arabic showed regulatory capacity for NO-dependent metabolism by reducing net water absorption in the absence of arginine, and sodium absorption after arginine stimulation, in the absence of glybenclamide. Addition of gum arabic to oral rehydration solution, in glybenclamide pretreated animals, and in the absence of arginine, normalized sodium absorption, but was less effective in restoring net water transport. Injection of glybenclamide sharply decreased all absorption markers in arginine supplemented oral rehydration solution, which were at least partially restored by addition of gum arabic to the oral rehydration solution. In the presence of glybenclamide, the effects of arginine became antiabsorptive, as had those observed in preceding studies with high arginine concentration. Gum arabic partially or fully reversed alterations produced by perfused 1 mmol/L arginine. CONCLUSIONS: Some of the effects of gum arabic on the small intestine are likely caused by its ability to remove NO as it diffuses into the lumen, thus reducing NO concentration in the enterocyte and indirectly affecting the absorptive/secretory response of the gut, which leads to normalization of absorptive function. These findings are consistent with the previously shown gum arabic-scavenging properties of NO and support a potential therapeutic role for this product.

Stimulation of non-sodium-dependent water, electrolyte, and glucose transport in rat small intestine by gum arabic.

In experimental models of gastroenterological disease, the soluble fiber gum arabic (GA) acts as a proabsorptive adjuvant. This study investigated which specific transport pathway(s) are affected by GA. Rat jejunum was perfused under anesthesia with a standardized oral rehydration solution (ORS) containing D-glucose, with or without GA (2.5 g/liter). In some preparations either phloridizin, a competitive inhibitor of Na+-coupled D-glucose transport, or phloretin, an inhibitor of basolateral glucose transport, were added to the ORS, with or without GA. Diffusion and paracellular transport changes due to GA were evaluated with L-glucose and [14C]polyethlyene glycol 4000 (PEG). GA partially reversed water, Na+, and D-glucose absorption inhibition induced by phloridzin and normalized water and Na+ absorption in the presence of phloretin. GA also increased absorption of water, Na+, and PEG from an L-glucose ORS. The data suggest that GA does not act via Na+ dependent mechanism(s), but stimulates transcellular and/or transjunctional transport pathways; therefore GA may be useful to increase absorption of solutes transported by diffusion.

A preliminary study of growth hormone therapy for Crohn's disease.

BACKGROUND: Crohn's disease is a chronic inflammatory disorder of the bowel. In a preliminary study, we evaluated whether the administration of growth hormone (somatropin) as well as a high-protein diet would ameliorate the symptoms of the disease. METHODS: We randomly assigned 37 adults with moderate-to-severe active Crohn's disease to four months of self-administered injections of growth hormone (loading dose, 5 mg per day subcutaneously for one week, followed by a maintenance dose of 1.5 mg per day) or placebo. We instructed all patients to increase their protein intake to at least 2 g per kilogram of body weight per day. Patients continued to be treated by their usual physicians and to receive other medications for Crohn's disease. The primary end point was the change in scores on the Crohn's Disease Activity Index from base line to month 4. Scores can range from 0 to 600, with higher scores indicating more disease activity. RESULTS: At base line, the mean (+/-SD) score on the Crohn's Disease Activity Index was somewhat higher among the 19 patients in the growth hormone group than among the 18 patients in the placebo group (287+/-134 vs. 213+/-120, P=0.09). Three patients in the placebo group withdrew before their first follow-up visit and were not included in the data analysis. At four months, the Crohn's Disease Activity Index score had decreased by a mean of 143+/-144 points in the growth hormone group, as compared with a decrease of 19+/-63 points in the placebo group (P=0.004). Side effects in the growth hormone group included edema (in 10 patients) and headache (in 5) and usually resolved within the first month of treatment. CONCLUSIONS: Our preliminary study suggests that growth hormone may be a beneficial treatment for patients with Crohn's disease.

Cholera toxin-induced secretion in rats is reduced by a soluble fiber, gum arabic.

Gum arabic (GA), a soluble fiber with emulsifying properties, enhances intestinal water and electrolyte absorption in normal and secreting rats. Our aim was to assess the effect of GA, 2.5 and 5.0 g/liter, on cholera toxin-induced water and electrolyte secretion in rat jejunum in vivo. After a 2-hr exposure to cholera toxin, jejunal segments of adult rats were perfused in vivo with at plasma electrolyte solution containing GA, 0, 2.5 or 5.0 g/liter. 24Na was used as a marker of sodium influx. Cholera toxin-induced secretion was reduced by GA, 2.5 and 5.0 g/liter. 24Na secretion into the lumen was reduced by GA. GA caused a morphological expansion of intercellular spaces in the villi but not crypts. In conclusion, GA promotes lumen to blood intestinal transport of water and sodium despite cholera toxin activation. These observations support a potential role for GA in enhancing the efficacy of ORS.

Development of the intestinal SGLT1 transporter in rats.

Glucose absorption from the small intestine is largely mediated via the sodium-coupled glucose transporter (SGLT1). The goal of this study was to investigate the ontogenesis of the SGLT1, using the rat as an animal model at three stages of development: during lactation, at weaning, and at physiologic maturity. The techniques involved upper small intestinal perfusions with solutions containing 200 mM glucose and 50 mM NaCl, with or without 1 mM phloridzin (Phl), as an inhibitor of SGLT1. Molecular expression of the SGLT1 was also investigated via Western blot analysis from intestinal specimens of the three growth periods. Glucose absorption in weanling rats, in the absence of Phl, was several times higher than in sucklings and approximately double that of mature animals, and the effects of Phl were the greatest in weanlings. Furthermore, the physiologic data correlate to the molecular analysis of the SGLT1 which showed an increase in expression of the SGLT1 in both the weanlings and the adults compared to the sucklings. At all three stages of development Phl abolished Na absorption, and in sucklings there was a net outflow of Na. Due to the coupling between Na and water transport, net water absorption and the influx/efflux ratio, a more sensitive indicator of changes in unidirectional fluid movement, were similarly affected by Phl at the three stages of development. Net water absorption was highest in weanling animals. These findings are consistent with an early development of SGLT1 in rat small intestine and an apparent burst of activity at weaning. Less than complete maturity of other absorptive mechansims is occurring at this time.

Effect of gum arabic in an oral rehydration solution on recovery from diarrhea in rats.

BACKGROUND: It has been shown that gum arabic, a soluble fiber, enhances water, electrolyte, and glucose absorption from oral rehydration solutions in jejunal perfusion of healthy rats and in animals with theophylline-induced secretion or chronic osmotic-secretory diarrhea. This report concerns a study of the effectiveness of an oral rehydration solution supplemented with gum arabic, during recovery from chronic osmotic secretory diarrhea in free-living rats. METHODS: Chronic diarrhea was induced in 60- to 80-g juvenile rats by providing a magnesium citrate-phenolphthalein solution as the sole fluid source for 7 days. This led to diarrhea characterized by dehydration, soft stools, increased cecal volume, decreased food and fluid intake and failure to gain weight. After 7 days of diarrhea, rats recovered for 24 hours with either tap water or an oral rehydration solution (90 mM Na, 111 mM glucose, 20 mM K, 80 mM chloride, 20 mM citrate) with or without 2.5 g/l gum arabic. RESULTS: Although all three solutions improved the diarrhea, optimal recovery from diarrhea was achieved with the gum arabic-supplemented oral rehydration solution. After 4 hours and 24 hours, rats drinking the gum arabic-supplemented solution gained more weight and had lower fecal output than rats receiving water or the rehydration solution without gum arabic. All three solutions normalized plasma osmolality after 24 hours. CONCLUSIONS: The positive effects of the gum arabic-supplemented rehydration solution on fluid and electrolyte absorption seen during jejunal perfusion also occurred during recovery from chronic osmotic secretory diarrhea, when free-living animals drank the solution ad libitum.

Promotion of copper excretion from the isolated rat heart attenuates postischemic cardiac oxidative injury.

This study examined the role of Cu as a mediator of cardiac postischemic oxidative injury. Isolated rat hearts were subjected to 20 min of normothermic global ischemia, followed by 30 min of reperfusion; after 20 min of preischemic loading with Krebs-Henseleit buffer +/- 20 or 30 microM zinc-bis-histidinate (Zn-His2), 0.5 mM deferoxamine (DEF) or 42 microM neocuproine (NEO). Postischemic developed systolic pressure and rate-pressure product were highest and postischemic end-diastolic pressure was lowest in hearts treated with 20 or 30 microM Zn-His2 and 0.5 mM DEF. Cu efflux was significantly increased by 225 and 290% (end of preischemic loading), and 325 and 375% (immediate postischemic period) of control basal rates in hearts treated with 30 microM Zn-His2 and 0.5 mM DEF, respectively. NEO did not effect any of these parameters. By the end of ischemia, protein carbonyls were lowest in Zn-His2-treated hearts and highest in DEF-treated hearts when compared with control hearts. The results of this study suggest that removal of redox-active Cu before ischemia has beneficial effects, indicating a mediatory role in postischemic cardiac oxidative injury.

Changes in ryanodine receptor-mediated calcium release during skeletal muscle differentiation.

We have observed a disparity between the actions of caffeine and ryanodine, two agents known to affect the same site of intracellular calcium (Ca2+) release in muscle. The site of intracellular Ca2+ release, the ryanodine receptor (RyR), is established as the route of Ca2+ movement from the sarcoplasmic reticulum (SR) to the cytosol during excitation-contraction coupling. We measured Ca2+ release fluorimetrically in both saponin-permeabilized and intact L6 cells, in response to known modulators (i.e., caffeine and ryanodine), during differentiation in vitro. The undifferentiated L6 cells showed little response to caffeine. However, a substantial caffeine-induced calcium release (caffCR) was evident by Day 3 of differentiation, and was nearly maximal by Day 7 of differentiation. By contrast, ryanodine failed to stimulate Ca2+ release until Day 4, lagging behind the caffeine response. Ryanodine-stimulated Ca2+ release was also maximal by Day 7. Higher concentrations of ryanodine, known to inhibit Ca2+ release, only began to affect caffCR at Day 4, indicating that cells were insensitive to both ryanodine stimulation and ryanodine inhibition prior to this time. Most of the results could be obtained both in permeabilized and intact cells. Using intact cells, we measured the time course of K+ -dependent (i.e., depolarization-induced) Ca2+ release. This time course matched caffeine and not ryanodine-induced Ca2+ release suggesting the action of caffeine was not due to Ca2+ release unrelated to excitation-contraction coupling. These findings suggest that ryanodine binding sites on the RyR may not be functional at early stages of muscle development, that ryanodine sensitivity is a poor indicator of Ca2+ flux through the RyR, or that other proteins are involved in Ca2+ release under certain circumstances.

Modified starch enhances absorption and accelerates recovery in experimental diarrhea in rats.

Rice gruels have been used as home remedies to treat dehydration associated with diarrheal illness in developing countries. These preparations have produced conflicting results, most likely due to the heterogeneity of starch used. We investigated whether the modified tapioca starch, Textra (TX), at 5.0 or 10.0 g/L added to a 90 mmol/L Na+-111 mmol glucose oral rehydration solution (ORS) enhanced water and electrolyte absorption in two models of diarrhea. To induce a secretory state (model A), the jejunum of juvenile rats was perfused with 10 mmol/L theophylline (THEO) under anesthesia and then perfused with the solutions indicated above. To produce chronic osmotic-secretory diarrhea (model B), rats had a magnesium citrate-phenolphthalein solution as the sole fluid source for 1 wk, and then were perfused as the THEO-treated rats. Water, electrolyte, and glucose absorption were measured during both perfusions. As an extension of the perfusion studies, we compared how fast rats recovered from chronic osmotic diarrhea by offering them either water, ORS, or ORS containing 5.0 g/L TX along with solid food. Recovery rate markers were measured after 24 h and included weight gain, food and fluid intake, and stool output. In model A, addition of 5.0 g/L TX to ORS reversed Na+ secretion and improved net water as well as K+ and glucose absorption, compared with THEO-treated rats perfused with ORS without TX. In model B, addition of TX to ORS increased water, Na+, K+, and glucose absorption, compared with rats perfused without TX. Increasing TX from 5.0 to 10.0 g/L had no additional benefit. In recovery experiments, animals with free access to ORS with TX had significantly greater weight gain and decreased stool output compared with animals recovering with water or ORS without TX. Our experiments suggest that TX may be a useful additive to standard ORS to promote fluid and electrolyte absorption and may provide additional energy without increasing ORS osmotic load.

Proabsorptive effect of glycerol as a glucose substitute in oral rehydration solutions.

We hypothesized that glycerol, a readily diffusable hydrophilic substance, may effectively substitute for glucose and enhance intestinal water and sodium absorption in an oral rehydration solution (ORS). This was evaluated using a low osmolality (230-240 mOsm/kg) ORS containing 75 mmol/L sodium and a combination of glucose:glycerol (in mmol/L) 75:0, 50:25; 37.5:37.5, 25:50, 10:65, or 0:75 during 3-hour long in vivo rat jejunal perfusions. Water, sodium, potassium, glucose and glycerol absorption, and unidirectional fluid movement (J(in), J(eff)) were determined. Sodium and net water absorptions were maximal at glucose:glycerol ratios between 37.5:37.5 and 10:65 mmol/L. In the absence of glucose (0:75), absorption of water and electrolytes was lower than at any other concentration. The greater net rehydration seemed to be due to a higher J(in) as glycerol was increased up to 65 mmol/L. Potassium absorption followed a similar pattern. With 50 mmol/L glycerol and 25 mmol/L glucose, there was a marked expansion of the lamina propria extracellular space and increased intercellular expansion between enterocytes. These results indicate that glycerol may be an effective partial substitute for glucose in ready-to-use ORS by producing an improved rate of water and electrolyte absorption.

Control of calcium in skeletal muscle excitation-contraction coupling: implications for malignant hyperthermia.

The missing link in our understanding of excitation-contraction coupling (ECC) in skeletal muscle is the mechanism by which Ca2+ increases in the cytosol to trigger contraction. We discuss here a general background of intracellular Ca2+ handling, some characteristics of the major proteins involved in Ca2+ flow during ECC, and mechanisms currently believed to explain the increase in Ca2+ upon stimulation of muscle cells. These mechanisms include the calcium-induced calcium release, the direct coupled mechanism in which a plasma membrane and sarcoplasmic reticulum membrane protein interact, and mechanisms involving Ca2+ secretagogues that are known to elicit increases in calcium in other cells, inositol trisphosphate, and cyclic ADP ribose. We also consider possible roles for proteins associated with the principal calcium release channel of the sarcoplasmic reticulum, the ryanodine receptor. Finally, we discuss malignant hyperthermia, a disease associated directly with aberrant control of muscle cell calcium release.

Insulin-like growth factor-I and high protein diet decrease calpain-mediated proteolysis in murine muscular dystrophy.

In muscular dystrophy (MD) the imbalance between muscle protein synthesis and degradation may be an important factor leading to muscle wasting. The three major pathways of muscle proteolysis identified in skeletal muscle are: the lysosomal cathepsin pathway, the calcium-dependent calpain pathway, and the ATP-dependent ubiquitin pathway. Insulin-like growth factor I (IGF-I) and a high-protein diet (HPD) have been shown to reduce proteolysis in skeletal muscle. We examined the effect of 6 weeks of recombinant human IGF-I (rhIGF-I) alone or in combination with HPD treatment on the proteolytic pathways in skeletal muscle of 129 ReJ dystrophic (dy) mice. (A group of normal (Norm) nondystrophic (129 J) mice were included as controls). Untreated dy mice exhibited increased net proteolysis (P < 0.05), elevated net calpain activity (P < 0.01), and increased ubiquitin levels when compared to control mice (P < 0.05). Our evidence suggests that HPD and rhIGF-I decrease proteolysis in the 129 ReJ dy mouse. This effect appears attributable, at least in part, to reduced calpain-mediated myofibrillar breakdown (P < 0.05) due to decreased calpain autolysis or increased calpastatin levels. In contrast to calpain, cathepsin B activity was increased in HPD and rhIGF-I + HPD-treated dy muscle (P < 0.05) and unaltered in the rhIGF-I treated animals. Levels of free and protein-conjugated ubiquitin were also increased in rhIGF-I, and rhIGF-I + HPD treated dyanimals (P < 0.05). The amelioration of muscle wasting in the 129 ReJ dy model by HPD and/or rhIGF-I may have potential implications in the treatment of human MD.

Proabsorptive effects of modified tapioca starch as an additive of oral rehydration solutions.

BACKGROUND: Partially hydrolyzed starches from staple cereals, obtained by heat or by enzymatic treatment, are often used in the formulation of homemade or extemporaneously used oral rehydration solutions used in developing countries. Conflicting or anecdotal results obtained thus far could be clarified with a standardized preparation tested under well-controlled laboratory conditions. METHODS: A modified commercial tapioca starch was tested. Textra (National Starch and Chemical Co. Bridgewater, NJ, U.S.A.) added at 0, 5 or 10 g/l to an oral rehydration solution with 90 mM sodium and 111 mM glucose, in 30 rats malnourished by a protein-deficient diet for 3 weeks and in 26 well-fed control animals, using a one-pass jejunal perfusion. RESULTS: In protein-deficient rats, Textra stimulated sodium absorption at 5 and 10 g/l (mean +/- SEM); 0 g/l Textra: 160 +/- 13 nmol/min x cm; 5 g/l Textra: 406 +/- 31 (p < 0.0001); and 10 g/l Textra 230 +/- 27 (p < 0.02). Potassium absorption was comparably increased. Textra also improved net water absorption and the water influx:efflux ratio. Glucose absorption was increased only at 10 g/l Textra. In control rats, Textra improved sodium and net water absorption at 5 g/l, but not at 10 g/l Textra; but the influx:efflux ratio and potassium absorption were unaltered. CONCLUSIONS: These data, obtained in normal and protein-deficient rats, support the view that modified starch is a potentially useful, energy-rich additive for oral rehydration solution, which does not introduce an osmotic penalty.

The role of dietary zinc in modifying the onset and severity of spontaneous diabetes in the BB Wistar rat.

The goal of this study was to determine whether zinc supplementation in the diet of diabetes-prone BB Wistar rats will delay or prevent the onset of overt diabetes. Male Wistar BB rats were fed diets containing either 1000 ppm (HZ), 50 ppm (NZ), or 1 ppm zinc (LZ) starting at 30 days of age. Non-diabetes-prone rats were fed NZ and designated as controls (NORM). Beginning at 60 days, the rats were checked for glycosuria and, if positive, were given an i.p. glucose tolerance test (IPGTT). All remaining animals underwent an IPGTT at 100 days and were sacrificed. At 90 days of age HZ rats had a lower incidence of diabetes (19%) than NZ (53%) or LZ (44%) animals (P < 0.015). By age 100 days, for the HZ group, there was a 60% reduction in the number of expected overt diabetic rats. HZ animals also had higher concentrations of both pancreatic and serum insulin and exhibited lower serum glucose and triglycerides. Immunohistochemistry of HZ rats was clearly different from NZ rats and showed evidence of nearly normal pancreatic endocrine activity. Data indicate that dietary treatment of diabetes-prone BB Wistar rats with zinc appears to be an effective approach for delaying or preventing the onset of diabetes in genetically predisposed rodents. This finding may suggest further experimental studies regarding dietary means for preservation of pancreatic function.

Cellulose derivatives and intestinal absorption of water and electrolytes: potential role in oral rehydration solutions.

The physicochemical and structural characteristics of several types of carboxymethylcellulose (CMC) and of methylcellulose (MC) were examined in relation to their capacity to modify water and sodium absorption in oral rehydration solutions (ORS) at various concentrations, using a jejunal perfusion procedure in rats. Comparison of intrinsic low-viscosity CMC of various degrees of substitution (DS) revealed that net water absorption increased as the DS was augmented. A stimulatory effect on sodium absorption occurred only at a low (2.5 g/l) CMC concentration. With products of medium DS, stimulation of net water and sodium absorption was observed only with low-viscosity CMC at 2.5 g/l, but not at 5.0 g/l. In perfusions with CMC of medium and high DS there was a reduction of water and sodium absorption, ultimately resulting in net sodium secretion with 5.0 g/l high-DS CMC. MC perfused at 5.0 or 10.0 g/l reduced net water absorption and reversed sodium transport from absorptive to secretory status. These results show that while low-viscosity-grade, low-DS CMC in low concentrations may facilitate solute uptake and concurrent water absorption from ORS by the jejunum, high intrinsic viscosity and possible chemical interaction of solutes with the modified celluloses tend to block water uptake and produce fluid stasis and electrolyte secretion. Thus, the data suggest that only certain types of CMC may be proabsorptive when added to ORS, while high-viscosity and high-DS CMC or MC induce electrolyte malabsorption and eventual catharsis.

Gum arabic promotes rat jejunal sodium and water absorption from oral rehydration solutions in two models of diarrhea.

BACKGROUND & AIMS: We have shown that addition of gum arabic (GA) to a 90 mmol/L sodium-111 mmol/L glucose oral rehydration solution (ORS) enhances its effectiveness for water and electrolyte absorption in normal rats. The present study extends these observations on GA in ORS to two rat models of diarrheal disease. METHODS: Juvenile rats were either treated for 1 week with magnesium citrate-phenolphthalein to produce chronic osmotic-secretory diarrhea or luminally exposed to 10 mmol/L theophylline to induce jejunal secretion. In both models jejunal perfusion was used to assess absorption. RESULTS: Addition of 2.5 or 5.0 g/L GA to ORS increased roughly twofold absorption of sodium, potassium, and water in the model of chronic osmotic-secretory diarrhea. Rats perfused with GA-supplemented ORS showed an expansion of the basolateral intercellular spaces between villus absorptive epithelial cells and the lamina propria, reflecting enhanced water and sodium absorption. Similarly, addition of 2.5, 5.0, or 10.0 g/L GA to the ORS neutralized theophylline-induced abolition of net sodium and potassium absorption and reversed water and glucose malabsorption. CONCLUSIONS: These experimental studies in models of diarrhea suggest that GA may be a useful additive to ORS for the potentiation of water and electrolyte absorption.

L-arginine in low concentration improves rat intestinal water and sodium absorption from oral rehydration solutions.

BACKGROUND: The nitric oxide (NO) precursor L-arginine has been shown to produce variable effects on intestinal absorptive function, including ion transport. AIMS: To determine whether there is an optimal concentration of L-arginine, promoting proabsorptive effects from oral rehydration solutions (ORS) with 90 or 60 mM sodium. SUBJECTS AND METHODS: In vivo perfusion of rat jejunum with determination of net water absorption, unidirectional fluid exchanges, sodium and calcium transport, and glucose absorption. RESULTS: L-Arginine (1 mM) added to the 90 mM sodium ORS increased intestinal absorption of both sodium and water. Higher concentrations of L-arginine (2 to 10 mM) lacked this stimulatory effect. At 20 mM, L-arginine decreased sodium absorption below baseline. With a 60 mM sodium ORS, 2 mM L-arginine had a maximal fluid and electrolyte proabsorptive effect. At 20 mM L-arginine, net water absorption was indistinguishable from that obtained in the absence of L-arginine, and lower than with 2 mM L-arginine. Sodium absorption remained raised above baseline in perfusions with 10 and 20 mM L-arginine. Morphologically, villi from perfusions with increased absorption showed a large expansion of intercellular and lamina propria intercellular spaces. CONCLUSIONS: Low concentrations of L-arginine seem to stimulate water and electrolyte absorption by the small intestine. This effect is consistent with NO induced vasodilation, may be vaso-constrictive and thereby reverse fluid and electrolyte transport.

Calcium mediated proteolysis enhances calcium release in skinned L6 myotubes.

The mechanism for calcium (Ca2+) release in heart and skeletal muscle during excitation-contraction coupling is currently unknown. A widely held hypothesis is that a small amount of Ca2+ enters the cell and elicits a larger intracellular release of Ca2+ from the sarcoplasmic reticulum (SR), termed "Ca2+-induced Ca2+-release" (CICR). In addition to its role in excitation-contraction coupling, Ca2+ is also known to activate the cysteine protease calpain, which has been recently found to specifically cleave the ryanodine receptor in vitro. The authors investigated the question of whether Ca2+ sensitive protease activation could account for an apparent CICR. The authors first reproduced the phenomenon of CICR using detergent treated L6 myotubes ("skinned cells"). Leupeptin, a cysteine protease inhibitor, reduced the initial velocity and extent of Ca2+ release from the SR; a similar result was obtained when skinned cells were treated with iodoacetate, a sulfhydryl alkylating agent. Dithiothreitol enhanced both the rate and extent of Ca2+ release. Caffeine-induced Ca2+-release was unaffected by the thiol protease inhibitors or activators. This suggests that a cysteine protease may be responsible, in part, for CICR in vitro. The authors also found that vesicles exposed to Ca2+ to induce CICR were unable to fully reaccumulate Ca2+ a second time. Yet, when caffeine released comparable amounts of Ca2+, the initial Ca2+ level was fully restored. Similarly, leupeptin protected the vesicles from the reaccumulation deficit induced by Ca2+. The authors' findings suggest that proteolysis activated by a Ca2+-sensitive protease may account for the direct in vitro demonstration of CICR; such an effect may more likely reflect a role in apoptosis than excitation-contraction coupling.