Atomoxetine reverses locomotor hyperactivity, impaired novel object recognition, and prepulse inhibition impairment in mice lacking pituitary adenylate cyclase-activating polypeptide.

Attention-deficit/hyperactivity disorder (ADHD) is a complex neurobehavioral disorder that is characterized by attention difficulties, impulsivity, and hyperactivity. A non-stimulant drug, atomoxetine (ATX), which is a selective noradrenaline reuptake inhibitor, is widely used for ADHD because it exhibits fewer adverse effects compared to conventional psychostimulants. However, little is known about the therapeutic mechanisms of ATX. ATX treatment significantly alleviated hyperactivity of pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient (PACAP(-/-)) mice with C57BL/6J and 129S6/SvEvTac hybrid background. ATX also improved impaired novel object recognition memory and prepulse inhibition in PACAP(-/-) mice with CD1 background. The ATX-induced increases in extracellular noradrenaline and dopamine levels were significantly higher in the prefrontal cortex of PACAP(-/-) mice compared to wild-type mice with C57BL/6J and 129S6/SvEvTac hybrid background. These results suggest that ATX treatment-induced increases in central monoamine metabolism may be involved in the rescue of ADHD-related abnormalities in PACAP(-/-) mice. Our current study suggests that PACAP(-/-) mice are an ideal rodent model with predictive validity for the study of ADHD etiology and drug development. Additionally, the potential effects of differences in genetic background of PACAP(-/-) mice on behaviors are discussed.

The effect of complement regulatory protein expression on pig endothelial cells to porcine endogenous retrovirus lyses by human sera.

INTRODUCTION: Expression of human complement regulatory proteins (CRP) on pig endothelial cells (PEC) has been useful to avoid hyperacute rejection by human sera. On the other hand, porcine endogenous retrovirus (PERV) from PEC transfectants with CRP may acquire resistance to human sera. In this study, we investigated the effects of the transfected CRP on PERV neutralization and/or lysis by human sera. METHODS: cDNA of membrane cofactor protein (MCP: CD46), decay accelerating factor (DAF: CD55), and CD59 were transfected to PEC lines by lipofection. The expressions of these CRPs were verified by FACS analysis. The PEC lines with human CRPs were then transfected with the LacZ gene and PERV subtype B (PERV-B) to investigate PERV infectivity by LacZ pseudotype assay. Culture supernates of PEC were inoculated to HEK293 cells with or without 10% human sera. The inoculated 293 cells were then histochemically stained to count the LacZ-positive blue foci and calculated the rate of reduction of LacZ-positive cells by serum. RESULTS: PERV from the PEC with DAF or CD59 showed a resistance to human sera compared with those of control PEC (DAF: 59.6% +/- 5.3%, CD59: 61.1% +/- 3.9% vs control: 31.3% +/- 3.6%; P < .01). However, PEC with MCP did not cause such an effect (28.8% +/- 2.5%). CONCLUSIONS: While expression of DAF and CD59 on PEC changed its PERV responsiveness to human sera, MCP did not improve it.

[Cavernous hemangioma in the anterior mediastinum; report of a case].

A rare case of mediastinal hemangioma was reported in this article. A 63 years old male was pointed out an abnormal shadow in the chest CT scan though he had no symptoms. It showed a well-defined round mass with low density in the anterior mediastinum. MRI (T2 weight) showed the lesion as a high intensity tumor. We diagnosed it thymoma and planned the surgical treatment. The tumor was resected completely through median partial sternotomy. The tumor was 2 cm in diameter. Histological examination revealed it cavernous hemangioma, and neither coagulations nor phleboliths were identified in vessels of the tumor.

The influence of node-fibril morphology on healing of high-porosity expanded polytetrafluoroethylene grafts.

PURPOSE: To manufacture high-porosity expanded polytetrafluoroethylene (ePTFE) vascular grafts with the same internodal distance but different node-fibril morphology, and to evaluate their biologic behaviors in a canine carotid artery implantation model. MATERIALS AND METHODS: Several types of high-porosity ePTFE vascular grafts with the same inside diameter (4 mm) and wall thickness (650 microm) were manufactured under different heating, stretching conditions. The luminal surface and cross section of the grafts were photographed by scanning electron microscopy and the node-fibril structure was examined. Two typical types of high-porosity ePTFE vascular grafts were then selected and proceeded to an animal study. The test grafts were explanted after an interval of 12 weeks and subjected to histomorphometric analyses. RESULTS: The following two types of high-porosity ePTFE vascular grafts were selected; one had a through-pore structure extending from the outer to the inner surface and the other had a random-node architecture with tortuous path channels extending from the outer to the inner surface. The histomorphometric analyses of thrombus-free surface, thickness of pseudointima, cellular ingrowth, capillary ingrowth, and cellular proliferation revealed no significant differences between the grafts. CONCLUSION: In high-porosity ePTFE vascular grafts, graft healing enhanced by transmural tissue ingrowth may be not largely dependent on node-fibril morphology. This knowledge will be helpful to design a new type of high-porosity ePTFE vascular grafts available for clinical use.

An analysis of video-assisted thoracoscopic resection for mediastinal masses in 150 cases. An overview of the pansternal approach, histology, and complications.

BACKGROUND: To clarify the usefulness of the diagnosis and treatment of mediastinal masses, by video-assisted thoracoscopic surgery (VATS), we performed a retrospective multi-institutional study to delineate the type of approach, histopathology, and complications associated with these entities. METHODS: We analyzed 150 patients who underwent the VATS procedure at several institutions between 1991 and 1999. RESULTS: VATS resections were performed using various combinations of the "pansternal approach." The unilateral thorax approach was applied in 135 patients, the bilateral thorax approach combined with the suprasternum approach in seven patients, the unilateral thoracic approach combined with the supraclavicular approach in three patients, the infrasternal approach in three patients, and the bilateral thoracic approach combined with both the infrasternal and the suprasternal approaches in two patients. Thoracoscopic resections or biopsies diagnosed 140 benign and 10 malignant mediastinal masses. There were operative complications in nine patients (6%). Eight patients (5.3%) were converted to conventional thoracotomy. CONCLUSION: VATS is a safe, effective, minimally invasive technique that can facilitate the resection of mediastinal masses when the pansternal approach is applied as appropriate for the location of the tumor.

[Persistent left-sided superior vena cava diagnosed after flow-directed pulmonary artery catheterization; report of a case].

We describe a case of persistent left-sided superior vena cava discovered after insertion of a pulmonary artery (PA) catheter. The diagnosis was suggested by chest X-ray after PA catheter placement and was subsequently confirmed by an echocardiograph. A 68-year-old man was admitted to our ICU because of septic shock induced by MRSA enterocolitis. In order to monitor the hemodynamic state of the patient, a PA catheter was inserted through the left subclavian vein after placement of a central venous and flexible double lumen catheters through the right internal jugular and subclavian veins, respectively. A chest X-ray showed the PA catheter passing along the left border of the heart. An echocardiograph showed the PA catheter passing through the coronary sinus into the pulmonary artery. Anesthesiologists and intensivists should be aware of the occurrence of left-sided superior vena cava in order not to mistake catheters placed in it as being in the arterial circulation or malpositioned outside of the venous circulation.

Videoendoscopic surgery combined with a minimal sternotomy for removing a thyroid tumor extending into the mediastinum. A case report.

We report the case of a 55-year-old man with a giant goiter descending to the mediastinum. Video-endoscopic surgery combined with a minimal sternotomy was performed to remove a thyroid tumor. In the course of our dissection of the subplatysmal space, an endoscopic approach was applied to avoid incisions of the neck. Three trocars were inserted from the anterior chest wall, and carbon dioxide (CO2) was insufflated at a pressure of 5 mmHg to create a working space. This technique improves the cosmesis of thyroidectomies and cervical operations.

[Successful thoracoscopic resection of pulmonary arterio-venous fistula].

A 65-year-old female was admitted for further examination of an abnormal shadow on a chest roentgenogram. Chest computed tomography revealed a lobular nodule with blood vessels, which was diagnosed as pulmonary arterio-venous fistula (PAVF). Thoracoscopic resection was performed under general anesthesia. The fistula was situated directly below the pleura of the left lower lobe. Partial resection of the left lung including the PAVF was performed with an autosuture device dedicated to endoscopic surgery (Endo GIA II). The patient was discharged from our hospital 3 days after surgery without major complications. Mild hypoxemia was corrected after the surgery. Thoracoscopic resection is considered to be safe and useful for a solitary PAVF existing a peripheral field of the lung.

Peripheral nitric oxide in carrageenan-induced inflammation.

Recent studies have suggested that nitric oxide (NO) peripherally produced by different nitric oxide synthase (NOS) isoforms contributes to edema formation and development of hyperalgesia. The present study was designed to examine the effects of NOS isoforms on NO release in carrageenan-induced inflammation at various time points. A microdialysis probe was implanted subcutaneously into the glabrous skin of hindpaws of Sprague-Dawley rats under pentobarbital anesthesia. After sample collection to obtain the basal level of the total amount of nitrite and nitrate (NO2-/NO3-), modified Ringer solution, a non-selective NOS inhibitor, NG monomethyl-L-arginine acetate (L-NMMA), or an iNOS inhibitor, aminoguanidine hemisulfate (AG) was perfused through the microdialysis probe. 2 mg of carrageenan was injected into the plantar surface of the probe-implanted hindpaw. Carrageenan was also injected in rats that had undergone sciatic nerve sectioning. Carrageenan significantly increased the dialysate concentrations of NO2-/NO3- for more than 8 h. L-NMMA suppressed the carrageenan-induced increase in NO2-/NO3- concentration. Although AG did not suppress the increase in NO2-/NO3- for the first 2 h after carrageenan injection, significant suppression of the increase in NO2-/NO3- was observed from 2.5 h after carrageenan injection. In the rats in which the sciatic nerves had been denervated, the increases in concentrations of NO2-/NO3- were completely suppressed up to 3 h and partially suppressed 4.5-8 h after carrageenan injection. The results of the current study show that carrageenan induces peripheral release of NO, the production of which is mediated by nNOS in the early phase and by both nNOS and iNOS in the late phase of carrageenan-induced inflammation.

Minimally invasive surgery for lung cancer with coronary artery disease.

We report a 69-year-old woman with lung cancer and severe stenosis in the left anterior descending coronary artery. To perform a curative operation for the lung cancer without myocardial infarction, minimally invasive direct coronary artery bypass and left lower lobectomy with video-endoscopic assistance were performed simultaneously. There was no major complication, and she was discharged at 14 days after the operation. This procedure may be useful and safe for patients with lung cancer and coronary artery disease.

Identification of active regions for neurite outgrowth activity of neurocrescin.

We previously identified and cloned a neurite outgrowth promoting protein, Neurocrescin (NC), from the extract of the chick denervated leg muscles. In this study, we explored the active region of NC for neurite outgrowth. Using the deletion mutants of NC, we tested their neurite outgrowth activity in the cultured telencephalic neurons of E5 chick embryos. We found three regions which independently had significant neurite outgrowth activity comparable with that of the extract of the chick denervated leg muscles. These regions were not homologous to any well-known active sites such as the laminin active region, IKVAV. In parallel, searching the endogenous deletion mutants of NC in the rat brain, we cloned a mutant in which the region including the larger part of one of the three active regions was deleted. The neurite outgrowth activity of the mutant was significantly lower than that of normal NC. These results suggest the physiological significance of these active regions.

[Generalized tonic-clonic seizure induced by propofol in a patient with epilepsy].

A 47-year-old female was scheduled for ulnar osteotomy under general anesthesia combined with brachial plexus block. She had a history of symptomatic epilepsy due to subarachnoid hemorrhage. Immediately after giving 100 mg bolus of propofol to the patient, she developed generalized convulsion similar to a grand mal. The seizure was suppressed by the administration of thiamylal. After that no further convulsive attack occurred. Although it has been known that propofol has anticonvulsive properties, there have been several reported cases of seizure following the administration of propofol. Further studies are needed to clarify the mechanism of seizure induced by propofol in the patients with epilepsy.

The effects of peripheral administration of a novel selective antagonist for prostaglandin E receptor subtype EP(1), ONO-8711, in a rat model of postoperative pain.

UNLABELLED: Mechanically evoked pain, also known as incident pain, induced by coughing or deep breathing after surgery leads to potentially devastating consequences. It is generally thought that the prostaglandin receptor- (especially, the receptor for prostaglandin E(2), EP receptor) mediated sensitization of sensory nerve fibers is a key contributor to the generation of hyperalgesia. We examined whether a peripherally administered novel selective EP(1) antagonist, ONO-8711, would be a potential analgesic for incision-induced mechanical hyperalgesia. We used a rat model of postoperative pain introduced by Brennan et al. (1). Withdrawal thresholds to punctate stimulation and response frequencies to nonpunctate mechanical stimulation were determined by using von Frey filaments applied adjacent to the wound and directly to the incision site of the hind paw, respectively. Mechanical hyperalgesia to punctate and nonpunctate stimuli was observed 2 and 24 h after the incision. ONO-8711 (2, 10, or 50 microg) or saline was administered subcutaneously into the hind paw on the ipsilateral side to the incision. ONO-8711 significantly (P < 0.01) increased the withdrawal thresholds to punctate mechanical stimulation and significantly (P < 0.01) decreased the response frequencies to nonpunctate mechanical stimulation in a dose- and time-dependent manner 2 and 24 h after the incision. We conclude that EP(1) receptor-mediated sensitization of sensory nerve fibers may contribute to the generation of mechanical hyperalgesia produced by incisional surgery, and that the EP(1) receptor antagonist ONO-8711 may be an option for treatment of postoperative pain, especially incident pain. IMPLICATIONS: The peripheral administration of an antagonist for EP(1) receptor that is a subtype of prostaglandin E receptors can inhibit the mechanical hyperalgesia induced by a surgical incision.

Direct evidence for Mendelian inheritance of the variations in the ribosomal protein gene introns in yellowfin tuna (Thunnus albacares).

Restriction fragment length polymorphism found in the S7 ribosomal protein gene introns of yellowfin tuna (Thunnus albacares) was compared between a single pair of parents and their offspring. The sizes of the first intron ( RP1) and second intron ( RP2) amplified by polymerase chain reaction were 810 bp and 1400 bp, respectively. The dam and sire had different restriction types from one another in HhaI and RsaI digestions for RP1 and in DdeI, HhaI, and ScrFI digestions for RP2. Putative genotypes in both introns of 64 larvae were found to be segregated in Mendelian proportions. Genotype distributions in a wild yellowfin tuna sample ( n = 34) were in Hardy-Weinberg proportions, and observed heterozygosity ranged from 0.149 to 0.388. This study presents novel Mendelian markers, which are feasible for tuna population genetic study and pedigree analysis.

Thymic carcinoma successfully resected with superior vena cava after chemoradiotherapy.

A 57-year-old woman hospitalized for thymic cancer invading the superior vena cava and left brachiocephalic vein evidenced both pleural and pericardial effusion. After chemotherapy with cisplatin and docetaxel and concurrent radiotherapy, the entire tumor was successfully resected along with the pericardium, superior vena cava, and left brachiocephalic vein, followed by vascular reconstruction. Pathologically, viable tumor cells were identified only in the center of the tumor as anaplastic cell carcinoma. Induction chemoradiotherapy thus appears useful in enabling complete resection of advanced thymic carcinoma.

[A case of anaphylaxic shock due to latex glove used on internal examination and on the probe of intrauterine echogram].

A 15 year old female with uterus bicornis bicollis was admitted for operation. She had a history of atopic dermatitis and allergy to buckwheat, raw egg and latex. Two months previously she had developed whole body flushing during dental treatment, and latex glove used by the dentist had been suspected as the cause. Prior to the operation she underwent internal examination and intrauterine echogram in which a latex glove was carelessly used by another gynecologist who had not confirmed her past history. After 30 minutes, dyspnea and urticaria without itching, appeared suddenly. Blood pressure decreased to 80/50 mmHg and heart rate increased to 120 beats.min-1. She was then transferred to our ICU. Methylprednisolone was administered intravenously for dyspnea and circulatory collapse. After 3 hours, the patient made an uneventful recovery. The increased plasma latex protein-specific IgE levels confirmed anaphylaxis to latex. The increasing incidence of potentially life-threatening allergic reactions to latex has caused mounting concern over recent years. We may suspect latex allergy when an anaphylaxic reaction or shock of unknown origin occurs. In hospitals, latex free products must be prepared for use with latex allergic patients and for protection of medical staff with this allergy.

Activation of peripheral NMDA-nitric oxide cascade in formalin test.

BACKGROUND: It has been suggested that peripheral glutamate and nitric oxide (NO) released by tissue-damaging stimuli play an important role in peripheral nociceptive transmission. This study was conducted to determine whether NO was released in the periphery after subcutaneous injection of formalin and whether the peripheral N-methyl-d-aspartate (NMDA)-NO cascade was activated. METHODS: During pentobarbital anesthesia, a microdialysis probe was implanted subcutaneously into the glabrous skin of both hind paws of Sprague-Dawley rats. After sample collection to obtain the basal level of NO metabolites (total amount of nitrite [NO2-] and nitrate [NO3-] [NO2--NO3-]), 5% formalin was injected into the plantar surface of the right hind paw during perfusion of the dialysis catheters with artificial cerebrospinal fluid (ACSF), the NO synthase inhibitor NG-monomethyl-L-arginine acetate, or the NMDA antagonist D,l-2-amino-5-phosphonovaleric acid through a microdialysis probe. Formalin also was injected in the animals that underwent sciatic nerve sectioning. In another series of experiments, NMDA was perfused through one probe. Samples for measurement of NO2--NO3- were collected and immediately analyzed using high-performance liquid chromatography. RESULTS: Subcutaneous formalin significantly increased the dialysate concentrations of NO2--NO3- (maximum increase 144 +/- 12% of baseline value 30 min after formalin administration; P < 0.05) on the side ipsilateral to the injection. Both NG-monomethyl-l-arginine acetate and D, l-2-amino-5-phosphonovaleric acid significantly (P < 0.05) suppressed the formalin-induced increases in NO2--NO3- concentration. In the rats with denervation of the sensory nerves, formalin did not change the NO2--NO3- concentration. In addition, NMDA perfusion significantly (P < 0.05) increased the concentrations of NO2--NO3-. CONCLUSION: The results of the current study show that subcutaneous formalin injection induces peripheral release of NO, the production of which is mediated by activation of NMDA receptors in the peripheral nervous system.