A single-arm pilot study of guided self-help treatment based cognitive behavioral therapy for bulimia nervosa in Japanese clinical settings.

OBJECTIVE: Guided self-help treatments based on cognitive behavioral therapy (CBT-GSH) are regarded as a first-line effective treatment for bulimia nervosa (BN). With limited application for CBT-GSH in Japanese clinical settings, we conducted a single arm pilot study in order to confirm the acceptability and availability of CBT-GSH in Japan. RESULTS: 25 women with BN received 16-20 sessions of face-to-face CBT-GSH. Primary outcomes were the completion rate of intervention and abstinence rates from objective bingeing and purging as assessed by the Eating Disorder Examination. Secondary outcomes were other self-report measurements of the frequency of bingeing and purging, and characteristic psychopathologies of eating disorders. Assessments were conducted before CBT as baseline as well as after CBT. 92% (23/25) of the participants completed the CBT sessions. After CBT-GSH, 40% (10/25) of the participants (intention-to-treat) achieved symptom abstinence. The mean binge and purge episodes during the previous 28 days improved from 21.88 to 10.96 (50% reduction) and from 22.44 to 10.88 (52% reduction), each (before CBT-GSH to after CBT-GSH), and the within-group effect sizes were medium (Cohen's d = 0.67, 0.65, each). Our study provided a preliminary evidence about the feasibility of CBT-GSH in Japanese clinical settings for the future. Trial registration This study was registered retrospectively in the national UMIN Clinical Trials Registry on July 10, 2013 (registration ID: UMIN000011120).

Vascular endothelial growth factor in dialysate in relation to intensity of peritoneal inflammation.

BACKGROUND: Peritoneal inflammation may induce changes in peritoneal microvessels, including neoangiogenesis/vasculogenesis, leading to increased peritoneal solute transport rate (PSTR) and loss of ultrafiltration capacity. We hypothesized that an inflammatory reaction in the peritoneal cavity during peritonitis induces increased synthesis of vascular endothelial growth factor (VEGF). We therefore studied the relationship between peritoneal inflammation markers, VEGF, and transport of fluid and solutes in rats during acute peritoneal inflammation induced by lipopolysaccharide (LPS) added to standard glucose-based dialysis solution. METHODS: Under ether anesthesia, male Wistar rats were injected intraperitoneally with 30 mL Dianeal 3.86% without (Control; n=6) or with LPS (microg/mL): 0.001 (LPS 0.001; n=6), 0.01 (LPS 0.01; n=7), 0.1 (LPS 0.1; n=7), 1.0 (LPS 1.0; n=8). After 8 hours, dialysate volume (IPV), peritoneal solute transport rate (PSTR) and dialysate cell count (DCC) were measured and effluent samples were collected. RESULTS: LPS i.p. resulted in increased PSTR and decreased IPV (p<0.005). DCC (cells/microL) and the neutrophil/macrophage ratio were higher for all LPS concentrations compared to the control group. After 8 hours, LPS-exposed rats had significantly higher dialysate levels of all investigated cytokines (TNF-alfa, MCP-1 and IL-10) than the control group. Addition of LPS resulted in increased dialysate VEGF concentrations (pg/mL) (LPS 0.001, 28.2+/-5.9; LPS 0.01, 38.9+/-11.6; LPS 0.1, 43.0+/-5.9; LPS 1.0, 46.6+/-11.3; Control, 14.5+/-9.8; p<0.0005 for all LPS vs. Control). CONCLUSIONS: The infusion of Dianeal 3.86% with different doses of LPS induced a strong acute intraperitoneal inflammatory reaction with increased DCC and cytokine levels, resulting in increased peritoneal solute transport and decreased IPV. LPS induced a dose-dependent parallel increase of the intraperitoneal concentrations of MCP-1, IL-10 and TNF-alfa, as well as of VEGF. These results suggest that intraperitoneal VEGF synthesis is induced in response to inflammation, and that this may be an important component in the process leading to peritoneal transport alterations.

Characterization of the influence of polyol fatty acid esters on the permeation of diclofenac through rat skin.

In this study, we investigated the effect of sefsols on the skin to clarify the mechanism of the sefsol enhancement effect. In vitro percutaneous absorption experiments were performed using Franz diffusion cells. Removal of the stratum corneum and delipidization of the skin increased the permeation of diclofenac from aqueous suspension, with the enhancement effects being similar for both treatments. Further enhancement effects of diclofenac permeation by sefsol through the stripped and delipidized skin were not observed. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was employed to investigate the biophysical changes in the stratum corneum lipids by sefsols. One of the sefsols, propylene glycol mono caprylate (S-218), induced higher and broader absorbance shifts in both asymmetric and symmetric C-H bond stretching regions. However, no significant differences were observed among the sefsols with respect to peak heights and areas for both absorbances when compared with H2O treatment. These results suggest that sefsol may change the lipid-chain fluidity of the stratum corneum without lipid extraction. The accumulated amounts of diclofenac in the skin significantly increased in the presence of sefsol. Also, the amounts of diclofenac in the skin increased with the amount of sefsol in the skin. This sefsol enhancement effect was reversed at 12 h after treatment. Thus, enhancement of the diclofenac flux by sefsols is reversible and may be due to a change in the lipid-chain fluidity of the stratum corneum and improvement in drug partitioning to the stratum corneum.

Influence of pH on the permeability of p-toluidine and aminopyrine through shed snake skin as a model membrane.

The influence of pH on the permeability of p-toluidine (pKa, 5.3) and aminopyrine (pKa, 5.0) through shed snake skin as a model membrane was studied. The pH was adjusted to several values, and the solubility of the drugs in each donor was measured. Flux rates and permeability coefficients were calculated from the steady-state penetration portions. The flux rates of p-toluidine decreased as the pH value in the donor solution increased. On the other hand, the flux rates of aminopyrine were constant at any pH value. The permeability coefficients of each drug increased as the pH value in the donor solution increased. The partition coefficients (octanol/buffer) of each drug were dependent on the molecular fraction of un-ionized species. From these results, it is suggested that ionized species of p-toluidine transports through shed snake skin, but the ionized species of aminopyrine does not.

Improvement of intestinal absorption of macromolecules by nitric oxide donor.

Nitric oxide (NO) is one of the most versatile mediators in mammalian biology. In the present study, we investigated the absorption-enhancing effects of an NO donor, 3-(2-hydroxy-1-methylethyl-2-nitrosohydrazino)-N-methyl-1-propa namine (NOC7), on drugs that are poorly absorbed from the gastrointestinal tract. NOC7 significantly increased the jejunal absorption of fluorescein isothiocyanate dextrans (FDs) of different average molecular weights (4000-20,000). This enhancing effect decreased as the FD molecular weight increased. Another NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), also increased the absorption of FD-4 from the jejunum. The absorption enhancement effect of NOC7 significantly decreased after coadministration with an NO scavenger, 2-(4-carboxyphenyl)-4,4,5, 5-tetramethylimidazole-1-oxyl-3-oxide, sodium salt. Furthermore, the enhancement effect of NOC7 was reversed shortly after cessation of the enhancer treatment. Little damage by NOC7 to the intestinal mucosa was observed in terms of release of lactose dehydrogenase and protein from the intestinal mucosa. NOC7 also increased the absorption of FD-4 by the colon and rectum. The findings suggest that an NO donor can improve the absorption of macromolecules from all regions of the rat intestine with very little mucosal damage and that an NO donor can act as a potent absorption enhancer.

The relationship between lifestyle, social characteristics and obesity in 3-year-old Japanese children.

It has been observed that obese children receive genetic and environmental effects that are associated with them being overweight. With regard to the latter, lifestyles such as eating habits and physical activity have been focused on. In the present study, the social characteristics which would dominate their lifestyles were investigated as background variables. For this purpose, 9668 Japanese children aged three years who were all born in Toyama prefecture, Japan, in 1998, served as birth cohort subjects. For the comparison between obese (Kaup Index; mass in kg/(height in m)2 > or = 18) and nonobese (Kaup index < 18) children, irregular snack intake, physical inactivity and reduced sleeping hours were chosen as statistically significant obesity-related lifestyle indicators for the children. For social characteristics, family construction (expanded family with grandparents/nonexpanded family), main caregiver (mother/other), attending a nursery school (yes/no) and mother's employment (full-time worker/other) were chosen. These were significantly associated with the obesity-related lifestyles mentioned above using multiple logistic regression analysis adjusted for other variables of social characteristics as well as for gender and birth month (July-December/January-June). The two greatest population-attributable risk percentages were observed for mother as main caregiver (-36.5%) and attending a nursery school (-28.9%) for irregular snack intake. Therefore, these two social characteristics substantially reduced the number of children with irregular snack intake. On the other hand, the two social characteristics were reversed in children with reduced sleeping hours (population-attributable risk percentage of mother as main caregiver: 15.4%; attending a nursery school: 17%). In contrast with favourable effects on snack intake these social characteristics showed an adverse influence on the sleeping habits of children.

Molecular mechanisms of promoter regulation of the gp34 gene that is trans-activated by an oncoprotein Tax of human T cell leukemia virus type I.

We investigated the molecular mechanism of transcriptional activation of the gp34 gene by the Tax oncoprotein of human T cell leukemia virus type I (HTLV-I). gp34 is a type II transmembrane molecule belonging to the tumor necrosis factor family and is constitutively expressed on HTLV-I-producing cells but not normal resting T cells. The transcriptional regulatory region of the gp34 gene was activated by HTLV-I Tax in the human T cell line Jurkat, in which endogenous gp34 is induced by Tax. Sequence analysis demonstrated that two NF-kappaB-like elements (1 and 2) were present in the regulatory region. Both NF-kappaB-like elements were able to bind to NF-kappaB or its related factor(s) in a Tax-dependent manner. Chloramphenicol acetyltransferase assays indicated that NF-kappaB-like element 1 was Tax-responsive, although the activity was lower than that the native promoter. NF-kappaB-like element 2 elevated promoter activity when combined with NF-kappaB-like element 1, indicating cooperative function of the elements for maximum promoter function. Unlike typical NF-kappaB elements, the NF-kappaB-like elements in gp34 were not activated by treatment of Jurkat cells with phorbol ester despite induction of the NF-kappaB-like binding activity. Chloramphenicol acetyltransferase reporter assays using the region upstream of the NF-kappaB-like elements identified an upstream region that reduced transcription from cognate and noncognate core promoters in a Tax-independent manner. Our results imply complex regulation of expression of the gp34 gene and suggest implication of gp34 in proliferation of HTLV-I infected T cells.

Serological and histological features of anti-HCV-positive individuals without serum HCV RNA.

Antibody to hepatitis C virus (anti-HCV) in patients who are negative for HCV RNA in serum may indicate a memory of past infection of HCV. However, their clinical features have not been well understood. Fourteen anti-HCV-positive but HCV RNA-negative individuals were examined for serological and histological features. As a result, it was found that they had only antibody to HCV core antigen C22-3 with or without antibody to nonstructural viral antigen C33c on a recombinant immunoblot assay (RIBA), and that an concentration of anti-C22 was low. Liver biopsy showed two having no evidence of an obvious hepatic injury, two having a minimal change, and two having portal fibrosis. HCV RNA was not found in the liver. These results corroborate an idea that the anti-HCV in HCV RNA-negative individuals implies a past infection of HCV. Furthermore, it is suggested that a combination of an appearance pattern of antibody to HCV antigens on RIBA and anti-C22 titer are an useful marker to distinguish anti-HCV-positive individuals without viremia from those with viremia.

Impaired response of gastric vessels to prostaglandin E2 in rats with persistent obstructive jaundice.

We investigated the response of gastric vessels to prostaglandin (PG) E2 after intra-duodenal release of bile in rats with obstructive jaundice. The animals were divided in four groups according to duration of bile duct obstruction (BDO): control and 1 week (W), 2W, and 3W groups. Prolonged BDO decreased gastric mucosal blood flow (BF) significantly. The BF recovered after the release of BDO in the 1W and 2W groups, but not in the 3W group. BDO decreased PGE2 content in gastric mucosa in the 1W, 2W, and 3W groups. PGE2 decreased vascular perfusion pressure of the isolated stomach in the control and 2W groups, but not in the 3W group. The response of gastric vessels to PGE2 was poor in the 3W group compared with the control and 2W groups. Decreased PGE2 in the gastric mucosa and decreased response of gastric vessels to PGE2 may affect gastric blood flow in obstructive jaundice.

Preventive effect of whey hydrolysate formulas for mothers and infants against allergy development in infants for the first 2 years.

We studied the preventive effect against allergies in infants who and whose mothers consumed hypoallergenic formulas until 6 months after birth. Mother and infant pairs were divided into three groups, and the infants were monitored for the development of allergies for the first 2 years. In the MD group (n = 102; n = number of infants), the mothers were given a hypoallergenic formula for mothers (MOM HA), which contained hydrolyzed whey protein as the only protein source, as a substitution for cow's milk during late pregnancy and lactation. In the CD group (n = 127), the mothers were given cow's milk during the corresponding period. All infants in the MD and CD groups were exclusively breast-fed or mixed-fed with breast milk and hypoallergenic infant formula (NAN HA), which contains the same hydrolyzed protein as MOM HA. In the AF group (n = 54), the mothers consumed MOM HA and their infants were mixed-fed with breast milk and a cow's milk-based adopted infant formula during the corresponding period. In the MD group, no infants were positive to cow's milk-specific immunoglobulin E (RAST) at 4 months of age, in contrast to 6% and 3% of infants in the CD and AF groups, respectively. The infants in the MD group showed low incidence of various allergies, especially of eczema, as compared to the CD and AF groups. These results suggest that consumption of cow's milk by mothers and cow's milk-based formula feeding to infants elevate the risk of allergies in infants, and that consumption of hypoallergenic formula for pregnant and lactating women and for infants could be helpful in preventing allergy development in infants.

An analysis of spatiotemporal variability during prehension movements: effects of object size and distance.

Human prehension movements have been studied with regard to the parallel processing of motor control and sensorimotor coordination. Temporal aspects of the movement (e.g., onset time and duration) have been studied extensively, while spatial aspects have not been studied systematically. Thus, the purpose of this study was to examine spatiotemporal variability of the transport (wrist trajectory) and grasp (grip aperture between the index finger and the thumb) components. In this experiment, the extrinsic (e.g., distance) and intrinsic object properties (e.g., object size) were manipulated. Subjects were required to pick up an aluminum cylinder as quickly and accurately as possible using the index finger and the thumb. It was found that object size significantly affected both transport and grasp components. Distance mainly affected the transport component. These kinematic results were consistent with the findings of earlier studies. Furthermore, the distribution of mean within-subject variability across normalized movement time for the transport component was not the same as that of the grasp component, suggesting that the different motor control processes exist. The peak amplitudes in variability of the wrist trajectory and the grip aperture were obtained at similar points throughout movement time. Furthermore, the peak of wrist variability depended on distance not object size, while that of aperture variability depended on both distance and object size. These results strongly support the hypothesis that the grasp component is adjusted using dynamic information provided from the transport component as the wrist moves toward the object. We also found that wrist variability converged to the target point, while aperture variability was biphasic: it converged, at least, around the point of maximum aperture in the first phase and then remained constant in the second phase. This result suggests that the two components are under different control processes. We hypothesize that the transport component can be modeled as a single feedforward system, while the grasp component can be divided into two separate mechanisms.

Helicobacter pylori may cause "reflux" gastritis after gastrectomy.

Patients with "reflux" gastritis after gastrectomy suffer from a variety of symptoms, and this type of gastritis may sometimes compromise the quality of life of these patients. Since Helicobacter pylori is considered to be one of the most important pathogenetic factors in gastritis, the association between H. pylori and reflux gastritis was investigated in this study. A total of 145 patients with gastrectomy were entered into the study. Five biopsy specimens from the gastric remnant were taken at upper gastrointestinal endoscopy. One specimen was examined pathohistologically, and the remaining four were examined for H. pylori infection. Fifty-two patients (36%) demonstrated H. pylori infection. The prevalence of H. pylori was significantly higher in patients who had a partial gastrectomy, and it was significantly lower in patients who had undergone gastrectomy more than 4 years previously. The histologic gastritis score in patients with H. pylori infection was significantly higher. Furthermore, H. pylori was eradicated in patients with some symptoms of gastritis and no bile reflux to the residual stomach at endoscopy; in these patients the symptoms were relieved and the histologic gastritis score decreased significantly. In conclusion, possible involvement of H. pylori is suspected in the pathogenesis of "nonreflux" gastritis after gastrectomy.

Etiological involvement of Helicobacter pylori in "reflux" gastritis after gastrectomy.

OBJECTIVES: "Reflux" gastritis after gastrectomy is associated with various symptoms that are often detrimental to the patients' quality of life. However, prevention of the reflux does not always bring relief from the symptoms of gastritis. Helicobacter pylori (H. pylori) is now considered one of the most important pathogenetic factors in gastritis. The association between H. pylori infection and reflux gastritis after gastrectomy was investigated in the present study. METHODS: In total, 115 patients who had undergone gastrectomy were entered in this study. Five biopsy specimens from the gastric remnant were taken during upper GI endoscopy. One specimen was examined pathohistologically, and the remaining four were examined for H. pylori infection. The histological degree of gastritis was determined according to the score system of Rauws et al. RESULTS: Forty-six patients (40%) demonstrated H. pylori infection in their stomachs. The prevalence of the infection was significantly higher in patients with conventional gastrectomy than in those with subtotal gastrectomy. The prevalence of H. pylori infection was significantly lower in patients who had undergone gastrectomy more than 4 yr ago. The histological gastritis score in patients with H. pylori infection was significantly higher than in those without H. pylori infection. Furthermore, the eradication of H. pylori in patients with both serious gastritis symptoms and no bile reflux improved the symptoms and significantly decreased the histological gastritis score. CONCLUSIONS: The results suggest that H. pylori is a factor in the pathogenesis of reflux gastritis after gastrectomy.

Ramification patterns of the nerves innervating the forearm extensors in mammals and reptiles.

This paper discusses muscle phylogeny based on muscle innervation and defends a new concept of nerve-muscle specificity. Some researchers argued strongly against this concept in the first half of this century. However, we think their arguments were partially based on insufficiently examined findings of the ramification manner of the radial nerve. We have dissected 140 limbs of 25 species in mammals and reptiles to examine the manners of ramification of nerves supplying the forearm extensors. The pattern of the radial nerve has been revealed to consist of consistent and inconsistent elements. The branches to the forearm extensors except for the supinator follow quite consistent patterns, while the branch(es) to the muscle is much less consistent. Comparing the ramification patterns of the nerves between mammals and lizards, it can be concluded that the radial nerve in mammals is formed by the phylogenetic path alteration of its partial nerve fibers from the pathway along the flexor side in lizards to the route in the extensor side.

[Residual gastritis after gastrectomy and Helicobacter pylori--its clinical significance].

Residual gastritis after gastrectomy brings the various symptoms such as abdominal pain, nausea, emesis and loss of appetite, and often hazards quality of life of the patient. Bile reflux to the stomach is believed as one of the important pathogenesis of residual gastritis, however the prevention for bile reflux cannot always heal the gastritis. Helicobacter pylori (H. pylori) is considered as one of the most important pathogenesis of gastroduodenal ulcer and gastritis, and H. pylori may possibly cause residual gastritis after gastrectomy. However, the association between infection with H. pylori and the residual gastritis has not revealed yet. In the present study, the association with H. pylori and the residual gastritis after gastrectomy was investigated in 56 patients who had undergone gastrectomy before. Twenty-four patients (42.9%) had H. pylori infection at their stomachs and the incidence of the infection in the patients with gastrectomy was significantly higher with subtotal gastrectomy. As for the histological gastritis score of Rauws (Rauws' score), Rauws' score of H. pylori positive group was significantly higher than H. pylori negative group. Furthermore, the eradication of H. pylori for the patients with serious symptoms of gastritis improved the symptoms and decreased significantly Rauws' score. These results suggest that H. pylori was associated with the pathogenesis of residual gastritis after gastrectomy.

Changes of serum hepatitis C virus levels in patients with chronic hepatitis C treated with two courses of interferon administration.

To assess the efficacy of repeated interferon (IFN) administration in patients with chronic hepatitis C unresponsive to initial therapy, serum hepatitis C virus (HCV)-RNA levels were measured in 12 patients who had failed prior IFN therapy. Serum HCV-RNA was assayed by measuring DNA complementary to HCV-RNA using a quantitative reverse transcription-polymerase chain reaction assay. The mean total dose of IFN was 227.8 mega-units for first treatment and 270.7 mega-units for second treatment. Five responders with a normal alanine aminotransferase (ALT) concentration (less than 40 IU/liter) at the end of the first treatment also had a normal ALT concentration at the end of the second treatment. By contrast, all nonresponders with an elevated ALT concentration during the first treatment likewise had an elevated ALT concentration at the end of the second treatment. HCV-RNA levels before the first treatment varied from 10(6) to 10(8) copies/microliters. The serum HCV-RNA levels fell in 9 out of 10 patients after the first treatment and in 11 out of 12 patients after the second treatment. One patient had unchanged normal serum ALT levels after two courses of IFN treatment. These results suggested that the outcome of a second course of IFN treatment was similar biochemically and virologically to a first course, and that patients who did not respond initially seldom respond to additional IFN therapy. Therefore, readministration of IFN should be restricted to patients who respond biochemically and virologically to initial treatment. The optimal second dose shall be determined with further studies.

Two cases of porphyria cutanea tarda associated with chronic hepatitis positive for the antibody against hepatitis C virus.

We report two cases of porphyria cutanea tarda (PCT) positive for the antibody against hepatitis C virus (anti-HCV). The serological and histological examinations revealed that they were persistently infected with HCV and were suffering from liver disease compatible with chronic viral hepatitis. It is suggested that one of the factors which contribute to liver damage of patients with PCT may be HCV infection. It now may be advisable to examine anti-HCV in PCT patients with liver disease.