Global parental leave in surgical careers: differences according to gender, geographical regions and surgical career stages.

BACKGROUND: There is a lack of information regarding the provision of parental leave for surgical careers. This survey study aims to evaluate the experience of maternity/paternity leave and views on work-life balance globally. METHODS: A 55-item online survey in 24 languages was distributed via social media as per CHERRIES guideline from February to March 2020. It explored parental leave entitlements, attitude towards leave taking, financial impact, time spent with children and compatibility of parenthood with surgical career. RESULTS: Of the 1393 (male : female, 514 : 829) respondents from 65 countries, there were 479 medical students, 349 surgical trainees and 513 consultants. Consultants had less than the recommended duration of maternity leave (43.8 versus 29.1 per cent), no paid maternity (8.3 versus 3.2 per cent) or paternity leave (19.3 versus 11.0 per cent) compared with trainees. Females were less likely to have children than males (36.8 versus 45.6 per cent, P = 0.010) and were more often told surgery is incompatible with parenthood (80.2 versus 59.5 per cent, P < 0.001). Males spent less than 20 per cent of their salary on childcare and fewer than 30 hours/week with their children. More than half (59.2 per cent) of medical students did not believe a surgical career allowed work-life balance. CONCLUSION: Surgeons across the globe had inadequate parental leave. Significant gender disparity was seen in multiple aspects.

Application and outcomes of a standardized lymphadenectomy in laparoscopic right hemicolectomy requiring ligation of the middle colic artery.

BACKGROUND: Complete mesocolic excision with central vessel ligation may be important for accurate staging and improving the prognosis of right-sided colon cancer. Although the procedure is often performed laparoscopically, approaching the middle colic artery (MCA) is technically demanding, especially when complete ligation of arteries at their roots is desired. We standardized our laparoscopic approach by establishing the dissection boundary along the superior mesenteric artery to achieve D3 lymphadenectomy in the region of the MCA. The aim of the present study was to evaluate, on the basis of perioperative and short-term oncologic outcomes, the feasibility and safety of our technique METHODS: We conducted a retrospective study on consecutive patients with cancer located at the ascending colon and transverse colon who had laparoscopic right hemicolectomy requiring ligation of the MCA. RESULTS: There were 41 patients (22 males, median age 71 years [range 49-86] years). The median operation time was 285 min, and blood loss volume was 40 mL. Conversion to open surgery was required in 1 case. Complications that were Clavien-Dindo grade III or above occurred in 3 patients (7.3%). There was no anastomotic leakage. The median number of lymph nodes harvested was 46. CONCLUSIONS: Our technique was shown to be a safe, feasible, and useful strategy for performance of right hemicolectomy requiring ligation of the MCA in cases of colon cancer. The technique facilitates maximal lymph node dissection. Having obtained favorable outcomes, we look forward to investigation into long-term outcomes.

Trends in the serovar and antimicrobial resistance in clinical isolates of Salmonella enterica from cattle and pigs between 2002 and 2016 in Japan.

AIMS: Given the significance of Salmonella enterica in both human and animal health, and a recent global dissemination of Salmonella 4,[5],12:i:-, changes in the prevalent serovars and antimicrobial resistance in clinical isolates of Salmonella from cattle and pigs were investigated in Japan. METHODS AND RESULTS: The serovars and antimicrobial susceptibilities of 1605 Salmonella enterica isolated from cattle (n = 894) and swine (n = 711) between 2002 and 2016 were examined. The most common serovar among all samples was Salmonella Typhimurium. However, its monophasic variant with antigenic structure S. 4,[5],12:i:-, which was first detected in cattle in 2006 and swine in 2010, has been rapidly increasing in incidence and resistance. Resistance rates to cefotaxime and ciprofloxacin were generally low (<10% in the cattle isolates and <5% in the swine isolates); however, isolates resistant to more than five antimicrobials, which often include these antimicrobials, were recently detected in Salmonella Dublin, S. 4,[5],12:i:-, S. Typhimurium, Salmonella Newport, Salmonella Choleraesuis and Salmonella 6,7:c:-. Among them, two S. 4,[5],12:i:- isolates possessed extended-spectrum ß-lactamase-encoding genes; blaSHV-12 or blaCTX-M-55 , respectively, while all the five S. Typhimurium isolates possessed AmpC-type ß-lactamase gene of blaCMY-2 . CONCLUSIONS: S. 4,[5],12:i:- has been rapidly increasing and exhibiting a remarkable change in antimicrobial resistance in Japan. Considering certain serovars are characterized by multidrug resistance including medically important antimicrobials, continuous monitoring and appropriate measures are required to protect public health and veterinary husbandry. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents a trend in the serovars and antimicrobial resistance in clinical isolates of Salmonella from cattle and pigs in Japan, and showed that there were certain types of Salmonella serovars depending on the animal origin which needs more attention.

Centrifugal lipodystrophy of the scalp manifesting as centrifugal lipodystrophic alopecia.

Centrifugal lipodystrophy (CLD), characterized by a depressed lesion in the abdominal skin, is a chronic disease occurring more often among younger patients of East Asian descent. We present an extremely unusual case of CLD of the scalp associated with reversible hair loss. The patient demonstrated alopecia in the frontal, temporal and occipital areas of the scalp, which connected to form a ring-shaped area of hair loss. Curiously, the area of hair loss gradually expanded outwards while the central region showed normal hair regrowth. Immunohistochemical analysis demonstrated reduced expression of leptin, an adipokine capable of inducing the anagen phase of the hair cycle, in the adipose tissue, associated with active inflammation. By contrast, recovery of leptin expression was observed at sites of healed inflammatory lesions, suggesting that reversible hair loss might be caused by a change in leptin expression in adipose tissue.

Photophysical, amplified spontaneous emission and charge transport properties of oligofluorene derivatives in thin films.

We investigate the photophysical and amplified spontaneous emission properties of a series of monodisperse solution-processable oligofluorenes functionalized with hexyl chains at the C9 position of each fluorene unit. Thin films of these oligofluorenes are then used in organic field-effect transistors and their charge transport properties are examined. We have particularly focused our attention on the influence of oligofluorene length on the absorption and steady-state fluorescence spectra, on the HOMO/LUMO energy levels, on the photoluminescence lifetime and quantum yield as well as on the amplified spontaneous emission properties and the charge carrier mobilities. Differential scanning calorimetry and X-ray diffraction measurements demonstrate that, among all oligofluorene derivatives used in this study, only the structure and morphology of the pentafluorene film is significantly modified by a thermal treatment above the glass transition temperature, resulting in a 9 nm blue-shift of the fluorescence spectrum without significant changes in the photoluminescence quantum yield and in the amplified spontaneous emission threshold. In parallel, hole field-effect mobility is significantly increased from 8.6 × 10(-7) to 3.8 × 10(-5) cm(2) V(-1) s(-1) upon thermal treatment, due to an increase of crystallinity. This study provides useful insights into the morphological control of oligofluorene thin films and how it affects their photophysical and charge transport properties. Moreover, we provide evidence that, because of the low threshold, the tunability of the amplified spontaneous emission and the photostability of the films, these oligofluorenes are promising candidates for organic solid-state laser applications.

Electronic excited states of a strongly correlated organic radical 1,3,5-trithia-2,4,6-triazapentalenyl (TTTA) adsorbed on a Si(001) surface.

Electronic excited states of a strongly correlated organic radical, 1,3,5-trithia-2,4,6-triazapentalenyl (TTTA), adsorbed on a Si(001) surface were investigated by means of two-photon photoemission spectroscopy (2PPE) to elucidate the functional organic thin-film formation on a typical semiconductor substrate. The spectra were interpreted with the aid of density functional theoretical calculations. The unpaired electron of TTTA forms a covalent bond with the dangling bond of the Si-dimer initially, and there are resonant states of TTTA to Si near the surface. The molecules adsorbed at room temperature form dimers having diamagnetic properties at thicknesses of a few monolayers, while the paramagnetic phase appears at multilayer thickness. From the change in the work function, the orientation of the adsorbed TTTA molecules was determined to change depending on the thickness of the adsorbed layer.

Exciton diffusion in near-infrared absorbing solution-processed organic thin films.

We report on singlet-singlet annihilation and exciton diffusion in as-prepared p-type and annealed n-type thin films of the low-bandgap quinoidal quaterthiophene [QQT(CN)4] using ultrafast transient absorption measurements. The decay dynamics of exciton populations are well described by a one-dimensional diffusion-limited bimolecular recombination, indicating that the singlet excitons migrate preferentially along the stacking direction. Our results show that the exciton diffusion constants in QQT(CN)4 films do not vary significantly upon thermal annealing. Exciton diffusion lengths are measured to be as high as 4 and 5 nm in as-prepared and annealed QQT(CN)4 films, respectively. We also observe an influence of the excitation densities on the singlet exciton diffusion, which is attributed to phonon scattering. Because of the possibility of patterning p-n regions in QQT(CN)4 films by thermal nanolithography techniques, this study provides important insight not only into the photophysical properties of quinoidal oligothiophene derivatives but also for their future integration into high-performance p-n nanostructured near infrared light-sensing devices.

Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation.

The composite structure of the mammalian skull, which forms predominantly via intramembranous ossification, requires precise pre- and post-natal growth regulation of individual calvarial elements. Disturbances of this process frequently cause severe clinical manifestations in humans. Enhanced DNA binding by a mutant MSX2 homeodomain results in a gain of function and produces craniosynostosis in humans. Here we show that Msx2-deficient mice have defects of skull ossification and persistent calvarial foramen. This phenotype results from defective proliferation of osteoprogenitors at the osteogenic front during calvarial morphogenesis, and closely resembles that associated with human MSX2 haploinsufficiency in parietal foramina (PFM). Msx2-/- mice also have defects in endochondral bone formation. In the axial and appendicular skeleton, post-natal deficits in Pth/Pthrp receptor (Pthr) signalling and in expression of marker genes for bone differentiation indicate that Msx2 is required for both chondrogenesis and osteogenesis. Consistent with phenotypes associated with PFM, Msx2-mutant mice also display defective tooth, hair follicle and mammary gland development, and seizures, the latter accompanied by abnormal development of the cerebellum. Most Msx2-mutant phenotypes, including calvarial defects, are enhanced by genetic combination with Msx1 loss of function, indicating that Msx gene dosage can modify expression of the PFM phenotype. Our results provide a developmental basis for PFM and demonstrate that Msx2 is essential at multiple sites during organogenesis.

Counting-backward test for executive function in idiopathic normal pressure hydrocephalus.

OBJECTIVES: The aim of this study was to develop and validate a bedside test for executive function in patients with idiopathic normal pressure hydrocephalus (INPH). MATERIALS AND METHODS: Twenty consecutive patients with INPH and 20 patients with Alzheimer's disease (AD) were enrolled in this study. We developed the counting-backward test for evaluating executive function in patients with INPH. Two indices that are considered to be reflective of the attention deficits and response suppression underlying executive dysfunction in INPH were calculated: the first-error score and the reverse-effect index. Performance on both the counting-backward test and standard neuropsychological tests for executive function was assessed in INPH and AD patients. RESULTS: The first-error score, reverse-effect index and the scores from the standard neuropsychological tests for executive function were significantly lower for individuals in the INPH group than in the AD group. The two indices for the counting-backward test in the INPH group were strongly correlated with the total scores for Frontal Assessment Battery and Phonemic Verbal Fluency. The first-error score was also significantly correlated with the error rate of the Stroop colour-word test and the score of the go/no-go test. In addition, we found that the first-error score highly distinguished patients with INPH from those with AD using these tests. CONCLUSION: The counting-backward test is useful for evaluating executive dysfunction in INPH and for differentiating between INPH and AD patients. In particular, the first-error score may reflect deficits in the response suppression related to executive dysfunction in INPH.

Structures and immunolocalization of Na+, K+ -ATPase, Na+ /H+ exchanger 3 and vacuolar-type H+ -ATPase in the gills of blennies (Teleostei: Blenniidae) inhabiting rocky intertidal areas.

The structure and immunolocalization of the ion transporters Na(+) ,K(+) -ATPase (NKA), Na(+) /H(+) exchanger (NHE3) and vacuolar-type H(+) -ATPase (VHA) were examined in the gills of teleosts of the family Blenniidae, which inhabit rocky shores with vertical zonation in subtropical seas. These features were compared among the following species with different ecologies: the amphibious rockskipper blenny Andamia tetradactylus, the intertidal white-finned blenny Praealticus tanegasimae and the purely marine yaeyama blenny Ecsenius yaeyamaensis. Light and electron microscopic observations indicated that thick gill filaments were arranged close to each other and alternately on two hemibranches of a gill arch in the opercular space of A. tetradactylus. Many mucous cells (MC) and mitochondrion-rich cells (MRC) were present in the interlamellar regions of the gill filament. An immunohistochemical study demonstrated that numerous NKA, NHE3 and some VHA were located predominantly on presumed MRCs of gill filaments and at the base of the lamellae. Analyses using serial (mirror image) sections of the gills indicated that only a few NKA immunoreactive cells (IRC) were colocalized with VHA on some MRCs in the filaments. In the gills of P. tanegasimae, NKA- and NHE3-IRCs were observed in the interlamellar region of the filaments and at the base of the lamellae. VHA-IRCs were located sparsely on the lamellae and filaments. In the gills of E. yaeyamaensis, the lamellae and filaments were thin and straight, respectively. MCs were located at the tip as well as found scattered in the interlamellar region of gill filaments. NKA-, NHE3- and VHA-IRCs were moderately frequently observed in the filaments and rarely on the lamellae. This study shows that the structure and distribution of ion transporters in the gills differ among the three blennid species, presumably reflecting their different ecologies.

Formaldehyde measurements in residential indoor air using a developed sensor element in the Kanto area of Japan.

UNLABELLED: We undertook this to determine the formaldehyde concentration in Japanese houses and the relationship between formaldehyde levels and the age and temperature of a house using a sensor element that we developed for time-integrated measurements of formaldehyde concentration in actual environments. We evaluated the correlation between the formaldehyde concentration estimated by the dinitrophenylhydrazine (DNPH)-derivatization method and that obtained with our sensor element. We found a linear relationship between the two results indicating that reliable measurements can be performed using the developed sensor element in actual environments. The indoor concentration of formaldehyde was determined in a study of 34 homes in the Kanto area of Japan, between September 28 and October 27, 2007. We obtained the highest formaldehyde concentrations of 92 ± 15 µg/m(3) for apartments 0-2 years after their renovation, and a simple linear relationship was found between formaldehyde concentration and the age of the apartment. We also found that the formaldehyde concentration in a room containing furniture increased by 10% when the temperature increased by 1°C. PRACTICAL IMPLICATIONS: This study contributed to the measurements of indoor formaldehyde levels. We have used a newly developed sensor for time-integrated measurements of formaldehyde concentrations. This sensor does not need a power supply during exposure to air, and does not need special skills to use. This research showed that homeowners successfully deployed the sensor at the desired place and desired period in their house by themselves. Formaldehyde is emitted by various off-gassing sources, such as furniture. Therefore, for example, homeowners may want to measure the change of formaldehyde levels in their house before and after installing new furniture. This sensor may also be deployed by occupants to reduce the cost of a large-scale exposure assessment study.

Bacillus cereus nosocomial infection from reused towels in Japan.

It was noticed that there was an increase in Bacillus cereus nosocomial infections in the summer from 2000 to 2005. In 2005, five bloodstream infections occurred in five patients related to catheter use. The causative strains were distinct from each other and belonged to novel multilocus sequence types (ST): ST365, ST366, ST367 and ST368. Two ST365 strains from two patients were further distinguished by pulsed-field gel electrophoresis. B. cereus contamination was observed with reused (dried and steamed) towels (>10(6)cfu/towel) and washing machines in hospital linen rooms. B. cereus strains from towels belonged to ST167, ST365, ST380 and ST382, and a proportion of these were the same, or similar, to strains from patients. All the hospital strains of B. cereus were distinct from those from food-poisoning strains (ST26, ST142, ST381). Ciprofloxacin resistance was observed only in hospital strains. Neither emetic toxin nor cytotoxin K gene, usually present in food poisoning strains, were found in the hospital strains, except for one patient isolate. The data suggest that specific B. cereus strains are circulating within a hospital, with genotypes, antibiotic susceptibilities and virulence gene patterns generally distinct from those of food poisoning, and that in Japan, towels are an important source of contamination, especially in summer.

Induction of Regulatory CD4+ Cells and Prolongation of Fully Major Histocompatibility Complex Mismatched Murine Cardiac Allograft by Shigyakusan.

Shigyakusan (also known as Tsumura Japan [TJ]-35) is composed of peony, bitter orange, licorice, and Bupleuri radix is used for cholecystitis and gastritis as an anti-inflammatory agent. We investigated the effect of TJ-35 on alloimmune response in a murine heart transplantation model. CBA mice that underwent transplantation of a C57BL/6 (B6) heart were assigned to four groups: no treatment, TJ-35-exposed, each component-exposed, or each component missing-exposed. The four groups above each received oral administration of TJ-35, each component, or TJ-35 with each component missing from the day of transplantation until 7 days, respectively. Untreated CBA recipients rejected B6 cardiac grafts acutely (median survival time [MST], 7 days). TJ-35-exposed CBA recipients had significantly prolonged B6 allograft survival (MST, 20.5 days). However, MSTs of CBA recipients that had been administered each component and TJ-35 with each component missing did not reach that of TJ-35-exposed recipients. Adoptive transfer of CD4+ splenocytes from TJ-35-exposed primary allograft recipients resulted in significant prolonged allograft survival in naïve secondary recipients (MST, 63 days). Flow cytometry studies showed that the percentage of CD4+CD25+Foxp3+ cell population was increased in TJ-35-exposed CBA recipients. In conclusion, TJ-35-induced prolongation of fully allogeneic cardiac allografts and may generate regulatory CD4+CD25+Foxp3+ cells in our model. The effect seemed to require all components of TJ-35.

Rikkunshito (TJ-43) Improved Reduction of Food Intake in a Murine Cardiac Transplantation Model.

Rikkunshito (TJ-43), an eight-component traditional Japanese herbal medicine, has been used in clinics for gastritis, vomiting, and appetite loss. We investigated the effects of TJ-43 on the amelioration of appetite loss in the surgical-exposed model of murine cardiac allograft transplantation. CBA mice underwent transplantation of a CBA (syngeneic group) or C57BL/6 heart (allogeneic group) and received oral administration of 2 g/kg/d of TJ-43 from the day of transplantation until 7 days afterward. The amount of food intake (FI) and weight change after operation were recorded from 1 to 28 postoperative days. The allogeneic group had less average amounts of FI for 1 week compared with the syngeneic group (FI was 1.90 ± 0.43 g and 2.66 ± 0.46 g, respectively). Average FIs between the syngeneic and allogeneic groups with TJ-43 for 1 week were 2.36 ± 0.44 g and 2.30 ± 0.13 g, respectively, and those with distilled water were 2.66 ± 0.46 g and 1.90 ± 0.43 g, respectively, suggesting that exposure with TJ-43 tended to ameliorate the reduction of FI. Similarly, the effect on the amelioration of average FI in syngeneic and allogeneic groups exposed for 2 weeks was confirmed. However, exposure to with TJ-43 had no effects on FI after 4 weeks. TJ-43 could prevent reduction of average FI induced by the surgical-exposed model of murine cardiac allograft transplantation.

Graft Protective Effect of HMG-CoA Reductase Inhibitor Pravastatin in Murine Cardiac Allograft Transplantation.

The HMG-CoA reductase inhibitor (statin), which reduces serum cholesterol, has been demonstrated in the control of immune responses and may potentially play an important role in the regulation of acute and chronic rejection in organ transplantations. We investigated the graft-protective effect of a kind of statin, pravastatin, in the survival of fully major histocompatibility complex--mismatched murine cardiac allograft transplantation. Fully vascularized heterotopic hearts from C57BL/6 donors were transplanted into CBA recipients through microsurgical techniques. CBA recipients transplanted with a C57BL/6 heart received oral administration of 40, 120, or 400 µg/kg/day of pravastatin from the day of transplantation to 7 days afterward. Immunohistochemical staining studies were performed to determine whether intimal formation of coronary arteries in the transplanted cardiac allografts was preserved and also to conduct morphometric analysis. Untreated CBA recipients rejected C57BL/6 cardiac grafts acutely (median survival time [MST] 7 days). CBA recipients exposed with 40 and 120 µg/kg/day of pravastatin had a small prolonged allograft survival (MSTs of 10 and 9 days, respectively). However, the MST of CBA recipients exposed to 400 µg/kg/day of pravastatin was significantly effective for allograft survival (MST 50 days). Immunohistochemical staining assessments on 4 weeks after grafting showed suppression of intimal hyperplasia in allograft coronary arteries. Pravastatin could induce the prolongation of fully major histocompatibility complex--mismatched cardiac allograft through the protection of the coronary artery.

More Hippocampal Weight and Cells in Cardiac Allograft Transplanted Mice.

The hippocampus is a brain structure that plays a fundamental role in memory and learning. Many animal studies have demonstrated that the structure of the hippocampus has evolved through exercise and play. However, little is known on the relationship between the brain and immunological reaction. In this study, we investigated the correlation between the weight of the hippocampus and transplant immunology in a murine heart transplant model. Fully vascularized heterotopic hearts from CBA (H2k, allogeneic group) or C57BL/6 (H2b, syngeneic group) donors were transplanted into C57BL/6 recipients by using microsurgical techniques. The weights of the whole brain and hippocampus from syngeneic and allogeneic groups were recorded 1, 2, and 4 weeks after grafting, and histologic assessments were performed. The syngeneic group maintained beating cardiac grafts for over 30 days, but the allogeneic group rejected CBA cardiac allografts acutely within 8 days. The average weight of whole brain from syngeneic and allogeneic group 1, 2, and 4 weeks had no significant differences. However, the average weight of hippocampus at 2 and 4 weeks was considerably increased in the allogeneic group compared with the syngeneic group. Histologic assessments with hematoxylin-eosin and Kluver-Barrera staining of hippocampus from allogeneic group 1 week after grafting demonstrated a greater number of granule and pyramidal cells in the hippocampus. Alloimmune responses in our model increase the weight of hippocampus.

Administration of Thrombomodulin (CD141) Could Improve Cardiac Allograft Survival in Mice.

Thrombomodulin (TM) is a promising natural anti-coagulant therapeutic protein that is effective in the treatment of disseminated intravascular coagulation. However, the mechanisms by which TM on micro-vessels enable the regulation of intimal hyperplasia remain elusive. We investigated the graft-protective effects of TM in a fully major histocompatibility complex-mismatched murine cardiac allograft transplantation model. CBA recipients transplanted with a C57BL/6 heart received intraperitoneal administration of 0.2, 2.0, and 20.0 µg/day of TM for 8 days. Histological staining was conducted to assess the degree of inflammation and infiltration in the transplanted cardiac grafts. Untreated CBA recipients rejected C57BL/6 cardiac grafts acutely (median survival time [MST] was 7 days). CBA recipients exposed to the above dosages had significantly prolonged allograft survival (MSTs were 16, 21, and 37.5 days, respectively). Histologic assessments from TM-exposed recipients 2 weeks after grafting showed that the myocardium and vessel structure in their allografts were clearly preserved, and that the infiltration of inflammatory cells around coronary arteries was suppressed. TM can induce the prolongation of fully major histocompatibility complex-mismatched cardiac allograft by exerting graft protective effects within the myocardium and coronary arteries.

Seven Japanese Herbals Prolonged Cardiac Allograft Survival.

Japanese herbal medicines have long been used as alternative therapy because of their immunomodulatory effects. In recent years, use herbal medicines is rapidly increasing worldwide. In this study, we investigated the effect of 17 components of traditional Japanese herbal medicines on alloimmune responses in a murine model of cardiac allograft transplantation. Fully vascularized heterotopic hearts from C57BL/6 donors were transplanted into CBA mice by using microsurgical techniques. Artemisiae capillaris herba (Inchinko) was given to CBA recipients at a dosage of 1 g/kg/day from the day of transplantation until 7 days afterward. The other 16 components were given at a dosage of 2 g/kg/day for the same time period. Naïve CBA mice rejected C57BL/6 cardiac grafts acutely (median survival time [MST] of 7 days). CBA transplant recipients given 2 g/kg/day of Glycyrrhizae radix (Kanzou), Poria sclerotium (Bukuryo), Pinellia tuber (Hange), Cnidii rhizome (Senkyu), Paeoniae radix (Shakuyaku), and Scutellariae radix (Ogon) had prolonged C57BL/6 allograft survival significantly (MSTs were 18, 18, 17, 14, 12, and 12 days, respectively). Moreover, CBA transplant recipients given 1g/kg/day of Artemisiae capillaris herba had prolonged C57BL/6 allograft survival (MST >100 days); however, none of other 10 components prolonged allograft survival. In conclusion, administration of 7 components of traditional Japanese herbal medicines might induce prolongation of fully major histocompatibility complex-mismatched cardiac allografts.

Effect of the diazepam-binding inhibitor-derived peptide, octadecaneuropeptide, on food intake in goldfish.

An endogenous ligand of central-type benzodiazepine receptors (CBR), the endozepine octadecaneuropeptide (ODN), is a very potent inhibitor of food intake in rodents. Although endozepines have been localized and characterized in the trout hypothalamus, so far, the action of these neuropeptides on feeding behavior has never been investigated in fish. In the present study, we have examined the effect of i.c.v. administration of synthetic rat ODN, its C-terminal octapeptide (OP) and the head-to-tail cyclic analog cyclo(1-8)OP (cOP) on feeding behavior in the goldfish model. i.c.v. injection of graded doses of ODN (2.5-10 pmol/g body weight (BW)) induced a dose-dependent inhibition of food intake, a significant decrease in cumulative food intake during the 60-min period after feeding being observed at doses of 5 and 10 pmol/g BW. The inhibitory effect of a 10 pmol/g BW dose of ODN on food consumption (-39%) was mimicked by an equimolar dose of OP (-42%) and cOP (-53%). The food intake-suppressing activity of ODN (10 pmol/g BW) was not affected by pre-injection of the CBR antagonist flumazenil (200 pmol/g BW). In contrast, the anorexigenic effect of ODN (10 pmol/g BW) was totally suppressed by a selective antagonist of metabotropic endozepine receptors, cyclo(1-8)[dLeu(5)]OP. These data indicate that, in goldfish as in rodents, ODN is a potent inhibitor of food consumption, and that the anorexigenic effect of ODN is not mediated through CBR but through the metabotropic endozepine receptor.