Stable paclitaxel formulations in oily contrast medium.

Stable paclitaxel/Lipiodol solutions as well as emulsions were developed for the treatment of solid tumors including hepatocellular carcinoma. Paclitaxel could be dissolved in Lipiodol, an oily contrast medium, but precipitated out and formed aggregates with time. Paclitaxel precipitation was due to the inter- and intra-molecular hydrogen bonding of paclitaxel molecules. Time-dependent paclitaxel aggregation was completely prevented by adding small amounts of additional solvents, which are miscible with Lipiodol. It was also notable that paclitaxel helped in stabilizing the water-in-oil (w/o) type emulsion of Lipiodol and Iopamiro. The stability, physical properties and in vitro drug release profiles of the stable paclitaxel solutions and emulsions were characterized. When the stable oily paclitaxel solution was used for the treatment of B16F10 melanoma in C57BL/6 mice, the malignant cells were eradicated completely in 2 weeks, whereas the solid tumor grew rapidly and metastasized to the thigh and to other organs in the control group. Also, the mice survived for more than 1 year after the paclitaxel treatment, whereas all of those in the control group died in 40 days.     

Interventions for residents with dementia and their family and staff caregivers: evaluating the effectiveness of measures of outcomes in long-term care

This article describes six instruments developed for programs of research testing nursing interventions for individuals with dementia in Special Care Units and their family and staff caregivers. The Functional Abilities Checklist measures the functional abilities of residents with dementia. The Family Perceptions of Care Tool assesses family member satisfaction with care of the institutionalized relative with dementia. The Family Perceptions of Caregiving Role instrument evaluates stress experienced by family members of individuals with dementia related to their caregiving roles in long-term care settings. The Caregiver Stress Inventory and Staff Perceptions of Caregiving Role tools measure staff stress related to caring for residents with dementia. Finally, the Attitudes About Families Checklist assesses general staff attitudes about families of residents with dementia. Each instrument and its psychometric properties are described. The advantages of these instruments for research and clinical use with individuals with dementia are discussed.     

Cloning of the low-affinity murine granulocyte-macrophage colony-stimulating factor receptor and reconstitution of a high-affinity receptor complex.

A cDNA clone (clone 71) that encodes a low-affinity receptor for murine granulocyte-macrophage colony-stimulating factor (GM-CSF) has been isolated by direct expression. This molecule is the homologue of the human GM-CSF receptor alpha subunit, although homology between these molecules is surprisingly low (less than 35% amino acid identity). The cDNA encodes a polypeptide of 387 amino acids, which contains the conserved features of the hematopoietin receptor superfamily. When expressed in COS-7 cells, this clone encodes a protein that binds radiolabeled murine GM-CSF with low affinity. Coexpression of clone 71 with a cDNA corresponding to a low-affinity interleukin 3 (IL-3) receptor (AIC2A) did not alter the affinity of binding of either GM-CSF or IL-3. However, coexpression of clone 71 with the IL-3 receptor-related cDNA AIC2B generated high-affinity binding sites for murine GM-CSF but not murine IL-3. These studies show that clone 71 and AIC2B are capable of forming an alpha beta complex capable of binding murine GM-CSF with high affinity, while AIC2A appears not to be a component of the murine GM-CSF receptor.     

Long-Term Potentiation of Excitatory Synaptic Strength in Spinothalamic Tract Neurons of the Rat Spinal Cord

Spinal dorsal horn nociceptive neurons have been shown to undergo long-term synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). Here, we focused on the spinothalamic tract (STT) neurons that are the main nociceptive neurons projecting from the spinal cord to the thalamus. Optical technique using fluorescent dye has made it possible to identify the STT neurons in the spinal cord. Evoked fast mono-synaptic, excitatory postsynaptic currents (eEPSCs) were measured in the STT neurons. Time-based tetanic stimulation (TBS) was employed to induce long-term potentiation (LTP) in the STT neurons. Coincident stimulation of both pre- and postsynaptic neurons using TBS showed immediate and persistent increase in AMPA receptor-mediated EPSCs. LTP can also be induced by postsynaptic spiking together with pharmacological stimulation using chemical NMDA. TBS-induced LTP observed in STT neurons was blocked by internal BAPTA, or Ni²⁺, a T-type VOCC blocker. However, LTP was intact in the presence of L-type VOCC blocker. These results suggest that long-term plastic change of STT neurons requires NMDA receptor activation and postsynaptic calcium but is differentially sensitive to T-type VOCCs.     

Yoga Training Improves Metabolic Parameters in Obese Boys

Yoga has been known to have stimulatory or inhibitory effects on the metabolic parameters and to be uncomplicated therapy for obesity. The purpose of the present study was to test the effect of an 8-week of yoga-asana training on body composition, lipid profile, and insulin resistance (IR) in obese adolescent boys. Twenty volunteers with body mass index (BMI) greater than the 95th percentile were randomly assigned to yoga (age 14.7±0.5 years, n=10) and control groups (age 14.6±1.0 years, n=10). The yoga group performed exercises three times per week at 40~60% of heart-rate reserve (HRR) for 8 weeks. IR was determined with the homeostasis model assessment of insulin resistance (HOMA-IR). After yoga training, body weight, BMI, fat mass (FM), and body fat % (BF %) were significantly decreased, and fat-free mass and basal metabolic rate were significantly increased than baseline values. FM and BF % were significantly improved in the yoga group compared with the control group (p<0.05). Total cholesterol (TC) was significantly decreased in the yoga group (p<0.01). HDL-cholesterol was decreased in both groups (p<0.05). No significant changes were observed between or within groups for triglycerides, LDL-cholesterol, glucose, insulin, and HOMA-IR. Our findings show that an 8-week of yoga training improves body composition and TC levels in obese adolescent boys, suggesting that yoga training may be effective in controlling some metabolic syndrome factors in obese adolescent boys.     

Effects of low-intensity laser therapy on periodontal tissue remodeling during relapse and retention of orthodontically moved teeth

This study was designed to investigate the effects of low-intensity laser therapy (LILT) on periodontal ligament (PDL) remodeling during relapse and retention after the completion of orthodontic movement. The maxillary central incisors (n?=?104) of the 52 rats were randomly divided into five groups according to the treatment modality: baseline control group without any intervention (n?=?8); relapse group without retainer after tooth movement (n?=?24); retention group with fixed retainer after tooth movement (n?=?24); lased relapse group without retainer after tooth movement and LILT (n?=?24); lased retention group with retainer after tooth movement and LILT (n?=?24). LILT was daily performed using a gallium–aluminum–arsenide diode laser in a biostimulation mode: wavelength of 780 nm, continuous waves at 70 mW output power, a preset low intensity of 1.75 W/cm² in contact mode, resulting in energy dose of 5 J/cm² per irradiation for 3 s. The animals were euthanized on days 1, 3, and 7 after removal of the orthodontic appliance. Real-time RT-PCR was performed for quantitative analysis of matrix metalloproteinases mRNA expression. Immunoreactivities of collagen and tissue inhibitor of metalloproteinase were observed on the compression and tension sides. LILT significantly facilitated the expression of five tested MMP mRNAs in both relapse and retention groups. TIMP-1 immunoreactivity was inhibited by LILT in both groups, whereas Col-I immunoreactivity was increased by LILT only in the retention group. These results indicate that LILT would act differently on the stability after orthodontic treatment according to additional retainer wearing or not. LILT when combined with a retainer on the moved teeth may shorten the retention period by accelerating periodontal remodeling in the new tooth position, whereas, LILT on the moved teeth left without any retainer would rather increase the rate of relapse after treatment.     

Expression and Activity of the Na-K ATPase in Ischemic Injury of Primary Cultured Astrocytes

Astrocytes are reported to have critical functions in ischemic brain injury including protective effects against ischemia-induced neuronal dysfunction. Na-K ATPase maintains ionic gradients in astrocytes and is suggested as an indicator of ischemic injury in glial cells. Here, we examined the role of the Na-K ATPase in the pathologic process of ischemic injury of primary cultured astrocytes. Chemical ischemia was induced by sodium azide and glucose deprivation. Lactate dehydrogenase assays showed that the cytotoxic effect of chemical ischemia on astrocytes began to appear at 2 h of ischemia. The expression of Na-K ATPase α1 subunit protein was increased at 2 h of chemical ischemia and was decreased at 6 h of ischemia, whereas the expression of α1 subunit mRNA was not changed by chemical ischemia. Na-K ATPase activity was time-dependently decreased at 1, 3, and 6 h of chemical ischemia, whereas the enzyme activity was temporarily recovered to the control value at 2 h of chemical ischemia. Cytotoxicity at 2 h of chemical ischemia was significantly blocked by reoxygenation for 24 h following ischemia. Reoxygenation following chemical ischemia for 1 h significantly increased the activity of the Na-K ATPase, while reoxygenation following ischemia for 2 h slightly decreased the enzyme activity. These results suggest that the critical time for ischemia-induced cytotoxicity of astrocytes might be 2 h after the initiation of ischemic insult and that the increase in the expression and activity of the Na-K ATPase might play a protective role during ischemic injury of astrocytes.