VGF function in depression and antidepressant efficacy.

Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behaviors and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in hippocampus (male/female) and upregulated in nucleus accumbens (NAc) (male) in depressed human subjects and in mice subjected to chronic social defeat stress (CSDS). Adeno-associated virus (AAV)-Cre-mediated Vgf ablation in floxed VGF mice, in dorsal hippocampus (dHc) or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc- or NAc-AAV-VGF overexpression induced opposite outcomes. Mice with reduced VGF levels in the germ line (Vgf+/-) or in dHc (AAV-Cre-injected floxed mice) showed increased susceptibility to CSDS and impaired responses to ketamine treatment in the forced swim test. Floxed mice with conditional pan-neuronal (Synapsin-Cre) but not those with forebrain (αCaMKII-Cre) Vgf ablation displayed increased susceptibility to subthreshold social defeat stress, suggesting that neuronal VGF, expressed in part in inhibitory interneurons, regulates depression-like behavior. Acute antibody-mediated sequestration of VGF-derived C-terminal peptides AQEE-30 and TLQP-62 in dHc induced pro-depressant effects. Conversely, dHc TLQP-62 infusion had rapid antidepressant efficacy, which was reduced in BDNF floxed mice injected in dHc with AAV-Cre, and in NBQX- and rapamycin-pretreated wild-type mice, these compounds blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling, respectively. VGF is therefore a critical modulator of depression-like behaviors in dHc and NAc. In hippocampus, the antidepressant response to ketamine is associated with rapid VGF translation, is impaired by reduced VGF expression, and as previously reported, requires coincident, rapid BDNF translation and release.

[Pleuroperitoneal communication due to diaphragmatic injury as a complication of chest wall resection in a peritoneal dialysis patient; report of a case].

A 78-year-old female undergoing peritoneal dialysis due to chronic renal failure was admitted to our hospital because of a tumor on her right chest wall. The diagnosis was recurrence of hepatocellular carcinoma in the thoracic wall, and a combined resection of the thoracic wall and diaphragm was performed. Peritoneal dialysis was resumed 7 days after surgery, but a right pleural effusion was observed after 6 days of dialysis. Surgery was performed because failure of sutures related to the excised diaphragm was suspected. A thoracotomy revealed a large defect, about 1 cm in size, caused by injury of the diaphragm by an edge of the resected rib at the another site of a previous resection of the diaphragm. This defect was closed with sutures and the diaphragm was reinforced with a polyglycolic acid felt and fibrin glue. Peritoneal dialysis was resumed 7 days after surgery and has continued to date without recurrence.

[Aortic valve replacement through right thoracotomy; report of a case].

A 78-year-old female was admitted to our hospital with a diagnosis of severe aortic valve regurgitation. She had had dyspnea on effort and syncope twice in 5 months. She had also suffered from right pneumonia 8 years before, and her respiratory function was severely constrictive. Chest X-ray showed her mediastinum significantly shifted toward the right side. Chest computed tomography (CT) revealed the main pulmonary artery, right atrium (RA) and right pulmonary veins also shifted toward the right. We planned right thoracotomy at 4th intercostals space to obtain a good surgical field. A cardiopulmonary bypass was established by RA appendage drainage and femoral artery perfusion. Aortic valve replacement(AVR) was performed successfully after aortic clamp. Though defibrillator pads were placed on her back and the anterior wall of the left chest during operation, no ventricular fibrillation occurred. AVR via right thoracotomy is considered to be a good option for such a mediastinum shifted case.

[Aortic root replacement for aortic dissection and aortic regurgitation due to aortitis syndrome].

Aortic aneurysms and aortic regurgitation (AR) with aortitis syndrome are occasionally reported in young women. We report a case of aortic dissection with severe AR in an 8-year-old girl. The patient underwent aortic root replacement with a composite graft. Pathological report revealed aortitis syndrome and steroid therapy was continued to suppress further inflammatory vascular reaction.

Spatial distribution of tuberculosis in Manaus and its social determinants, 2008-2013.

SETTING: Brazil ranks eighteenth worldwide in annual numbers of new tuberculosis (TB) cases. The municipality of Manaus, Amazonas State, has the highest incidence of TB in Brazil. OBJECTIVE: To evaluate the quality of TB epidemiological surveillance, and to describe the spatial distribution pattern of TB incidence in Manaus and its social determinants. DESIGN: An ecological study was performed based on secondary data from TB epidemiological surveillance reports. RESULTS: An index was developed to classify neighborhoods in terms of the quality of surveillance and suspected underreporting. Based on data from neighborhoods with better surveillance performance, we observed that the average number of residents per room, the unemployment rate and the proportion of households connected to a sewage system were significant predictors of TB incidence. Seven neighborhoods in the south and west of the city had clusters of high TB transmission. CONCLUSION: Our results suggest that the association between TB and social vulnerability is obscured by the poor quality of TB surveillance data. We identified priority areas that require immediate TB control interventions and those where local surveillance efforts should be improved, and generated information useful for formulating more effective actions.

Developmental expression of endogenous oscillations and waves in the auditory cortex involves calcium, gap junctions, and GABA.

Neuronal oscillations and population waves (OWs) may be important for the maturation of neural circuits in the cortex and other developing areas of the CNS. We examined endogenous network activity by whole-cell and paired extracellular recordings in the thalamorecipient auditory cortex (ACx) in slices of gerbil pups during the first three postnatal weeks. Separately, we examined network ensemble correlates of the OWs using population intracellular free calcium (Ca2+) imaging in slices bulk-loaded with fura-2 AM. In slices devoid of physiological or pharmacological manipulations, spontaneous multi-neuronal bursts recorded extracellularly at the perirhinal cortex precede bursts simultaneously recorded at the ACx, suggesting their caudorostral propagation. OWs waned after postnatal day (P) 7, ceased following hearing onset (P12), and accompanied altered membrane properties. Population imaging from P2-5 slices with fura-2 AM revealed endogenously generated waves that spread from the perirhinal cortex toward the thalamorecipient ACx. Wave incidence varied between 5 waves/min to 0.4 waves/min. OWs were disrupted by treatment of slices with [Ca2+]i chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, the gap junction blocker mefloquine or the GABAA receptor blocker bicuculline. These results suggest that propagating activity involving calcium, gap junctions and GABAergic transmission exists in the gerbil ACx and it correlates with key developmental events in vivo. We speculate such activity may be integral to postnatal maturation of ACx.

[Beating heart surgery for the patient of severe mitral regurgitation with a episode of ventricular fibrillation; report of a case].

A 77-year-old female was admitted to our hospital with a diagnosis of severe mitral regurgitation. Cardiopulmonary revival was done by an emergent resuscitation for the ventricular fibrillation before admission. She had mild anoxic brain damage and brain magnetic resonance imaging (MRI) revealed severe brain atrophy. Chest X-ray showed severe cardiomegaly and congestion. Beating heart mitral valve replacement was planned for the prevention of reperfusion injury. A cardiopulmonary bypass was established by bicaval drainage and aortic return. The prolapse of anterior leaflet was recognized through transeptal approach after aortic clamp. We selected continuous infusion of antegrade cardioplegia for intraoperative coronary perfusion. Mitral valve replacement was done successfully. During intraoperation and postoperation, ventricular fibrillation did not occur. On-pump beating mitral valve replacement is a good procedure to prevent perioperative ventricular arrhythmia especially such the case with a decompressed myocardial function and with a preoperative episode of lethal ventricular arrhythmia necessary for cardiopulmonary resuscitation.

Experimental study of cerebral autoregulation during cardiopulmonary bypass with or without pulsatile perfusion.

Twenty-four adult mongrel dogs were divided into four equal groups according to the following method of cardiopulmonary bypass: normothermic continuous (so-called nonpulsatile) perfusion, normothermic pulsatile perfusion, hypothermic continuous perfusion, and hypothermic pulsatile perfusion. Cerebral blood flow was determined by measuring the volume of sagittal sinus venous blood outflow with a transit-time ultrasonic flowmeter. Cardiopulmonary bypass was initiated at a flow rate of 80 ml/kg per minute. Cerebral temperature was maintained at 37 degrees C in the normothermic groups and at 25 degrees C in the hypothermic groups. Arterial pH and carbon dioxide were maintained within the physiologic range by alpha-stat acid-base regulation. Mean cerebral perfusion pressure and blood flow were not affected during 90 minutes of the bypass. The respective values were 67.1 mm Hg and 37.1 ml/100 gm brain per minute with normothermic continuous perfusion, 72.8 mm Hg and 39.0 ml/100 gm per minute with nonpulsatile perfusion, 98.0 mm Hg and 23.0 ml/gm per minute with hypothermic continuous perfusion, and 86.8 mm Hg and 22.3 ml/100 gm per minute with hypothermic pulsatile perfusion. Pump flow rates were altered from 10 to 120 ml/kg per minute in a stepwise fashion to obtain graded changes of perfusion pressure. Cerebral blood flow, however, was not changed significantly by cerebral perfusion pressure so long as perfusion pressure was greater than 50 mm Hg. Conversely, cerebral blood flow changed proportionally with cerebral perfusion pressure at a pressure less than 50 mm Hg. The correlation between cerebral blood flow and perfusion pressure was described as two separate lines determined by linear regression. The slope of the regression line relating cerebral blood flow to perfusion pressure was 0.16 +/- 0.08 for a cerebral perfusion pressure above 50 mm Hg and 0.68 +/- 0.11 below 50 mm Hg in the normothermic continuous perfusion group; 0.14 +/- 0.09 and 0.32 +/- 0.09 with normothermic pulsatile perfusion; 0.10 +/- 0.04 and 0.62 +/- 0.18 with hypothermic continuous perfusion; 0.09 +/- 0.08 and 0.39 +/- 0.04 in the hypothermic pulsatile perfusion group. The slope above 50 mm Hg was significantly smaller and closer to zero in all groups than it was at a perfusion pressure below 50 mm Hg (p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Selective motor neuron death and heat shock protein induction after spinal cord ischemia in rabbits.

Paraplegia is a serious complication that sometimes results from operation on the thoracic aorta. The mechanism of spinal cord injury has been thought to involve tissue ischemia, and spinal motor neurons are suggested to be vulnerable to ischemia. The exact mechanism, however, is not fully understood. To evaluate the mechanism of such vulnerability of motor neurons, we attempted to make a reproducible model for spinal cord ischemia and statistically analyzed cell damage. With this model, induction of heat shock protein 70 (HSP70) and heat shock cognate protein (HSC70) messenger ribonucleic acid molecules were investigated with Northern blot analysis for up to 7 days of reperfusion after 5 or 15 minutes of ischemia. Immunohistochemical studies of their proteins were also done. (heat shock proteins are a set of markers of neuronal injury after ischemia.) After 5 minutes of ischemia, there was no induction of HSP70 and HSC70 messenger ribonucleic acid molecules or their proteins, and all cells remained intact. In contrast, after 15 minutes of ischemia, HSP70 messenger ribonucleic acid was induced at 8 hours of reperfusion, and HSC70 messenger ribonucleic acid was expressed continuously at the control level. Immunoreactivity of HSP70 protein was slightly induced at 8 hours of reperfusion selectively in motor neurons, and about 70% of motor neuron cells showed selective cell death after 7 days of reperfusion. This study demonstrated induction of HSP70 messenger ribonucleic acid and its protein in motor neuron cells after transient ischemia in the spinal cord. This phenomenon was not accompanied by HSC70 induction.

Delayed and selective motor neuron death after transient spinal cord ischemia: a role of apoptosis?

OBJECTIVE: The mechanism of spinal cord injury has been thought to be related to tissue ischemia, and spinal motor neuron cells are suggested to be vulnerable to ischemia. We hypothesized that delayed and selective motor neuron death is apoptosis. METHODS: Thirty-seven Japanese domesticated white rabbits weighing 2 to 3 kg were used in this study and were divided into two subgroups: a 15-minute ischemia group and a sham control group. Animals were allowed to recover at ambient temperature and were killed at 8 hours, and 1, 2, 4, and 7 days after reperfusion (n = 3 at each time point). By means of this model, cell damage was histologically analyzed. Detection of ladders of oligonucleosomal DNA fragment was investigated with gel electrophoresis up to 7 days of the reperfusion. Immunocytochemistry, in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining was also performed. RESULTS: After 15 minutes of ischemia, most of the motor neurons showed selective cell death at 7 days of reperfusion. Typical ladders of oligonucleosomal DNA fragments were detected at 2 days of reperfusion. Immunocytochemistry showed in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end staining was detected at 2 days of reperfusion selectively in the nuclei of motor neurons. CONCLUSION: These results suggest that delayed and selective death of the motor neuron cells after transient ischemia may not be necrotic but rather predominantly apoptotic.

Successful surgical repair of left atrial dissection after mitral valve replacement.

A rare case of left atrial dissection after mitral valve replacement is reported. Low output syndrome developed in the immediate postoperative period. Cardiac catheterization showed marked elevation of the pulmonary wedge pressure, and left ventriculography revealed massive paraprosthetic leakage with left atrial dissection. At the reoperation, the dissecting cavity was successfully closed from inside the left atrium under cardiopulmonary bypass. We consider this complication another variation of an atrioventricular discontinuity after mitral valve replacement.

Commissure holder: an innovative device for aortic valve-sparing technique.

The key to obtaining maximal valve coaptation from the aortic valve-sparing procedure is in appreciating the optimal geometry of each component of the aortic root. We describe a new device called the Commissure Holder (patent pending) that aids in the selection of an appropriate graft size and in the determination of the optimal position at which each commissure should be sutured to the graft.

Protection of the brain during hypothermic perfusion.

The adequacy of the circuits for brain perfusion has been explored by hemodynamic assessment using the ability of the brain to autoregulate blood flow as an indicator, and by morphologic observation using carbon black or Evans blue infusion into the brain perfused antegradely or retrogradely. It is concluded that the safe pressure of cerebral perfusion needed to maintain cerebral integrity is between 40 and 50 mm Hg in both normothermic and hypothermic perfusions, a pressure that can be generated by nonpulsatile pump flows through the pump greater than 40 mL.kg-1 x min-1. Morphologic studies revealed development of focal infarctions in the brain and destruction of the blood-brain barrier by retrograde cerebral perfusion. The retrograde approach, therefore, is definitely inferior to the antegrade method. Antegrade perfusion for 90 minutes, however, produced minimal cerebral edema, suggesting the need for further improvement even in techniques of antegrade perfusion.

Spontaneous rupture of the thoracic aorta.

BACKGROUND: Spontaneous rupture of the thoracic aorta without trauma, aneurysm, or dissection is an extremely rare but catastrophic disorder. Two cases of spontaneous aortic rupture are presented, both treated surgically with satisfactory results. METHODS: A review of the English literature found 16 patients with the diagnosis of spontaneous rupture of the thoracic aorta from 1961 through 1998. Eighteen reported cases, including the 2 cases presented herein, are reviewed. RESULTS: The representative clinical picture is one of a middle-aged hypertensive patient with acute chest pain and collapse, with imaging modalities demonstrating hemopericardium, hemomediastinum, or hemothorax. According to the reported experiences, aortography was accurate for identifying the rupture site although the findings were sometimes subtle. Misdiagnosis or nonsurgical management resulted in the patient's death. All 8 patients who did not undergo aortic repair died within 3 weeks after the onset, whereas 9 of 10 patients who underwent surgical aortic repair survived. CONCLUSIONS: For patients with a definitive or possible diagnosis of spontaneous rupture of the thoracic aorta, prompt operation is imperative through an optimal surgical approach to identify and repair the rupture site with appropriate circulatory support.

Remnant omental transfer for the mediastinitis after coronary bypass surgery with right gastroepiploic artery.

A one-stage procedure for the treatment of mediastinitis after coronary bypass surgery utilizing the right gastroepiploic artery is described. This procedure consists of thorough debridement of mediastinal pus and necrotic tissue, excision of infected sternal bone, mediastinal irrigation, and immediate transfer of the "remnant" omental pedicle based on the "left" gastroepiploic artery without postoperative drainage or irrigation. Recently, this procedure was applied to our patients followed by excellent results.

Brain damage after aortic arch repair using selective cerebral perfusion.

BACKGROUND: Selective cerebral perfusion is one of the most popular methods for cerebral protection during aortic arch repair. However, causes of postoperative brain damage are not fully understood. We analyzed brain damage after aortic arch repair using selective cerebral perfusion for true aortic arch aneurysm in regard to preoperative cerebral infarction and intracranial and extracranial occlusive arterial disease. METHODS: Over a 9-year period, 60 patients with true aortic arch aneurysm underwent aortic arch repair using selective cerebral perfusion. Postoperative brain damage was evaluated in regard to preoperative cerebral infarction detected by computed tomography, magnetic resonance imaging, or both in 50 patients and intracranial and extracranial occlusive arterial disease detected by digital subtraction angiography, magnetic resonance angiography, or both in 35 patients. RESULTS: Seven (12%) of the 60 patients died within 30 days of operation. Postoperative brain damage occurred in 6 (10.5%) (3, coma, and 3, hemiplegia) of 57 patients; 3 patients who died without awakening were excluded. Preoperatively, old cerebral infarction was detected in 9 patients (18%), and silent cerebral infarction (lacunar infarction and leukoaraiosis) was diagnosed in 26 patients (52%). Postoperative brain damage occurred in 3 (33%) of the 9 patients with preoperative cerebral infarction and in 3 (23%) of 13 patients with negative preoperative brain findings; this excludes 2 patients who died without awakening. No patient with silent cerebral infarction had postoperative brain damage. Occlusive arterial disease was detected in 7 patients (20%). The incidence of brain damage in these patients was 71% (5/7), which was significantly greater than that of 4% (1/28) in patients without occlusive arterial disease (p < 0.001). CONCLUSIONS: Silent cerebral infarction may not be a risk factor for postoperative brain damage. Preoperative evaluation of intracranial and extracranial occlusive arterial disease provides important information as to whether a patient might sustain brain damage after aortic arch repair using selective cerebral perfusion.

Delayed selective motor neuron death and fas antigen induction after spinal cord ischemia in rabbits.

The mechanism of spinal cord injury has been thought to be related with tissue ischemia, and spinal motor neuron cells are suggested to be vulnerable to ischemia. To evaluate the mechanism of such vulnerability of motor neurons, we attempted to make a reproducible model for spinal cord ischemia. Using this model, cell damage was histologically analyzed. Detection of ladders of oligonucleosomal DNA fragment was investigated with gel electrophoresis up to 7 days of the reperfusion. Time course expression of Fas antigen, identified as a apoptosis-regulating molecules, was also assessed in rabbit spinal cord following transient ischemia. Spinal cord sections from animals sacrificed at 8 h, 1 day, 2 days, and 7 days following 15-min ischemia were immunohistochemically evaluated using monoclonal antibodies for Fas antigen. Following 15-min ischemia, the majority of motor neuron showed selective cell death at 7 days of reperfusion. Typical ladders of oligonucleosomal DNA fragments were detected at 2 days of reperfusion. Immunoreactivity of Fas antigen were induced at 8 h to 1 day of reperfusion selectively in motor neuron cells. The expression of Fas antigen may be related to the activation of apoptosis signal in motor neuron cells after spinal cord ischemia in rabbits.

Inductions of Cu/Zn superoxide dismutase- and nitric oxide synthase-like immunoreactivities in rabbit spinal cord after transient ischemia.

The distributions and inductions of Cu/Zn superoxide dismutase (SOD), neuronal and endothelial nitric oxide (NO) synthase (nNOS and eNOS), and nitrotyrosine (NT) were immunohistochemically examined in rabbit spinal cords after 5 and 15 min of transient ischemia. The neurons in the anterior horns (AH) were selectively lost 7 days after 15-min ischemia as compared with those of sham-operated controls. In the normal spinal cords, a number of neurons in the AHs were positive for the nNOS, and only slightly positive for the Cu/Zn SOD and the eNOS. Immunoreactivities for the proteins were induced at 8-24 h both after 5- and 15-min ischemia. In contrast, NT-like immunoreactivity was negative both in the normal and postischemic spinal cords. These results suggest that Cu/Zn SOD- and nNOS-, and eNOS-like immunoreactivities are induced, but that, even though an interaction of Cu/Zn SOD with NO could be present, NT was not detected in the motor neurons in the rabbit spinal cords after transient ischemia. Other factors could be required for NT formation found in degenerative motor neuron death in humans.

Dissociation of HSP72 and HSC73 heat shock mRNA inductions after spinal cord ischemia in rabbit.

The inductions of HSP72 and HSC73 mRNAs were investigated with Northern blot and immunohistochemical analyses for up to 7 days of the reperfusion after 5 or 15 min ischemia in rabbit spinal cord. Following 15 min ischemia, HSP72 mRNA was induced at 8 h of reperfusion, while HSC73 mRNA continuously remained at the control level. Immunoreactivity of HSP72 protein was slightly induced at 8 h of reperfusion selectively in motor neurons, and the majority of motor neuron showed selective cell death at 7 days of reperfusion. This study demonstrated selective induction of HSP72 mRNA and the protein in motor neuron cells that eventually showed selective delayed neuronal death after transient ischemia in the spinal cord. This phenomenon was not accompanied by HSC73 induction.

Recent advance in treatment of Stanford type A aortic dissection.

During the period between November 1986 and November 1988, 13 consecutive patients with Stanford type A aortic dissection (8 acute and 5 chronic) were treated as follows: (1) urgent operation for cases with pericardial tamponade or severe heart failure, (2) initial medical treatment followed by elective operation for acute but stable cases or chronic cases, and (3) routine use of open distal anastomosis or selective cerebral perfusion. One patient died during medical treatment: 5 patients were operated on emergently. The remaining 2 acute and 5 chronic cases were operated on electively. There were no operative deaths, neurological disturbances, or late deaths. It is suggested that acute dissection of the ascending aorta requires immediate surgical intervention, especially when the entry is in the ascending aorta. On the other hand, it is also suggested that one could avoid emergency operations in selected cases with retrograde extension of the aortic dissection.