Activation of mu-opioid pathway is associated with the canceling effect of footshock stimulus on the restraint stress-induced inhibition of small intestinal motility in rats.

We previously reported that small intestinal motility was significantly inhibited by restraint stress, but not by footshock stress. In the present study, we found that plasma beta-endorphin levels were more significantly elevated by footshock stress than restraint stress, and that preloading of footshock stimulus canceled the inhibition of small intestinal motility by restraint stress. Pretreatment with the mu-opioid receptor antagonist naltrexone significantly attenuated this canceling effect of footshock stimulus. These results suggest that footshock stimulus may cancel the inhibition of small intestinal motility by restraint stress via activation of mu-opioid receptors.     

Factors associated with a low initial cerebral oxygen saturation value in patients undergoing cardiac surgery

Regional cerebral oximetry using near-infrared spectroscopy device, an INVOS 5100 C (Medtronic, Minneapolis, MN, USA), during cardiac surgery aims to avoid perioperative neurological impairment, especially during cardiopulmonary bypass. However, it is not uncommon to encounter critically low initial cerebral regional oxygen saturation or a low value unresponsive to intervention. Therefore, it is important to identify factors associated with low saturation value other than true cerebral hypoxia. We investigated the relationship between preoperative regional cerebral oxygen saturation and clinical variables during cardiac surgery. From January 2013 to May 2016, 462 patients underwent elective cardiac surgery. Patient’s?≤12 years of age, with acute cerebral infarction, with previous intracranial hemorrhage or neurosurgery, with concomitant aortic surgery, and having off-pump coronary artery bypass surgery were excluded. The remaining 223 patients were monitored by intraoperative regional cerebral oximetry. Univariate analysis found that scalp-cortex distance, cerebrospinal fluid thickness, left ventricular ejection fraction, hemoglobin concentration, estimated glomerular filtration rate, and hemodialysis were significantly correlated with the initial regional oxygen saturation value. Multiple regression analysis revealed that scalp-cortex distance, left ventricular ejection fraction, hemoglobin, and hemodialysis remained as significant variables. A receiver operating characteristic analysis found that for a low initial regional oxygen saturation value of 40%, the thresholds of scalp-cortex distance, left ventricular ejection fraction, and hemoglobin concentration were 17.6 mm, 45.2%, and 7.5 g/dl, respectively. In conclusion, brain atrophy, poor left ventricular function, anemia, and hemodialysis were associated with low initial cerebral regional oxygen saturation values in adult cardiac surgery patients.     

The efficacy of dental therapy for an adult case of Henoch–Schönlein purpura

Henoch–Schönlein purpura (HSP) is a disease that involves palpable purpura on the skin, joint pain, and gastrointestinal problems. An acute bacterial infection is one of the causes of HSP. Odontogenic infectious diseases have also been implicated in causing HSP. However, there are only a few reports describing the correlation between HSP and odontogenic infectious diseases. The present study describes a case in which a patient was cured of HSP following dental treatment.     

Two cases of acute lupus peritonitis]

We report two cases of systemic lupus erythematosus (SLE) diagnosed when acute peritonitis was appeared. Case 1 was a 20 year-old woman suffering from stomachache and right lower abdominal pain. Case 2 was a 40 year-old woman with diarrhea, epigastralgia, pollakisuria. In both cases, their peritoneal fluids were exudative with positive autoantibodies. After high dose steroid therapy, abdominal symptoms and ascites improved promptly. However, due to the complication of lupus nephritis, additional therapy was necessary. To characterize the feature of lupus peritonitis (LP), we examined the clinical and laboratory findings of LP from the literature. In patients with acute LP, abdominal pain, vomiting, diarrhea were significantly more common compared with chronic LP patients (P < 0.05), and fever, arthritis, central nervous system involvement and cystitis were more common. In patients with chronic LP, pleural effusion and pericardial effusion were more common compared with acute LP patients. Gastrointestinal manifestations such as abdominal pain, vomiting and diarrhea were more common in patients with acute LP compared with patients with chronic LP. Most patients with chronic LP were asymptomatic, ascites and serositis being the only clinical findings. The response to steroid therapy was better in acute LP.     

Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids).

Tacrolimus (FK506) ointment showed remarkable efficacy against atopic dermatitis in animal models and clinical trials. The suppressive effect of tacrolimus on the production of the cytokines involved in atopic dermatitis (IL-2, IL-3, IL-4, IL-5, IFN-gamma and GM-CSF) from human peripheral blood mononuclear cells (PBMC) was investigated. We constructed a new cytokine production system in which T cells are activated by direct stimulation in vitro with anti-CD3/CD2 or anti-CD3/CD28 antibody combination. Tacrolimus inhibited the production of these cytokines by both stimulations. In a comparative study with steroids (alclometasone dipropionate and betamethason valerate) in anti-CD3/CD2 system, tacrolimus and both steroids inhibited Th1 cytokines (IL-2, IFN-gamma), Th2 cytokines (IL-4, IL-5) and IL-3, GM-CSF (produced by both Th1 and Th2). The suppressive effect of tacrolimus on cytokine production was stronger than that of alclometasone dipropionate and equal to or stronger than that of betamethason valerate. The effective dose of tacrolimus (IC50, 0.02-0.11 ng/ml) is almost the same as for Th1 and Th2 cytokines, and 1 ng/ml of tacrolimus suppressed all cytokines completely. These results suggest that tacrolimus suppresses the allergic cytokines from T cells, and that tacrolimus ointment is effective against atopic dermatitis through the inhibition of cytokine production.     

Coordinate expression of Fgf8, Otx2, Bmp4, and Shh in the rostral prosencephalon during development of the telencephalic and optic vesicles.

Previous studies suggest that Fgf8 has a key role in regulating vertebrate development. In the rostral head of the embryonic chicken, there are increasing numbers of separate Fgf8 domains; these are present in tissues that appear to have previously expressed Otx2. As Fgf8 expression becomes established, Otx2 expression weakens, but remains in cells abutting the Fgf8 expression domain. These Fgf8 expression domains are closely associated with tissues expressing Bmp4 and Shh. Based on analogy with the embryonic limb, we suggest that Fgf8, Bmp4 and Shh function together in patterning regions of the embryonic head. Gene expression changes are particularly prominent in 14-21 somite stage embryos in the rostral forebrain, during early morphogenesis of the telencephalic and optic vesicles, when several new interfaces of Fgf8, Bmp4 and Shh are generated. To gain insights into the functions of fibroblast growth factor 8 (FGF8) in the embryonic forebrain, we studied the effects of implanting beads containing this protein in the dorsal prosencephalon of embryonic day 2 chicken embryos. Ectopic FGF8 had profound effects on morphogenesis of the telencephalic and optic vesicles. It disrupted formation of the optic stalk and caused a transformation of the pigment epithelium into neural retina. Within the telencephalon, FGF8 beads frequently induced a sulcus that had features of an ectopic rostral midline. The sulcus separated the telencephalon into rostral and caudal vesicles. Furthermore, we present evidence that FGF8 can regulate regionalization of the prosencephalon through inhibition of Otx2 and Emx2 expression. Thus, these experiments provide evidence that FGF8 can regulate both morphogenesis and patterning of the rostral prosencephalon (telencephalic and optic vesicles). FGF8 beads can induce midline properties (e.g. a sulcus) and can modulate the specification and differentiation of adjacent tissues. We suggest that some of these effects are through regulating the expression of homeobox genes (Otx2 and Emx2) that are known to participate in forebrain patterning.     

Effect of FK506 eye drops on late and delayed-type responses in ocular allergy models

Background It is well‐known that FK506 strongly inhibits cytokine production by T cells in vitro. However, less evidence is available from in vivo studies of ocular allergy. Objective To study the anti‐inflammatory effect of FK506 eye drops on late and delayed‐type responses in several animal models of ocular allergy. Methods Rats and guinea‐pigs were sensitized with egg albumin (EA) in adjuvant and later challenged by topical EA application to their eyes to examine the late response. Biopsy specimens of conjunctiva were stained with haematoxylin–eosin or stained for T cells and eosinophils. In addition, rats, rabbits and guinea‐pigs were sensitized with complete Freund's adjuvant and later challenged by injecting purified protein derivatives for the delayed‐type response. Bulbar conjunctival oedema and hyperaemia were graded by score in rabbits, and Evans blue (EB) extravasation was measured in rats and guinea‐pigs. FK506 (0.01–1%) and steroid (0.1%) eye drops were instilled in the eyes of animals several times, before and after challenge. Results FK506 eye drops inhibited T cell and eosinophil infiltration in the late response and EB extravasation in the delayed‐type response in rats. Also, they inhibited conjunctival oedema, hyperaemia and ocular mucus in the delayed‐type response in rabbits. These effects were similar to those of steroid eye drops (betamethasone sodium phosphate, fluorometholone). FK506 eye drops also inhibited inflammatory cell infiltration, the loss of conjunctival epithelium and decrease of goblet cells in the late response as well as EB extravasation in the delayed‐type response in guineapigs, a steroid‐resistant species. Conclusion FK506 eye drops inhibit late and delayed‐type responses in animal models of ocular allergy.     

A case report of radiation osteomyelitis 9 years after irradiation for thymoma]

Radiation osteomyelitis of the sternum is rare and usually difficult to cure. A 75-year-old man, who had undergone an exploratory sternotomy for a mediastinal tumor, not resected after all, 9 years earlier and received radiation therapy successively for the histological diagnosis of malignant thymoma, was admitted to our hospital with the chief complaint of fever and pus discharge of the anterior chest wall. He also suffered from diabetes mellitus. The skin around the fistula was dark-red and atrophic due to irradiation dermatitis and the manubrium was fissured in the midline. Open drainage and two-stage operation of direct closure was tried in vain. This case was treated successfully by resection of necrosed portion of sternum and pectoral muscle flap closure.     

Reproducibility of nocturnal blood pressure assessed by self-measurement of blood pressure at home.

To assess the reproducibility of nocturnal blood pressure (BP) during sleep as measured using a self-measurement device at home, we obtained repeated nocturnal home BP at 0200 h and quality of sleep assessment from a diary in 556 subjects (71% women, 62.4+/-11.1 years) in the general population. We used an Omron device (HEM-747IC-N, Omron Healthcare Co., Ltd., Kyoto, Japan), with which the time and frequency of monitoring can be preset and the readings stored. The mean+/-SD of the difference between test-retest BP measurements was 0.7+/-15.1 mmHg systolic and 0.2+/-9.7 mmHg diastolic with a mean interval of 5.9 days. The absolute differences were greater than 10 mmHg in 261 (46.9%) subjects for systolic and 145 (26.0%) subjects for diastolic. There was no evidence of regression to the mean in nocturnal measurements over at least three nights (n=390, p>0.22). The differences (the first minus the second measurement) were large in subjects who experienced sleep disturbance only in the first (n=64, 2.3+/-13.6 mmHg and 1.6+/-9.6 mmHg for systolic and diastolic, respectively) or second sessions (n=56, -4.1+/-16.4 mmHg and -2.5+/-11.4 mmHg) compared with the subjects without sleep disturbance (n=66, 1.5+/-17.8 mmHg and 0.8+/-10.3 mmHg) and those with sleep disturbance (n=370, 0.9+/-14.5 mmHg and 0.2+/-9.3 mmHg) in both sessions. In conclusion, the reproducibility of single nocturnal BP as assessed using a self-measurement device at home was not good, especially for subjects who experienced different quality of sleep in each session. To evaluate nocturnal BP using a self-measurement device, estimation of quality of sleep is indispensable.