Alternative Therapies for Otitis Media |
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Teresa Binstock Introduction: Comment: Bacteria
associated with otitis media (18, 50, 67): Conclusion: vitamin C in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled, multicenter study. Cohen HA et al. Arch Pediatr Adolesc Med. 2004 Mar;158(3):217-21. [free online] http://archpedi.ama-assn.org/cgi/content/full/158/3/217 OBJECTIVE: To evaluate the effectiveness and safety of a preparation containing echinacea, propolis, and vitamin C in the prevention of respiratory tract infections in children during a 12-week winter period. DESIGN: Randomized, double-blind, placebo-controlled study. SUBJECTS: Four hundred thirty children, aged 1 to 5 years, were randomized to an herbal extract preparation (n = 215) or a placebo elixir (n = 215). INTERVENTION: Administration of an herbal preparation (Chizukit) containing 50 mg/mL of echinacea, 50 mg/mL of propolis, and 10 mg/mL of vitamin C, or placebo (5.0 mL and 7.5 mL twice daily for ages 1 to 3 years and 4 to 5 years, respectively) for 12 weeks. RESULTS: Significant mean ± SD reductions of illnesses were seen in the Chizukit group in the number of illness episodes, 138 vs 308 (55% reduction); number of episodes per child, 0.9 ± 1.1 vs 1.8 ± 1.3 (50% reduction, P<.001); and number of days with fever per child, 2.1 ± 2.9 vs 5.4 ± 4.4) (62% reduction, P<.001). The total number of illness days and duration of individual episodes were also significantly lower in the Chizukit group. Adverse drug reactions were rare, mild, and transient. CONCLUSION: A preventive effect of a product containing echinacea, propolis, and vitamin C on the incidence of respiratory tract infections was observed. 26. Comparison of bee products based on assays of antioxidant capacities. Nakajima Y et al. BMC Complement Altern Med. 2009 Feb 26;9:4. [free online] http://www.biomedcentral.com/1472-6882/9/4 BACKGROUND: Bee products (including propolis, royal jelly, and bee pollen) are popular, traditional health foods. We compared antioxidant effects among water and ethanol extracts of Brazilian green propolis (WEP or EEP), its main constituents, water-soluble royal jelly (RJ), and an ethanol extract of bee pollen. METHODS: The hydrogen peroxide (H2O2)-, superoxide anion (O2.-)-, and hydroxyl radical (HO.)- scavenging capacities of bee products were measured using antioxidant capacity assays that employed the reactive oxygen species (ROS)-sensitive probe 5-(and-6)- chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA) or aminophenyl fluorescein (APF). RESULTS: The rank order of antioxidant potencies was as follows: WEP > EEP > pollen, but neither RJ nor 10-hydroxy-2-decenoic acid (10-HDA) had any effects. Concerning the main constituents of WEP, the rank order of antioxidant effects was: caffeic acid >artepillin C > drupanin, but neither baccharin nor coumaric acid had any effects. The scavenging effects of caffeic acid were as powerful as those of trolox, but stronger than those of N-acetyl cysteine (NAC) or vitamin C. CONCLUSION: On the basis of the present assays, propolis is the most powerful antioxidant of all the bee product examined, and its effect may be partly due to the various caffeic acids it contains. Pollen, too, exhibited strong antioxidant effects. 26b. Cow's milk allergy is associated with recurrent otitis media during childhood. Juntti H et al. Acta Otolaryngol. 1999;119(8):867-73. To determine whether cow's milk allergy (CMA) in infancy is associated with recurrent otitis media (ROM) or other chronic ear infections, we conducted a cohort study by enrolling 56 milk-allergic and 204 control schoolchildren. We also studied the association between ear problems and different atopic manifestations. A higher proportion of children with CMA had had ROM. defined as at least 15 acute otitis media episodes by the age of 10 years (27%, vs 12%, p = 0.009), and had undergone adenoidectomy and or tympanostomy compared with the controls (48%, vs 28%, p = 0.005). However, this was only true of the children who had developed respiratory atopy. Asthma and/or allergic rhinitis, but not atopic dermatitis, posed a significant risk for ROM, while all the three atopic manifestations enhanced the risk for secretory otitis media. Positive skin prick tests with food, but not with inhaled allergens, tended to be associated with ear problems. In conclusion, we found that children with CMA in infancy, even when properly treated, had experienced significantly more ROM, the risk associating with concomitant development of respiratory atopy. 27. Oxidant and antioxidant levels in children with acute otitis media and tonsillitis: a comparative study. Cemek M et al. Int J Pediatr Otorhinolaryngol. 2005 Jun;69(6):823-7. OBJECTIVE: Recurrent episodes of acute otitis media (AOM) and acute tonsillitis (AT) are a common problem in infectious disorders during childhood and are major cause of morbidity in children. The organism maintains defense systems including nonenzymatic antioxidants such as Vitamins A, E and C and reduced glutathione (GSH) against reactive oxygen species (ROS). In the present study, lipid peroxidation status and nonenzymatic antioxidant capacity were investigated in children with AOM and AT. Our aim was to compare the lipid peroxidation and responses of the body's antioxidant status in the closely associated infections such as AOM and acute tonsillitis. METHODS: The study included 23 (14 males, 9 females) children with AOM, 27 (14 males, 13 females) with AT and 29 (16 males, 13 females) healthy control subjects. The ages of the study and control subjects were between 2 and 7 years. Serum beta- carotene, retinol, Vitamin E, Vitamin C, and whole blood malondialdehyde (MDA) (as an indicator of lipid peroxidation) and GSH levels were studied in all subjects. RESULTS: There was a statistically significant difference between the groups for all parameters (P<0.05). All of the antioxidant vitamins such as beta-carotene, retinol, Vitamin E, and Vitamin C levels were observed to be significantly decreased in the both patient groups. Nevertheless, GSH levels were also decreased in the patient groups. MDA levels were found to be higher in children with AOM and AT than in the healthy control subjects. When compared the AOM and AT groups, there was statistically significant difference between the groups for whole blood MDA (P<0.05). 28. Malondialdehyde http://en.wikipedia.org/wiki/Malondialdehyde 29. Complementary and alternative medicine for upper-respiratory-tract infection in children. Carr RR, Nahata MC. Am J Health Syst Pharm. 2006 Jan 1;63(1):33-9. http://www.ajhp.org/cgi/content/full/63/1/33 30. Nutrition and the immune system from birth to old age. Chandra RK. Eur J Clin Nutr. 2002 Aug;56 Suppl 3:S73-6. [free online] http://www.nature.com/ejcn/journal/v56/n3s/abs/1601492a.html For millennia, food has been at the center ff social events, in times of joy and in times of sorrow. Protein-energy malnutrition is associated with a significant impairment of cell-mediated immunity, phagocyte function, complement system, secretory immunoglobulin A antibody concentrations, and cytokine production. Deficiency of single nutrients also results in altered immune response: this is observed even when the deficiency state is relatively mild. Of the micronutrients, zinc, selenium, iron, copper, vitamins A, C, E and B(6), and folic acid have important influences on immune responses. Overnutrition and obesity also reduce immunity. Low-birth-weight infants have a prolonged impairment of cell-mediated immunity that can be partly restored by providing extra amounts of dietary zinc. In the elderly, impaired immunity can be enhanced by modest amounts of a combination of micronutrients. These findings have considerable practical and public health significance. 31. The history of nutrition: malnutrition, infection and immunity. Keusch GT. J Nutr. 2003 Jan;133(1):336S-340S. [free online] http://jn.nutrition.org/cgi/content/full/133/1/336S The relationship between nutritional status and the immune system has been a topic of study for much of the 20th century. Dramatic increases in our understanding of the organization of the immune system and the factors that regulate immune function have demonstrated a remarkable and close concordance between host nutritional status and immunity. This report traces the increasing sophistication of our understanding of these relationships and their impact on susceptibility to infection through six stages to the present time. The cyclical relationship between poor nutrition, increased susceptibility to infectious diseases, leading to immunological dysfunction and metabolic responses that further alter nutritional status is described and, wherever possible, related to physiological mechanisms. In addition, the particular role of Nevin Scrimshaw in guiding the progress over the past 50 y is discussed. 32. Epidemiology of otitis media onset by six months of age. Daly KA et al. Pediatrics. 1999 Jun;103(6 Pt 1):1158-66. http://pediatrics.aappublications.org/cgi/content/full/103/6/1158 OBJECTIVE: Although early otitis media (OM) onset predicts later recurrent and chronic OM, little research has been directed at illuminating the role of prenatal exposures in early OM. This prospective study examined prenatal, innate, and early environmental exposures associated with acute otitis media (AOM) onset and recurrent OM (ROM) by age 6 months. DESIGN AND METHODS: Prospective study of 596 infants from a health maintenance organization followed from birth to 6 months. Mothers completed monthly forms on prenatal exposures (diet, medications, and illnesses) and infant risk factors (eg, smoke exposure and child care) during pregnancy and until infants were 6 months old. Urine samples were collected when infants were 2 months of age and analyzed for cotinine and creatinine. Physicians and nurse practitioners examined infants at each clinic visit and completed standard ear examination forms. RESULTS: Thirty-nine percent had an episode of AOM and 20% had ROM by age 6 months. Using Cox's regression models to control for confounding, respiratory tract infection (relative risk [RR] 7.5), day care (RR 1. 7), >1 sibling (RR 1.4), maternal, paternal, and sibling OM history (RR 1.6, 1.5, and 1.7, respectively) were significantly related to early OM onset. ROM was related to respiratory tract infection (RR 9. 5), day care (RR 1.9), conjunctivitis (RR 2.0), maternal OM history (RR 1.9), and birth in the fall (RR 2.6). Among prenatal exposures, only high prenatal dietary vitamin C intake was significantly inversely related to early AOM with univariate but not multivariate analysis. CONCLUSION: Prenatal factors were not linked to early AOM onset with multivariate analysis, but environmental and innate factors play an important role in early AOM onset. Strategies to reduce exposure to environmental variables could reduce rates of early AOM, which could potentially result in declining rates of ROM and chronic OME. 33. The role of free oxygen radicals on the development of otitis media with effusion. Yariktas M, Doner F, Dogru H, Yasan H, Delibas N. Int J Pediatr Otorhinolaryngol. 2004 Jul;68(7):889-94. OBJECTIVE: The purpose of this study was to determine if free oxygen radicals (FORs) and antioxidant enzyme activities have some role in pathogenesis of otitis media with effusion (OME) in children with adenoid hyperplasia. METHODS: Seventy-four patients were enrolled in three groups of this study. The study group (Group I) included 26 patients who had adenoidectomy with ventilation tube placement due to chronic OME. The control adenoid group (Group II) consisted of 28 age-matched patients who had adenoidectomy without ventilation tube insertion. Twenty children were included in the healthy control group (Group III). Erythrocyte malondialdehyde (MDA) levels, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) enzyme activities were investigated in the venous blood sample. RESULTS: Erythrocyte MDA level and GSH-Px enzyme activity in the blood samples of study group (Group I) were significantly higher than those of Group II and Group III (P < 0.05). SOD enzyme activity in the blood samples of Group I was significantly lower than Group II (P < 0.05), and were significantly higher than Group III (P < 0.05). CAT enzyme activity of Group I was significantly lower than that of Group III (P < 0.05). However, there was no statistically significant difference between Group I and Group II regarding CAT antioxidant enzyme activity (P < 0.05). CONCLUSIONS: The inflammation of the middle ear increases the level of FORs in erythrocyte. FOR level is normally maintained at a steady state by antioxidant enzymes. When the antioxidant defense system is weakened, the increased FORs may contribute to OME formation. We supposed that, antioxidant vitamins C and E, and scavenger enzymes such as CAT, SOD and GSH-Px may be added in the management of OME. 34. The role of oxidants and antioxidants in otitis media with effusion in children. Yilmaz T et al. Otolaryngol Head Neck Surg. 2004 Dec;131(6):797-803. OBJECTIVE: Determine the possible role of oxidants and antioxidants in the pathogenesis of otitis media with effusion in children. STUDY DESIGN AND SETTING: Randomized controlled trial, tertiary referral center. The study group was made up of children with otitis media with effusion who were to undergo bilateral ventilation tube insertion and adenoidectomy. The control group was comprised of otherwise healthy children. The blood levels of antioxidants (retinol, beta- carotene, alpha-tocopherol, laycopene, ascorbic acid, superoxide dismutase, glutathione peroxidase, GSH) and oxidation products (malondialdehyde) were determined before and 1 month after the operation in the study group and once only in the control group. These substances were also measured in the adenoid tissue and middle ear fluids. RESULTS: In the study group, the blood levels of antioxidants and oxidants before and after the operation were significantly different when compared with the control group (P < 0.05). In the study group, the blood antioxidant levels increased and oxidant levels decreased significantly after the operation (P < 0.05). The levels after the operation never reached those of the control group. CONCLUSIONS AND SIGNIFICANCE: Oxidants and antioxidants played a significant role in the pathogenesis of otitis media with effusion in children. These children are under significant oxidative stress. Insertion of a ventilation tube and adenoidectomy significantly decreased the oxidative stress in these patients, but could not normalize it completely. Additional studies are necessary in the clinical use of antioxidants in otitis media with effusion. 35. Exposure to environmental tobacco smoke as a risk factor for recurrent acute otitis media in children under the age of five years. Stenstrom R et al. Int J Pediatr Otorhinolaryngol. 1993 Aug;27(2):127-36. Exposure to environmental tobacco smoke (ETS) has remained a controversial risk factor for otitis media in children. This study evaluates the association between exposure to ETS and recurrent acute otitis media (RAOM) in 85 cases and 85 age and gender matched controls under the age of 5 years. Cases and controls were obtained from outpatient otolaryngology and ophthalmology clinics, respectively, at the Children's Hospital of Eastern Ontario. Cases were defined as having four or more physician documented AOM episodes in the preceding 12 months and controls were otitis free in the prior 12 months. Exposure status was assessed via parental questionnaire. Controlling for other risk factors (via conditional logistic regression), such as daycare attendance, socioeconomic status, prematurity and family history of otitis media, a significant association between ETS and RAOM was evident (odds ratio = 2.68, 95% CI = 1.27-5.65). When categorized, a significant exposure response relationship between increasing level of exposure to ETS and increased risk of RAOM was evident. The population etiologic fraction indicated that up to 34% of RAOM cases may be accounted for by ETS exposure. We conclude that exposure to ETS is an important and modifiable risk factor for RAOM in children under the age of 5 years. 36. Traffic-related air pollution and otitis media. Brauer M et al. Environ Health Perspect. 2006 Sep;114(9):1414-8. [free online] http://www.ehponline.org/members/2006/9089/9089.html BACKGROUND: Otitis media is one of the most common infections in young children. Although exposure to environmental tobacco smoke is a known risk factor associated with otitis media, little information is available regarding the potential association with air pollution. OBJECTIVE: We set out to study the relationship between exposure to traffic-related air pollution and otitis media in two birth cohorts. METHODS: Individual estimates of outdoor concentrations of traffic-related air pollutants-nitrogen dioxide, fine particles [particulate matter with aerodynamic diameters </= 2.5 microm (PM2.5)], and elemental carbon-were calculated for home addresses of approximately 3,700 and 650 infants from birth cohort studies in the Netherlands and Germany, respectively. Air pollution exposure was analyzed in relation to physician diagnosis of otitis media in the first 2 years of life. RESULTS: Odds ratios (adjusted for known major risk factors) for otitis media indicated positive associations with traffic-related air pollutants. An increase in 3 microg/m3 PM2.5, 0.5 microg/m3 elemental carbon, and 10 microg/m3 NO2 was associated with odds ratios of 1.13 (95% confidence interval, 1.00-1.27) , 1.10 (1.00-1.22) , and 1.14 (1.03-1.27) in the Netherlands and 1.24 (0.84-1.83) , 1.10 (0.86-1.41) , and 1.14 (0.87-1.49) in Germany, respectively. CONCLUSIONS: These findings indicate an association between exposure to traffic-related air pollutants and the incidence of otitis media. Given the ubiquitous nature of air pollution exposure and the importance of otitis media to children's health, these findings have significant public health implications. 37. Association of early-onset otitis media in infants and exposure to household mould. Pettigrew MM et al. Paediatr Perinat Epidemiol. 2004 Nov;18(6):441-7. Otitis media is one of the most common infections of early childhood. Children who first experience acute otitis media at an early age (before 6 months) are at increased risk for recurrent otitis media. This prospective study investigated exposure to measured levels of airborne household mould and the risk of early otitis media in the first 6 months of life among a cohort of infants at high risk for asthma. Between September 1996 and December 1998, women were invited to participate if they had at least one other child with physician-diagnosed asthma. Mothers were given a standardised questionnaire within 4 months of their infant's birth. Airborne mould samples were also taken at this time, and culturable fungi were categorised into four levels according to the report of the Commission of European Communities: 0 (undetectable), 1-499 colony forming units (CFU)/m(3) (low), 500-999 CFU/m(3) (medium), > or =1000 CFU/m(3) (high). Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Of the 806 children in the study, 27.8% experienced otitis media before six months of age. Household levels of Penicillium and Cladosporium were modestly associated with the number of otitis media episodes (P = 0.056 and 0.081 respectively). After controlling for potential confounders, Penicillium and Cladosporium were not associated with early otitis media. High levels of 'other' mould (defined as total spore count minus counts for Penicillium, Cladosporium, and yeast) were associated with early otitis media (OR 3.49; 95% CI [1.38, 8.79]). We also found associations between day-care outside of the home and birth during the summer or fall season with early otitis media. This study is suggestive of a relationship between otitis media and mould that warrants further study. 38. Acute otitis media in children: association with day care centers--antibacterial resistance, treatment, and prevention. Greenberg D et al. Paediatr Drugs. 2008;10(2):75-83. Children attending day care centers (DCCs) frequently carry antibacterial-resistant organisms in their nasopharynx, leading to acute otitis media (AOM) that may be refractory to antibacterial treatment. The development and spread of resistant organisms are facilitated in DCCs as a result of the following: (i) large numbers of children; (ii) frequent close person-to-person contact; and (iii) a wide use of antimicrobial medications. Intensive antimicrobial usage provides the selection pressure that favors the emergence of resistant organisms, while DCCs provide an ideal environment for transmission of these organisms... 39. Incidence of acute otitis media and sinusitis complicating upper respiratory tract infection: the effect of age. Revai K et al. Pediatrics. 2007 Jun;119(6):e1408-12. [free online] http://pediatrics.aappublications.org/cgi/reprint/119/6/e1408 Infants and young children are prone to developing upper respiratory tract infections, which often result in bacterial complications such as acute otitis media and sinusitis. We evaluated 623 upper respiratory tract infection episodes in 112 children (6-35 months of age) to determine the proportion of upper respiratory tract infection episodes that result in acute otitis media or sinusitis. Of all upper respiratory tract infections, 30% were complicated by acute otitis media and 8% were complicated by sinusitis. The rate of acute otitis media after upper respiratory tract infection declined with increasing age, whereas the rate of sinusitis after upper respiratory tract infection peaked in the second year of life. Risk for acute otitis media may be reduced substantially by avoiding frequent exposure to respiratory viruses (eg, avoidance of day care attendance) in the first year of life. 40. Oxidative stress http://en.wikipedia.org/wiki/Oxidative_stress 41. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. James SJ et al. Am J Clin Nutr. 2004 Dec;80(6):1611-7. [free online] http://www.ajcn.org/cgi/content/full/80/6/1611 BACKGROUND: Autism is a complex neurodevelopmental disorder that usually presents in early childhood and that is thought to be influenced by genetic and environmental factors. Although abnormal metabolism of methionine and homocysteine has been associated with other neurologic diseases, these pathways have not been evaluated in persons with autism. OBJECTIVE: The purpose of this study was to evaluate plasma concentrations of metabolites in the methionine transmethylation and transsulfuration pathways in children diagnosed with autism. DESIGN: Plasma concentrations of methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), adenosine, homocysteine, cystathionine, cysteine, and oxidized and reduced glutathione were measured in 20 children with autism and in 33 control children. On the basis of the abnormal metabolic profile, a targeted nutritional intervention trial with folinic acid, betaine, and methylcobalamin was initiated in a subset of the autistic children. RESULTS: Relative to the control children, the children with autism had significantly lower baseline plasma concentrations of methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione and significantly higher concentrations of SAH, adenosine, and oxidized glutathione. This metabolic profile is consistent with impaired capacity for methylation (significantly lower ratio of SAM to SAH) and increased oxidative stress (significantly lower redox ratio of reduced glutathione to oxidized glutathione) in children with autism. The intervention trial was effective in normalizing the metabolic imbalance in the autistic children. CONCLUSIONS: An increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism. 42. Oxidative stress in autism. McGinnis WR. Altern Ther Health Med. 2004 Nov-Dec;10(6):22-36. STATEMENT OF PURPOSE: Indirect markers are consistent with greater oxidative stress in autism. They include greater free-radical production, impaired energetics and cholinergics, and higher excitotoxic markers. Brain and gut, both abnormal in autism, are particularly sensitive to oxidative injury. Higher red-cell lipid peroxides and urinary isoprostanes in autism signify greater oxidative damage to biomolecules. A preliminary study found accelerated lipofuscin deposition-- consistent with oxidative injury to autistic brain in cortical areas serving language and communication. Double-blind, placebo-controlled trials of potent antioxidants--vitamin C or carnosine--significantly improved autistic behavior. Benefits from these and other nutritional interventions may be due to reduction of oxidative stress. Understanding the role of oxidative stress may help illuminate the pathophysiology of autism, its environmental and genetic influences, new treatments, and prevention. OBJECTIVES: Upon completion of this article, participants should be able to: 1. Be aware of laboratory and clinical evidence of greater oxidative stress in autism. 2. Understand how gut, brain, nutritional, and toxic status in autism are consistent with greater oxidative stress. 3. Describe how anti-oxidant nutrients are used in the contemporary treatment of autism. 43. Altered vascular phenotype in autism: correlation with oxidative stress. Yao Y et al. Arch Neurol. 2006 Aug;63(8):1161-4. [free online] http://archneur.ama-assn.org/cgi/content/full/63/8/1161 BACKGROUND: Autism is a neurologic disorder characterized by impaired communication and social interaction. Results of previous studies showed biochemical evidence for abnormal platelet reactivity and altered blood flow in children with autism. OBJECTIVE: To evaluate the vascular phenotype in children with autism. DESIGN AND MAIN OUTCOME MEASURES: Urinary levels of isoprostane F(2alpha)-VI, a marker of lipid peroxidation; 2,3-dinor-thromboxane B(2), which reflects platelet activation; and 6- keto-prostaglandin F(1alpha), a marker of endothelium activation, were measured by means of gas chromatography-mass spectrometry in subjects with autism and healthy control subjects. SETTING AND SUBJECTS: Children with a clinical diagnosis of autism attending the Pfeiffer Treatment Center. RESULTS: Compared with controls, children with autism had significantly higher urinary levels of isoprostane F(2alpha)-VI, 2,3-dinor-thromboxane B(2), and 6-keto-prostaglandin F(1alpha). Lipid peroxidation levels directly correlated with both vascular biomarker ratios. CONCLUSION: Besides enhanced oxidative stress, platelet and vascular endothelium activation also could contribute to the development and clinical manifestations of autism. 44. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. James SJ et al. Am J Med Genet B Neuropsychiatr Genet. 2006 Dec 5;141B(8):947-56. [free online] http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2610366&blobtype=pdf Autism is a behaviorally defined neurodevelopmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social withdrawal. Although both genetic and environmental factors are thought to be involved, none have been reproducibly identified. The metabolic phenotype of an individual reflects the influence of endogenous and exogenous factors on genotype. As such, it provides a window through which the interactive impact of genes and environment may be viewed and relevant susceptibility factors identified. Although abnormal methionine metabolism has been associated with other neurologic disorders, these pathways and related polymorphisms have not been evaluated in autistic children. Plasma levels of metabolites in methionine transmethylation and transsulfuration pathways were measured in 80 autistic and 73 control children. In addition, common polymorphic variants known to modulate these metabolic pathways were evaluated in 360 autistic children and 205 controls. The metabolic results indicated that plasma methionine and the ratio of S- adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), an indicator of methylation capacity, were significantly decreased in the autistic children relative to age-matched controls. In addition, plasma levels of cysteine, glutathione, and the ratio of reduced to oxidized glutathione, an indication of antioxidant capacity and redox homeostasis, were significantly decreased. Differences in allele frequency and/or significant gene-gene interactions were found for relevant genes encoding the reduced folate carrier (RFC 80G > A), transcobalamin II (TCN2 776G > C), catechol-O- methyltransferase (COMT 472G > A), methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C), and glutathione-S-transferase (GST M1). We propose that an increased vulnerability to oxidative stress (endogenous or environmental) may contribute to the development and clinical manifestations of autism. (c) 2006 Wiley- Liss, Inc. 45. Lipid profile, fatty acid composition and pro- and anti-oxidant status in pediatric patients with attention-deficit/hyperactivity disorder. Spahis S et al. Prostaglandins Leukot Essent Fatty Acids. 2008 Jul-Aug;79(1-2):47- 53. Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent behavioral disorder in children and the pathophysiology remains obscure. In addition to the pharmacotherapy, which is the primary treatment of ADHD, nutritional intervention may have a significant impact on ADHD symptoms. We studied lipid and lipoprotein profiles, fatty acid (FA) composition, and oxidant-antioxidant status in 37 pediatric ADHD patients and 35 healthy control subjects. Our results show that plasma triacylglycerols and phospholipids were lower, whereas free cholesterol, HDL, and apolipoprotein A-I were higher in ADHD patients compared with controls. The proportion of plasma EPA and DHA was higher, but that of oleic and alpha-linolenic (ALA) acids was lower. As expected from these findings, the proportions of both total saturates and polyunsaturates fatty acids (PUFA) were higher and lower, respectively, in ADHD patients than in controls, which led to a significant decrease in the PUFAs/saturates ratio. On the other hand, the ratios of eicosatrienoic acid to arachidonic acid and of palmitoleic acid to linoleic acid, established indexes of essential fatty acid (EFA) status remained unchanged revealing that EFA did not affect ADHD patients. Similarly, the activity of delta-6 desaturase, estimated by the ratio of 18:2(n-6)/20:4(n-6), was found unaffected, whereas ALA/EPA was diminished. Lessened lipid peroxidation was noted in ADHD subjects as documented by the diminished values of plasma malondialdehyde accompanied by increased concentrations of gamma-tocopherol. In conclusions, significant changes occur in the lipid and lipoprotein profiles, as well as in the oxidant-antioxidant status of ADHD patients, however, the FA distribution does not reflect n-3 FA deficiency. 46. Malondialdehyde levels in adult attention-deficit hyperactivity disorder. Bulut M et al. J Psychiatry Neurosci. 2007 Nov;32(6):435-8.[free online] http://www.cma.ca/multimedia/staticContent/HTML/N0/l2/jpn/vol-32/issue- 6/pdf/pg435.pdf OBJECTIVE: To evaluate the biochemical basis of adult attention-deficit hyperactivity disorder (A-ADHD), we compared lipid peroxidation status in the plasma of A-ADHD patients, and that of control subjects without A-ADHD by quantifying the levels of malondialdehyde (MDA), an end product of fatty acid oxidation. We aimed to examine the association between MDA and A-ADHD. METHOD: The study comprised 20 A- ADHD patients from Gaziantep University Sahinbey Research Hospital Psychiatry Clinic, diagnosed by 2 psychiatrists (H.A.S. and S.S.) according to the Turkish version of the adult ADD/ADHD DSM-IV-Based Diagnostic Screening and Rating Scale, and 21 healthy volunteers. Malondialdehyde levels were measured in plasma samples of both study groups. RESULTS: The mean (standard deviation [SD]) MDA levels in patients (2.44 [0.84] nmol/mL) were significantly higher than those of control subjects (0.36 [0.20] nmol/mL) (t=11.013, df=39, p<0.01). MDA levels were correlated with overall number of criteria met (n=20, p=0.01, Ro=0.56) and total hyperactivity/impulsivity score (n=20, p=0.02, Ro=0.51). CONCLUSION: The fact that MDA levels were increased in A-ADHD could be an indication of increased oxidative stress in this disease. We suggest that such changes may have a pathological role in A-ADHD. This is the first study evaluating the MDA levels in A-ADHD, and our findings may provide a scientific guide for the further clinical enzymologic and biochemical studies on this disorder. 47. Oxidative imbalance in adult attention deficit/hyperactivity disorder. Selek S et al. Biol Psychol. 2008 Oct;79(2):256-9. Epub 2008 Jul 3. OBJECTIVE: There are few studies evaluating the biochemical basis of adult attention deficit/hyperactivity disorder (A-ADHD). In the present study, we evaluated whether nitric oxide (NO), an oxidant, level and superoxide dismutase (SOD), an antioxidant, activity are associated with A-ADHD or not. METHODS: Twenty A-ADHD patients from Gaziantep University Sahinbey Research Hospital, Psychiatry Clinic, diagnosed according to The Turkish version of Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale by two psychiatrists (H.A.S. and S.S.), and twenty-one healthy volunteer controls were included. Blood samples were collected; NO levels and SOD activities were measured. RESULTS: The mean NO levels in patients were significantly higher than those of controls and SOD activity of patients was significantly lower than controls. CONCLUSIONS: Remarkable high levels of oxidant NO, and low SOD activities suggest an oxidative imbalance in A-ADHD. This is the first study evaluating the oxidative metabolism in A-ADHD. 48. Pseudomonas aeruginosa: resistance and therapy. Cunha BA. Semin Respir Infect. 2002 Sep;17(3):231-9. Pseudomonas aeruginosa resistance to antimicrobials is an important therapeutic consideration. Antibiotic resistance to P. aeruginosa may be chromosomally or plasmid mediated. Resistance to P. aeruginosa may also be affected by changes in the cellular membrane or intracellular environment. P. aeruginosa is primarily a nosocomial organism that most commonly colonizes respiratory secretions and urine. The selection of an antipseudomonal antibiotic depends on its inherent in vitro activity and its resistance potential. Anti-P. aeruginosa antibiotics with a high- resistance potential include gentamicin, tobramycin, ciprofloxacin, ceftazidime, and imipenem. Anti-P. aeruginosa antibiotics with a low-resistance potential include amikacin, piperacillin, cefoperazone, cefepime, meropenem, and polymyxin B. 49. Detection of fungal DNA in effusion associated with acute and serous otitis media. Kim EJ et al. Laryngoscope. 2002 Nov;112(11):2037-41. OBJECTIVES/HYPOTHESIS: Routine bacterial and viral cultures of middle ear fluid are often negative, suggesting that other infectious agents may be involved. Because of the similarities between the paranasal sinuses and middle ear space and the recent recognition of fungi as important pathogens in inflammation of the paranasal sinuses, we investigated the potential role of fungi in acute otitis media and serous otitis media using culture and polymerase chain reaction techniques. STUDY DESIGN: Prospective study. METHODS: Middle ear effusions of 29 patients who underwent myringotomy and pressure equalization tube placement for persistent serous otitis media or recurrent acute otitis media were collected. Fungal culture of the effusion samples was performed on potato flake agar. DNA from the effusion was isolated using standard techniques. Polymerase chain reaction, using radiolabeled universal fungus primer for internal transcribed spacer of 5.8s ribosomal DNA, was performed to detect the presence of any fungal DNA in the samples. RESULTS: Culture of middle ear effusions showed no evidence of fungal growth. Polymerase chain reaction analysis was able to detect the constituent ribosomal DNA of a single fungal genome. Fungal DNA was present in 34% of middle ear effusion samples. CONCLUSIONS: Fungal DNA is present in recurrent acute otitis media and serous otitis media suggesting that it may play an etiological role in serous otitis media and acute otitis media. However, additional studies are necessary to delineate the role of fungi in the pathogenesis of otitis media. 50. Microbiologic characteristics of persistent otitis media. Brook I, Gober AE. Arch Otolaryngol Head Neck Surg. 1998 Dec;124(12):1350-2. [free online] http://archotol.ama-assn.org/cgi/content/full/124/12/1350 OBJECTIVE: To identify the pathogens isolated from children with acute otitis media who did not respond to antimicrobial drug therapy. METHODS: Retrospective analysis of cultures obtained by tympanocentesis from 46 children. RESULTS: Organisms were recovered from 34 children (74%), and 43 isolates were recovered from these individuals. The organisms were Streptococcus pneumoniae (16 isolates), Haemophilus influenzae non-type b (12 isolates), Moraxella catarrhalis (5 isolates), Streptococcus pyogenes (5 isolates), Staphylococcus aureus (3 isolates), and Peptostreptococcus species (2 isolates). Resistance to the antimicrobial agent used was found in 27 (63%) of 43 isolates found in 22 patients (48%). Of patients who did not respond to amoxicillin therapy, H influenzae predominated. Streptococcus pneumoniae was recovered from 5 (56%) of 9 of those who did not respond to trimethoprim and sulfamethoxazole therapy, 4 (44%) of 9 patients after azithromycin therapy, 3 (25%) of 12 patients after amoxicillin therapy, and 2 (40%) of 5 patients after cefixime therapy. Streptococcus pyogenes was recovered from 2 (40%) of 5 patients after trimethoprim and sulfamethoxazole therapy and from 2 (40%) of 5 patients after cefixime therapy. CONCLUSIONS: The data illustrate the relation between resistance to antimicrobial drug therapy and failure of patients with otitis media to improve. They also highlight the importance of diagnostic tympanocentesis in establishing the presence of resistant microorganisms. 51. Community factors in the development of antibiotic resistance. Larson E. Annu Rev Public Health. 2007;28:435-47. The global impact of antibiotic resistance is potentially devastating, threatening to set back progress against certain infectious diseases to the pre-antibiotic era. Although most antibiotic-resistant bacteria originally emerged in hospitals, drug- resistant strains are becoming more common in the community. Factors that facilitate the development of resistance within the community can be categorized as behavioral or environmental/policy. Behavioral factors include inappropriate use of antibiotics and ineffective infection control and hygiene practices. Environmental/policy factors include the continued use of antibiotics in agriculture and the lack of new drug development. A multifaceted approach that includes behavioral strategies in the community and the political will to make difficult regulatory decisions will help to minimize the problem of antimicrobial resistance globally. 52. Experimental study of the effect of Astragalus membranaceus against herpes simplex virus type 1 Sun Y, Yang J. [Article in Chinese] Di Yi Jun Yi Da Xue Xue Bao. 2004 Jan;24(1):57-8. OBJECTIVE: To study the inhibitory effects of Astragalus membranaceus on herpes simplex virus type 1(HSV-1). METHODS: In the 2BS cells infected with HSV-1, the antiviral effect of Astragalus membranaceus decoction was investigated by observing the inhibition of HSV-1-induced cytopathic effect in response to treatment with the decoction. RESULTS: The half inhibition concentration (IC50) and minimal inhibition concentration (MIC) of Astragalus membranaceus were 0.98 and 1.95 g/ml respectively, with the therapeutic index (TI) of 128. CONCLUSION: Astragalus membranaceus has obvious HSV-1-inhibiting efficacy and low cytotoxicity. 53. Macrophage activation by polysaccharide isolated from Astragalus membranaceus. Lee KY, Jeon YJ. Int Immunopharmacol. 2005 Jul;5(7-8):1225-33. We show that APS, a polysaccharide isolated from the roots of Astragalus membranaceus, significantly induces nitric oxide (NO) production and inducible NO synthase (iNOS) transcription through the activation of nuclear factor-kappaB/Rel (NF-kappaB/Rel). In vivo administration of APS induced NO production by peritoneal macrophages of B6C3F1 mice. APS also dose-dependently induced the production of NO in isolated mouse peritoneal macrophages and RAW 264.7, a mouse macrophage-like cell line. Moreover, iNOS protein and mRNA transcription were strongly induced by APS in RAW 264.7 cells. To further investigate the mechanism responsible for the induction of iNOS gene expression, we investigated the effect of APS on the activation of transcription factors including NF-kappaB/Rel and Oct, whose binding sites were located in the promoter of iNOS gene. Treatment of RAW 264.7 cells with APS produced strong induction of NF-kappaB/Rel-dependent reporter gene expression, whereas Oct- dependent gene expression was not affected by APS. Nuclear translocation and DNA binding activity of NF-kappaB/Rel was significantly induced by APS. The treatment with NF-kappaB SN50, an inhibitor of NF-kappaB/Rel nuclear translocation, effectively inhibited the activation of NF-kappaB/Rel binding complexes and NO production. In conclusion, we demonstrate that APS stimulates macrophages to express iNOS gene through the activation of NF-kappaB/Rel. 54. Effects of triterpene saponins from Astragalus species on in vitro cytokine release. Yesilada E et al. J Ethnopharmacol. 2005 Jan 4;96(1-2):71-7. Roots of Astragalus species are used to treat leukemia and for wound healing in Turkish folk medicine. In order to evaluate this information, the effect of 13 cycloartane- and 1 oleanan-type triterpene saponins isolated from Turkish species (Astragalus brachypterus, Astragalus cephalotes, Astragalus microcephalus, and Astragalus trojanus), as well as methanol extracts from the roots of three Astragalus species (Astragalus cephalotes, Astragalus oleifolius and Astragalus trojanus) were studied. Cytokine concentrations of interleukins IL-1beta, IL-8 and TNF-alpha after bacterial lipopolysaccharide (LPS) and IL-2, IL-4 and INF-gamma after phorbolacetate (PHA) stimulation were determined using commercial enzyme- linked immunosorbent assay (ELISA) kits. All triterpene saponins tested in the present study showed a prominent IL-2 inducing activity between 35.9% and 139.6%. Among the extracts the highest score was obtained for Astragalus oleifolius (141.2%). Glycosides of 20,24-epoxy and 20,25-epoxy cycloartanes showed higher IL-2 inducing activity than those of acyclic-cycloartane derivatives as well as aglycone of 20,24-epoxy cycloartanes, cycloastrogenol. Especially the activity of Astragaloside VII, a tridesmosidic glycoside of cycloastrogenol, was the most remarkable. The oleanan-type triterpene saponin also showed a prominent IL-2 inducing activity. IL-2 is a cytokine produced by activated T cells, which has shown powerful immunostimulatory and antineoplastic properties. Accordingly, the IL-2 inducing activity of the triterpene saponins might be the mechanism involved in order to explain the immunomodulatory and anticancer effects of Astragalus species. 55. Antimicrobial activity of Uncaria tomentosa against oral human pathogens. Ccahuana-Vasquez RA et al. Braz Oral Res. 2007 Jan-Mar;21(1):46-50. [free online] http://tinyurl.com/dz2h9e Uncaria tomentosa is considered a medicinal plant used over centuries by the peruvian population as an alternative treatment for several diseases. Many microorganisms usually inhabit the human oral cavity and under certain conditions can become etiologic agents of diseases. The aim of the present study was to evaluate the antimicrobial activity of different concentrations of Uncaria tomentosa on different strains of microorganisms isolated from the human oral cavity. Micropulverized Uncaria tomentosa was tested in vitro to determine the minimum inhibitory concentration (MIC) on selected microbial strains. The tested strains were oral clinical isolates of Streptococcus mutans, Staphylococcus spp., Candida albicans, Enterobacteriaceae and Pseudomonas aeruginosa. The tested concentrations of Uncaria tomentosa ranged from 0.25-5% in Müeller-Hinton agar. Three percent Uncaria tomentosa inhibited 8% of Enterobacteriaceae isolates, 52% of S. mutans and 96% of Staphylococcus spp. The tested concentrations did not present inhibitory effect on P. aeruginosa and C. albicans. It could be concluded that micropulverized Uncaria tomentosa presented antimicrobial activity on Enterobacteriaceae, S. mutans and Staphylococcus spp. isolates. 56. Ethnobotany, phytochemistry and pharmacology of Uncaria (Rubiaceae). Heitzman ME et al. Phytochemistry. 2005 Jan;66(1):5-29 The Uncaria genus is an important source of medicinal natural products, particularly alkaloids and triterpenes. The collected information is an attempt to cover the more recent developments in the ethnobotany, pharmacology and phytochemistry of this genus. During the past 20 years, alkaloids, terpenes, quinovic acid glycosides, flavonoids and coumarins have been isolated from Uncaria. Fifty-three novel structures are reported in this review. The species in which the largest number of compounds has been identified is the Peruvian Uncaria tomentosa or 'cat's claw.' Pharmacological studies are described according to cytotoxicity, anti-inflammatory, antiviral, immunostimulation, antioxidant, CNS-related response, vascular, hypotensive, mutagenicity and antibacterial properties. The potential for development of leads from Uncaria continues to grow, particularly in the area of immunomodulatory, anti-inflammatory and vascular-related conditions. The information summarized here is intended to serve as a reference tool to practitioners in the fields of ethnopharmacology and natural products chemistry. 57. Anti-inflammatory activity of two different extracts of Uncaria tomentosa (Rubiaceae). Aguilar JL et al. J Ethnopharmacol. 2002 Jul;81(2):271-6. We assessed in vivo the anti-inflammatory activity of two Cat's claw bark extracts, by comparing a spray-dried hydroalcoholic extract against an aqueous freeze-dried extract, to determine which extract was more effective. We used the carrageenan- induced paw edema model in mice. In addition, to assess the molecular mechanism of action, we determined the inhibition of NF-kappa B through the Electrophoretic Mobility Shift Assay (EMSA) and the effects on cycloxygenase-1 and -2. Results showed that the anti-inflammatory activity was significantly higher using the hydroalcoholic compared with the aqueous extract (P<0.05). The extracts also showed little inhibitory activity on cyclooxygenase-1 and -2. It cannot be excluded that the slight inhibitory activity on DNA binding of NF-kappa B is due to cytotoxic effects. 58. Inhibitory effect of cinnamaldehyde, derived from Cinnamomi cortex, on the growth of influenza A/PR/8 virus in vitro and in vivo. Hayashi K et al. Antiviral Res. 2007 Apr;74(1):1-8. We have investigated the inhibitory effect of trans-cinnamaldehyde (CA), one of the principal constituents of essential oil derived from Cinnamomi cortex, on the growth of influenza A/PR/8 virus in vitro and in vivo. When 1-h drug treatment was initiated at various times post-infection (p.i.) in Madin-Darby canine kidney cells using a fixed dose of CA (40 microM), the maximum inhibitory effect (29.7% virus yield of control) was obtained when drug treatment was started at 3h p.i. Under the same treatment schedule, CA inhibited the virus growth in a dose-dependent manner (20-200 microM), and, at 200 microM, the virus yield was reduced to an undetectable level. RT-PCR and SDS-PAGE analyses showed that CA inhibited viral protein synthesis at the post-transcriptional level. In mice infected with the lung-adapted PR-8 virus, inhalation (50mg/cage/day) and nasal inoculation (250 microg/mouse/day) of CA significantly increased survival rates on the 8 days to 100% and 70%, respectively, in contrast to a survival rate of 20% in the untreated control group. Importantly, inhalation of CA caused virus yield reduction by 1 log in bronchoalveolar lavage fluid on day 6 after infection, compared with that of the untreated control group. These findings might provide further support to the empirical indication of Cinnamomi cortex-containing Kampo medicines for acute respiratory infectious diseases. 59. Antimicrobial activities of cinnamon oil and cinnamaldehyde from the Chinese medicinal herb Cinnamomum cassia Blume. Ooi LS et al. Am J Chin Med. 2006;34(3):511-22. Both Cinnamomum verum J.S. Presl. and Cinnamomum cassia Blume are collectively called Cortex Cinnamonmi for their medicinal cinnamon bark. Cinnamomum verum is more popular elsewhere in the world, whereas C. cassia is a well known traditional Chinese medicine. An analysis of hydro-distilled Chinese cinnamon oil and pure cinnamaldehyde by gas chromatography/mass spectrometry revealed that cinnamaldehyde is the major component comprising 85% in the essential oil and the purity of cinnamaldehyde in use is high (>98%). Both oil and pure cinnamaldehyde of C. cassia were equally effective in inhibiting the growth of various isolates of bacteria including Gram-positive (1 isolate, Staphylococcus aureus), and Gram-negative (7 isolates, E. coli, Enterobacter aerogenes, Proteus vulgaris, Pseudomonas aeruginosa, Vibrio cholerae, Vibrio parahaemolyticus and Samonella typhymurium), and fungi including yeasts (four species of Candida, C. albicans, C. tropicalis, C. glabrata, and C. krusei), filamentous molds (4 isolates, three Aspergillus spp. and one Fusarium sp.) and dermatophytes (three isolates, Microsporum gypseum, Trichophyton rubrum and T. mentagraphytes). Their minimum inhibition concentrations (MIC) as determined by agar dilution method varied only slightly. The MICs of both oil and cinnamaldehyde for bacteria ranged from 75 microg/ml to 600 microg/ml, for yeasts from 100 microg/ml to 450 microg/ml, for filamentous fungi from 75 microg/ml to 150 microg/ml, and for dermatophytes from 18.8 microg/ml to 37.5 microg/ml. The antimicrobial effectiveness of C. cassia oil and its major constituent is comparable and almost equivalent, which suggests that the broad-spectrum antibiotic activities of C. cassia oil are due to cinnamaldehyde. The relationship between structure and function of the main components of cinnamon oil is also discussed. 60. Antibacterial activity of leaf essential oils and their constituents from Cinnamomum osmophloeum. Chang ST, Chen PF, Chang SC. J Ethnopharmacol. 2001 Sep;77(1):123-7. The antibacterial activities of the essential oils from leaves of two Cinnamomum osmophloeum clones (A and B) and their chemical constituents were investigated in this study. The nine strains of bacteria, including Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Salmonella sp., and Vibrio parahemolyticus, were used in the antibacterial tests. Results from the antibacterial tests demonstrated that the indigenous cinnamon B leaf essential oils had an excellent inhibitory effect. The MICs (minimum inhibitory concentrations) of the B leaf oil were 500 microg/ml against both K. pneumoniae and Salmonella sp. and 250 microg/ml against the other seven strains of bacteria. Cinnamaldehyde possessed the strongest antibacterial activity compared to the other constituents of the essential oils. The MICs of cinnamaldehyde against the E. coli, P. aeruginosa, E. faecalis, S. aureus, S. epidermidis, MRSA, K. pneumoniae, Salmonella sp., and V. parahemolyticus were 500, 1000, 250, 250, 250, 250, 1000, 500, and 250 microg/ml, respectively. These results suggest that C. osmophloeum leaf essential oil and cinnamaldehyde are beneficial to human health, having the potential to be used for medical purposes and to be utilized as anti-bacterial additives in making paper products. 61. Antimicrobial effect and resistant regulation of Glycyrrhiza uralensis on methicillin-resistant Staphylococcus aureus. Lee JW et al. Nat Prod Res. 2009;23(2):101-11. In the present study, we investigated antimicrobial activity of Glycyrrhiza uralensis against various strains of methicillin-resistant Staphylococcus aureus (MRSA) (KCCM 11812, 40510, 40512). Glycyrrhiza uralensis was extracted by 80% MeOH and fractionated by organic solutions. The extract and fractions showed antimicrobial activity against standard S. aureus as well as MRSA. In the minimum inhibitory concentration test, G. uralensis showed 0.25 mg mL(-1) in hexane fraction and 0.10-0.12 mg mL(-1) in chloroform fraction. Especially, chloroform fraction showed 2.5 times higher antimicrobial activity than penicillin. Furthermore, chloroform fraction correlated with MRSA gene expression (MecA, MecI, MecRI, FemA). These results suggest that G. uralensis may have potent antimicrobial activity and thus, this medicinal herb can be a suitable phytotherapeutic agent for treating MRSA infections. 62. Antifungal activity of Glycyrrhiza glabra extracts and its active constituent glabridin. Fatima A et al. Phytother Res. 2009 Jan 23. [Epub ahead of print] Glabridin, an active constituent of Glycyrrhiza glabra roots, was found to be active against both yeast and filamentous fungi. Glabridin also showed resistance modifying activity against drug resistant mutants of Candida albicans at a minimum inhibitory concentration of 31.25-250 microg/mL. Although the compound was reported earlier to be active against Candida albicans, but this is the first report of its activity against drug resistant mutants. 63. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Asl MN, Hosseinzadeh H. Phytother Res. 2008 Jun;22(6):709-24. The roots and rhizomes of licorice (Glycyrrhiza) species have long been used worldwide as a herbal medicine and natural sweetener. Licorice root is a traditional medicine used mainly for the treatment of peptic ulcer, hepatitis C, and pulmonary and skin diseases, although clinical and experimental studies suggest that it has several other useful pharmacological properties such as antiinflammatory, antiviral, antimicrobial, antioxidative, anticancer activities, immunomodulatory, hepatoprotective and cardioprotective effects. A large number of components have been isolated from licorice, including triterpene saponins, flavonoids, isoflavonoids and chalcones, with glycyrrhizic acid normally being considered to be the main biologically active component. This review summarizes the phytochemical, pharmacological and pharmacokinetics data, together with the clinical and adverse effects of licorice and its bioactive components. 64. Antiviral effects of Glycyrrhiza species. Fiore C et al. Phytother Res. 2008 Feb;22(2):141-8. Historical sources for the use of Glycyrrhiza species include ancient manuscripts from China, India and Greece. They all mention its use for symptoms of viral respiratory tract infections and hepatitis. Randomized controlled trials confirmed that the Glycyrrhiza glabra derived compound glycyrrhizin and its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In hepatitis C virus- induced cirrhosis the risk of hepatocellular carcinoma was reduced. Animal studies demonstrated a reduction of mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia. In vitro studies revealed antiviral activity against HIV-1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus. Mechanisms for antiviral activity of Glycyrrhiza spp. include reduced transport to the membrane and sialylation of hepatitis B virus surface antigen, reduction of membrane fluidity leading to inhibition of fusion of the viral membrane of HIV-1 with the cell, induction of interferon gamma in T-cells, inhibition of phosphorylating enzymes in vesicular stomatitis virus infection and reduction of viral latency. Future research needs to explore the potency of compounds derived from licorice in prevention and treatment of influenza A virus pneumonia and as an adjuvant treatment in patients infected with HIV resistant to antiretroviral drugs. 65. Antimicrobial activity of commercial Olea europaea (olive) leaf extract. Sudjana AN et al. Int J Antimicrob Agents. 2009 May;33(5):461-3. The aim of this research was to investigate the activity of a commercial extract derived from the leaves of Olea europaea (olive) against a wide range of microorganisms (n=122). Using agar dilution and broth microdilution techniques, olive leaf extract was found to be most active against Campylobacter jejuni, Helicobacter pylori and Staphylococcus aureus [including meticillin-resistant S. aureus (MRSA)], with minimum inhibitory concentrations (MICs) as low as 0.31-0.78% (v/v). In contrast, the extract showed little activity against all other test organisms (n=79), with MICs for most ranging from 6.25% to 50% (v/v). In conclusion, olive leaf extract was not broad-spectrum in action, showing appreciable activity only against H. pylori, C. jejuni, S. aureus and MRSA. Given this specific activity, olive leaf extract may have a role in regulating the composition of the gastric flora by selectively reducing levels of H. pylori and C. jejuni. 66. In vitro antimicrobial activity of olive leaves. Markin D et al. Mycoses. 2003 Apr;46(3-4):132-6. We investigated the antimicrobial effect of olive leaves against bacteria and fungi. The microorganisms tested were inoculated in various concentrations of olive leaf water extract. Olive leaf 0.6% (w/v) water extract killed almost all bacteria tested, within 3 h. Dermatophytes were inhibited by 1.25% (w/v) plant extract following a 3-day exposure whereas Candida albicans was killed following a 24 h incubation in the presence of 15% (w/v) plant extract. Olive leaf extract fractions, obtained by dialysis, that showed antimicrobial activity consisted of particles smaller than 1000 molecular rate cutoffs. Scanning electron microscopic observations of C. albicans, exposed to 40% (w/v) olive leaf extract, showed invaginated and amorphous cells. Escherichia coli cells, subjected to a similar treatment but exposed to only 0.6% (w/v) olive leaf extract showed complete destruction. These findings suggest an antimicrobial potential for olive leaves. 67. Emergence of ciprofloxacin-resistant pseudomonas in pediatric otitis media. Jang CH, Park SY. Int J Pediatr Otorhinolaryngol. 2003 Apr;67(4):313-6. OBJECTIVE: The widespread use of fluoroquinolone otic drops has resulted in the emergence and subsequent increase of fluoroquinolone resistance, at rates greater than anticipated. To evaluate the patients with recurrent otorrhea that were unresponsive to topical ciprofloxacin. METHODS: Seventeen pediatric patients who were treated with refractory otorrhea between 2000 and 2001 were reviewed retrospectively. RESULTS: All patients had ciprofloxacin-resistant pseudomonas on culture and sensitivity test. Ciprofloxacin-resistant pseudomonas from these patients were multidrug resistant. Imipenem was the most sensitive antibiotic agent, followed by amikacin. Most patients were treated with intramuscular amikacin and two patients were treated with intravenous imipenem. CONCLUSION: In our series, resistance to cirpfloxacin in patients with otitis media is increasing recently. Culture and antibiotic sensitivity test may help guide management. Continuous surveillance is necessary to monitor antibiotic resistance and to guide antibacterial therapy. 68. Investigation of functional and morphological changes in Pseudomonas aeruginosa and Staphylococcus aureus cells induced by Origanum compactum essential oil. Bouhdid S et al. J Appl Microbiol. 2009 Feb 16. [Epub ahead of print] Abstract Aims: Evaluation of the cellular effects of Origanum compactum essential oil on Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 29213. Methods and Results: The damage induced by O. compactum essential oil on these two strains has been studied using different techniques: plate count, potassium leakage, flow cytometry (FC) and transmission electron microscopy (TEM). The results showed that oil treatment led to reduction of cells viability and dissipated potassium ion gradients. Flow cytometric analysis showed that oil treatment promoted the accumulation of bis-oxonol and the membrane-impermeable nucleic acid stain propidium iodide (PI), indicating the loss of membrane potential and permeability. The ability to reduce 5-cyano-2,3-ditolyl tetrazolium chloride was inhibited. Unlike in Ps. aeruginosa, membrane potential and membrane permeability in Staph. aureus cells were affected by oil concentration and contact time. Finally, TEM showed various structural effects. Mesosome-like structures were seen in oil-treated Staph. aureus cells whereas in Ps. aeruginosa, coagulated cytoplasmic material and liberation of membrane vesicles were observed, and intracellular material was seen in the surrounding environment. Both FC and TEM revealed that the effects in Ps. aeruginosa were greater than in Staph. aureus. Conclusions: Oregano essential oil induces membrane damage showed by the leakage of potassium and uptake of PI and bis-oxonol. Ultrastructural alterations and the loss of cell viability were observed. Significance and Impact of the Study: Understanding the mode of antibacterial effect of the oil studied is of a great interest in it further application as natural preservative in food or pharmaceutical industries. 69. Effects of oregano, carvacrol and thymol on Staphylococcus aureus and Staphylococcus epidermidis biofilms. Nostro A et al. J Med Microbiol. 2007 Apr;56(Pt 4):519-23. http://jmm.sgmjournals.org/cgi/content/full/56/4/519 The aim of this study was to evaluate the effect of oregano essential oil, carvacrol and thymol on biofilm-grown Staphylococcus aureus and Staphylococcus epidermidis strains, as well as the effects of the oils on biofilm formation. For most of the S. aureus (n=6) and S. epidermidis (n=6) strains tested, the biofilm inhibitory concentration (0.125-0.500 %, v/v, for oregano, and 0.031-0.125 %, v/v, for carvacrol and thymol) and biofilm eradication concentration (0.25-1.0 %, v/v, for oregano and 0.125-0.500 %, v/v, for carvacrol and thymol) values were twofold or fourfold greater than the concentration required to inhibit planktonic growth. Subinhibitory concentrations of the oils attenuated biofilm formation of S. aureus and S. epidermidis strains on polystyrene microtitre plates. 70. Inhibition of Helicobacter pylori and associated urease by oregano and cranberry phytochemical synergies. Lin YT et al. Appl Environ Microbiol. 2005 Dec;71(12):8558-64. [free online] http://aem.asm.org/cgi/content/full/71/12/8558?view=long&pmid=16332847 Ulcer-associated dyspepsia is caused by infection with Helicobacter pylori. H. pylori is linked to a majority of peptic ulcers. Antibiotic treatment does not always inhibit or kill H. pylori with potential for antibiotic resistance. The objective of this study was to determine the potential for using phenolic phytochemical extracts to inhibit H. pylori in a laboratory medium. Our approach involved the development of a specific phenolic profile with optimization of different ratios of extract mixtures from oregano and cranberry. Subsequently, antimicrobial activity and antimicrobial-linked urease inhibition ability were evaluated. The results indicated that the antimicrobial activity was greater in extract mixtures than in individual extracts of each species. The results also indicate that the synergistic contribution of oregano and cranberry phenolics may be more important for inhibition than any species-specific phenolic concentration. Further, based on plate assay, the likely mode of action may be through urease inhibition and disruption of energy production by inhibition of proline dehydrogenase at the plasma membrane. eof
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