Combination effect of photodynamic and sonodynamic therapy on experimental skin squamous cell carcinoma in C3H/HeN mice

We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide-a derivative PH-1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX-70, a commonly used sonosensitizer. Mice were injected with either PH-1126 or ATX-70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX-70) or 36 hr (PH-1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX-70; 44J/cm2 of 650 nm for PH-1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH-1126 or ATX-70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92-98%) (additive effect) as compared to either single treatment (27-77%). The combination using PH-1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT-treated mice (> 120 days) was significantly greater than that in single treatment groups (77-95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2-3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non-superficial or nodular tumors.     

Robotic gait trainer in water: Development of an underwater gait-training orthosis

Purpose.?To develop a robotic gait trainer that can be used in water (RGTW) and achieve repetitive physiological gait patterns to improve the movement dysfunctions.

Method.?The RGTW is a hip-knee-ankle-foot orthosis with pneumatic actuators; the control software was developed on the basis of the angular motions of the hip and knee joint of a healthy subject as he walked in water. Three-dimensional motions and electromyographic (EMG) activities were recorded in nine healthy subjects to evaluate the efficacy of using the RGTW while walking on a treadmill in water.

Results.?The device could preserve the angular displacement patterns of the hip and knee and foot trajectories under all experimental conditions. The tibialis anterior EMG activities in the late swing phase and the biceps femoris throughout the stance phase were reduced whose joint torques were assisted by the RGTW while walking on a treadmill in water.

Conclusion.?Using the RGTW could expect not only the effect of the hydrotherapy but also the standard treadmill gait training, in particular, and may be particularly effective for treating individuals with hip joint movement dysfunction.     

Association analysis of FEZ1 variants with schizophrenia in Japanese cohorts.

BACKGROUND: DISC1 has been suggested as a causative gene for psychoses in a large Scottish family. We recently identified FEZ1 as an interacting partner for DISC1. To investigate the role of FEZ1 in schizophrenia and bipolar disorder, case-control association analyses were conducted in Japanese cohorts. METHODS: We performed a mutation screen of the FEZ1 gene and detected 15 polymorphisms. Additional data on informative polymorphisms were obtained from public databases. Eight single nucleotide polymorphisms (SNPs) were analyzed in 119 bipolar disorder and 360 schizophrenic patients and age- and gender-matched control subjects. All genotypes were determined with the TaqMan assay, and selected samples were confirmed by sequencing. RESULTS: The two adjacent polymorphisms displayed a nominally significant association with schizophrenia (IVS2+ 1587G>A, p = .014; 396T   

Gastric bleeding detected by transesophageal echocardiography during cardiopulmonary bypass

Gastric bleeding during cardiopulmonary bypass (CPB) is a rare but life-threatening complication for patients undergoing cardiac surgery. We present a case of a patient undergoing coronary bypass grafting in whom we detected gastric bleeding by transesophageal echocardiography (TEE) during CPB. After separation from CPB, bleeding was stopped by endoscopic clipping of the mucosa. If a fluid deficit is noted and TEE reveals a hypoechoic space within the stomach, gastric bleeding might be suggested.     

Successful therapy of macrophage activation syndrome with dexamethasone palmitate

Macrophage activation syndrome (MAS) is a severe and potential life-threatening complication of childhood systemic inflammatory disorders. Corticosteroids are commonly used as the first-line therapy for MAS. We report four patients with MAS who were successfully treated with dexamethasone palmitate (DexP), a liposome-incorporated dexamethasone, much more efficient than free corticosteroids. DexP effectively inhibited inflammation in MAS patients in whom the response to pulse methylprednisolone was not sufficient to manage their diseases. DexP was also effective as the first-line therapy for MAS. Based on these findings, DexP is an effective therapy in treating MAS patients.     

An intranasal administration of Lactococcus lactis strains expressing recombinant interleukin‐10 modulates acute allergic airway inflammation in a murine model

Background Around 300 million people world‐wide suffer from asthma, and the prevalence of allergic diseases has increased. Much effort has been used in the study of mechanisms involved in the immune response observed in asthma to intervene for the treatment of this condition. During inflammation in asthma, Th2 cytokines and eosinophils are essential components of the host immune system. Furthermore, for therapeutic interventions against this disease, IL‐10 is an important cytokine because it has a central role in the regulation of inflammatory cascades. Objective To evaluate the immunomodulatory effect of Lactococcus lactis strains expressing recombinant IL‐10 in a mouse model of ovalbumin (OVA)‐induced acute airway inflammation. Methods L. lactis expressing recombinant IL‐10 in a cytoplasmic (LL‐CYT) or secreted form (LL‐SEC) and wild‐type (LL‐WT) were used. IL‐10 production by the recombinant strains was evaluated by ELISA. After an intranasal administration of L. lactis producing recombinant IL‐10 and the induction of acute allergic airway inflammation in mice, blood samples were collected to detect IgE anti‐OVA, and bronchoalveolar lavage (BAL) was harvested for eosinophil count. Additionally, the lungs were collected for the detection of the eosinophil peroxidase (EPO) activity, measurement of cytokines and chemokines and evaluation of pathology. Results Mice that received LL‐CYT and LL‐SEC strains showed a significant decrease in eosinophils numbers, EPO activity, anti‐OVA IgE and IgG1 levels, IL‐4 and CCL3 production and pulmonary inflammation and mucus hypersecretion, compared with the asthmatic group. Only the LL‐CYT/OVA group showed reduced levels of IL‐5, CCL2, CCL5 and CCL11. Conclusion Treatment with L. lactis producing recombinant IL‐10 used in this study (LL‐CYT and LL‐SEC) modulated experimental airway inflammation in the mouse model independently of Treg cells. Additionally, the LL‐CYT strain was more efficient in the suppression of lung inflammation. Cite this as: F. A. V. Marinho, L. G. G. Pacífico, A. Miyoshi, V. Azevedo, Y. Le Loir, V. D. Guimarães, P. Langella, G. D. Cassali, C. T. Fonseca and S. C. Oliveira, Clinical & Experimental Allergy, 2010 (40) 1541–1551.     

Primary cutaneous diffuse large B‐cell lymphoma,leg type,with features simulating POEMS syndrome

A 91‐year‐old woman presented with a rapidly proliferative cutaneous lesion on the left lower limb, which was identified as a primary cutaneous diffuse large B‐cell lymphoma (PCLBCL), leg type, on biopsy. The patient also showed complications of hepatomegaly, endocrinopathy, edema, skin change, and polyneuropathy without monoclonal plasma cell proliferative disorder, and was therefore diagnosed with POEMS‐like syndrome owing to the lack of monoclonal plasma cell proliferative disorder. Levels of serum vascular endothelial growth factor (VEGF) and interleukin‐6 (IL‐6) were high with the lymphoma cells immunostained positively for VEGF and IL‐6. To the best of our knowledge, this is the first case report of PCLBCL, leg type, with POEMS‐like syndrome. The findings in this case suggest that the symptoms of POEMS‐like syndrome might be caused by the cytokines produced by the lymphoma cells. Furthermore, a wider range of diagnostic criteria associated with the result of abnormal secretion of cytokine may have to be considered for the diagnosis and evaluation of patients with possible POEMS syndrome, as against the present criteria specifying monoclonal plasma cell proliferative disorder as the essential criterion.     

Flow cytometric analysis of cellular DNA content in ovarian cancer

A total of 169 paraffin-embedded tissue sections from 42 patients with epithelial ovarian cancer were subjected to analysis of cellular DNA content by flow cytometry. Twenty-three cases were found to be homogenously diploid, whereas 19 cases were aneuploid. A "mosaic" type containing both aneuploid and diploid cell populations was found in 11 of 19 aneuploid cases. Clinical features showed significant correlation with tumor ploidy of FIGO stage and bulky disease. In evaluation of the prognostic value of tumor ploidy, "mosaic" tumors were frequently observed in women who died of disease (DOD), whereas women with diploid tumors survived longer than those with "mosaic" tumors. The present results suggest that determination of DNA heterogeneity may be a valuable parameter in the prognosis of epithelial ovarian cancer.     

Vaccination of rabbits with recombinant vaccinia virus carrying the envelope gene of human T-cell lymphotropic virus type I

Two groups of 3 rabbits each were immunized with either recombinant vaccinia virus, WR-SFB5env, carrying the human T-cell lymphotropic virus type I (HTLV-1) env gene at the site of the hemagglutinin gene of the WR strain, or control vaccinia virus, HA-WR, lacking the functional hemagglutinin gene. All 6 rabbits responded with anti-vaccinia virus antibodies. WR-SFB5env elicited anti-HTLV-1 env antibodies but no vesicular stomatitis virus (HTLV-1) pseudotype neutralizing antibodies in all 3 rabbits. After 10 weeks, the animals were challenged by transfusion of blood from an HTLV-1-infected rabbit. Two of the 3 vaccinated rabbits and all 3 control rabbits became infected with HTLV-1, as indicated by seroconversion and detection of HTLV-1 proviral sequences by polymerase chain reaction. The rabbit that had been protected from initial challenge became infected with HTLV-1 upon rechallenge 12 weeks after the first challenge. In view of the proven prophylactic effect of passive immunization against HTLV-1, our vaccine trial failed because WR-SFB5env was incapable of inducing neutralizing antibodies against HTLV-1 in the immunized animals. It remains to be studied whether cell-mediated immunity such as antibody-dependent cellular cytotoxicity was involved in the temporary protection of I vaccinated rabbit.     

Lysosomal thiol proteases (cathepsin B-like proteases) in serous middle ear effusions from adult patients

Hydrolytic activity of cathepsins B, H and trypsin-like proteases was measured in 38 serous middle ear effusion (MEE) samples. The concentrations of (alpha 1-AT) and alpha 2-macroglobulin (alpha 2-M) were also quantitated. The mean value of cathepsin B activity was 25.0 +/- 20.7 RFU and that of cathepsin H was 14.3 +/- 3.0--both significantly higher than those in plasma (1.8 +/- 0.4 RFU, 1.2 +/- 0.3 RFU, p less than 0.005). Very low trypsin-like protease activity could be observed. The mean concentrations of alpha 1-AT and alpha 2-M were 368 +/- 94.8 mg/dl and 57.5 +/- 57.3 mg/dl. The bulk of alpha 1-AT in MEEs was occupied by free alpha 1-AT, which can saturate exogenous trypsin. Due to the very low molar concentration of alpha 2-M in MEEs, thiol proteases (mainly cathepsin B) could be a possible major factor inflicting proteolytic injury on the middle ear mucosa and reflecting the severity of the inflammatory process.