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Large Doses (large + dose)
Selected AbstractsImproving Botulinum Toxin Therapy for Palmar Hyperhidrosis: Wrist Block and Technical ConsiderationsDERMATOLOGIC SURGERY, Issue 1 2001Ada Regina Trindade De Almeida MD Botulinum A exotoxin has become an excellent therapeutic option to treat focal hyperhidrosis, but when the problem affects the palmar region the technique has some drawbacks. Pain with injection is difficult to tolerate and the large dose needed to treat both hands are two concerns, as well as muscle weakness secondary to botulinum toxin diffusion and the possibility of antibody production. All these problems limit the number of patients treated. The author's suggestion is to treat only the dominant hand, after performing a wrist block. The use of a device adapted from a cartridge rubber may help to control the injection depth and the risk of muscular weakness. [source] Evidence for a cost of immunity when the crustacean Daphnia magna is exposed to the bacterial pathogen Pasteuria ramosaJOURNAL OF ANIMAL ECOLOGY, Issue 6 2007TOM J. LITTLE Summary 1The deployment of the immune system has the obvious potential to ameliorate infection outcomes, but immune responses can also harm hosts by either damaging host tissues or monopolizing resources, leading to enhanced mortality. To gain insight into such a ,cost of immunity' when the crustacean Daphnia magna is challenged with the bacterium Pasteuria ramosa, we measured survivorship among hosts that resisted infection following exposure to various strains and doses of the parasite. 2In the first of two experiments, these exposures were: single exposures with relatively non-aggressive strains, double exposures with non-aggressive strains, and exposure to aggressive strains. Mortality increased across this gradient of exposure. In a second experiment, we varied the dose of the most aggressive P. ramosa strain and found that resisting infection when a large dose was applied resulted in greater mortality than when a medium or low dose was applied. 3Assuming that resistance is accomplished with an immune response, and that more aggressive parasites and/or larger doses of parasites are more immunostimulatory, these data are compatible with a cost of immunity. Indeed, in terms of survival, resisting parasites can be more harmful than infection. [source] The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective?JOURNAL OF NEUROCHEMISTRY, Issue 1 2003Guohua Xi Abstract In the last two decades it has become apparent that thrombin has many extravascular effects that are mediated by a family of protease-activated receptors (PARs). PAR-1, -3 and -4 are activated via cleavage by thrombin. The importance of extravascular thrombin in modulating ischemic, hemorrhagic and traumatic injury in brain has recently become clear. Thus, in vitro, thrombin at low concentration protects neurons and astrocytes from cell death caused by a number of different insults. In vivo, pretreating the brain with a low dose of thrombin (thrombin preconditioning), attenuates the brain injury induced by a large dose of thrombin, an intracerebral hemorrhage or by focal cerebral ischemia. Thrombin may also be an important mediator of ischemic preconditioning. In contrast, high doses of thrombin kill neurons and astrocytes in vitro and cause disruption of the blood,brain barrier, brain edema and seizures in vivo. This review examines the role of thrombin in brain injury and the molecular mechanisms and signaling cascades involved. [source] SIAM-Like Phenomenon Caused by Low Doses of AlcoholALCOHOLISM, Issue 2010Akiko Shimamoto Background:, Swift increase in alcohol metabolism (SIAM) is usually evoked by a large dose of ethanol, which is often demonstrated by an abrupt increase in oxygen uptake. SIAM was induced by low doses of ethanol and evaluated by pharmacokinetic analyses of ethanol and its metabolites. Methods:, Rabbits were initially administered 1.0 g/kg of ethanol solution and the same dose was given to the bolus group 6 hours after the first injection. The infusion group was administered 0.25 g/kg/h of ethanol 2 hours after the first injection. Blood concentrations of ethanol, acetaldehyde, and acetate were then determined and comparisons were made using pharmacokinetic parameters. Results:, A significantly higher ethanol elimination rate was observed after re-administration of ethanol to the bolus group. Other pharmacokinetic parameters were unaffected. The concentration at steady state (Css) for the infusion group was stable. A significantly higher level of mean residence time (MRT) in blood acetaldehyde was observed for the bolus group, whereas no MRT changes were observed for the infusion group. A significantly higher level of blood acetate Css was observed after re-administration of ethanol to the bolus group, following the changes in area under concentration and MRT. No Css changes were observed for the infusion group. The Css of acetate at stage 2 was significantly higher for the bolus group, compared to the infusion group. Conclusion:, Low doses of ethanol enhanced alcohol metabolism in rabbits, according to a pharmacokinetic analysis of circulating ethanol concentrations. Simultaneous analyses of its metabolites followed the kinetic of ethanol. [source] The Effect of Acute Ethanol Intoxication on Salivary Proteins of Innate and Adaptive ImmunityALCOHOLISM, Issue 4 2008Napoleon Waszkiewicz Background:, Human salivary proteins: peroxidase, lysozyme, lactoferrin, and IgA, participate in the protection of oral tissues, as well as upper digestive and respiratory tracts, against a number of microbial pathogens. In the current study, we investigated the effect of acute consumption of a large dose of ethanol on representative human salivary proteins of the innate and adaptive immune systems. Methods:, Eight healthy male volunteers drank an average of 2.0 g (1.4 to 2.5 g/kg) body weight of ethanol, in the form of vodka, in the 6-hour period. Samples of resting whole saliva were collected 12 hours before, then 36 and 108 hours after, the alcohol consumption. The levels of total protein, immunoglobulin A, lysozyme and lactoferrin as well as peroxidase activity were determined in saliva. Results:, At 36 hours after alcohol consumption, salivary protein and lysozyme concentrations as well as peroxidase activity were significantly decreased (p = 0.002, p = 0.043, and p = 0.003, respectively), in comparison to the values obtained at 12 hours before drinking. Between 36 and 108 hours after alcohol consumption, the salivary protein and lysozyme concentrations, as well as peroxidase activity showed a tendency to increase, although at 108 hours after the drinking session, the concentration of protein and peroxidase activity were still significantly lower than before drinking. There was no significant change in the level of lactoferrin, after the drinking session. The salivary concentration of IgA tended to increase at 36 hours after alcohol consumption, and at 108 hours it was significantly higher (p = 0.028), when compared to IgA concentration in the saliva collected before drinking (from 8% to 26% and 32% of total protein content, respectively). Conclusion:, Our report is the first to show that acute ingestion of relatively large, yet tolerable dose of alcohol, significantly disturbs salivary antimicrobial defense system. Reduced lysozyme level and decreased peroxidase activity may contribute to increased susceptibility to infections, when acute alcohol intake coincides with exposure to pathogens. [source] Clinical implications of sugammadexANAESTHESIA, Issue 2009J. E. Caldwell Summary Sugammadex is a cyclodextrin molecule that encapsulates and inactivates rocuronium and vecuronium. As a result, any degree of neuromuscular block produced by rocuronium or vecuronium can be rapidly and completely reversed without autonomic effects. Because sugammadex is optimised for reversing rocuronium it is most likely to be used in conjunction with this drug. Sugammadex will allow deep levels of block to be maintained until the very end of surgery, and will allow block to be reversed at any time after rocuronium administration, even just a few minutes. The recommended dose-range is 2,16 mg.kg-1 (ascender), depending on the level of block. The availability of sugammadex reversal may increase the use of rocuronium, and decrease the use of suxamethonium and benzylisoquinoline neuromuscular blocking drugs. In addition, it will certainly increase pharmacy costs, which may be offset by faster recovery and discharge from the post-anesthesia recovery unit. Sugammadex may also change monitoring practices in that post-tetanic count will be required to quantify deep block, and quantitative monitoring of recovery may be driven by cost concerns in order to allow the use of the smallest dose of sugammadex that gives a satisfactory train-of-four ratio. Alternatively, monitoring may essentially be abandoned since a large dose of sugammadex will reliably reverse any degree of rocuronium-induced block. The ultimate clinical utility of sugammadex will be clear only after large-scale clinical use. [source] Botulinum Toxin Type B for Dynamic Glabellar Rhytides Refractory to Botulinum Toxin Type ADERMATOLOGIC SURGERY, Issue 5 2003Tina S. Alster MD Background. Botulinum toxin type B (BTX-B; Myobloc) has recently been introduced for the treatment of dynamic rhytides. This serotype is structurally similar to botulinum toxin type A (BTX-A; Botox) and appears to produce equivalent muscular paralysis. Because of the fact that some patients may become resistant to the effects of BTX-A with its continued use or may require large doses of type A to exert adequate muscular paralysis, the use of BTX-B may prove beneficial in these cases. Objective. To determine the effect of BTX-B on glabellar rhytides refractory or showing decreased clinical effect to treatment with BTX-A. Methods. Twenty females (mean age, 43 years) with vertical glabellar rhytides showing decreased or negligible clinical effect to BTX-A were treated with intramuscular injections of BTX-B. Five standardized intramuscular sites (procerus, inferomedial corrugator muscles, superior middle corrugator muscles) received a total dose of 2,500 U. Patients were evaluated at pretreatment and 48 to 72 hours, 1 week, and 2 and 4 months after injection. Results. All glabellar rhytides improved after treatment with BTX-B injections. Peak clinical effect was noted 1 month after treatment, with 50% of peak effect evident at the 2-month follow-up. Near complete dissolution of effect was seen at 4 months after treatment. Side effects were transient and were limited to moderate injectional pain and rare bruising and frontal brow tightness. Conclusions. BTX-B is an effective treatment modality for glabellar rhytides refractory or exhibiting decreased clinical effect to BTX-A. The duration of effect using the 2,500 U dosing schedule described herein was shorter than that typically achieved after equivalent BTX-A injection. [source] Arachidonic acid as a retrograde signal controlling growth and dynamics of retinotectal arborsDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2008B.H. Leu Abstract In the developing visual system, correlated presynaptic activity between neighboring retinal ganglion cells (RGC) stabilizes retinotopic synapses via a postsynaptic NMDAR (N -methyl- D -aspartate receptor)-dependent mechanism. Blocking NMDARs makes individual axonal arbors larger, which underlies an unsharpened map, and also increases branch turnover, as if a stabilizing factor from the postsynaptic partner is no longer released. Arachidonic acid (AA), a candidate retrograde stabilizing factor, is released by cytoplasmic phospholipase A2 (cPLA2) after Ca2+ entry through activated NMDARs, and can activate presynaptic protein kinase C to phosphorylate various substrates such as GAP43 to regulate cytoskeletal dynamics. To test the role of cPLA2 in the retinotectal system of developing zebrafish, we first used PED6, a fluorescent reporter of cPLA2 activity, to show that 1,3 min of strobe flashes activated tectal cPLA2 by an NMDAR-dependent mechanism. Second, we imaged the dynamic growth of retinal arbors during both local inhibition of tectal cPLA2 by a pharmacological inhibitor, arachidonic tri-fluoromethylketone, and its suppression by antisense oligonucleotides (both injected intraventricularly). Both methods produced larger arbors and faster branch dynamics as occurs with blocking NMDARs. In contrast, intraocular suppression of retinal cPLA2 with large doses of antisense oligos produced none of the effects of tectal cPLA2 inhibition. Finally, if AA is the retrograde messenger, the application of exogenous AA to the tectum should reverse the increased branch turnover caused by blocking either NMDARs or cPLA2. In both cases, intraventricular injection of AA stabilized the overall branch dynamics, bringing rates down below the normal values. The results suggest that AA generated postsynaptically by cPLA2 downstream of Ca2+ entry through NMDARs acts as a retrograde signal to regulate the dynamic growth of retinal arbors. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Nutritional supplements, foods, and epilepsy: Is there a relationship?EPILEPSIA, Issue 11 2008Ali A. Asadi-Pooya Summary Anecdotal reports suggest that certain foods and dietary contents might influence the occurrence of seizures. However, the existing data are scanty and sometimes controversial. Some studies have found that the supplementation with individual nutrients reduced seizure frequency or improved other aspects of health in patients with epilepsy, while other studies have failed to confirm those findings. Nutrient supplementation may be necessary to prevent or reverse the effects of certain deficiencies that frequently result from the use of antiepileptic drugs (AEDs). However, the potential benefits of nutrient supplementation in patients with epilepsy must be weighed against reports that large doses of certain nutrients can interfere with the action of some AEDs. This paper reviews dietary and nutritional considerations in patients with epilepsy and also the relationship between foods, dietary elements, and seizures. [source] A potent adjuvant effect of CD40 antibody attached to antigenIMMUNOLOGY, Issue 1 2003Tom A. Barr Summary There is great potential for novel vaccines based on recombinant proteins and synthetic peptides. Unfortunately these antigens often lack the immunogenicity of whole, killed pathogens used in traditional vaccines. Thus there is strong interest in the identification of immunological adjuvants with low reactogenicity, but high potency, to enhance immune responses and realize the potential of these new vaccine strategies. CD40 antibodies have been shown to have adjuvant effects when administered at very high doses. These large doses are impractical and induce a cascade of cytokine release giving rise to septic shock-like symptoms, as well as splenomegaly and polyclonal antibody production. We show here that a very small amount of CD40 antibody can exhibit potent adjuvant effects when attached to soluble antigen. The lack of detectable systemic effects indicates that this method may be a powerful and practical means of enhancing the efficacy of recombinant vaccines. [source] Remifentanil post-conditioning attenuates cardiac ischemia,reperfusion injury via , or , opioid receptor activationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010G. T. C. WONG Background: Ischemic pre- or post-conditioning of the heart has been shown to involve opioid receptors. Remifentanil, an ultra-short-acting selective , opioid receptor agonist in clinical use, pre-conditions the rat heart against ischemia,reperfusion injury. This study investigates whether remifentanil post-conditioning is also cardioprotective. Methods: Remifentanil post-conditioning (5-min infusion at 1, 5, 10 or 20 ,g/kg/min) or ischemic post-conditioning (three cycles of a 10 s reperfusion interspersed with a 10 s ischemia) was induced in an open-chest rat heart model of ischemia and reperfusion injury, in the presence or absence of nor-binaltorphimine, naltrindole or CTOP, specific ,, , and , opioid receptor antagonists, respectively. The same sequence of experiments was repeated in the isolated heart model using the maximal protective dose of remifentanil from the dose,response studies. Results: Both ischemic and remifentanil post-conditioning reduced the myocardial infarct size relative to the control group in both models. This cardioprotective effect for both post-conditioning regimes was prevented by the prior administration of nor-binaltorphimine and naltrindole but not CTOP. The sole administration of the antagonists had no effect on the size of myocardial infarction. Conclusions: These results indicate that remifentanil post-conditioning protects the heart from ischemia,reperfusion injury to a similar extent as of ischemic post-conditioning. This protection involves , and , but not , opioid receptor activation. This drug has great potential as a clinical post-conditioning modality as it can be given in large doses without prolonged opioid-related side effects. [source] Brain metabolism of exogenous pyruvateJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Susana Villa Gonzalez Abstract Pyruvate given in large doses may be neuroprotective in stroke, but it is not known to what degree the brain metabolizes pyruvate. Intravenous injection of [3- 13C]pyruvate led to dose-dependent labelling of cerebral metabolites so that at 5 min after injection of 18 mmoles [3- 13C]pyruvate/kg (2 g sodium pyruvate/kg), approximately 20% of brain glutamate and GABA were labelled, as could be detected by 13C nuclear magnetic resonance spectrometry ex vivo. Pyruvate, 9 mmoles/kg, was equivalent to glucose, 9 mmoles/kg, as a substrate for cerebral tricarboxylic acid (TCA) cycle activity. Inhibition of the glial TCA cycle with fluoroacetate did not affect formation of [4- 13C]glutamate or [2- 13C]GABA from [3- 13C]pyruvate, but reduced formation of [4- 13C]glutamine by 50%, indicating predominantly neuronal metabolism of exogenous pyruvate. Extensive formation of [3- 13C]lactate from [2- 13C]pyruvate demonstrated reversible carboxylation of pyruvate to malate and equilibration with fumarate, presumably in neurones, but anaplerotic formation of TCA cycle intermediates from exogenous pyruvate could not be detected. Too rapid injection of large amounts of pyruvate led to seizure activity, respiratory arrest and death. We conclude that exogenous pyruvate is an excellent energy substrate for neurones in vivo, but that care must be taken to avoid the seizure-inducing effect of pyruvate given in large doses. [source] Altered White Matter Integrity in Adolescent Binge DrinkersALCOHOLISM, Issue 7 2009Tim McQueeny Background:, White matter integrity has been found to be compromised in adult alcoholics, but it is unclear when in the course of alcohol exposure white matter abnormalities become apparent. This study assessed microstructural white matter integrity among adolescent binge drinkers with no history of an alcohol use disorder. Methods:, We used diffusion tensor imaging to examine fractional anisotropy (FA), a measure of directional coherence of white matter tracts, among teens with (n = 14) and without (n = 14) histories of binge drinking but no history of alcohol use disorder, matched on age, gender, and education. Results:, Binge drinkers had lower FA than controls in 18 white matter areas (clusters ,27 contiguous voxels, each with p < 0.01) throughout the brain, including the corpus callosum, superior longitudinal fasciculus, corona radiata, internal and external capsules, and commissural, limbic, brainstem, and cortical projection fibers, while exhibiting no areas of higher FA. Among binge drinkers, lower FA in 6 of these regions was linked to significantly greater lifetime hangover symptoms and/or higher estimated peak blood alcohol concentrations. Conclusions:, Binge drinking adolescents demonstrated widespread reductions of FA in major white matter pathways. Although preliminary, these results could indicate that infrequent exposure to large doses of alcohol during youth may compromise white matter fiber coherence. [source] Vitamin A toxicity: When one a day doesn't keep the doctor awayLIVER TRANSPLANTATION, Issue 12 2006Rekha Cheruvattath Vitamin A toxicity has been reported to cause severe liver disease and, occasionally, liver failure. Herein we present the case of a 60-year-old male with symptoms of muscle soreness, alopecia, nail dystrophy, and ascites. He continued to deteriorate with the development of refractory ascites, renal insufficiency, encephalopathy, and failure to thrive. A liver biopsy demonstrated presence of Ito cells and vacuolated Kupffer cells without the presence of cirrhosis. His clinical history revealed ingestion of large doses of vitamin A. His worsening clinical situation ruled out the possibility of a transjugular intrahepatic portosystemic shunt. The patient underwent orthotopic liver transplantation with resolution of symptoms. Vitamin A toxicity should be considered in the differential diagnosis of noncirrhotic portal hypertension. In conclusion, liver transplantation is a valid option if no improvement occurs in spite of cessation of the medication. Liver Transpl 12:1888,1891, 2006. © 2006 AASLD. [source] Complete recovery from prolonged cardio-pulmonary resuscitation following anaphylactic reaction to readministered intravenous cefazolinACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2003M. W. Gibbs We describe a patient who developed a type I anaphylactic reaction to intravenous cefazolin. The patient had no known drug allergies and had previously received intraoperative intravenous cefazolin 2 months prior without any problems. Forty-fives after receiving cefazolin 1 g i.v. and while fully awake, the patient experienced shortness of breath, became unconscious, and then suffered a cardiac arrest. Resuscitation included endotracheal intubation, external cardiac compression, electrical defibrillation and multiple large doses of epinephrine, atropine, and sodium bicarbonate over the course of 2.5 h and three cardiac arrests. Nevertheless, the patient fully recovered. The intent of this case report is to address widely held concerns regarding cross-reactivity of cephalosporin, particularly cefazolin, to penicillin, the legitimacy of test dosing as a means to safely identify patients who will have an allergic reaction to cephalosporins and comment on patient-related predictors of survival following cardiopulmonary resuscitation and the good outcome in this case. [source] (635) The Advantages and Adverse Effects of Long-Term Intrathecal Delivery of Opioid and Clonidine HCL AdmixturePAIN MEDICINE, Issue 2 2000Article first published online: 25 DEC 200 Introduction: Intrathecal clonidine may be effective in neuropathic pain situations where large doses of opioids and local anesthetics or baclofen result in side effects and inadequate pain control. Addition of clonidine activates K (ATP) channels via a-2 receptors. Clonidine administered intrathecally provides fourfold better pain control with lower side effects than systemic clonidine. Because clonidine does not interact with opioid receptors, it fails to cause opioid-like side effects. Clonidine and opioids may have a synergistic efficacy. Materials & Methods: We performed a retrospective analysis of 23 patients, 10 male and 13 female, with a mean age of 55.4 years. Seventeen patients had neuropathic pain and 6 patients had mixed (neuropathic-nociceptive) nonmalignant pain. They had failed to achieve satisfactory analgesia despite preclinical infusion of high dose morphine sulfate, hydromorphone HCL, or combinations of bupivacaine HCL/opioid or baclofen. The range of initiating daily dose of clonidine was 25 ,g to 50 ,g, to a maximum of 900 ,g/day. The clonidine doses were titrated upwards to the end point of either efficacy or adverse effects. Clinical parameters studied were patient vital signs, pain intensity, pain relief, quality of sleep, drug intake, and side effects. Results: The preclonidine VAPS scores were on average 7.67 and the postclonidine VAPS scores were 5.82. Sleep improved for 50% of patients having poor to fair sleep. Length of therapy ranges from 1 month to 35 months with an average of 14.7 months of therapy. Of the 23 patients studied, 8 patients have been satisfied, coping with any side effects, and are still receiving mixed clonidine/opioid therapy. The side effects noted were nausea (9), sleepiness (8), dry mouth (7), dizziness (7), orthostatic hypotension (2), short term memory loss (2), headache (2), edema (2), depression (2), tinnitus (1), lethargy (1), nausea with vomiting (1), decreased energy (1), decreased libido (1), impotence (1), fine tremor (1), and anxiety (1). Conclusions: Intraspinal infusion of clonidine plus opioid may provide safer and better synergistic control of intractable neuropathic or mixed nonmalignant pain than pure intraspinal infusions of u-opioid with local anesthetic. [source] Neuroexcitatory Effects Of Morphine And Hydromorphone: Evidence Implicating The 3-Glucuronide MetabolitesCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2000Mt Smith SUMMARY 1. Morphine is recommended by the World Health Organization as the drug of choice for the management of moderate to severe cancer pain. 2. Education of health professionals in the past decade has resulted in a large increase in the prescribing of opioids, such as morphine, and in the magnitude of the doses administered, resulting in an improvement in the quality of pain relief available for many cancer patients. 3. However, the reported incidence of neuroexcitatory side effects (allodynia, myoclonus, seizures) in patients administered large doses of systemic morphine or its structural analogue, hydromorphone (HMOR), has also increased. 4. Clinically, increasing the magnitude of the morphine or HMOR dose administered to patients already exhibiting neuroexcitatory opioid related side effects, results in an exacerbation rather than an attenuation of the excitatory behaviours. 5. In contrast, cessation of the opioid or rotation to a structurally dissimilar opioid (e.g. from morphine/HMOR to methadone or fentanyl), usually results in a restoration of analgesia and resolution of the neuroexcitatory opioid side effects over a period of hours to days. 6. To explain the clinical success of ,opioid rotation', it is essential to understand the in vivo metabolic fate of morphine and HMOR. 7. Following systemic administration, morphine and HMOR are metabolized primarily to the corresponding 3-glucuronide metabolites, morphine-3-glucuronide (M3G) and hydromorphone-3-glucuronide (H3G), which are not only devoid of analgesic activity but evoke a range of dose-dependent excitatory behaviours, including allodynia, myoclonus and seizures, following intracerebroventricular (i.c.v.) administration to rats. 8. Several studies have shown that, following chronic oral or subcutaneous morphine administration to patients with cancer pain, the cerebrospinal fluid (CSF) concentrations of M3G exceed those of morphine and morphine-6-glucuronide (analgesically active morphine metabolite) by approximately two- and five-fold, respectively. 9. These findings suggest that when the M3G concentration (or H3G by analogy) in the CSF exceeds the neuroexcitatory threshold, excitatory behaviours will be evoked in patients. 10. Thus, rotation of the opioid from morphine/HMOR to a structurally dissimilar opioid, such as methadone or fentanyl, will allow clearance of M3G/H3G from the patient central nervous system over hours to days, thereby producing a time-dependent resolution of the neuroexcitatory behaviours while maintaining analgesia with methadone or fentanyl. [source] Folic acid supplementation on red kidney bean-induced diarrhoea and enteric bacterial translocation into mesenteric lymph nodes in rats: a pilot studyACTA PAEDIATRICA, Issue 1 2002R Shoda Deaths following childhood diarrhoea, a major health problem in developing countries, are often associated with malnutrition and septicaemic complications. Folic acid has been used in the treatment of acute and chronic diarrhoea in the tropics. Using a rat model, we evaluated the protective effect of large doses of folic acid on diarrhoea, small intestinal bacterial overgrowth and translocation of enteric bacteria into mesenteric lymph nodes induced by a raw red kidney bean-based diet containing lectin (phytohemagglutinin). Long-Evans rats in 2 groups of 5 each (60 g to 70 g in weight, 28 d old) were used. All 10 rats, individually kept in metabolic cages, received a raw red kidney bean-based diet for 10 d, and 5 of them also received a daily folic acid supplement (160 ,g/g feed) both during and for 10 d before the experiment. The faecal weight was measured and a quantitative aerobic bacterial culture of the small intestinal mucosal scrapings and of the mesenteric lymph nodes was made. Folic acid supplementation did not reduce faecal output nor did it prevent loss of body weight associated with lectin-induced diarrhoea. However, the mean total count of enteric bacteria translocated to the mesenteric lymph nodes was significantly reduced in the supplemented rats (1.27 ± 0.61 vs 2.66 ± 0.84, p= 0.028) and a trend towards reduced bacterial count in the small intestinal mucosal scrapings (0.40 ± 0.89 vs 1.42 ± 1.31, p= 0.16) was documented. A significant positive correlation was also seen between the bacterial count in the jejunal mucosal scrapings and in the mesenteric lymph nodes. Conclusion: Although large-dose folic acid supplementation did not prevent diarrhoea and malnutrition induced by a lectin-based diet, it substantially reduced the count of enteric bacteria translocated into the mesenteric lymph nodes and showed a trend towards a reduction in indigenous bacteria adhering to jejunal mucosa. These findings could be of relevance in the prevention of septicaemic complications following many clinical conditions, including diarrhoea with malnutrition in children known to have bacteraemic and septicaemic complications. [source] | |||||||||||||