Effects of intraperitoneal administration of liposomes and methods of preparing liposomes for local therapy.

Many different methods of preparing liposomes exist, but the biological and physical properties of these preparations are not known. We therefore investigated the physical properties of liposomal doxorubicin (DOX) and found it to be most effective when administered intraperitoneally for carcinoma in the abdominal cavity. Liposomal DOX was prepared in three ways, by the Bangham method (BLDOX), pH gradient method, and gelation method. We investigated the physical properties of each preparation. And then we investigated the effects of the liposomes and liposomal lipids on the uptake of DOX by carcinoma cells in vitro and on the survival of Ehrlich ascites carcinoma-bearing mice in vivo. The uptake of DOX by the cells differed significantly with each liposome in vitro. The physical properties of the liposomes, including liposomal membrane lipids, size, zeta potentials and fluidity of liposomal membrane, were not so different, but the leak level of entrapped DOX from the liposomes was. Furthermore, the survival of ascites tumor-bearing mice also differed with each liposome preparation, DMPC containing BLDOX being the most effective when administered intraperitoneally. The method of preparation is an important factor affecting the properties of liposomes, and for local therapy, DMPC containing BLDOX is most effective because of its leaky property.     

Liposomal photofrin enhances therapeutic efficacy of photodynamic therapy against the human gastric cancer

Photodynamic therapy (PDT) has been established as a potent and less invasive treatment for gastrointestinal tumors. The aim of the present study was to investigate whether or not liposomalization of the photosensitizer enhanced the therapeutic efficacy of PDT. Photofrin (PF) was entrapped in multilammelar liposomes. Mice implanted with a human gastric cancer xenograft, were divided into a PF group and a liposomal photofrin (LPF) group and intravenously administered 10 mg/kg of PF or LPF (as a dose of PF), respectively. At 8 h after injection PF level in tumor tissue in the LPF group was significantly higher level by 2.4-fold of that in the PF group, whereas the PF levels in the skin were almost equal. Irradiation was performed with the excimer dye laser at 150 mW/cm(2), total dose 40 J, at 8 h after PF or LPF administration. The results revealed that the volume of necrotic tumor tissue was significantly higher in the LPF group than in the PF group. The apoptotic index of the tumor was also significantly higher in the LPF group. In conclusion, the liposomalization of the photosensitizer increased its tumor accumulation, with a resulting enhancement of the therapeutic effect of PDT.     

A voxel-based morphometry study of gray and white matter correlates of a need for uniqueness

People appear to derive intrinsic satisfaction from the perception that they are unique, special, and separable from the masses, which is referred to as a need for uniqueness (NFU). NFU is a universal human trait, along with a tendency to conform to the beliefs and attitudes of others and social norms. We used voxel-based morphometry and a questionnaire to determine individual NFU and its association with brain structures in healthy men (94) and women (91; age, 21.3±1.9years). Individual NFU was associated with smaller gray matter volume of a cluster that included areas in (a) the left middle temporal gyrus, left superior temporal gyrus, and left superior temporal sulcus (STS); (b) the dorsal part of the anterior cingulate gyrus and the anterior part of the middle cingulate gyrus; and (c) the right inferior frontal gyrus and the ventral part of the precentral gyrus. Individual NFU was also associated with larger white matter concentration of a cluster that mainly included the body of the corpus callosum. These findings demonstrated that variations in NFU reflect the gray and white matter structures of focal regions. These findings suggest a biological basis for individual NFU, distributed across different gray and white matter areas of the brain.     

Regional gray and white matter volume associated with Stroop interference: evidence from voxel-based morphometry

During Stroop tasks, subjects experience cognitive interference when they resolve interferences such as identifying the ink color of a printed word while ignoring the word's identity. Stroop paradigms are commonly used as an index of attention deficits and a tool for investigating the functions of the frontal lobes and other associated structures. Despite these uses and the vast amount of attention given to Stroop paradigms, the regional gray matter volume/regional white matter volume (rGMV/rWMV) correlates of Stroop interference have not yet been identified at the whole brain level in normal adults. We examined this issue using voxel-based morphometry in right-handed healthy young adults. We found significant negative relationships between the Stroop interference rate and rGMV in the anterior cingulate cortex (ACC), right inferior frontal gyrus, and cerebellum. Furthermore, we found relationships between the Stroop interference rate and rWMV in bilateral anatomical clusters that extended around extensive WM regions in the dorsal part of the frontal lobe. These findings are the first to reveal rGMV/rWMV that underlie the performance of the Stroop task, a widely used psychological paradigm at the whole brain level. Of note, our findings support the notion that ACC contributes to Stroop performance and show the involvement of regions that have been implicated in response inhibition and attention.     

Correlation among body height, intelligence, and brain gray matter volume in healthy children

A significant positive correlation between height and intelligence has been demonstrated in children. Additionally, intelligence has been associated with the volume of gray matter in the brains of children. Based on these correlations, we analyzed the correlation among height, full-scale intelligence quotient (IQ) and gray matter volume applying voxel-based morphometry using data from the brain magnetic resonance images of 160 healthy children aged 5-18 years of age. As a result, body height was significantly positively correlated with brain gray matter volume. Additionally, the regional gray matter volume of several regions such as the bilateral prefrontal cortices, temporoparietal region, and cerebellum was significantly positively correlated with body height and that the gray matter volume of several of these regions was also significantly positively correlated with full-scale intelligence quotient (IQ) scores after adjusting for age, sex, and socioeconomic status. Our results demonstrate that gray and white matter volume may mediate the correlation between body height and intelligence in healthy children. Additionally, the correlations among gray and white matter volume, height, and intelligence may be at least partially explained by the effect of insulin-like growth factor-1 and growth hormones. Given the importance of the effect of environmental factors, especially nutrition, on height, IQ, and gray matter volume, the present results stress the importance of nutrition during childhood for the healthy maturation of body and brain.     

Successful treatment of congenital cytomegalovirus infection with valganciclovir

Congenital cytomegalovirus (CMV) infection occurs frequently in neonates. However, there are no screening tests or definitive treatments for this infection in Japan. We report a case of a 21-day-old Japanese boy with congenital CMV infection. He was referred to our hospital for treatment of congenital bilateral deafness. Brain magnetic resonance imaging (MRI) revealed cortical dysplasia of the temporal poles, enlarged ventricles, and areas of abnormal intensity in the white matter. He was given a diagnosis of congenital CMV infection based on the detection of CMV DNA in his urine and the umbilical cord. After the administration of valganciclovir, no CMV DNA was detected in his serum, and brain MRI and electroencephalogram findings, motor development, and deafness improved. Further investigation is needed to establish a screening test and treatment for congenital CMV infection in Japan.     

Fatigue and weight loss in Parkinson's disease

Fatigue is a common, under recognized, and poorly understood nonmotor symptom in Parkinson's disease (PD). Fatigue frequently presents early in PD, and its prevalence increases with disease progression, affecting up to 60% of patients. Fatigue has a negative impact on quality of life. Fatigue is often associated with other nonmotor symptoms, including sleep disturbance, excessive daytime sleepiness, and depression. Only a few reports have been published on the treatment of fatigue in PD (methylphenidate, levodopa, and pramipexole). Further well-designed studies, including physiotherapy, are necessary to develop more effective treatments for PD-associated fatigue. A number of patients with PD lose weight because of loss of fat. However, the evolution and determinants of weight loss are not well established. Possible determinants of weight loss in PD include loss of appetite, impaired hand-mouth coordination, difficulty in chewing and dysphagia, nausea, intestinal hypomotility, and increased energy requirements because of muscular rigidity and involuntary movements. Noticeable weight gain has repeatedly been reported after subthalamic or pallidal deep brain stimulation. Because low body weight is associated with negative health effects and a poor prognosis, monitoring weight and nutritional status should be part of PD management.