Cereal-based oral rehydration solutions in Sudanese children with diarrhoea: a comparative clinical trial of rice-based and sorghum-based oral rehydration solutions

We describe 4 patients with onset or aggravation of thyroid dysfunction induced by interferon (IFN) treatment of hepatitis type C. All 4 patients were females; 2 had hyperthyroidism and 2 had hypothyroidism during or after IFN therapy. The onset or aggravation of thyroid dysfunction occurred during administration of IFN in 1 patient and 4 weeks after the end of IFN therapy in the remaining 3 patients. The 2 patients who demonstrated hyperthyroidism were euthyroid and negative for thyroid autoantibodies before receiving IFN therapy. The remaining 2 patients who demonstrated hypothyroidism were positive for thyroid autoantibodies before IFN therapy. One of these patients had a slight decrease in thyroid function before IFN therapy. Anti-thyroid stimulating hormone (TSH) receptor antibodies became positive in all 4 patients. Since there may have been a causal relationship between IFN therapy and the onset or aggravation of thyroid dysfunction, IFN therapy should be administered with caution.     

Electrolyte fluxes in the gut and oral rehydration solutions

This article provides a brief overview of the normal physiology of water and electrolyte fluxes across the gut as a prerequisite for understanding the pathologic disturbances occurring with diarrheal illnesses. In turn, the rationale for the use of oral rehydration solutions in diarrheal disorders is explored.     

Efficacy of standard glucose-based and reduced-osmolarity maltodextrin-based oral rehydration solutions: effect of sugar malabsorption

Previously we reported that standard oral rehydration salts (ORS) solution is not as effective as a reduced-osmolarity glucose-based ORS for the treatment of children with acute noncholera diarrhoea: with standard ORS the diarrhoea lasts longer, stool output is greater, serum sodium is higher, and there is more need for supplemental intravenous infusion. We studied a reduced-osmolarity maltodextrin (MD)-based ORS to determine whether it had similar benefits, and also the effect of sugar malabsorption on the efficacy of standard and MD-based ORS. A total of 90 boys aged 3-24 months with acute noncholera diarrhoea and moderate dehydration were randomly assigned to either standard ORS (glucose 20 g/l, osmolarity 311 mmol/l) or MD-ORS (MD 50 g/l, osmolarity 227 mmol/l). There were no differences in treatment results. Some 46% of subjects had a high total stool output (> 300 g/kg), which was unrelated to the type of ORS given. High stool output was significantly associated with a longer duration of diarrhoea (33 vs. 15 hours; P < 0.001), a persistently elevated serum sodium (149 vs. 144 mmol/l at 24 h; P < 0.02), the need for intravenous infusion (11/41 vs. 0/48; P < 0.002), and an increase in faecal reducing substances (10.8 vs. 3.4 g/l at 24 h; P < 0.001). We conclude that some children given standard ORS develop osmotic diarrhoea owing to the combined effect of transient sugar malabsorption and slight hypertonicity of the ORS. Earlier studies show that this adverse outcome can largely be avoided when extra water is given in reduced-osmolarity glucose-based ORS. Reduced osmolarity has no benefit, however, when glucose is replaced by maltodextrin, probably because the sugars released by hydrolysis of MD, when malabsorbed, raise the intraluminal osmolarity to equal or exceed that of standard ORS. Thus, reduced-osmolarity glucose-based ORS is superior to both standard ORS and reduced-osmolarity solutions based on maltodextrin and probably other complex carbohydrates. Studies are in progress to define the optimal formulation of reduced-osmolarity glucose-based ORS.     

Evidence of a dominant role for low osmolality in the efficacy of cereal based oral rehydration solutions: studies in a model of secretory diarrhoea

Clinical trials suggest that including naturally occurring complex carbohydrate in oral rehydration solutions (ORS) in place of glucose increases water absorption and reduces stool volume during acute diarrhoea. The mechanisms for this greater clinical efficacy has not been established. This study examined the ability of two hypotonic rice based ORS, RS-ORS (137 mOsm/kg) and RP-ORS (143 mOsm/kg), and HYPO-ORS (240 mOsm/kg) a glucose equivalent ORS, to effect water absorption by in vivo perfusion of normal and secreting rat small intestine. The results were compared with those for two widely used conventional hypertonic ORS, WHO-ORS (331 mOsm/kg) and UK-ORS (310 mOsm/kg). In the normal intestine, water absorption was similar from WHO-ORS (87.4 (45.1-124.6) microliters/min/g; median and interquartile range) and UK-ORS (57.6 (41.5-87)) but less than from the hypotonic solutions (p < 0.02); water absorption from RS-ORS (181.8 (168.5-193.8)) and RP-ORS (195.7 (179.3-207.9)) was similar but less than from HYPO-ORS (241.3 (230.6-279.7); p < 0.005). In the secreting intestine, all ORS reversed net secretion of fluid to net absorption; the hypotonic solutions, HYPO-ORS (105.2 (95.2-111)), RS-ORS (127.7 (118.3-169.4)) and RP-ORS (133.7 (122.1-174.5)), produced more water absorption (p < 0.005) than the hypertonic solutions WHO-ORS (47.1 (29-75.9)) and UK-ORS (24.9 (18.4-29.4)). The rice based ions promoted most water absorption in secreting intestine (p < 0.007). These data indicate that low osmolality is of primary importance in mediating the increased water absorption from cereal based ORS.     

The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling

Caspase-3-mediated proteolysis is a critical element of the apoptotic process. Recent studies have demonstrated a central role for mitochondrial proteins (e.g., Bcl-2 and cytochrome c) in the activation of caspase-3, by a process that involves interaction of several protein molecules. Using antibodies that specifically recognize the precursor form of caspase-3, we demonstrate that the caspase-3 proenzyme has a mitochondrial and cytosolic distribution in nonapoptotic cells. The mitochondrial caspase-3 precursor is contained in the intermembrane space. Delivery of a variety of apoptotic stimuli is accompanied by loss of mitochondrial caspase-3 precursor staining and appearance of caspase-3 proteolytic activity. We propose that the mitochondrial subpopulation of caspase-3 precursor molecules is coupled to a distinct subset of apoptotic signaling pathways that are Bcl-2 sensitive and that are transduced through multiple mitochondrion-specific protein interactions.     

The use of non-human primates as animal models for the study of hepatitis viruses

Hepatitis viruses belong to different families and have in common a striking hepatotropism and restrictions for propagation in cell culture. The transmissibility of hepatitis is in great part limited to non-human primates. Enterically transmitted hepatitis viruses (hepatitis A virus and hepatitis E virus) can induce hepatitis in a number of Old World and New World monkey species, while the host range of non-human primates susceptible to hepatitis viruses transmitted by the parenteral route (hepatitis B virus, hepatitis C virus and hepatitis delta virus) is restricted to few species of Old World monkeys, especially the chimpanzee. Experimental studies on non-human primates have provided an invaluable source of information regarding the biology and pathogenesis of these viruses, and represent a still indispensable tool for vaccine and drug testing.     

Fallibility of plasma urea and creatinine as indices of renal function in diarrhoeic calves treated with conventional or nutritional oral rehydration solutions

The prevalence and severity of gingival overgrowth in organ-transplant patients medicated with cyclosporin are greater in patients concomitantly medicated with nifedipine; however, no relationship between the gingival overgrowth and any of the nifedipine pharmacological variables has been demonstrated. The study examined the effect of five nifedipine pharmacological variables (nifedipine dosage, plasma concentration and gingival crevicular fluid concentration, M1 metabolite plasma concentration and the nifedipine: M1 ratio). The effect of the nifedipine variables on the gingival overgrowth score were examined using univariate and multivariate regression analysis. Adjustment for the effect of other risk factors was made by adding the distribution of each of the nifedipine variables in turn to a stepwise regression model containing previously identified risk factors for this condition. Despite the high levels of nifedipine sequestered in the GCF, only the plasma concentration of nifedipine was identified as a risk factor for the severity of gingival overgrowth in these patients (P = 0.01) once adjusted for other known risk factors (R2 for the model = 55%).     

Animal models of neuromuscular diseases: pathophysiology and implications for rehabilitation

This article explains how animal models can be utilized to develop rehabilitation approaches to minimize the pathophysiology of neuromuscular diseases (NMD). Homologous animal models can be used to understand the pathogenesis of each NMD and the effect of physical interventions. Much of the current work using animals has been conducted to show how gene therapy could be used to ameliorate these diseases. Although we applaud this work, animal models should also be used to determine how the phenotypic expression of the disease can be modified by such physical interventions as exercise, stretching, and immobilization. Methods that can be experimentally applied to animals but not to humans can be used to determine the underlying causes of the pathologic process and to identify potential therapies for NMD.     

Repair of myelin disease: strategies and progress in animal models

Myelin disorders form an important group of human neurological diseases that are as yet incurable. Recent studies on experimental remyelination have suggested that it might be feasible to repair the CNS, either by transplanting normal myelinating cells or by enhancing endogenous repair. Progress in animal models, particularly in transplanting cells of the oligodendrocyte lineage, has resulted in significant focal remyelination and physiological evidence of restoration of function. These data suggest that focal lesions in multiple sclerosis could be repaired by the transplantation of myelin-forming cells. Future therapies could involve both transplantation and promotion of endogenous repair, and the two approaches could be combined with ex vivo manipulation of the donor tissue.     

Ototoxicity of carboplatin: comparing animal and clinical models at the Hospital for Sick Children

Carboplatin was introduced to the paediatric population as an alternative chemotherapeutic agent in the management of various malignant neoplasms, including sarcomas of the head and neck, in the hope that it would have fewer side effects than pre-existing agents. While many investigators have considered the ototoxicity of this drug only incidentally, others have presumed it to be of negligible importance. A recent animal model of its use has demonstrated damage to the inner hair cells of the cochlea, particularly at the basal turn, with a corresponding high incidence of hearing loss. Similarly, 11 of 22 patients who received this agent at the Hospital for Sick Children over the past 2 years demonstrated a sensorineural hearing loss in the 4 to 12 kHz range. This complication occurred as early as after the first dose and was generally progressively worse with subsequent doses. Consequently, we recommend careful audiologic monitoring of children receiving this agent.     

Gender- and age-dependent differences in latent inhibition following pre-weaning non-handling: implications for a neurodevelopmental animal model of schizophrenia

Latent inhibition (LI) refers to retarded conditioning to a stimulus as a consequence of its prior nonreinforced pre-exposure, and is considered to index the capacity of an organism to ignore irrelevant stimuli. LI disruption has received increasing attention as an animal model of the widely described attentional deficit of schizophrenia, consisting of an inability to ignore irrelevant stimuli. The present experiments investigated the effects of infantile manipulations on the development of LI. Male and female rats handled or nonhandled in infancy (days 1-22), were tested at 3 and 16 months. Young handled animals had lower emotional reactivity than nonhandled, and this difference persisted in females at 16 months. At 3 months. LI, poorer conditioning of stimulus pre-exposed as compared to nonpre-exposed rats, was obtained in handled and nonhandled females, as well as in handled males, but was absent in nonhandled males. This pattern changed at 16 months: both nonhandled males and females failed to show LI. These gender- and age-dependent effects of pre-weaning manipulations on LI loss may provide an animal parallel to the susceptibility of young adult males to schizophrenia and the attenuation of gender differences in long-term outcome schizophrenia.     

Role conflicts in psychology and their implications for a reevaluation of training models.

For 25 years training in clinical psychology has followed the Boulder model, attempting to make the clinical psychologist both a scientist and a professional. In this paper arguments are advanced which suggest that it is usually difficult and frequently impossible to make the same person into both a scientist and a professional. Science abhors secrecy, but professionals must keep their knowledge secret. Differences exist in personality characteristics in individuals attracted to the science or the profession. Training requirements are clearly different. Readiness to participate in social and political action also differentiates the groups. For these and other reasons the authors advance the argument that separate professional training schools for psychology must be established, following the historically evolving model provided by other professions. A division of training of psychologists in scientific and professional work may have beneficial effects by eliminating role conflicts in the professional and by making clear the essential division of labor. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of hygiene measures, water sanitation and oral rehydration therapy on diarrhea in children less than five years old in the south of Ivory Coast

BACKGROUND: Gastric sucrose permeability is a noninvasive marker that reliably increases in association with gastrointestinal injury due to use of nonsteroidal antiinflammatory drugs. Despite the effect of Helicobacter pylori infection on the gastric mucosa, in a previous study we were unable to demonstrate that H. pylori infection was associated with abnormal gastric sucrose permeability. Our goal in this study was to explore further whether H. pylori infection changed gastric permeability; therefore, we evaluated the effect of treatment of H. pylori infection on gastric permeability to sucrose and the relation of sucrose permeability to density of polymorphonuclear leukocytes. MATERIALS AND METHODS: Five hundred milliliters of a solution containing 100 gm of sucrose was ingested by the subject at bedtime. Overnight urine was collected and assayed for sucrose by high-performance liquid chromatography. Sucrose permeability was assessed both before and approximately 4 weeks after anti-H. pylori therapy. RESULTS: Seventeen asymptomatic H. pylori-infected volunteers participated; 8 were cured. Sucrose permeability was in the range commonly found in normal controls both before and after anti-H. pylori therapy (mean excretion, 76.3 mg; range, 13-171 mg). Gastric sucrose permeability correlated with the density of polymorphonulcear cell infiltration of the mucosa. Cure of the H. pylori infection was associated with a small but significant decrease in sucrose permeability (98.8 +/- 18 mg to 51.7 +/- 9.8 mg (p = .01). Sucrose permeability was greater in those with a high density of mucosal polymorphonuclear cells compared to those with lower scores (119.5 +/- 4 vs 71.4 +/- 13 for those with scores > or = 5 compared to scores < or = 4; p = .023). Failed therapy resulted in an increase in the mucosal density of polymorphonuclear infiltration and sucrose permeability (56.4 +/- 13 mg-99.7 +/- 19 mg pretreatment vs posttreatment, respectively; p = .031). CONCLUSION: H. pylori gastritis causes a small but measurable increase in gastric permeability to sucrose that may reflect epithelial transmigration of neutrophils.     

A broad line NMR and MRI study of water and water transport in Portland cement pastes

The results of a magnetic resonance spin-spin relaxation analysis and broad-line magnetic resonance imaging (MRI) (gradient-echo and stray-field imaging) study of water and water transport in Portland cement pastes are presented. The effect of varying the cure conditions and the water to cement (w/c) ratio of the sample of mix are discussed. The water sorptivity and the concentration dependence of the hydraulic diffusion coefficient are calculated for samples prepared with a 0.5 w/c ratio and, therefore, an open pore structure. In the case of 0.3 w/c ratio samples, little water transport is observed, and a closed pore structure is inferred.     

Working models of attachment: implications for explanation, emotion and behavior

Two studies examined attachment style differences in social perception. In Study 1, participants wrote open-ended explanations for hypothetical relationship events and described how they would feel and behave in response to each event. Compared with secure participants, preoccupied participants explained events in more negative ways; they also reported more emotional distress and behaviors that were likely to lead to conflict. Avoidant participants also provided negative explanations, but did not report emotional distress. Path analysis indicated that attachment style differences in behavior were mediated by explanation patterns and emotional distress. Study 2 was designed to replicate Study 1 and test the relative importance of attachment style and relationship quality to predicting each outcome. Results indicated that both variables were significant predictors of explanations, but only attachment style predicted emotional responses. These findings are consistent with the idea that adults with different working models of attachment are predisposed to think, feel, and behave differently in their relationships.     

Animal models and in vitro models for the study of aetiopathogenesis of spondyloarthropathies

Among several animal models, HLA-B27 transgenic rodents proved useful for investigating the interplay between genetic factors and the bacterial environment in the aetiopathogenesis of the spondyloarthropathies (SpA). HLA-B27 transgenic rats spontaneously develop a multisystemic inflammatory disease resembling human SpA. This disease is dependent on the presence of a normal bacterial flora and implicates the immune system. The presence of both T cells and antigen-presenting cells expressing high levels of HLA-B27 seems of critical importance in its pathogenesis. HLA-B27 transgenic mice also develop arthritis, under the influence of the bacterial flora. In both types of model, CD8+ T cells seem not to be necessary, arguing against the 'arthritogenic peptide' hypothesis. In vitro models have been used to study the immune response against bacterial agents and the role of HLA-B27 in human SpA. It appears that an impaired immune response against bacteria could be involved in the triggering of human SpA. HLA-B27 could be implicated at the level of interaction between host cells and bacteria in the driving of a specific immune response against bacterial antigens or as a target of an autoimmune response.     

Cholinergic/serotonergic interactions in hypothermia: implications for rat models of depression

Vietnam combat veterans (N = 151) with chronic posttraumatic stress disorder (PTSD) completed measures of atrocities exposure, combat exposure, PTSD symptom severity, guilt and interpersonal violence. PTSD symptom severity, guilt and interpersonal violence rates were similar to previously reported studies that examined treatment seeking combat veterans with PTSD. Controlling for combat exposure, endorsement of atrocities exposure was related to PTSD symptom severity, PTSD B (reexperiencing) symptoms, Global Guilt, Guilt Cognitions, and cognitive subscales of Hindsight-Bias/Responsibility and Wrongdoing. These results are discussed in the context of previous research conducted regarding atrocities exposure and PTSD.     

Discontinuities in the temperature function of transmembrane water transport in Chara: relation to ion transport

The NMR (nuclear magnetic resonance) method of Conlon and Outhred (1972) was used to measure diffusional water permeability of the nodal cells of the green alga Chara gymnophylla. Two local minima at 15 and 30 degreesC of diffusional water permeability (Pd) were observed delimiting a region of low activation energy (Ea around 20 kJ/mol) indicative of an optimal temperature region for membrane transport processes. Above and below this region water transport was of a different type with high Ea (about 70 kJ/mol). The triphasic temperature dependence of the water transport suggested a channel-mediated transport at 15-30 degreesC and lipid matrix-mediated transport beyond this region. The K+ channel inhibitor, tetraethylammonium as well as the Cl- channel inhibitor, ethacrynic acid, diminished Pd in the intermediate temperature region by 54 and 40%, respectively. The sulfhydryl agent p-(chloromercuri-benzensulfonate) the water transport inhibitor in erythrocytes also known to affect K+ transport in Chara, only increased Pd below 15 degreesC. In high external potassium ('K-state') water transport minima were pronounced. The role of K+ channels as sensors of the optimal temperature limits was further emphasized by showing a similar triphasic temperature dependence of the conductance of a single K+ channel also known to cotransport water, which originated from cytoplasmic droplets (putatively tonoplast) of C. gymnophylla. The minimum of K+ single channel conductance at around 15 degreesC, unlike the one at 30 degreesC, was sensitive to changes of growth temperature underlining membrane lipid involvement. The additional role of intracellular (membrane?) water in the generation of discontinuities in the above thermal functions was suggested by an Arrhenius plot of the cellular water relaxation rate which showed breaks at 13 and 29 degreesC.