Growth of Japanese breastfed infants compared to national references and World Health Organization growth standards.

AIM: The aim of this study was to compare the growth of Japanese infants that were exclusively breastfed to those of national references and World Health Organization (WHO) standards. METHODS: Mothers, who delivered a normal term baby and had been exclusively breastfeeding for at least 4 months, were enrolled. The lengths, body weights and head circumferences of 647 children, aged 0-24 months, were obtained and compared to national references and WHO standards. RESULTS: Comparisons of the national references for both length and body weight indicated that breastfed infants were significantly shorter and lighter almost throughout the first 24 months. Conversely, head circumferences of breastfed infants were significantly larger at 1 and 6 months of age in boys and 6 months in girls. Compared to WHO standards, similar trends to the comparisons with national references were found. CONCLUSION: There were significant differences identified between the growth of breastfed infants and existing national references and WHO standards.

Association of Daily Physical Activity with Disability in Community-Dwelling Older Adults With/Without Chronic Kidney Disease.

OBJECTIVES: Physical activity is recommended for disability prevention in the older adult population; however, the level of physical activity required for older adults with chronic kidney disease (CKD) remains unknown. This study aimed to examine the associations between daily physical activity and disability incidence in older adults with and without CKD to determine relevant daily physical activity levels. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: 3,786 community-dwelling older adults aged ≥65 years. MEASUREMENTS: Mean daily times spent in light- (LPA) and moderate-to-vigorous physical activity (MVPA) were measured using triaxial accelerometers. CKD was defined by a creatinine estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Disability incidence was identified as long-term care insurance certification during a 60-month follow-up period. Associations between physical activity and disability incidence were examined using Cox proportional hazard models stratified by the CKD status. Non-linear and linear associations were tested using the restricted cubic spline. RESULTS: A total of 1,054 individuals were identified to have CKD. Disability incidence was higher in the CKD group than in the non-CKD group. The adjusted cox proportional hazard models indicated that a 10-minute increase in MVPA time was associated with lower disability incidence in the non-CKD group (hazard ratio [HR], 0.838; 95% confidence interval [CI]: 0.764-0.918) and the CKD group (HR, 0.859; 95% CI: 0.766-0.960). Linear associations were observed in MVPA for the non-CKD and CKD groups. CONCLUSION: Increasing MVPA was associated with lower disability incidence in older adults with and without CKD. These findings can help devise disability prevention strategies for older CKD patients.

Quantitative reverse transcription-PCR assay for the rapid detection of methicillin-resistant Staphylococcus aureus.

AIM: To evaluate a new quantitative reverse transcription-PCR (qRT-PCR) assay for the rapid detection of methicillin-resistant Staphylococcus aureus (MRSA). METHODS AND RESULTS: Primers for Staphylococcus-specific regions of 16S rRNA gene, spa gene and mecA gene were newly designed. RNAs extracted from broth-cultured strains were tested by qRT-PCR targeting each primer, and the bacterial counts obtained correlated well with those counted by the plating method with detection limits of 10(0), 10(1) and 10(2) CFU. The qRT-PCR assay targeting the 16S rRNA was 6430-fold or more sensitive than qPCR assay. All Staph. aureus strains tested were detected and none of the other Staphylococcus species and genus strains tested cross-reacted with the assay targeting the spa gene. All MRSAs tested were detected by the assay targeting the mecA gene. Clinical samples, faecal material and bronchial washout solutions were tested by our assay, and MRSAs were detected with a high sensitivity within 6 h. CONCLUSION: Our qRT-PCR assay targeting three new primers to the target genes is a rapid and sensitive tool for the detection of MRSA directly from clinical samples. SIGNIFICANCE AND IMPACT OF THE STUDY: Because of its sensitivity and rapidity, our qRT-PCR assay is considered to be a valuable tool for clinical management.

Rates and determinants of antibiotics and probiotics prescription to children in Asia-Pacific countries.

Antibiotic therapy may have important side effects. Guidelines recommend the administration of specific probiotics to reduce the risk of antibiotic-associated diarrhoea (AAD). The rates and determinants of antibiotics and co-prescription of probiotics in children remain poorly known in Asia-Pacific countries, which are very heterogenous in terms of economic development, health care organization and health policies. A survey among general practitioners (GPs) and paediatricians was performed in seven countries of the Asia-Pacific area (Australia, Japan, Indonesia, India, China, Singapore, and South Korea). Physicians completed an online questionnaire that explored their current habits and the determinants for prescribing antibiotics and probiotics. For the 731 physicians who completed the questionnaire (390 paediatricians and 341 GPs), 37% of all consultations for a child led to the prescription of antibiotics (ranging from 17% in Australia to 47% in India). A large majority of physicians (84%) agreed that antibiotics disrupted gut microbiota and considered probiotics an effective intervention to prevent AAD (68%). However, only 33% co-prescribed probiotics with antibiotics (ranging from 13% in Japan to 60% in South Korea). The main reasons for prescribing probiotics were previous episodes of AAD (61%), presence of diarrhoea (55%), prolonged antibiotic treatment (54%) or amoxicillin-clavulanic acid therapy (54%). Although current local guidelines recommend the use of selected probiotics in children receiving antibiotics in Asia-Pacific area, the rates of antibiotics and probiotics prescription significantly vary among countries and are deeply affected by country-related cultural and organisational issues.

Is single-daily low-dose cyclosporine therapy really effective in children with idiopathic frequent-relapsing nephrotic syndrome?

BACKGROUND: A recent study on renal transplant patients has shown that a single dose of cyclosporine (CsA) has added the advantage of decreasing dosages and adverse effects, while maintaining graft function. However, the efficacy of this regimen in children with idiopathic frequent-relapsing nephrotic syndrome (NS) remains controversial. METHODS: 20 children with steroid-dependent NS or CsA-dependent NS (18 with minimal change disease, MCD and 2 with focal segmental glomerulosclerosis, FSGS) were enrolled in this prospective study. CsA was commenced at 1.5 â 2 mg/kg, given as a single daily dose before breakfast, and the dose was adjusted to reach 2 hours post-dose CsA levels (C2) of 600 - 800 ng/ml. RESULTS: In 9 out of 18 patients with MCD, treatment with single-daily CsA for a median of 13 months (range 7 - 21) resulted in a reduction of mean minimum prednisolone (PSL) dose from 1.1 A+/- 0.55 to 0.04 A+/- 0.09 mg/kg on alternate days (p < 0.01), and the median relapse rate from 1.3 (1.1 - 2.5) to 0 (0 - 0.2) episodes/6 months (p < 0.01). Of them, PSL could be weaned off in 7 patients (4 of 6 with steroid-dependent NS, only 3 of 14 with CsA-dependent NS) without relapse of NS while on this therapy. However, 11 out of 20 were considered to have treatment failure: 1 with steroid-dependent NS and 10 with CsA-dependent NS. In 2 patients having FSGS, this method showed no beneficial effects. In 18 patients with MCD, relapse free ratio on single-daily CsA therapy was significantly higher in patients whose average C2 levels were greater than 700 ng/ml (p < 0.05). CONCLUSIONS: Our experience demonstrates that single-daily low-dose CsA therapy maintaining C2 levels greater than 700 ng/ml may be effective in children with steroid-dependent NS or MCD, with no relapse. In contrast, the usefulness of this regimen in children with CsA-dependent NS appears to be limited.

Plasma levels of active ghrelin until 8 weeks after birth in preterm infants: relationship with anthropometric and biochemical measures.

This study investigated the relationship between plasma levels of ghrelin and postnatal growth in preterm infants. The levels of active ghrelin in cord blood and in plasma in 25 very low birthweight (VLBW) infants were measured. The results indicate that the levels of circulating active ghrelin markedly increases after birth in VLBW infants, and suggest that the increased levels of ghrelin reflects the maturation of ghrelin production in the stomach and an increased physiological need for ghrelin.

The effects of the Lactobacillus casei strain on obesity in children: a pilot study.

There are few data regarding the role of probiotics as a dietary intervention in the management of obesity in children. An open prospective examination was conducted to clarify the effects of Lactobacillus casei strain Shirota (LcS)-containing beverages in obese children. We compared the intestinal microbiota and organic acid levels between 12 obese (average age, 10.8 years; body mass index (BMI) Z score, 2.7±1.7) and 22 control children(average age, 8.5 years; BMI Z score, 0.1±0.7), and pre- and post-intervention in the obese children. The obese group underwent diet and exercise therapy for 6 months and then were given an LcS beverage daily for another 6 months and the body weight and serological markers were monitored. Significant reductions in the faecal concentrations of Bifidobacterium (obese group, 7.9±1.5 vs non-obese group, 9.8±0.5 Log10cells/g; P<0.01) along with a significant decline in the Bacteroides fragilis group, Atopobium cluster and Lactobacillus gasseri subgroup, and acetic acid (obese group, 45.1±16.9 vs non-obese group, 57.9±17.6 µmol/g; P<0.05) were observed in the obese group at baseline. A significant decline in body weight (-2.9±4.6%; P<0.05) and an elevation in the high density lipoprotein cholesterol level (+11.1±17.6%; P<0.05) were observed 6 months after ingestion of the LcS beverage compared to baseline. Furthermore, a significant increase in the faecal concentration of Bifidobacterium (7.0±1.2 before ingestion vs 9.1±1.2 Log10cells/g after ingestion; P<0.01) and an apparent increase in the acetic acid concentration (7.0±1.2 before ingestion vs 9.1±1.2 Log10cells/g after ingestion; P<0.01) were observed 6 months after ingestion. LcS contributed to weight loss while also improving the lipid metabolism in obese children via a significant increase in the faecal Bifidobacterium numbers and the acetic acid concentration.

Gut dysbiosis following C-section instigates higher colonisation of toxigenic Clostridium perfringens in infants.

Herein we investigated the intestinal carriage of α-toxigenic and enterotoxigenic Clostridium perfringens during infancy, focusing on its association with other gut microbes and mode of delivery and feeding. Faecal samples from 89 healthy term infants were collected at age 7 days, 1 month, 3 months, 6 months and 3 years. C. perfringens was quantified by qPCR; other gut bacteria were quantified by reverse-transcription-qPCR. Alpha-toxigenic C. perfringens was detected in 3.4% infants at day 7 but was present in 35-40% infants at subsequent time-points, with counts ranging from 103-107 cells/g faeces. Enterotoxigenic C. perfringens remained undetected at day 7 but was detected in 1.1, 4.5, 10.1 and 4.5% infants at 1 month, 3 months, 6 months and 3 years, respectively. Intriguingly, infants carrying α-toxigenic C. perfringens had lower levels of Bacteroides fragilis group, bifidobacteria, lactobacilli and organic acids as compared to non-carriers. Further analyses revealed that, compared to vaginally-born infants, caesarean-born infants had higher carriage of C. perfringens and lower levels of B. fragilis group, bifidobacteria, lactobacilli and faecal organic acids during first 6 months. Compared to formula-fed infants, breast-fed infants were slightly less often colonised with C. perfringens; and within caesarean-born infants, breast-fed infants had slightly lower levels of C. perfringens and higher levels of B. fragilis group, bifidobacteria, and lactobacilli than formula-fed infants. This study demonstrates the quantitative dynamics of toxigenic C. perfringens colonisation in infants during the early years of life. Caesarean-born infants acquire a somewhat perturbed microbiota, and breast-feeding might be helpful in ameliorating this dysbiosis. Higher carriage of toxigenic C. perfringens in healthy infants is intriguing and warrants further investigation of its sources and clinical significance in infants, particularly the caesarean-born who may represent a potential reservoir of this opportunistic pathogen and might be more prone to associated illnesses.

Gut microbiota in health and disease: an overview focused on metabolic inflammation.

In concern to the continuously rising global prevalence of obesity, diabetes and associated diseases, novel preventive and therapeutic approaches are urgently required. However, to explore and develop such innovative strategies, a meticulous comprehension of the biological basis of these diseases is extremely important. Past decade has witnessed an enormous amount of research investigation and advancement in the field of obesity, diabetes and metabolic syndrome, with the gut microbiota receiving a special focus in the triangle of nutrition, health and diseases. In particular, the role of gut microbiota in health and diseases has been one of the most vigorous and intriguing field of recent research; however, much still remains to be elucidated about its precise role in host metabolism and immune functions and its implication in the onset, progression as well as in the amelioration of metabolic ailments. Recent investigations have suggested a significant contribution of the gut microbiota in the regulation and impairment of energy homeostasis, thereby causing metabolic disorders, such as metabolic endotoxemia, insulin resistance and type 2 diabetes. Numerous inflammatory biomarkers have been found to be associated with obesity, diabetes and risk of other associated adverse outcomes, thereby suggesting that a persistent low-grade inflammatory response is a potential risk factor. In this milieu, this review intends to discuss potential evidences supporting the disturbance of the gut microbiota balance and the intestinal barrier permeability as a potential triggering factor for systemic inflammation in the onset and progression of obesity, type 2 diabetes and metabolic syndrome.

cDNA cloning and chromosomal mapping of the gene encoding adenylate kinase 2 from Drosophila melanogaster.

As a step toward understanding of the role of adenylate kinase (AK) in energy metabolism, we analyzed this enzyme in Drosophila melanogaster. The enzyme activities of all three AK isozymes were determined in cell-free extracts of flies, and their proteins were detected by Western blot analysis using polyclonal antibodies against the mammalian isozymes. A cDNA encoding adenylate kinase was isolated from D. melanogaster cDNA library. The cDNA encodes a 240-amino acid protein, which shows high similarity to bovine, human and rat AK2, and hence was named DAK2. Preliminary subcellular fractionation analysis indicated that DAK2 is localized in both cytoplasm and mitochondria. In situ hybridization to salivary gland polytene chromosomes revealed that the Dak2 gene is located at 60B on the right arm of the second chromosome.

Acute effect of nasal CPAP on periodic limb movements associated with breathing disorders during sleep.

Sleep-disordered breathing is commonly associated with periodic limb movements (PLMS). Nasal continuous positive airway pressure (nCPAP) is the most widely used treatment for sleep-disordered breathing. However, it is not clear whether nCPAP treatment of apnea also has a systematic effect on PLMS. We studied 15 patients with sleep-disordered breathing and PLMS in a split-night protocol in order to confirm the acute effects of nCPAP on PLMS. Although the PLMS index (PLMSI) did not change statistically (baseline, 38.7 +/- 20.5; CPAP, 31.3 +/- 17.0; p = ns), the PLMS-related index (PLMS-ArI) decreased significantly on nCPAP (baseline, 17.8 +/- 10.1; CPAP, 9.2 +/- 5.7; p < 0.05). Whether the reduced PLMS-ArI is sustained with chronic nCPAP is unknown and a matter of future investigation.

Nocturnal oximetry: is it a screening tool for sleep disorders?

The objective of this study was to examine the usefulness of home oximetry for the screening of sleep disorders presenting with excessive daytime sleepiness (EDS). This was accomplished by blinded comparison of diagnosis by oximetry alone versus polysomnographic diagnosis carried out at a sleep disorders center at a tertiary referral hospital. This study included three hundred patients who had been referred because of EDS and suspected sleep apnea. A number of measurements were made. The arterial oxygen saturation (SaO2) data were sampled at 2 Hz and stored digitally during polysomnography (PSG). From the SaO2 data recorded onto paper six scorers calculated the number of desaturations > 3% per hour (desaturation index: DI) and then made a diagnosis [normal, DI < 5; mild obstructive sleep apnea (OSA), 5 < DI < 20; moderate OSA, 20 < DI < 40; severe OSA, DI > 40]. Upper airway resistance syndrome (UARS) was diagnosed when DI was < 5 but associated with small fluctuations in SaO2. The diagnosis made by each of six scorers was compared to the clinical diagnosis made independently using PSG. Thirty-one (10.3%) of all the records were rejected by scorers because of inadequate SaO2 signals requiring technologist intervention. Sensitivity of screening for sleep-breathing disorders was 90.0% and specificity was 75.0%. All moderate and severe OSA patients were detected by oximetry. However, among the 66 patients who were classified as normal by oximetry, 1 had mild OSA, 20 had UARS, 9 had periodic limb movements in sleep, 4 had narcolepsy and 2 had a parasomnia. In conclusion, home oximetry may not have sufficient sensitivity and specificity to detect breathing disorders reliably during sleep and is useless for other disorders of sleep.

A familial awake movement disorder mimicking restless legs in a sleep apnea patient.

We report on a patient with sleep apnea and an unusual familial movement disorder. The movements were present only during wakefulness and nocturnal arousals caused by disordered breathing. A 27-year-old obese man was referred with sleep onset insomnia, symptoms suggesting restless legs syndrome, daytime sleepiness, loud snoring and awakening with choking sensations. He was proven to have obstructive sleep apnea (apnea hypopnea index = 60.6). He also had a daytime movement disorder that was characterized by almost continuous stereotypic tapping of one or both legs. The movements were suppressible and not associated with any unpleasant or abnormal leg sensation. Virtually identical movements were present in three generations of his family. The severity of the movements did not worsen late in the day or with supine posturing. The nocturnal movements, consisting of a visible shaking of one or both legs, occurred only during arousals secondary to the apnea, had a mean duration of 5.7 +/- 3.0 (standard deviation) seconds and could not be defined as periodic limb movements in sleep (PLMS). Successful treatment of apnea by nasal continuous positive airway pressure dramatically reduced the movements during sleep (from 88.2 to 1.9 per hour). The clinical significance and the mechanism of this movement disorder is unknown. We discuss the features inconsistent with restless legs syndrome and consider other possible phenomenology, including akathisia. We conclude that this patient may have a previously unreported familial movement disorder and in addition developed the sleep apnea syndrome related to obesity.

CPAP titration for sleep apnea using a split-night protocol.

We studied 107 patients with sleep-disordered breathing to confirm the effectiveness of continuous positive airway pressure (CPAP) titration using a split-night protocol. Patients spent two consecutive nights in our laboratory with complete polysomnography. On the first night, we applied a split-night protocol; the first half of the night was used as a baseline (B), and after a diagnosis was made, CPAP was applied during the second half of the night (SN). On the second night (2N), patients spent the entire night on CPAP to confirm the effectiveness of CPAP treatment. The SN and 2N both revealed a significant reduction in arousal index (37.8 +/- 27.9 on B, 13.2 +/- 12.1 on SN, 11.4 +/- 8.0 on 2N, values are mean +/- SD, p < 0.001), apnea hypopnea index (AHI) (23.6 +/- 26.3/h on B, 3.0 +/- 3.7/h on SN, 2.4 +/- 2.6/h on 2N, p < 0.001), percent total sleep time below 90% SaO2 (21.0 +/- 27.2% on B, 8.2 +/- 13.8% on SN, 4.9 +/- 10.2% on 2N, p < 0.001), and percent total sleep time below 80% SaO2 (1.1 +/- 3.8% on B, 0.0 +/- 0.1% on SN, 0.1 +/- 0.5% on 2N, p < 0.001). There were no significant differences between the SN and the 2N for these measurements. Final CPAP pressure was significantly lower at the end of the SN when compared with the 2N (8.8 +/- 2.7 cm H2O on SN, vs 10.3 +/- 2.8 cm H2O on 2N, p < 0.001). When patients were divided into three groups (AHI < 20, n = 69; 20 < AHI < 40, n = 18; AHI > 40, n = 20), the final CPAP pressure was different only in the group with AHI < 20 (8.1 +/- 2.3 cm H2O on SN, 9.6 +/- 2.3 cm H2O on 2N, p < 0.001). We conclude that a split-night protocol may be sufficient to determine the effective CPAP pressure, especially in patients with an AHI > 20.

The effect of nasal CPAP on nocturnal reflux in patients with aperistaltic esophagus.

It has been shown that nasal continuous positive airway pressure (nasal CPAP) significantly reduces nocturnal reflux both in patients with sleep apnea and in patients without sleep apnea but consistent abnormal nocturnal reflux. The mechanism by which CPAP is thought to reduce reflux includes the elevation of the resting lower esophageal sphincter (LES) pressure. In this study, we tested the effect of nasal CPAP in two groups of patients with aperistaltic esophagus but with different resting LES pressure. Seven patients with scleroderma esophagus and six patients treated for achalasia were tested over a 48-h period. On the first night, the patients were untreated; on the second night, both groups received applied nasal CPAP at 8 cm H2O pressure. The percentage of time the pH < 4.0, the number of reflux events > 5 min, and the length of the longest reflux event were all significantly reduced in the patients with achalasia (p < 0.03), but not in the scleroderma group (p > 0.20). These results suggest that a residual resting LES pressure greater than that demonstrated by patients with scleroderma (> 10 mm Hg) may be necessary for nasal CPAP to affect nocturnal reflux.

The effects of posture change and continuous positive airway pressure on cardiac natriuretic peptides in congestive heart failure.

We studied changes in the peripheral plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in seven patients with congestive heart failure (CHF) during four 1-h protocols during which patients maintained either an upright or a supine posture with or without nasal continuous positive airway pressure therapy (N-CPAP) at a pressure of 10 cm H2O (FIO2 = 0.21). The mean plasma ANP concentration of patients increased significantly from baseline at the end of 1 h of recumbency (65.9 +/- 5.8 to 82.6 +/- 8.3 pg/mL (mean +/- standard error); p < 0.05). This increase was prevented by concomitant N-CPAP therapy (72.1 +/- 8.0 to 61.0 +/- 8.8 pg/mL; p = NS). The mean level of ANP decreased significantly (71.9 +/- 9.0 to 62.5 +/- 8.0 pg/mL; p < 0.05) while patients simply maintained an upright posture. A significant reduction was also observed when patients remained upright with accompanying N-CPAP (72.6 +/- 10.9 to 54.6 +/- 4.3 pg/mL; p < 0.05). There were no significant changes observed in the mean level of BNP for any of the protocols undertaken. We conclude that in patients with chronic CHF, (1) an increase in ANP concentration occurs with recumbency, and this can be prevented by N-CPAP therapy; (2) a decrease in ANP occurs with maintenance of an upright posture, and that this reduction may be augmented by N-CPAP; and (3) no net change in BNP concentration occurs with either posture change or N-CPAP.

Assay of serum immunoreactive trypsin in dried blood spots and the early detection of cystic fibrosis.

Immunoreactive trypsin (IRT) content in blood spots from 17 cystic fibrosis (CF) children born between 1975-80 were assayed with reagents from two commercial radioimmunoassay kits. The manufacturers' procedures were modified to allow assay of blood spot IRT. Half of the CF samples had a significantly raised IRT content compared to normal blood spots. Of the blood spots from five children whose meconium screening gave negative results, three or five (depending on the kit used) had a raised IRT content. On the other hand, less than 50% of children initially detected by meconium screening had raised blood spot IRT values. In our hands, analysis of blood spots for IRT does not consistently identify the newborn with CF and offers no advantage over other screening methods.

Fatty acid and prostaglandin metabolism in children with diabetes mellitus. II. The effect of evening primrose oil supplementation on serum fatty acid and plasma prostaglandin levels.

Our previous study demonstrated that levels of dihomo-gamma-linolenic acid (DGLA) and arachidonic acid in serum total lipids decreased in association with increased plasma levels of prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) in patients with insulin-dependent diabetes mellitus. In this study, 11 children with insulin-dependent diabetes mellitus completed a double-blind, placebo-controlled study to assess the effect of dietary supplementation with gamma-linolenic acid (GLA) on serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. GLA was given as the seed oil from the evening primrose (EPO) and all patients received either EPO capsules (containing 45 mg of GLA and 360 mg of linoleic acid) or indistinguishable placebo capsules for 8 months. Initially patients took 2 capsules daily for 4 months then 4 capsules daily for a further 4 months. All patients were assessed at the start of the study, after 4 months and at the end of the study, by measuring serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. After administration of 4 capsules daily the DGLA levels increased and PGE2 levels decreased significantly (p less than 0.01) in the EPO compared with the placebo group. Neither fatty acid nor PGE2 and PGF2 alpha levels were altered by administration of 2 EPO capsules daily. This suggests that the altered essential fatty acid and PG metabolism in diabetes may be reversed by direct GLA supplementation.

Inhibitory effects of azelastine and tranilast on leukotriene B4 and leukotriene C4 generation by rat colonic mucosa.

Anti-allergic drugs such as sodium cromoglycate are known to be effective for the treatment of ulcerative colitis (UC). Because leukotriene (LT) production is considered to play an important role in the pathophysiology of UC, we examined the effect of the anti-allergic drugs, azelastine and tranilast, and the 5-lipoxygenase inhibitor, AA861, on LTB4 and LTC4 production by isolated rat colonic mucosa treated with the calcium ionophore, A23187. Preincubation of colonic mucosa with AA861 (10(-4) M) or azelastine (10(-4) M) significantly reduced AA23187-induced LTB4 (p < 0.01 and p < 0.05, respectively) and LTC4 (p < 0.01) production. Pretreatment with tranilast (10(-3) M) also significantly reduced A23187-induced LTC4 production (p < 0.05). These findings suggest that azelastine and tranilast can inhibit LT production in colonic mucosa and may be beneficial in the treatment of patients with UC.

Effects of n-3 polyunsaturated fatty acids on dermatitis in NC/Nga mice.

The administration of n-3 polyunsaturated fatty acids (PUFAs) is known to be effective against allergic diseases by suppressing the production of eicosanoids derived from arachidonic acid. To investigate the mechanisms and efficacy of n-3 PUFA treatment in patients with atopic dermatitis (AD), we administered four different formulas of alpha-linolenic acid for 6 weeks in an AD model using NC/Nga mice. According to the doses of alpha-linolenic acid given, the levels of alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid in the red blood cell membranes increased while the levels of linoleic acid and arachidonic acid decreased. However, there was no significant difference among the four dose groups in clinical skin severity score, histopathological findings of skin lesions, or levels of total plasma IgE. Moreover, there was no significant difference in the production of leukotriene B(4) and Leukotriene C(4) from skin lesions after stimulation with A23187 among the groups, although the production of prostaglandin E(2) (PGE(2)) was significantly reduced and skin blood flow in the ear was significantly higher in the group given the highest dose of alpha-linolenic acid. Our results suggest that the administration of alpha-linolenic acid can change the fatty acid composition, PGE(2) production, and skin blood flow but may not prevent the development of dermatitis in NC/Nga mice.