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Objective: To determine the effects and safety of dioctahedral smectite (DS) on the duration of acute watery diarrhea in children., Methods: A Randomized, open labeled, clinical controlled trial in a tertiary care hospital outpatient department (OPD) and emergency department. Participants were one hundred and seventeen children without any chronic illness between 2 and 5 years presenting to OPD, having acute watery diarrhea for <48 h with mild to moderate dehydration, not on antibiotics and requiring oral rehydration therapy. Intervention done was DS with a dose of 1.5 g thrice daily., Results: Freshly dissolved DS in a dose of 1.5 g thrice daily for 5 days significantly shortened the duration of acute watery diarrhea in children aged 2-5 years. There were no adverse effects on the use of DS. DS was acceptable to the children, and its administration was not accompanied with any side effects., Conclusion: DS reduces the duration of diarrhea in Indian children and prevents a prolonged course, and therefore, may consistently reduce the costs in treatment of acute watery diarrhea.

Study Objective: To compare the effect of normal saline (NS), lactated Ringer's, and Plasmalyte on the acid-base status of dehydrated patients in the emergency department (ED)., Method: We conducted a prospective, double-blind, randomized trial of consecutive adult patients who presented to the emergency department with moderate-severe dehydration. Patients were randomly allocated to blindly receive normal saline (NS), lactated Ringer's or Plasmalyte at 20 ml/kg/h for 2 hours. Outcome measures of the study were pH and changes in electrolytes, including serum potassium, sodium, chloride and bicarbonate levels at 0, 60, and 120 minutes in venous blood gas samples., Results: Ninety patients participated in the study and were randomized to NS (30 patients), lactated Ringer's (30 patients) and Plasmalyte (30 patients) groups. Mean age was 48±20 years and 50% (n=45) of the patients were female. All pH values were in the physiological range (7.35-7.45) throughout the study period. In the NS group there was a significant tendency to lower pH values, with pH values of 7.40, 7.37, and 7.36 at 0, 1, and 2 hours respectively. Average bicarbonate levels fell in the NS group (23.1, 22.2, and 21.5 mM/L) and increased in the Plasmalyte group (23.4, 23.9, and 24.4 mM/L) at 0, 1, and 2 hours, respectively. There were no significant changes in potassium, sodium, or chloride levels., Conclusions: NS, lactated Ringer's, and Plasmalyte have no significant effect on acid-base status and all can be used safely to treat dehydrated patients in the emergency department. However, NS can effect acidosis which might be significant in patients who have underlying metabolic disturbances; thus, its use should be weighed before fluid administration in the ED.

Hypernatremic dehydration in breast fed neonates is a rare but increasingly recognized problem. If not identified early, it may lead to potentially life threatening complications. The authors describe a neonate who developed thrombosis and lower limb ischemia secondary to hypernatremic dehydration. Peripheral gangrene, as a result of hypernatremic dehydration is extremely uncommon and has rarely been reported before.

Introduction: Acute gastroenteritis results from infection of the gastrointestinal tract, most commonly with a virus. It is characterised by rapid onset of diarrhoea with or without vomiting, nausea, fever, and abdominal pain. Diarrhoea is defined as the frequent passage of unformed, liquid stools. Regardless of the cause, the mainstay of management of acute gastroenteritis is provision of adequate fluids to prevent and treat dehydration., Methods and Outcomes: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent acute gastroenteritis in children? What are the effects of treatments for acute gastroenteritis in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA)., Results: We found 42 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions., Conclusions: In this systematic review, we present information relating to the effectiveness and safety of: rotavirus vaccines for the prevention of gastroenteritis; enteral rehydration solutions (oral or gastric), lactose-free feeds, loperamide, probiotics, and zinc for the treatment of gastroenteritis; and ondansetron for the treatment of vomiting.

Severely burned patients need extensive initial fluid resuscitation. Formulas to calculate fluid needs during burn shock are well established. However, protocols for normalizing circulating fluid volume after cellular integrity has recovered do not exist. Resultant electrolyte shifts can cause hypernatremia, a possible sign of hypovolemia, which may in turn result in decreased tissue perfusion, subsequently affecting burn wound healing. The purpose of this retrospective chart review was to explore the hypothesis that hypernatremia in burn patients is a possible sign of systemic dehydration and that dehydration may affect burn wound skin graft take. Medical chart data from otherwise healthy burn victims with deep partial-thickness burns (total burn surface area [TBSA] >10%) who underwent skin grafting 7 days post injury were reviewed. Thirty (11 female; 19 male) patients with an average TBSA of 30% (± 11%) and an Abbreviated Burn Severity Index (ABSI) score of 7.9 (± 1.8) were included. Of those, 17 had normal average serum levels between day 2 and 6 following injury and 13 developed hypernatremia (serum sodium ≥146 mmol/L) an average of 5.5 days (± 1.5) after injury. Patients in this group underwent an average of 1.3 (± 0.8) re-grafting procedures compared to 0.35 (± 0.5) for patients without hypernatremia (P = 0.001). There was good correlation (r = 0.525) between daily infusion-diuresis ratios (IDR) and serum sodium levels, as well as between serum sodium levels and re-skin grafting occurrences (r = 0.62). The results indicate that research to confirm that hypernatremia is an indicator of dehydration and affects skin graft take is warranted and that protocols to optimize fluid volume following burn shock treatment are needed.

B-type natriuretic peptide is secreted primarily by cardiomyocytes in response to increased ventricular or atrial wall stress reflecting volume or pressure overload. The relationship between natriuretic peptides and the severity of heart failure is well established. We present here a case where natriuretic peptide levels were increased due to dehydration in the abscence of renal impairment. Normalization of natriuretic peptide level was achieved by stopping the diuretics and the administration of normal saline., (Copyright © 2011 S. Karger AG, Basel.)

Background: Ondansetron is increasingly used to prevent emesis in children with acute gastroenteritis; however, the optimal dose is unknown., Objective: To determine if higher doses of oral ondansetron are associated with greater efficacy or side effects., Methods: We analyzed data from a prospective clinical trial performed between January 2004 and April 2005. Data were collected on 105 children with dehydration due to gastroenteritis who received an ondansetron oral disintegrating formulation. The following outcomes of efficacy were analyzed: number of vomiting episodes, volume of oral rehydration fluids consumed, percent weight gain, and the proportions of children who had ongoing vomiting, received intravenous rehydration, and were hospitalized. In addition, the number of episodes of diarrhea was evaluated to measure whether there were dose-dependent side effects., Results: Participants were aged 0.5-8.2 years and the dose ranged between 0.13 and 0.26 mg/kg. There was no significant association between the dose of ondansetron and the outcomes of number of vomiting episodes, volume of fluids consumed, increase in bodyweight, or number of diarrhea episodes/hour. The mean dose of ondansetron (mg/kg) administered was not different amongst those who did and did not have ongoing vomiting, undergo hospitalization, and receive intravenous rehydration., Conclusions: Within the dose range of 0.13-0.26 mg/kg, higher doses of ondansetron were not superior to lower doses, nor were they associated with increased side effects. Thus, ondansetron in this dose range was shown to result in a similar reduction in emesis in children with acute gastroenteritis.

Objective: Stroke volume variation (SVV) during controlled mechanical ventilation is a useful predictor in response to volume expansion, and pleth variability index (PVI), a novel algorithm allowing for automated and continuous calculation of the respiratory variations in the pulse oximeter waveform amplitude, can also predict fluid responsiveness non-invasively in mechanically ventilated patients. The aim of this study was (1) to determine whether acute fluid infusion affects SVV and PVI, and (2) to compare the two values in the case of acute fluid infusion after a preoperative fast following general anesthesia induction., Methods: After tracheal intubation, the patients' lungs were mechanically ventilated. Subjects were anesthetized using sevoflurane and were given a rapid, constant-rate infusion of crystalloid (500 ml in 15 min). Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), heart rate (HR), cardiac output (CO), cardiac index (CI), SVV, and PVI were measured at baseline and after 250 and 500 ml had been infused, and these values were compared., Results: SAP, DAP, CO, and CI were unchanged after the infusion. HR and SVV decreased significantly after the infusion. SVI increased significantly after the infusion. There was a significant difference in PVI only between the post 250 ml and post 500 ml infusions., Conclusions: A rapid infusion of 250-500 ml of a crystalloid in nearly healthy subjects who had fasted overnight returned their SVV to within the normal range. In such cases, SVV is a more sensitive predictor of fluid responsiveness than is PVI, and the infusion gradually increased SVI.

OBJECTIVE-To compare the effects of IV administration of isotonic (1.3%) and hypertonic (8.4%) sodium bicarbonate (NaHCO(3)) solutions on acid-base status in dehydrated calves with strong ion (metabolic) acidosis. DESIGN-Randomized controlled clinical trial. ANIMALS-50 calves with diarrhea and severe dehydration. PROCEDURES-Calves were randomly assigned to receive isotonic NaHCO(3) solution (65 mL/kg [29.5 mL/lb], IV) over 3 hours (n = 30) or hypertonic NaHCO(3) solution (10 mL/kg [4.5 mL/lb], IV) over 20 minutes (20). Blood samples were collected at 0 hours (immediately prior to solution administration) and at 0.5, 1, 2, and 4 hours after administration began. Samples were submitted for blood gas analysis, serum biochemical analysis, and determination of blood Na(+), K(+), and Cl(-) concentrations and percentage change in plasma volume. RESULTS-Calves that received isotonic NaHCO(3) solution had an increase in venous blood pH, HCO(3) concentration, and base excess; a small, transient increase in Po(2); and no change in Pco(2) within 4 hours after administration began. Calves that received hypertonic NaHCO(3) solution had an immediate increase in venous blood pH, HCO(3) concentration, and base excess; a small, transient increase Pco(2); and no change in Po(2) within 0.5 hours after treatment began. Plasma volume increased to a greater extent following administration of isotonic solution than after administration of hypertonic solution. CONCLUSIONS AND CLINICAL RELEVANCE-IV administration of 8.4% NaHCO(3) solution in small volumes provided fast and effective improvement of severe acid-base abnormalities in calves with severe strong ion acidosis but did not improve hydration status as well as administration of a larger volume of isotonic NaHCO(3) solution.

Effects of synthesized desmopressin, analog of antidiuretic hormone, and water-salt supplement on the renal function and orthostatic stability were studied in 6 normal male subjects after 12-hr. head-down tilt (12 degrees). The combination of water-salt homeostasis normalizing methods was effective in retaining excessive liquid and salts. Moreover, tolerance of the standard 20-min. passive standing test improved significantly. Hence, it was demonstrated that intake of synthetic vasopressin analog combined with WSS counteracted hypohydration of organism due to HDT and improved orthostatic tolerance.

Urogenital atrophy resulting from postmenopausal estrogen deficiency has numerous clinical effects, including vaginal dryness, sexual dysfunction, urinary incontinence, and recurrent urinary tract infections (UTIs), all of which can cause significant distress and reduction in quality of life. Although nearly one third to one half of postmenopausal women experience these symptoms, they are often overlooked because patients may be reluctant to discuss them and clinicians fail to screen for them. As these symptoms are unlikely to resolve without treatment, the prompt diagnosis and treatment of urogenital atrophy is essential. Estrogen therapy, administered either locally or systemically, provides significant relief from symptoms related to urogenital atrophy. However, systemic estrogen therapy is contraindicated in some women and may not be accepted in women without other menopausal symptoms. Local low-dose vaginal estrogen therapy, in the form of vaginal estrogen tablets, creams, or rings, has been shown to reduce dyspareunia and vaginal dryness, restore vaginal pH, and restore normal vaginal cytology. All forms of vaginal estrogen therapy are effective and well tolerated, although vaginal tablets and rings may have fewer adverse effects and have higher rates of adherence than creams.

A female, mixed-breed dog was presented with signs of abdominal discomfort and vomiting of 24 h duration following an episode of dietary indiscretion. Clinical signs, previous medical history, and diagnostic tests supported a diagnosis of acute pancreatitis. Specific and supportive treatment was instituted, and clinical signs resolved 10 d after presentation.

Dehydration or water deprivation in the body decreases urinary excretion and allows urea and other protein waste products to accumulate in the blood. The aim of the present study is to evaluate the association of uremia and oxidative stress by applying the herbal plant Withania somnifera (W. somnifera) (Aswagandha). The study was performed on male Wister strain rats in which, dehydration was achieved by water withdrawal. A total of 18 rats were studied and were randomly divided into three Groups: Group-1, control, Group-2, only dehydration and Group-3, dehydration + administration of aqueous root extract of W. somnifera, orally (50 mg/100 gm body weight/day) for 25 days. After 25 days of treatment, it was observed that the body weight of Group-3 animals had increased significantly, while that in Group-2 had decreased significantly. The liver enzymes in both blood and kidneys did not show any significant change in the three groups implying absence of any toxicity of the root extract. In Group-2 animals, the serum urea and creatinine levels increased sig-nificantly when compared with animals in Groups-1 and 3. The low levels of serum urea and crea-tinine in Group-3 animals indicates the protective effect of the plant extract against renal injury caused by dehydration. Dehydration-induced oxidative stress was established in our study by noting the low activities of super-oxide dismutase and catalase, both important antioxidant enzymes, in Group-2 animals; both enzymes were stabilized in animals of Groups-3 and 1. In conclusion, it is hypothesized that there is an antioxidative role of W. somnifera resulting in reducing the extent of renal injury as a result of oxidative stress.

Eight volunteered male test-subjects (20-40 y.o.) took part in an experiment with 21-hr bed rest aimed to investigate trends in the hemostasis parameters (activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen, plasminogen, D-dimers, soluble fibrin-monomer complexes (SFMC), as well as antithrombin III (ATIII) and protein C (antiplasmin) activities) after diuretics-induced dehydration followed by intravenous infusion of colloid and crystalloid solutions. It was shown that noncompensible dehydration during bed rest does not lead to noteworthy alterations in the procoagulating component of hemostasis. Intravenous infusion of blood substituting sterofundin (crystalloid) and venofundin (colloid) to the bedrested human subjects accelerated coagulation within the physiological norm. In all series of the experiment ATIII was suppressed and plasminogen content went down causing growth in SFMC. Fibrinogen concentration remained essentially unchanged pointing to the absence of acute reaction of organism to the experimental conditions.

This represents the third clinical update based on presentations at the American Medical Directors Association (AMDA) annual meeting. Topics covered this year include hypertension, heart failure, cachexia, dehydration, falls, depression, constipation, and aspiration pneumonia.

Objective: To evaluate in real conditions the role of drugs in heat-related adverse effects., Methods: We performed a multicentric case-control study in 3 university hospitals in France, including 36 cases (patients older than 65 years hospitalized with hyperthermia or dehydration between 1st July and 31st August 2007) and 51 controls. We compared drugs and changes in drug dosage according to the values of renal function., Results: At inclusion, clearance creatinine was available for only 12 patients (mean = 31.6 ml/min), and three-fold higher in controls (p < 0.001). Cases took more drugs than controls (4.3 vs. 3.9; p < 0.001), particularly neuroleptic drugs (3.6% vs. 0.5%; p = 0.007)., Conclusion: Despite its small size, our study shows that patients suffering from dehydration in summer are those with more severe renal impairment, taking more drugs (particularly neuroleptics). This pilot work could allow to improve methodology of further studies on drugs during heat waves.

Background: It has been suggested that some of the symptoms typically attributed to menopause may be more related to premenstrual syndrome (PMS) than menopause, as perimenopausal women appear to be more prone to PMS-like symptoms, or at least to tolerate them less well., Objective: The objective of this study was to evaluate the effectiveness of a phytotherapeutic intervention comprising a combination of Hypericum perforatum (St. John's wort) and Vitex agnus-castus (chaste tree/berry) in the management of PMS-like symptoms in perimenopausal women., Design: A double-blind, randomized, placebo-controlled parallel trial was conducted over 16 weeks on menopause-related symptoms. Data on PMS-like symptoms were collected at 4-weekly intervals from a small subgroup of late-perimenopausal women (n = 14) participating in this study. The primary endpoint was PMS scores measured on the Abrahams Menstrual Symptoms Questionnaire, comprising the subclusters of PMS-A (anxiety), PMS-D (depression), PMS-H (hydration), and PMS-C (cravings). Herbal combination therapy or placebo tablets were administered twice daily., Results: At the end of the 16-week treatment phase, analyses of covariance showed the herbal combination to be superior to placebo for total PMS-like scores (p = 0.02), PMS-D (p = 0.006), and PMS-C clusters (p = 0.027). The active treatment group also showed significant reductions in the anxiety (p = 0.003) and hydration (p = 0.002) clusters, using paired-samples t tests. Results of trend analyses showed significant treatment group effects across the five phases for total PMS and all subscales, all in the clinically expected direction. No significant trends were evident in the placebo group., Conclusions: These results suggest a potentially significant clinical application for this phytotherapeutic combination in PMS-like symptoms among perimenopausal women. Further research is warranted through a randomized, controlled trial dedicated to investigation of these symptoms.

This trial sought to evaluate our experience using the antimigraine prophylactic drug, use of valproate for the prophylactic management of cyclic vomiting syndrome (CVS) in children. Thirteen children diagnosed with severe CVS were enrolled. Prophylactic therapy consisted of valproate administered at a dose of 10-40 mg/kg/day. Upon enrollment in the study, all patients underwent diagnostic tests to rule out organic causes of their symptoms. Vomiting was severe enough in all patients to cause dehydration requiring hospitalization for intravenous rehydration. Nine of 13 patients did not respond to numerous previous medical therapies like propranolol, amitriptyline, cyproheptadine, phenobarbital, phenytoin, and carbamazepine. Three of 13 patients required combination therapy with valproate and phenobarbital. Of the 13 patients, two showed complete resolution of their symptoms, nine had marked improvement in their symptoms, as evidenced by infrequent attacks of reduced severity, and two failed to respond to valproate therapy. Four patients experienced relapse with a decreased dosage of valproate. Side effects associated with long-term valproate administration were not observed. Valproate appears to be effective for the prophylactic management of severe CVS, with 85% of all patients achieving at least a reduction in the frequency of attacks.

Objective: To study the effect of water stress on the content of scutellarin and caffeate in Erigeron breviscaps., Method: Fv/Fm, N content, as well as the content of scutellarin and caffeate under three water grads were measured., Result and Conclusion: Fv/Fm of the plant decreased significantly in 8% and 23% water treatment, that proved drought and waterlogging occurred. Under the two conditions, the contents of N were lower but the contents of active constituents were higher than those under 15% treatment. The results support the carbon-nutrient balance hypothesis and the "stress effect hypothesis" for the formation of geo-herbs.

Pulmonary and cerebral lipiodol embolism after transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma is rare. To our knowledge, only 7 cases have been reported in the literature. We present a case of pulmonary and cerebral lipiodol embolism, and analyzed retrospectively the imaging and clinical data of the patient and conclude the most probable mechanism of pulmonary and cerebral lipiodol embolism, which is different from that of the cases reported previously.

Objective: To evaluate the efficacy and safety of Bifilac on reducing the episodes (frequency) and duration of diarrhea induced by rotaviral infection and to evaluate the efficacy of Bifilac to ameliorate the associated symptoms like dehydration and duration of rotaviral shedding in faeces., Methods: 80 children aged between 3 months and 3 years were enrolled and divided into 2 groups, one group received standard therapy + placebo, the other group received standard therapy + probiotic (Bifilac) randomly. Children assessed for frequency and duration of diarrhea. Degree of dehydration, duration and volume of oral rehydration salt [ORS] therapy, duration and volume of Intra venous fluids and duration of rotaviral shedding., Results: When compared to the placebo, Bifilac showed clinical as well as statistically significant reduction in Number of episodes (frequency) of diarrhea in a day, mean duration of diarrhea (in days) degree of dehydration, duration and volume of oral rehydration salt [ORS] therapy, duration and volume of intravenous fluid [IVF] therapy, duration of rotaviral shedding (P<0.01)., Conclusion: The synbiotic, bifilac, appears to be a safe and very effective adjuvant in the management of acute rotaviral diarrhea.

A feeling of mouth dryness occurs from actual drying of the oral surfaces or from sampling astringent substances such as polyphenols (e.g., tannins in brewed tea and wine), which bind proline-rich proteins in saliva to reduce its lubricity. Here we investigated the interactions between physical drying and the effect of polyphenols on the subjective state of oral hydration. Twelve subjects rated the perceived wetness/dryness of their mouth using a labeled magnitude scale, after the mouth was dried with air for 35 s, or the subjects waited for an equal period of time during which the mouth was not dried. Subsequently, 1.5 mL volumes of an astringent solution (5 g L(-1) tannic acid in distilled water), distilled drinking water, or a sweet solution (40 g L(-1) sugar in mango tea with no tannins) were introduced into the mouth. After swishing and swallowing, the subject rated the wetness of the mouth for 4.3 min. The liquids were found to differ in their ability to wet the mouth (p<0.0001). The least wet sensations were reported for the astringent solution, on average; however, the differences among liquids were not equally pronounced at all times during the observation period (p<0.02). When the mouth was normally hydrated (i.e., had not been dried), the wetting effectiveness of the three liquids, based on the ratings, differed most greatly immediately after they had been received and swallowed. In contrast, when the mouth was dried, the liquids did not differ at this time. That the astringent solution did not have less wetting effectiveness in the dried mouth was attributed to the absence of precipitable salivary proteins. The findings suggest that the refreshment value of astringent drinks, based on their perceived wetting effectiveness, may vary with the state of oral hydration.

Background: The clinical efficacy of IV administered hypertonic saline solution and hypertonic bicarbonate solution (HBS) in the treatment of inappetent diarrheic calves has not been compared yet., Hypothesis: HBS is more advantageous than hypertonic saline in the treatment of calves with severe metabolic acidosis., Animals: Twenty-eight dehydrated, inappetent calves with neonatal diarrhea., Methods: In 2 consecutive clinical studies, calves were initially treated with saline (5.85%; 5 mL/kg body weight [BW] over 4 minutes; study I: N = 16) or bicarbonate solution (8.4%; 10 mL/kg BW over 8 minutes; study II: N = 12), respectively, followed by oral administration of 3 L isotonic electrolyte solution 5 minutes after injection. Clinical and laboratory variables were monitored for 72 hours., Results: Treatment failed in 6 calves of study I and in 1 calf of study II as indicated by a deterioration of the general condition. All treatment failures had more severe metabolic acidosis compared with successfully treated calves before treatment. In the latter, rehydration was completed within 18 hours after injection; metabolic acidosis was corrected within 24 hours (study I) and 6 hours (study II) after injection., Conclusions and Clinical Importance: Diarrheic calves with slight metabolic acidosis (base excess [BE] >-10 mM) can be treated successfully with hypertonic saline. HBS is appropriate in calves without respiratory problems with more severe metabolic acidosis (BE up to -20 mM). Intensive care of the calves is required to ensure a sufficient oral fluid intake after the initial IV treatment.

The present investigation was conducted to determine whether CaCl(2) increases Catharanthus roseus drought tolerance and if such tolerance is correlated with changes in oxidative stress, osmoregulation and indole alkaloid accumulation. C. roseus plants were grown under water deficit environments with or without CaCl(2). Drought induced oxidative stress was measured in terms of lipid peroxidation (LPO) and H(2)O(2) contents, osmolyte concentration, proline (PRO) metabolizing enzymes and indole alkaloid accumulation. The plants under pot culture were subjected to 10, 15 and 20 days interval drought (DID) stress and drought stress with 5mM CaCl(2) and 5mM CaCl(2) alone from 30 days after planting (DAP) and regular irrigation was kept as control. The plants were uprooted on 41 DAS (10 DID), 46 DAS (15 DID) and 51 DAS (20 DID). Drought stressed plants showed increased LPO, H(2)O(2), glycine betaine (GB) and PRO contents and decreased proline oxidase (PROX) activity and increased gamma-glutamyl kinase (gamma-GK) activity when compared to control. Addition of CaCl(2) to drought stressed plants lowered the PRO concentration by increasing the level of PROX and decreasing the gamma-GK activities. Calcium ions increased the GB contents. CaCl(2) appears to confer greater osmoprotection by the additive role with drought in GB accumulation. The drought with CaCl(2)-treated C. roseus plants showed an increase in total indole alkaloid content in shoots and roots when compared to drought stressed and well-watered plants.

Background & Aims: Inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel are predicted to prevent intestinal fluid secretion in cholera. We previously discovered low- affinity glycine hydrazide (GlyH) CFTR inhibitors that block CFTR at its external pore. The goal of this study was to develop potent CFTR inhibitors that are minimally absorbed and washed out of the intestinal lumen for application as antisecretory agents in cholera., Methods: GlyH analogs (malonic hydrazides, MalH) were chemically conjugated to various lectins ("MalH-lectin") and purified. CFTR inhibition potency was measured by short-circuit current analysis, mechanism of action by patch-clamp, and antidiarrheal efficacy in closed-loop and suckling mouse models., Results: By lectin conjugation, we improved CFTR inhibitory potency by approximately 100-fold (to 50 nmol/L) and retarded washout. High-affinity CFTR inhibition was abolished by MalH-lectin heat denaturation, protease digestion, or competition by mannose or unconjugated lectin. Patch-clamp analysis indicated CFTR inhibition by an external pore occlusion mechanism. Fluorescently labeled MalH-lectin remained membrane bound for >6 hours after washout, whereas washout occurred in a few minutes without the lectin. MalH-ConA and MalH-wheat (IC50 50-100 pmol) blocked cholera toxin-induced intestinal fluid secretion in closed intestinal loops in mice and greatly reduced mortality in a suckling mouse model of cholera., Conclusions: The high potency of MalH-lectin conjugates results from "anchoring" the CFTR-blocking MalH to cell surface carbohydrates by the lectin. The high-affinity, slow washout, and external site of action of the MalH-lectin conjugates support their further development as antisecretory drugs for enterotoxin-mediated secretory diarrheas.

Background: Loperamide is widely used in adults for acute diarrhea. However, its use in children has been discouraged by the World Health Organization and the American Academy of Pediatrics owing to concerns over safety and efficacy in young children., Methods and Findings: To assess the efficacy and adverse effects of loperamide compared with placebo for acute diarrhea in children, we reviewed Medline, EMBase, the Cochrane Central Register of Controlled Trials, and bibliographies of known clinical trials and of review articles, and we also interviewed key investigators in the field. We undertook a systematic review and meta-analysis of randomized controlled trials of children younger than 12 y of age with acute diarrhea, comparing loperamide with placebo. Included trials reported data on diarrhea duration or severity, or provided data on adverse effects. Compared with patients who received placebo, patients allocated to loperamide were less likely to continue to have diarrhea at 24 h (prevalence ratio 0.66, 95% confidence interval [CI]: 0.57 to 0.78), had a shorter duration of diarrhea by 0.8 d (95% CI: 0.7 to 0.9 d), and had a lower count of stools at 24 h (0.84, 95% CI: 0.77 to 0.92). Results were similar when random-effects summaries were estimated. Serious adverse events, defined as ileus, lethargy, or death, were reported in eight out of 927 children allocated to loperamide (0.9%, 95% CI: 0.4% to 1.7%). Serious adverse events were not reported in any of the 764 children allocated to placebo (0%, 95% CI: 0% to 0.5%). Among the children allocated to loperamide, serious adverse events were reported only among children younger than 3 y., Conclusions: In children who are younger than 3 y, malnourished, moderately or severely dehydrated, systemically ill, or have bloody diarrhea, adverse events outweigh benefits even at doses

Ninety, seven- to 10-day-old calves were allocated to three groups of 30 and treated daily for seven days with either 100 microg/kg halofuginone hydrobromide or 2.5 mg/kg decoquinate orally or left untreated as controls. The levels of diarrhoea and dehydration were monitored daily for 28 days from the first day of treatment (day 0) and samples of faeces were collected on days 0, 7, 14, 21 and 28, to quantify the excretion of Cryptosporidium parvum oocysts. The calves were weighed on days 3 and 28. The treatments had no effect on the levels of diarrhoea or dehydration, the proportions of diarrhoeic calves or the proportions of calves shedding oocysts. However, unlike decoquinate, halofuginone significantly reduced the excretion of oocysts on day 7 (P<0.0001), and decoquinate increased the average daily weight gain of the calves (P=0.049).

Background/aims: Patients severely dehydrated from diarrhea are at risk of developing hyperkalemia consequent to fluid therapy treatment. In parallel with the regulation of external potassium balance by the kidney and gastrointestinal tract, plasma potassium is rapidly regulated by redistribution of potassium between the extracellular and intracellular compartments. Erythrocytes contain ATPases that play a role in this potassium movement. In this study, erythrocyte ATPase effectiveness was evaluated in infants dehydrated from diarrhea and compared to that of healthy infants., Methods: Blood samples were collected from dehydrated and healthy infants. The activity of Na+,K+-ATPase and of an ouabain-insensitive K+-ATPase were assessed. Serum electrolytes and blood pH were also determined., Results: No hyperkalemia was found, even in dehydrated infants presenting with severe hyperchloremic metabolic acidosis. In the erythrocytes of dehydrated infants, Na+,K+-ATPase activity was increased correlating positively with the amount of sodium administered. High K+-ATPase activity in the erythrocytes correlated with low plasma potassium. The K+-ATPase activity correlated positively with the amount of potassium administered to dehydrated infants., Conclusion: These findings suggest that the erythrocytes Na+,K+-ATPase and K+-ATPase both protect against plasma potassium abnormalities in dehydrated infants. In such infants, the risk of hyperkalemia is probably low., (Copyright 2006 S. Karger AG, Basel)

Enterotoxin-mediated secretory diarrheas such as cholera involve chloride secretion by enterocytes into the intestinal lumen by the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. We previously identified glycine hydrazide CFTR blockers that by electrophysiological studies appeared to block the CFTR anion pore at its lumen-facing surface. Here, we synthesize highly water-soluble, nonabsorbable malondihydrazides by coupling 2,4-disulfobenzaldehyde, 4-sulfophenylisothiocyante, and polyethylene glycol (PEG) moieties to 2-naphthalenylamino-[(3,5-dibromo-2,4-dihydroxyphenyl) methylene] propanedioic acid dihydrazide, and aminoacethydrazides by coupling PEG to [(N-2-naphthalenyl)-2-(2-hydroxyethyl)]-glycine-2-[(3,5-dibromo-2,4-dihydroxyphenyl) methylene] hydrazide. Compounds rapidly, fully and reversibly blocked CFTR-mediated chloride current with Ki of 2-8 microM when added to the apical surface of epithelial cell monolayers. Compounds did not pass across Caco-2 monolayers, and were absorbed by <2%/hr in mouse intestine. Luminally added compounds blocked by >90% cholera toxin-induced fluid secretion in mouse intestinal loops, without inhibiting intestinal fluid absorption. These orally administered, nonabsorbable, nontoxic CFTR inhibitors may reduce intestinal fluid losses in cholera.

Dehydration is a serious risk for the long-term tube-fed patient who is not allowed oral intake, has an altered mental status, is unable to communicate, is elderly or fluid-restricted, or has thirst impairment. The intent of this review is to provide a case-based discussion regarding the evaluation, treatment, and prevention of dehydration in these types of patients. Identification of risk factors, along with evaluation of subjective, objective, and laboratory parameters, provides the basis for clinical evaluation. "Hidden" sources of fluid intake such as the water content of solid foods and water generated from nutrient oxidation and "hidden" sources of fluid output such as evaporative losses should be considered in waterbalance calculations. The method for treatment and prevention of dehydration depends on the presence or absence of hypovolemia, type of body fluid losses, and whether the patient demonstrates hypernatremia, normonatremia, or hyponatremia.

Twelve diarrhoeic calves were treated intravenously with an isotonic solution containing sodium bicarbonate, and their oxygen equilibrium curves (OECS) were calculated under standard conditions and compared with those of a group of healthy calves. The relationships between the OECS for arterial and venous blood and the oxygen extraction ratio were investigated. In the diarrhoeic calves, the affinity of haemoglobin for oxygen, measured under standard conditions, was increased compared with the healthy animals. During the infusion, the standard partial oxygen pressure at 50 per cent saturation of haemoglobin (P50) values stayed below the values recorded in the healthy animals. At the end of the infusion the mean standard P50 of the diarrhoeic calves was lower than before the infusion. The combined effects of all the regulating factors on blood oxygen binding resulted in the OECS of the arterial and jugular venous blood of the diarrhoeic calves remaining unchanged compared with the healthy calves. However, the administration of the infusion decreased the P50 of both the arterial and venous blood to below the value recorded in the healthy calves. Oxygen extraction by the tissues was impaired in the diarrhoeic calves throughout the infusion, and they remained dehydrated and depressed until 120 minutes after the infusion began.

Background: The success of oral rehydration therapy in cases of severe diarrheas have led to a need for locally based therapy preparations. A preparation consisting of a precooked plantain flour-based solution and standard rehydration electrolytes was examined for its effectiveness in treating dehydration, as well as its anti-diarrhoeal properties., Methods: A sample of 101 children, ranging in age from 1 to 48 months, was selected, which had presented diarrhea for less than one week from onset, with mild dehydration and no associated complications. Fifty-four children received the ORS/WHO standard treatment, and 47 received a solution with electrolytes similar to ORS/WHO, containing 50 g of precooked plantain flour instead of glucose (ORS/plantain)., Results: Successful rehydration was achieved in 94.4% of the children in the ORS/WHO group and 91.5% in the ORS/plantain group (p = 0.70). Required time for rehydration was 5.8 (SD +/- 3.0) hours in the ORS/WHO group and 6.2 (SD +/- 3.7) hours in the ORS/plantain group (p = 0.31). Stool output during rehydration was 7.5 g/kg body weight/hour (SD +/- 7.6) in the ORS/WHO group, and 7.05 g/kg/hour (SD +/- 9.4) in the ORS/plantain group (p = 0.78). No significant differences were noted in the concentrations of plasma sodium. The observation period was 22.3 hours (SD +/- 5.3) for the ORS/WHO group and 22.7 hours (SD +/- 4.7) for the ORS/plantain group. Stool output during the observation period was 5.7 g/kg/hour (SD +/- 4.7) in the ORS/WHO group and 6.3 g/kg/hour (SD +/- 7.9) in the ORS/plantain group (p = 0.67). The proportion of children requiring intravenous fluids during the first 24 hours was 11.1% in the ORS/WHO group and 8.5% in the ORS/plantain group (RR = 1.31; 95% CI 0.39-4.35)., Conclusions: The plantain flour-based solution proved effective and safe in correcting dehydration; however the antidiarrhoeal properties of ORS/plaintain were not demonstrated.

Osmotic myelinolysis is a rare, acute, demyelinating process that involves the pons (central pontine myelinolysis) and other locations of the central nervous system (extrapontine myelinolysis). Central pontine myelinolysis is described in children, usually associated with rapid correction of hyponatremia. Other conditions, such as hypernatremia and hyperglycemia, have also been reported as being responsible for pontine myelinolysis. Extrapontine myelinolysis in childhood is very rare and presents in a wide variety of locations. We report a patient who developed extrapontine myelinolysis in the cerebellum during treatment of hyponatremic dehydration. This is the first case reported during infancy.

The serotonin system may contribute to reduced human performance when hypohydrated in the heat. This study determined whether branched-chain amino acid (BCAA) supplementation could sustain exercise and cognitive performance in the heat (40 degrees C dry bulb, 20% relative humidity) when hypohydrated by 4% of body mass. Seven heat-acclimated men completed two experimental trials, each consisting of one preparation and one test day. On day 1, a low-carbohydrate diet was eaten and subjects performed exhaustive cycling (morning) and treadmill exercise in the heat (afternoon) to lower muscle glycogen and achieve the desired hypohydration level. On day 2, subjects consumed an isocaloric BCAA and carbohydrate (BC) or carbohydrate-only drink during exercise. Experimental trials included 60 min of cycle ergometry (50% peak oxygen uptake) followed by a 30-min time trial in the heat. A cognitive test battery was completed before and after exercise, and blood samples were taken. BC produced a 2.5-fold increase (P < 0.05) in plasma BCAA and lowered (P < 0.05) the ratios of total tryptophan to BCAA and large neutral amino acid. Blood prolactin, glucose, lactate, and osmolality were not different between trials but increased over time. Cardiovascular and thermoregulatory data were also similar between trials. BC did not alter time-trial performance, cognitive performance, mood, perceived exertion, or perceived thermal comfort. We conclude that BCAA does not alter exercise or cognitive performance in the heat when subjects are hypohydrated.

Emergency departments across the nation are faced with ever-increasing high volumes, overcrowding, and patient acuity. Along with these growing trends, the Joint Commission on the Accreditation of Healthcare Organizations is instituting new patient safety initiatives to reduce patient medical errors in the hospital setting. The emergency department is one area under great scrutiny with patient identification as primary concern. This article discusses a case study involving patient misidentification in the pediatric emergency department and reviews the legal and safety programs implemented at a children's hospital to improve patient safety outcomes.

Receptor-mediated endocytosis plays an important role in accumulation of aminoglycosides in renal proximal tubule. To prevent aminoglycoside-induced nephrotoxicity following concentrated accumulation of gentamicin in the kidney, effect of cationic proteins and their peptide fragments, which could inhibit gentamicin binding to its binding receptor(s), was investigated. Among several substrates for megalin, an endocytic receptor responsible for renal accumulation of aminoglycosides, cytochrome c potently inhibited gentamicin accumulation in renal cortex. Concentration-dependent inhibition by cytochrome c on gentamicin uptake was also observed in OK kidney epithelial cells expressing megalin. In addition, gentamicin-induced increase in urinary excretion of N-acetyl-beta-d-glucosaminidase (NAG), a marker of renal tubular damage, was significantly reduced by cytochrome c. We next attempted to find a peptide fragment with lower molecular size showing inhibitory effect on gentamicin uptake. Cyto79-88 inhibited gentamicin uptake in OK cells, but had little effect on renal accumulation of gentamicin in mice in vivo. On one hand, a peptide fragment of neural Wiskott-Aldrich syndrome protein (N-WASP), which interacts with acidic phospholipids like aminoglycosides, inhibited gentamicin accumulation not only in OK cells but also in mouse kidney. These results show that substrates and/or their peptide fragments for aminoglycoside binding receptor such as megalin might be useful for preventing aminoglycoside-induced nephrotoxicity.

Background/aims: Many claims are made as to the efficacy of topical preparations in moisturising the skin, yet most of these claims cannot be substantiated by scientific study for the skin layers beneath the stratum corneum, and yield no information on the remainder of the epidermis and dermis. This argues for an in vivo quantitative method for measuring the effect of water loading extended to various layers of the skin., Methods: Detailed high-resolution in vivo MRI studies of hydration and dehydration of finger pad skin layers were conducted on one normal subject using two moisturisation methods (topical white soft paraffin (Vaseline) and water immersion). The dehydration study was carried out immediately following removal from prolonged skin moisturisation. Inter-individual variability for skin hydration (group study) was studied in seven healthy volunteers at 0 and 7 h hydration with Vaseline. Location dependence in skin hydration was investigated on the same subject by looking into the hydration of forearm and finger pad skin. System stability and measurement reproducibility was verified through a detailed phantom study., Results: Images of normal and hydrated human skin were obtained in vivo at voxel dimensions of 50 micromx150 micromx1000 microm. The effect of hydration and dehydration as a function of exposure to moisturiser (i.e. water and Vaseline) on the image signal intensity, observed T1, and interaction of free and bound water in specific tissues were identified and correlated with existing physiological knowledge. Swelling of stratum corneum due to hydration was expressed as an in vivo model of tissue hydration., Conclusion: Results of the dehydration study showed that the changes due to the previous hydration of the skin are reversible for all skin layers. For both moisturisation methods (i.e. Vaseline and skin bathing), the effects of hydration and dehydration on the skin were similar. The trends of the MRI parameters for finger pad and arm skin were similar. The group study showed low inter-subject variability of hydration on stratum corneum and epidermis.

Sickle cell anemia is characterized by the presence of dense dehydrated erythrocytes that have lost most of their K content. Due to the unique dependence of Hb S polymerization on intracellular Hb S concentration, preventing this dehydration should markedly reduce polymerization. The erythrocyte intermediate conductance Ca-activated K channel (hSK4 or KCNN4), first described by Gardos, has been shown to be a major pathway for sickle cell dehydration. Studies with the imidazole antimycotic clotrimazole have shown reduction of sickle cell dehydration in vivo in a small number of patients with sickle cell disease; dose-limiting gastrointestinal and liver toxicities were observed. Based on the chemical structure of clotrimazole metabolites, a novel Gardos channel inhibitor, ICA-17043, has been developed. It has shown substantial activity both in vitro and in vivo in transgenic sickle mice. ICA-17043 is currently in phase 2 human trials. Another potential therapeutic target is the K-Cl cotransport. When sickle erythrocytes are exposed to relatively acidic conditions, they undergo cell shrinkage via activation of this pathway. K-Cl cotransport can be blocked by increasing the abnormally low erythrocyte Mg content of sickle erythrocytes. Oral Mg supplementation has been shown to reduce sickle cell dehydration in vivo in transgenic sickle mice and in patients in two separate clinical trials. Oral Mg pidolate is being tested in clinical trials in homozygous sickle cell disease and in Hb S/HbC (SC) disease, either as a single agent or in combination with hydroxyurea. The ongoing trials will determine the clinical effectiveness of therapies aimed at preventing sickle erythrocyte dehydration.

One of the most important objectives of the Pharmaceutical Industry is the development of new excipients as well as the optimization of other more traditional ones. Also, the investigation of new active substances able to prevent, palliate or treat the cutaneous dehydration is another of the most important of their objectives. Both tendencies are implanted in this experimental work: we propose an emulsion formulated with the base--Neo PCL' (25%), NMF (Lactil', 5%) and a peculiar active--Honey of Rosemary (15%). The working scheme is as follows: 1) Pharmacotechnical Characterization--organoleptic characteristics, Photomicrograph Study, Type of Emulsion, pH, Rheology; 2) Stability Study by means of accelerated tests based on temperature and centrifugation; 3) Effectiveness Study by applying of non-invasive assessment techniques. An emulsified dermopharmaceutical form is obtained (O/W) with a satisfactory organoleptic characteristics and eudermic pH (5.2), attributable to the acid character of Honey. From the rheological study, a very good results are obtained: viscosity (T = 408.8.D0.549), structural recuperation (30%) and thixotropy (AD1/AD2 = 1.36). On the other hand, from the effectiveness results (corneometric--P.I.120 = 43.2%- and sebumetric--E.I. = 33-144 mg/cm2-), a high level of moisturizing is deduced, which is attributable to the synergic action of both Lactil' and Honey. Finally, the proposed emulsion would serve as a treatment for all type of dry skin.

Background: The treatment of diarrhoea relies on the maintenance or restoration of hydration with maintenance of an adequate nutritional intake. Racecadotril has been shown to reduce the stools output during acute diarrhoea. The present work was aimed at measuring the number of emergency department visits for acute diarrhoea either the children received racecadotril or not., Method: Racecadotril and rehydration were compared with rehydration alone in children aged three months to three years who had acute diarrhoea and were evaluated in the emergency department (ED). The primary end point was the number of medical exams during the week after starting treatment. Secondary end points were the number of stools during the first 48 hours, the duration of the diarrhoea and the weight on day 7., Results: One hundred and sixty-six children were alternatively randomized to the treated and the control groups. There was no difference for age, degree of dehydration and length of illness before the first visit between the groups. Whatever type of rehydration (oral or i.v.), the treated group had a significant lower number of stools (p < 0.001) and a faster recovery (p < 10(-9)). The children receiving racecadotril needed less additional ED visits for the same episode (p < 0.05). There was no difference for the weight-gain on day 7., Conclusions: This study demonstrates the efficacy of racecadotril as adjuvant therapy to oral and i.v. rehydration in the treatment of acute diarrhoea and a fewer emergency department second visit before recovery.

To determine the effects of rapid infusion of essential fluids in a volume of hypotonic lactated Ringer's solution, the central venous pressure (CVP) and acid-base equilibrium were investigated in to mildly dehydrated heifers. Mild dehydration was induced in 9 Holstein heifers by withholding food and water until 7.0+/-5.7% of plasma volume had been lost. The heifers were randomly assigned to the ILG (lactated Ringer's + 5% dextrose), HLG (1/2 lactated Ringer's + 2.2% dextrose) or HRG (1/2 Ringer's + 2.5% dextrose) groups with 3 heifers in each group. Heifers received 30 ml/kg of one of the fluids, at a flow rate of 20 ml/kg/hr. The rapid intravenous (IV) infusions of HLG and HRG used in this study were found to be safe and effective in increasing plasma volume without increasing CVP, even though the infusion was given to the jugular vein at a dosage of 30 ml/kg. However, ILG infusion induced progressive increases in CVP, reaching 9.0+/-2.0 mmHg. No clinical signs, such as moist rales on auscultation, moist cough, jugular vein congestion, ophthalmoptosis, salivation or arrhythmia, were observed throughout the fluid infusion. The relative changes in base excess (rBE) for the ILG and HRG groups were significantly decreased until the end of fluid infusion. As for the HLG group, rBE slightly decreased until the end of the fluid infusion. Then the values significantly increased and exceeded the pre-infusion value at the end of the experiment. While IV infusion of HLG inhibited acidification caused by dilution, HRG infusion induced diluted acidification. It is suggested that HLG infusion should be examined as a treatment for cattle with dehydration and moderate metabolic acidosis, since rapid infusion of HLG may be more beneficial for rehydrating cattle with metabolic acidosis than current treatment.

Objective: To determine whether the composition of electrolyte pastes formulated for oral administration influences voluntary water intake (WI) by horses recovering from furosemide-induced dehydration., Animals: 6 horses., Procedures: Voluntary WI, body weight, and blood and urine constituents were measured before and after induction of dehydration by furosemide administration and overnight withholding of water; these same variables also were measured during a 36-hour rehydration period. Each horse was evaluated 4 times with random application of 4 treatments (electrolyte pastes) that provided 0.5 g of KCl/kg of body weight, 0.5 g of NaCl/kg, 0.25 g of NaCl and 0.25 g of KCl/kg, or no electrolytes (control treatment). Electrolyte pastes were administered 3 times (4, 8, and 12 hours after start of the rehydration period)., Results: Administration of all electrolyte pastes resulted in significantly greater voluntarily WI, compared with the control treatment, and was accompanied by significantly greater recovery of body weight when NaCl was a component of the paste. Administration of NaCl and NaCl-KCl pastes tended to produce a state of transient hyperhydration; however, electrolyte administration also resulted in significantly greater urine production and electrolyte excretion during the final 24 hours of the rehydration period. Adverse effects of oral administration of hypertonic electrolyte pastes were not observed., Conclusions and Clinical Relevance: Oral administration of electrolyte pastes to dehydrated horses increases voluntary WI and improves rehydration during the rehydration period. Rehydration is more rapid and complete when NaCl is a component of the electrolyte paste.

Background: The Institute of Medicine has recommended intraosseous (IO) infusion of 7.5% hypertonic saline (HTS) for combat casualties in shock. We tested the safety and efficacy of this recommendation in a long-term survival model of uncontrolled hemorrhagic shock using dehydrated swine., Methods: Fourteen dehydrated Yorkshire swine had placement of a 12G needle in the right anterior tibia under isoflurane anesthesia. Uncontrolled hemorrhage was induced via left iliac artery and vein injury. Animals were kept in shock for 2 hours and then resuscitated over 2 hours with 5 mL/kg of 7.5% HTS given either as 10 small boluses (group I, n = 4) or two large boluses (group II, n = 6) to compare the physiologic response and blood loss. Control animals (group III, n = 4) received an equal volume of 0.9% saline IO and additional intravenous saline to equalize the salt load in all groups., Results: The three groups had similar physiologic responses, with no increase in blood loss following HTS resuscitation. However, between the second and fifth postresuscitation days, the 7.5% HTS resuscitated animals developed soft tissue necrosis or bone marrow necrosis of the right hind leg (group I, 100%; group II, 66.6%; group III, 0%)., Conclusion: HTS resuscitation effectively restored hemodynamic stability in dehydrated swine without increased bleeding from an uncontrolled vascular injury. However, IO infusion of HTS in this model was associated with a very high rate of local complications. Further investigations should be undertaken before IO use of 7.5% HTS in humans.

In the stratum corneum, the water binds to the intracellular hygroscopic and hydrosoluble substances called "natural moisturizing factors" or NMF. These "natural moisturizing factors" contained in the corneocytes are formed during epidermal differentiation and may represent up to 10 p. cent of the corneocyte mass. They are principally amino acids, carboxylic pyrrolidone acid, lactic acid, urea, glucose and mineral ions. Keratinization plays an important part in the formation of NMF that exhibit strong osmotic potential attracting the water molecules. The binding of water to NMF is the static aspect of cutaneous hydration. The second, dynamic, aspect is related to the selective permeability of the stratum corneum and to its lipid barrier properties, the permeability of which depends on the integrity and nature of the inter-corneocyte lipids and their lamellar organization between the cells. In these conditions, hydration cosmetics rely on two concepts that can be isolated or associated: the supply of hydrophilic substances to the stratum corneum, capable of attracting and retaining water (moisturizer) or capable of restoring the barrier in order to restore normal water loss or of protecting it against aggression (occlusive).

The dehydration of sickle red blood cells (RBCs) through the Ca-activated K channel depends on the parallel movement of Cl ions. To study whether Cl-conductance block might prevent dehydration of sickle RBCs, a novel Cl-conductance inhibitor (NS3623) was characterized in vitro using RBCs from healthy donors and sickle cell patients and in vivo using normal mice and a transgenic mouse model of sickle cell disease (SAD mice). In vitro, NS3623 reversibly blocked human RBC Cl-conductance (g(Cl)) with an IC(50) value of 210 nmol/L and a maximal block of 95%. In vivo, NS3623 inhibited RBC g(Cl) after oral administration to normal mice (ED(50) = 25 mg/kg). Although g(Cl), at a single dose of 100 mg/kg, was still 70% inhibited 5 hours after dosing, the inhibition disappeared after 24 hours. Repeated administration of 100 mg/kg twice a day for 10 days caused no adverse effects; therefore, this regimen was chosen as the highest dosing for the SAD mice. SAD mice were treated for 3 weeks with 2 daily administrations of 10, 35, and 100 mg/kg NS3623, respectively. The hematocrit increased, and the mean corpuscular hemoglobin concentration decreased in all groups with a concomitant increase in the intracellular cation content. A loss of the densest red cell population was observed in conjunction with a shift from a high proportion of sickled to well-hydrated discoid erythrocytes, with some echinocytes present at the highest dosage. These data indicate feasibility for the potential use of Cl-conductance blockers to treat human sickle cell disease.

Both green tea extract (GTE or tea polyphenols) and aged garlic extract (AGE) effectively inhibited in vitro dehydration of sickle red blood cells induced by K-Cl cotransport or red cell storage. For K-Cl cotransport induced by 500 mM urea, 0.3 mg/ml EGCg (epigallocatechin gallate; a major component in GTE) almost completely inhibited dehydration, and 6 mg/ml AGE inhibited dehydration to 30% of the control level. Both vitamins E and C had no effect at the level of 2 mM. Different tea extracts had different degrees of inhibition, but the inhibitory activity increased when the number of hydroxyl groups in the compounds increased. With storage of sickle cells at 4 degrees C for 6 days, the cells started to undergo spontaneous dehydration when incubated at 37 degrees C. Neither inhibitors for Ca-induced K efflux nor K-Cl cotransport could inhibit cell dehydration of stored sickle cells, but both GTE and AGE effectively inhibited it. Chloride efflux measurements using a chloride electrode demonstrated that both GTE and AGE inhibited anion transport in red blood cells. The inhibitory mechanism of these compounds may be related to anion transport inhibition, although involvement of their antioxidant activities can not yet be ruled out., (Copyright 2001 Academic Press.)