Spirulina platensis and its ingredient biopterin glucoside improved insulin sensitivity in non-alcoholic steatohepatitis model.

Non-alcoholic steatohepatitis is the chronic liver disease leading to cirrhosis and cancer and its prevalence is increasing. Some agents are under clinical trials for non-alcoholic steatohepatitis treatment. We previously reported Spirulina (Arthrospira) platensis effectively prevented non-alcoholic steatohepatitis progression in our model rats. The contribution of phycocyanin, an ingredient of Spirulina (Arthrospira) platensis, was limited. We, therefore, have looked for more active components of Spirulina (Arthrospira) platensis. In this study, we pursued the effect of biopterin glucoside, another bioactive ingredient of Spirulina (Arthrospira) platensis. We found Spirulina (Arthrospira) platensis and biopterin glucoside oral administrations effectively alleviated oxidative stress, inflammation and insulin signal failure, and prevented fibroblast growth factor 21 gene overexpression in non-alcoholic steatohepatitis rat livers. We concluded biopterin glucoside is a major component of Spirulina (Arthrospira) platensis action.

Topological Regulation of the Bioactive Conformation of a Disulfide-Rich Peptide, Heat-Stable Enterotoxin.

Heat-stable enterotoxin (STa) produced by enterotoxigenic E. coli causes acute diarrhea and also can be used as a specific probe for colorectal cancer cells. STa contains three intra-molecular disulfide bonds (C1-C4, C2-C5, and C3-C6 connectivity). The chemical synthesis of STa provided not only the native type of STa but also a topological isomer that had the native disulfide pairings. Interestingly, the activity of the topological isomer was approximately 1/10-1/2 that of the native STa. To further investigate the bioactive conformation of this molecule and the regulation of disulfide-coupled folding during its chemical syntheses, we examined the folding mechanism of STa that occurs during its chemical synthesis. The folding intermediate of STa with two disulfide bonds (C1-C4 and C3-C6) and two Cys(Acm) residues, the precursor peptide, was treated with iodine to produce a third disulfide bond under several conditions. The topological isomer was predominantly produced under all conditions tested, along with trace amounts of the native type of STa. In addition, NMR measurements indicated that the topological isomer has a left-handed spiral structure similar to that of the precursor peptide, while the native type of STa had a right-handed spiral structure. These results indicate that the order of the regioselective formation of disulfide bonds is important for the regulation of the final conformation of disulfide-rich peptides in chemical synthesis.

A voxel-based analysis of brain activity in high-order trigeminal pathway in the rat induced by cortical spreading depression.

Cortical spreading depression (SD) is a self-propagating wave of depolarization that is thought to be an underling mechanism of migraine aura. Growing evidence demonstrates that cortical SD triggers neurogenic meningeal inflammation and contributes to migraine headaches via subsequent activation of trigeminal afferents. Although direct and indirect evidence shows that cortical SD activates the trigeminal ganglion (peripheral pathway) and the trigeminal nucleus caudalis (TNC, the first central site of the trigeminal nociceptive pathway), it is not yet known whether cortical SD activates the high-order trigeminal nociceptive pathway in the brain. To address this, we induced unilateral cortical SD in rats, and then examined brain activity using voxel-based statistical parametric mapping analysis of FDG-PET imaging. The results show that approximately 40h after the induction of unilateral cortical SD, regional brain activity significantly increased in several regions, including ipsilateral TNC, contralateral ventral posteromedial (VPM) and posterior thalamic nuclei (Po), the trigeminal barrel-field region of the primary somatosensory cortex (S1BF), and secondary somatosensory cortex (S2). These results suggest that cortical SD is a noxious stimulus that can activate the high-order trigeminal nociceptive pathway even after cortical SD has subsided, probably due to prolonged meningeal inflammation.

Blood transfusion therapy for traumatic cardiopulmonary arrest.

BACKGROUND: Blood transfusion therapy (BTT), which represents transplantation of living cells, poses several risks. Although BTT is necessary for trauma victims with hemorrhagic shock, it may be futile for patients with blunt traumatic cardiopulmonary arrest (BT-CPA). MATERIALS AND METHODS: We retrospectively examined the medical records of consecutive patients with T-CPA. The study period was divided into two periods: The first from 1995-1998, when we used packed red cells (PRC) regardless of the return of spontaneous circulation (ROSC), and the second from 1999-2004, when we did not use PRC before ROSC. The rates of ROSC, admission to the ICU, and survival-to-discharge were compared between these two periods. RESULTS: We studied the records of 464 patients with BT-CPA (175 in the first period and 289 in the second period). Although the rates of ROSC and admission to the ICU were statistically higher in the first period, there was no statistical difference in the rate of survival-to-discharge between these two periods. In the first period, the rate of ROSC was statistically higher in the non-BTT group than the BTT group. However, for cases in which ROSC was performed and was successful, there were no statistical differences in the rate of admission and survival-to-discharge between the first and second group, and between the BTT and non-BTT group. CONCLUSION: Our retrospective consecutive study shows the possibility that BTT before ROSC for BT-CPA and a treatment strategy that includes this treatment improves the success rate of ROSC, but not the survival rate. BTT is thought to be futile as a treatment for BT-CPA before ROSC.

[Retropharyngo-esophageal hematoma treated by open paramedian tracheostomy].

Forty eight year-old woman with untreated liver cirrhosis was transferred to our critical care and emergency center because of airway crisis due to retropharyngo-esophageal hematoma after slight chest contusion. We performed emergency tracheal intubation beyond stenotic part of the trachea. The hematoma did not diminished in a few days. Although we considered tracheostomy, we hesitated to perform conventional median tracheostomy because of the risk of complication of infection of the hematoma which might require drainage or removal resulting in contamination between tracheostomy site and cervical wound. We performed paramedian tracheostomy by antero-lateral skin incision to avoid these risks. Fortunately, the patient did not require drainage of the retropharyngo-esophageal hematoma. Paramedian tracheostomy should be taken into account for patients with presumably contaminated cervical wound.

Duodenal perforation due to compression necrosis by the tip of percutaneous endoscopic gastrostomy tube.

Percutaneous endoscopic gastrostomy (PEG) is a common and safe procedure for enteral nutrition. There are few reports concerning its complications. We managed a 31-y-old bedridden case with punched out duodenal perforation without inflammation, from which the tip of the PEG tube protruded. Simple x-ray and computed tomography showed incarceration of the balloon in the duodenal bulb and extravasation of the tip of the tube. We performed simple closure with omental patching for duodenal perforation. Postoperative gastrointestinal fiberscopy on the 11th day revealed scar phase. Some PEG tubes have a balloon, which can prevent the removal of the tube, fix the position of the tube, and prevent the leakage of gastric contents from fistula. However, in our case, the inflated balloon was transferred into the duodenal bulb according to gastric strong peristalsis. This pathophysiologic mechanism is the same as ball bulb syndrome, which is known as gastroduodenal obstruction by incarceration of the gastric submucosal tumor. There is a risk of wedging of the inflated balloon of the PEG tube and perforation of the duodenum. We must not insert the tube too deeply, must not continue to inflate the balloon for a long time, and must check its position using a stethoscope, simple x-ray examination, or ultrasound.

Outcomes from prehospital cardiac arrest in blunt trauma patients.

BACKGROUND: There are few strategies for treating patients who have suffered cardiopulmonary arrest due to blunt trauma (BT-CPA). The aim of this population-based case series observational study was to clarify the outcome of BT-CPA patients treated with a standardized strategy that included an emergency department thoracotomy (EDT) under an emergency medical service (EMS) system with a rapid transportation system. METHODS: The 477 BT-CPA registry data were augmented by a review of the detailed medical records in our emergency department (ED) and action reports in the prehospital EMS records. RESULTS: Of those, 76% were witnessed and 20% were CPA after leaving the scene. In all, 18% of the patients went to the intensive care unit (ICU), the transcatheter arterial embolization (TAE) room, or the operating room (OR). Only 3% survived to be discharged. Among the 363 witnessed patients-11 of whom had ventricular fibrillation (VF) as the initial rhythm, 134 exhibiting pulseless electrical activity (PEA), and 221 with asystole-13, 1, and 3%, respectively, survived to discharge. The most common initial rhythm just after collapse was not VF but PEA, and asystole increased over the 7 min after collapse. There were no differences in the interval between arrival at the hospital and the return of spontaneous circulation between the patients that survived to discharge and deceased patients in the ED, OR, TAE room, or ICU. The longest interval was 17 min. CONCLUSIONS: In BT-CPA patients, a 20-min resuscitation effort and termination of the effort are thought to be relevant. The initial rhythm is not a prognostic indicator. We believe that the decision on whether to undertake aggressive resuscitation efforts should be made on a case-by-case basis.

Usefulness and safety of open tracheostomy by a paramedian approach for cervical infection: esophageal and tracheal injury and necrotizing fascitis.

Tracheostomy is hardly performed in patients with cervical infection close to the site of the tracheostomy. This study aimed to present and clarify the usefulness and safety of open tracheostomy performed by the paramedian approach technique. The procedure is as follows. A 2.5-cm paramedian incision is made for the tracheostomy on the opposite side of infectious focus; the anterior neck muscles are dissected and split; the trachea is fenestrated by a reverse U-shaped incision; and the fenestral flap of the trachea is fixed to the skin. We used this technique in five patients. There were no complications such as bleeding, desaturation, and displacement of the tube; and there were no postoperative complications such as severe contamination or infection of the tracheostomy site from the nearby cervical wound, difficulty in securing the tracheostomy tube and connecting device to the ventilator, difficulties in daily management and care, or dislocation of the tracheostomy tube. All wounds resulting from the tracheostomy were kept separate from and not contaminated by the nearby dirty wounds. Open tracheostomy by the paramedian approach technique is useful and safe for patients with severe cervical infection requiring open drainage and long ventilatory management.

Cardiopulmonary arrest on arrival due to penetrating trauma.

INTRODUCTION: The aim of this study was to clarify the outcome of patients with cardiopulmonary arrest on arrival due to penetrating trauma (PT-CPA) and to establish the treatment strategy. PATIENTS AND METHODS: The clinical course of 29 patients with PT-CPA over the past 10 years was examined. We have taken three approaches to these patients: (i) an aggressive treatment strategy; (ii) an in-hospital system supporting this aggressive resuscitation; and (iii) the pre-hospital emergency medical service (EMS) system in our city. RESULTS: Although the return of spontaneous circulation (ROSC) was established in 59% of patients, only 17% survived for 7 days, 14% were discharged, and 7% were neurologically intact. Of 10 patients showing pulseless electrical activity (PEA) on the scene, ROSC was established in 100% and 30% were discharged; however, of 12 patients showing asystole, ROSC was established in 33% and no patient could be discharged. There was no difference in the time interval from the arrival at the emergency department to ROSC between discharged patients and patients who died. The time interval from collapse to arrival at the emergency department in discharged patients and patients who went to the intensive care unit was shorter than that of patients who died in the emergency department with and without ROSC. CONCLUSIONS: We cannot decide to give up and terminate resuscitation in any PT-CPA patients and cannot define salvageable patients. However, our data show that 30-min resuscitation is thought to be relevant and that we should not give up on resuscitation because of the time interval without ROSC after arrival at the hospital.

[Experience of damage control as the primary surgery for thoraco-abdominal injury with hemorrhagic shock].

We experienced a traumatic victim with thoracic and abdominal injury with hemorrhagic shock, who was successfully treated with damage control. Thoracic drainage revealed more than 300 ml/hour of continuous hemorrhage in the left thoracic cavity with 60-80 mmHg of non-responding hypotention. Although we performed emergency partial resection of the injured lung, intraabdominal packing and transcatheter arterial embolization, intrathoracic hemorrhage and hemorrhagic shock was not controlled. We decided re-thoracotomy and performed peri-pulmonary packing around the injured lung, by which we successfully controlled temporary intrathoracic hemorrhage and definitive left lower lobectomy. Peri-pulmonary packing was effective for intrathoracic hemostasis without lethal ventilatory and circulatory complication in this case.

Distribution of colour-selective activity in the monkey inferior temporal cortex revealed by functional magnetic resonance imaging.

Previous electrophysiological, neuroimaging and lesion studies have suggested that the anterior part of the monkey inferior temporal (IT) cortex, or area TE, plays an important role in colour processing. However, little is known about how colour information is distributed in these cortical regions. Here, we explored the distribution of colour-selective activity in alert macaque monkeys using functional magnetic resonance imaging (fMRI) with two types of stimuli: a multicoloured ('Mondrian') pattern and an isoluminant colour grating. These two types of stimuli are both commonly used in human fMRI studies, but Mondrian stimuli, which contain a richer variety of hues and hence might be more suitable for activating higher-order areas than grating stimuli, have not been used to examine colour-selectivity in higher-order areas in earlier monkey studies. With the Mondrian stimuli, we observed that areas along the ventral pathway, V1, V2/V3, V4 and the IT cortex, responded more strongly to colour stimuli than to luminance stimuli. In the IT cortex, we found that colour-selective activities are not distributed uniformly, but are localized in discrete regions, each extending several millimetres in the anterior or posterior part of the IT cortex. The colour-selective activation in the anterior IT was observed only with the Mondrian stimuli, whereas the colour-selective activation in the posterior IT was observed with both the Mondrian and grating stimuli, with little overlap. These findings suggest that there are multiple subregions with differing stimulus selectivities distributed in the IT cortex, and that colour information is processed in these discrete subregions.

Lethal obstructive colitis: how and when patients with colonic obstruction should be prevented from falling into a lethal condition.

BACKGROUND/AIMS: The objective of this study is to clarify the pathological condition and treatment strategy of lethal obstructive colitis (LOC), which is defined as obstructive colitis with severe shock or septic shock. METHODOLOGY: We examined 5 patients with LOC (colorectal cancer or suspected in 2, fecal impaction in 2, and volvulus in 1) and evaluated their pathophysiology and management strategy from their medical records. RESULTS: Emergency operations were performed within 150 minutes from arrival in all cases. Three were saved by repeat operations and 2 died. The systolic pressure of both survived and deceased patients were under 62 or palpable only on the common carotid artery, and there was no difference between survived and deceased patients. The mean pulse rate of the deceased patients was 76.5 while survived 117.7. Two deceased patients presented unconsciousness or conscious disorder while survived patients showed clear consciousness. The 2 deceased patients fell into VT just after arrival or during the operation. CONCLUSIONS: In managing colonic obstruction, we should be aware of this potentially lethal disease and surgical treatment should be performed as soon as possible before the patients fall into LOC. Early diagnosis and early aggressive surgery is essential for managing LOC.

Ultrasonography for the diagnosis of intraperitoneal free air in chest-abdominal-pelvic blunt trauma and critical acute abdominal pain.

OBJECTIVE: To clarify the usefulness of ultrasonography (US) as a diagnostic instrument for intraperitoneal free air (IPFA), which is thought to be useful in the fields of emergency medicine and traumatology. DESIGN: Prospective observational study. SETTING: Tertiary critical care and emergency center. PATIENTS: A total of 484 patients with severe chest-abdominal-pelvic blunt trauma or, in the absence of such trauma, severe acute abdominal pain were examined using US to detect IPFA. The exclusion criteria consisted of hemorrhagic shock with massive intraperitoneal fluid, penetrating or open abdominal trauma, and transfer to our center when general surgeons were absent. MAIN OUTCOME MEASURES: The primary outcome measure was the sensitivity and specificity of US for the diagnosis of gastrointestinal perforation performed by gastroenterologic or general surgeons with more than 5 years of experience with US. A US diagnosis of IPFA was made if high-echoic spots in the ventral space of the liver were detected. Conclusive diagnosis of gastrointestinal perforation was made based on the operative findings or on radiologic and clinical observation for more than 4 days. RESULTS: Fifty-four patients were diagnosed as having gastrointestinal perforation. In patients with blunt abdominal trauma, sensitivity for the diagnosis of gastrointestinal perforation by US was 85.7% and specificity was 99.6%; in patients with severe acute abdominal pain, sensitivity was 85.0% and specificity was 100.0%. CONCLUSION: Ultrasonography is useful for the diagnosis of IPFA with acute abdominal pain or blunt trauma, except in patients with gastrointestinal perforation without IPFA.

Primary osteosarcoma of the breast.

Presented herein is a case of primary pure osteosarcoma of the breast. A 59-year-old woman noticed a left breast tumor. Mammography showed a cluster of crushed stone-like calcifications, which gave the tumor a raw cotton-like appearance. Malignancy was suspected on fine-needle aspiration cytology of the tumor. An excisional biopsy was performed. The tumor was 2.0 x 2.4 cm in size. Histopathologically the tumor was composed of diffuse atypical cells with mitosis and a lot of bone. Atypical cells were thought to be neoplastic osteoblasts. Multinucleated osteoclastic cells were interspersed with osteoblasts. Spindle cells were found at the verge of the tumor. A few entrapped tubular structures were seen. Immunohistochemistry indicated that neoplastic osteoblastic cells of the tumor were stained positively for vimentin, but negatively for epithelial markers; which suggested that the tumor cell elements originated from epithelial cells. This tumor was diagnosed as primary extraskeletal osteosarcoma. Partial resection was additionally performed around the excisional biopsy without dissection of the axillary lymph nodes. Bone radionuclide scan after operation showed no abnormal uptake. At 5 years after surgery no recurrence was seen.

Lethal perianal infection with septic shock: how should we manage this critical condition?

Some patients with perianal infection fall into a critical condition with severe sepsis and septic shock (lethal perianal infection). The objective of this study is to clarify the clinicopathological characteristics of, and treatment strategies for, lethal perianal infection. The clinical records of 7 patients with lethal perianal infection were examined. For two rapidly dying cases (within 3 days), we performed resection of the rectum or local anal drainage as a primary management of damage control. These patients were transferred to our center because of septic shock and multiple organ dysfunction syndrome (MODS) and had received insufficient fluid resuscitation in the previous hospital. Another nonsurviving case who died on the 16th day was transferred without MODS and underwent perianal drainage but could not recover from shock, even after repeated surgical procedures were performed. To prevent a perianal infection from becoming lethal, it should be managed as early as possible with sufficient fluid resuscitation with adequate drainage.

Trans-abdominal-mediastinal approach with median phrenotomy for esophageal disruption.

BACKGROUND/AIMS: The prognosis for esophageal disruption is still poor. The aim of this study is to clarify the usefulness and safety of the transabdominal-mediastinal approach for spontaneous esophageal disruption. METHODOLOGY: The surgical procedure is as follows: upper median laparotomy with resection of the xyphoid process, folding up of the lateral segment of the left liver, median phrenotomy from the root of the xyphoid process to the esophageal hiatus, trans-mediastinal left thoracotomy by blunt dissection, blind lavage of the thoracic cavity, and simple interrupted suture and fundic patch of this suture line, if necessary. RESULTS: We managed 3 cases using this technique. Two cases had severe prior chronic diseases (poorly controlled diabetes and liver cirrhosis, and hemodialysis). In all cases, the lesions were completely exposed in the abdomen by and the ruptured sites were safely and completely sutured under a good field of view. The left thoracic cavity was adequately washed. All cases were saved without lethal complication. One case showed minor leakage, which was easily managed by continuous high pressure aspiration using double luminal drainage system (CHPA-DLD). CONCLUSIONS: We concluded that our technique is useful for esophageal disruption long after the onset, with severe prior chronic diseases, or with pleuritis.

Functional segregation of the inferior frontal gyrus for syntactic processes: a functional magnetic-resonance imaging study.

We used functional magnetic resonance imaging in 18 normal volunteers to determine whether there is separate representation of syntactic, semantic, and verbal working memory processing in the left inferior frontal gyrus (GFi). We compared a sentence comprehension task with a short-term memory maintenance task to identify syntactic and semantic processing regions. To investigate the effects of syntactic and verbal working memory load while minimizing the differences in semantic processes, we used comprehension tasks with garden-path (GP) sentences, which require re-parsing, and non-garden-path (NGP) sentences. Compared with the short-term memory task, sentence comprehension activated the left GFi, including Brodmann areas (BAs) 44, 45, and 47, and the left superior temporal gyrus. In GP versus NGP sentences, there was greater activity in the left BAs 44, 45, and 46 extending to the left anterior insula, the pre-supplementary motor area, and the right cerebellum. In the left GFi, verbal working memory activity was located more dorsally (BA 44/45), semantic processing was located more ventrally (BA 47), and syntactic processing was located in between (BA 45). These findings indicate a close relationship between semantic and syntactic processes, and suggest that BA 45 might link verbal working memory and semantic processing via syntactic unification processes.

Source of nonlinearity of the BOLD response revealed by simultaneous fMRI and NIRS.

The nonlinearity of the blood oxygenation level-dependent (BOLD) response to stimuli of different duration, particularly those of short duration, has been well studied by functional magnetic resonance imaging (fMRI). This nonlinearity is assumed to be due to neural adaptation and the nonlinearity of the response in the oxygen extraction fraction (OEF); the latter has not been examined quantitatively in humans. To evaluate how the OEF response contributes to the nonlinearity of the BOLD response to neural activity, we used simultaneous fMRI and near-infrared spectroscopy (NIRS). The responses to visual stimuli of four different durations were measured as changes in the BOLD signal and the NIRS-derived hemoglobin concentrations. The hemodynamic response nonlinearity was quantified using an impulse response function model with saturation nonlinearity scaling in the response amplitude, assuming that the unknown neural adaptation parameters varied within a physiologically feasible range. Independent of the degree of neural adaptation, the BOLD response consistently showed saturation nonlinearity similar to that of the OEF response estimated from the NIRS measures, the nonlinearity of which was greater than that of the response in the total hemoglobin concentration representing the cerebral blood volume (CBV). We also found that the contribution of the OEF response to the BOLD response was four to seven times greater than the contribution of the CBV response. Thus, we conclude that the nonlinearity of the BOLD response to neural activity originates mainly from that of the OEF response.