Genetically encoded Ca2+-sensor reveals details of porcine endothelial cell activation upon contact with human serum

The activation of the endothelial surface in xenografts is still a poorly understood process and the consequences are unpredictable. The role of Ca²⁺-messaging during the activation of endothelial cells is well recognized and routinely measured by synthetic Ca²⁺-sensitive fluorophors. However, these compounds require fresh loading immediately before each experiment and in particular when grown in state-of-the-art 3D cell culture systems, endothelial cells are difficult to access with such sensors. Therefore, we developed transgenic pigs expressing a Ca²⁺-sensitive protein and examined its principal characteristics. Primary transgenic endothelial cells stimulated by ATP showed a definite and short influx of Ca²⁺ into the cytosol, whereas exposure to human serum resulted in a more intense and sustained response. Surprisingly, not all endothelial cells reacted identically to a stimulus, rather activation took place in adjacent cells in a timely decelerated way and with distinct intensities. This effect was again more pronounced when cells were stimulated with human serum. Finally, we show clear evidence that antibody binding alone significantly activated endothelial cells, whereas antibody depletion dramatically reduced the stimulatory potential of serum. Transgenic porcine endothelial cells expressing a Ca²⁺-sensor represent an interesting tool to dissect factors inducing activation of porcine endothelial cells after exposure to human blood or serum.     

Infradiaphragmatic malperfusion of acute aortic dissection associated with previous abdominal aortic aneurysm repair

Purpose

To evaluate the association of previous abdominal aortic aneurysm (AAA) graft replacement with infradiaphragmatic malperfusion in patients with acute aortic dissection.

Methods

Between November 2006 and June 2011, 133 patients were referred to our hospital for management of acute aortic dissection. Eight (6.0 %) of these patients had undergone AAA graft replacement prior to the acute aortic dissection. We compared the computed tomography (CT) images of these 8 patients with those of the remaining 125 patients without previous AAA graft replacement, in terms of organ ischemia as a complication induced by acute aortic dissection.

Results

Infradiaphragmatic malperfusion from acute aortic dissection was confirmed in four of the eight patients who had undergone AAA graft replacement. Contrasted CT scan images indicated that the main cause of infradiaphragmatic malperfusion was collapse of the true lumen from compression by the false lumen into the suprarenal aorta. Although there was no significant difference between the groups in terms of cerebral ischemia and myocardial ischemia, bilateral leg ischemia and visceral ischemia occurred more frequently in the patients who had undergone AAA graft replacement.

Conclusion

Previous AAA graft replacement is a risk factor for infradiaphragmatic malperfusion in patients with acute aortic dissection.     

Glucose uptake of the muscle and adipose tissues in diabetes and obesity disease models: evaluation of insulin and β3-adrenergic receptor agonist effects by <Superscript>18</Superscript>F-FDG

Objective

One of the major causes of diabetes and obesity is abnormality in glucose metabolism and glucose uptake in the muscle and adipose tissue based on an insufficient action of insulin. Therefore, many of the drug discovery programs are based on the concept of stimulating glucose uptake in these tissues. Improvement of glucose metabolism has been assessed based on blood parameters, but these merely reflect the systemic reaction to the drug administered. We have conducted basic studies to investigate the usefulness of glucose uptake measurement in various muscle and adipose tissues in pharmacological tests using disease-model animals.

Methods

A radiotracer for glucose, ¹⁸F-2-deoxy-2-fluoro-d-glucose (¹⁸F-FDG), was administered to Wistar fatty rats (type 2 diabetes model), DIO mouse (obese model), and the corresponding control animals, and the basal glucose uptake in the muscle and adipose (white and brown) tissues were compared using biodistribution method. Moreover, insulin and a β3 agonist (CL316,243), which are known to stimulate glucose uptake in the muscle and adipose tissues, were administered to assess their effect. ¹⁸F-FDG uptake in each tissue was measured as the radioactivity and the distribution was confirmed by autoradiography.

Results

In Wistar fatty rats, all the tissues measured showed a decrease in the basal level of glucose uptake when compared to Wistar lean rats. On the other hand, the same trend was observed only in the white adipose tissue in DIO mice, while brown adipose tissue showed increments in the basal glucose uptake in this model. Insulin administration stimulated glucose uptake in both Wistar lean and fatty rats, although the responses were inhibited in Wistar fatty rats. The same tendency was shown also in control mice, but clear increments in glucose uptake were not observed in the muscle and brown adipose tissue of DIO mice after insulin administration. β3 agonist administration showed the similar trend in Wistar lean and fatty rats as insulin, while the responses were inhibited in the adipose tissues of Wistar fatty rats.

Conclusion

A system to monitor tissue glucose uptake with ¹⁸F-FDG enabled us to detect clear differences in basal glucose uptake between disease-model animals and their corresponding controls. The responses in the tissues to insulin or β3 agonist could be identified. Taken as a whole, the biodistribution method with ¹⁸F-FDG was confirmed to be useful for pharmacological evaluation of anti-diabetic or anti-obesity drugs using disease-model animals.

     

Effect of rotational alignment on patellar tracking in total knee arthroplasty

Forty-four consecutive patients (65 knees) who underwent identical condylar type total knee arthroplasty were evaluated retrospectively. In 22 of the patients (32 knees), the femoral component was set parallel to the posterior condylar axis (neutrally aligned group). In the remaining 22 patients (33 knees), it was set in an external rotation position of 3 degrees to 5 degrees relative to the axis (externally aligned group). Of the total knee arthroplasties in the neutrally aligned group, 34% required lateral release, compared with only 6% in the externally aligned group; patellar tracking in the externally aligned group was significantly better than that in the neutrally aligned group. Postoperative measurements performed using computed tomography scans showed that the mean angle between the prosthetic posterior condylar axis and the transepicondylar axis was 7.9 degrees in the neutrally aligned group and 3.2 degrees in the externally aligned group. The external rotation setting of the femoral component diminished the need for lateral retinacular release and may decrease the rate of patellofemoral complications that occur after total knee arthroplasty.     

Bilateral spinal anterior horn lesions in acute motor axonal neuropathy

Background

Guillain-Barré syndrome is an acute immune-mediated peripheral polyneuropathy. Neuroimaging findings from patients with this syndrome have revealed gadolinium enhancement in the cauda equina and in the anterior and posterior nerve roots, but intra-spinal lesions have never been described.

Factors disturbing treatment for cancer in patients with schizophrenia

Patients with schizophrenia who develop cancer often have a variety of complicated medical and psychiatric problems. Problems associated with receiving a diagnosis of cancer and with understanding or cooperating with medical treatment may develop. Research in managing and treating schizophrenia patients with cancer is scarce. Presented herein is the experience of the authors' consultation-liaison psychiatry service in treating patients with schizophrenia who have cancer, and discussion of the medical management of such cases. Fourteen patients were treated between April 1999 and March 2003 and included patients receiving consultation psychiatric services at Shimane University Hospital as well as patients referred from other psychiatric hospitals. These patients were divided into two groups based on whether they were amenable to cancer treatment or not. The treated group consisted of patients who accepted cancer treatment, and the untreated group consisted of patients who refused or interrupted the cancer treatment. The clinical course, clinical psychiatric symptoms, problems in understanding cancer, cancer treatment course and convalescence were retrospectively assessed. Psychiatric symptoms and state were measured using the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS). The mean of the duration of schizophrenia in these two groups was not significantly different. The mean scores on measures of psychiatric symptoms in each group (treated and untreated) were as follows: BPRS, 45.3+/-15.4 and 64.9+/-9.2 (P<0.05); positive symptoms scores on PANSS, 14.4+/-8.8 and 20.6+/-6.0 (NS); negative symptoms scores on PANSS, 20.6+/-4.7 and 33.6+/-4.4 (P<0.01); and total scores on PANSS, 31.7+/-7.0 and 48.6+/-7.4 (P<0.01). Patients with severe negative symptoms had greater difficulty understanding and cooperating with the cancer treatment. Regarding cancer stage, when cancer was discovered, the disease had already advanced and was no longer amenable to first-line treatment. Regarding notification of the diagnosis, it was rarely possible to give sufficiently early notice to patients in the untreated group. The important role of consultation-liaison psychiatrist in treating cancer patients is suggested. Some steps are proposed for managing schizophrenia patients with cancer who are not able to give informed consent.     

Yi-gan san for the treatment of neuroleptic-induced tardive dyskinesia: an open-label study

BACKGROUND: Recent studies indicate that the traditional Japanese herbal medicine yi-gan san (YGS, yokukan-san in Japanese), a serotonin modulator, may be safe and useful in treating behavioral and psychological symptoms in dementia and borderline personality disorder patients. The authors examined the efficacy, tolerability, and safety of YGS in patients with tardive dyskinesia. METHODS: Twenty-two patients with schizophrenia who had neuroleptic-induced tardive dyskinesia were given 7.5 g/day of YGS for 12 weeks in an open-label study. RESULTS: Administration of YGS resulted in a statistically significant improvement in tardive dyskinesia and psychotic symptoms. CONCLUSIONS: YGS may be an effective and safe therapy to control tardive dyskinesia and psychosis in patients with schizophrenia, that should be further tested in double-blind, placebo-controlled trials.     

Effect of Yi-Gan San on psychiatric symptoms and sleep structure at patients with behavioral and psychological symptoms of dementia

OBJECTIVE: Recently, traditional herbal medicines have been reported to be effective for behavioral and psychological symptoms of dementia (BPSD). This study aims to examine the efficacy of Yi-Gan San (YGS) in the improvement of BPSD and sleep disorders in patients with dementia. METHODS: Five patients (1 male and 4 female) with dementia in accordance with DSM-IV criteria were investigated. Participants were treated with YGS for 4 weeks. The Nursing Home version of Neuropsychiatric Inventory (NPI-NH) for the assessment of BPSD, the Mini-Mental State Examination (MMSE) for cognitive function, polysomnography for evaluation of sleep structure, and the Pittsburgh Sleep Quality Index for subjective sleep quality were carried out at baseline and at the end of treatment. RESULTS: All patients completed the trial. Significant improvements in the total NPI-NH score (34.0+/-6.5 to 12.8+/-6.6) as well as delusions, hallucinations, agitation/aggression, anxiety, and irritability/lability, whereas MMSE scores were unchanged. PSG revealed increases in total sleep time, sleep efficiency, stage 2 sleep, and decreases in the number of arousals and periodic limb movements. Subjective sleep quality was also improved. No adverse effects were observed. CONCLUSION: YGS was effective for BPSD and sleep disturbances, and well tolerated in patients with dementia. Further examinations using a double-blind placebo-controlled design are necessary.     

Two-dimensional and Doppler echocardiographic assessment of variably shaped ductus arteriosus by the parasternal approach

Summary Parasternal two-dimensional and Doppler echocardiography were compared with angiographic, surgical, and postmortem data in 213 patients with various forms of congenital heart disease for its accuracy in determining patency and anatomy of the ductus arteriosus (DA). The age range of the examined patients was from 1 day to 4 years (mean, 7.4 months). Echocardiography was always performed before any invasive procedure. An adequate window for imaging the DA was obtained by parasternal, two-dimensional echocardiography in 209 patients (98%). A persistent ductus arteriosus (PDA) was detected by invasive methods in 79 of 209 patients (38%), and by two-dimensional and Doppler echocardiography in 76 (sensitivity, 96%; specificity, 100%). The echocardiographic and angiographic findings agreed closely as to the duct's morphology. Our technique permits an accurate visualization of the duct in neonates, infants, and small children with various forms of congenital heart disease.