Liposome-mediated transfer of vascular endothelial growth factor cDNA augments survival of random-pattern skin flaps in the rat.

Tissue engineering is an application for gene therapy that is in its infancy. We show that simple liposomal-mediated gene transfer could result in a potentially useful biological effect in the field of wound healing. cDNA encoding the 165 amino acid form of vascular endothelial growth factor complexed to commercially available liposomes was injected into rat skin 1 week before raising a random pattern 3 x 10 cm flap. The flap survival was enhanced by 14 percent, and was accomplished without accessing the arterial inflow of the territory. These results were statistically significant (p<0.002) and reproducible. No adverse effects were seen. Histological analysis of the angiogenesis localized much of the new vessel formation to the area around the hair follicles. Polymerase chain reaction amplification of extracted flap tissue confirmed the presence of the transgene.     

Myasthenia Gravis Appearing After Thymectomy: a Case Report and Review of the Literature

A small proportion of thymoma patients without myasthenia gravis (MG) have been observed to develop MG after total removal of the thymoma. However, the underlying cause is not yet known due to the rarity of postoperative MG patients. We report a 39-year-old man in whom MG appeared after surgical removal of a thymoma. Computed tomography and magnetic resonance imaging showed no signs of recurrent or metastatic thymoma. Administration of pyridostigmine bromide resulted in the prompt improvement of myasthenic symptoms. Our observations indicate that postoperative follow-up care with monitoring of possible postoperative MG is necessary after resecting a thymoma.     

Comparison of the effects of three different combinations of general anesthetics on the electroretinogram of dogs

The objective of this study is to compare the effects of three different anesthetic combinations on the electroretinogram in the same animals under similar laboratory conditions. Thiopental–isoflurane (TI), medetomidine–ketamine (MK), and xylazine–ketamine (XK) were used on each of 12 healthy miniature schnauzer dogs (MS) with a period of at least 3 weeks in between subsequent anesthesia protocols, using the Dog Standard Protocol. The scotopic ERGs consisted of scotopic low stimulus strength (S) responses designated S1, S2, S3, S4, and S5, at 1, 5, 10, 15, and 20 min after dark adaptation, respectively, and scotopic standard stimulus strength (S-ST) responses. The photopic ERGs consisted of a photopic single flash (P) response and 31 Hz flicker (P-FL) responses. For S-ST (2.5 cd s/m²), the amplitude of the a-wave using TI was significantly lower than that using MK (adjusted P = 0.05) and XK (adjusted P = 0.03), and the implicit time of the a-wave was significantly shorter than that using MK (adjusted P = 0.04). For P (2.5 cd s/m²), the amplitude of the b-wave using XK was significantly higher than that using MK (adjusted P = 0.01). The implicit times of the b-wave using TI was significantly longer and shorter than that of MK for S1, S2 and P-FL and for S4 and S-ST, respectively, and than that of XK for S2 and P-FL and for S5 and S-ST, respectively. The results of the present study showed that TI affected both the amplitude and the implicit time of the a-wave for S-ST and the implicit time of the b-wave relatively more so than was the case when using XK or MK. Therefore, it appears that either XK or MK could be advantageous to use rather than TI for clinical studies.     

Reversal of vascular 18F-FDG uptake with plasma high-density lipoprotein elevation by atherogenic risk reduction

Vascular 18F-FDG uptake marker represents inflammation in atherosclerotic lesions, but whether inflammation can be reversed by risk-modifying interventions has not, to our knowledge, been demonstrated. In this study, we evaluated the change of vascular 18F-FDG uptake in response to lifestyle intervention on serial PET/CT scans and further assessed how the findings relate to atherogenic risk reduction. METHODS: A total of 60 healthy adults underwent 18F-FDG PET/CT scans and atherogenic risk-factor assessment at baseline and again after 17.1 +/- 8.3 mo of practicing lifestyle modification. The PET/CT images were evaluated for the presence of vascular 18F-FDG lesions, and vessel-to-blood-pool 18F-FDG ratios were measured. Indices from summed ratios of positive lesions were compared and correlated to atherogenic risk factors. RESULTS: At follow-up, significant reductions in diastolic blood pressure (P < 0.05), total cholesterol (P < 0.05), and low-density lipoprotein level (P < 0.05) and an increase in high-density lipoprotein (HDL) level (P < 0.0001) were demonstrated. On the initial PET/CT scan, 50 of 60 subjects showed 1 or more 18F-FDG-positive lesions (5.9 +/- 5.0/subject), leading to a total of 352 vascular sites. On follow-up, 18F-FDG-positive lesions were significantly reduced to 2.1 +/- 2.2 sites per subject (P < 0.0001) and a total of 124 sites (64.8% reduction). Follow-up 18F-FDG-positive rates were significantly reduced for the aorta and iliac arteries. In addition, significant reductions in the whole-body 18F-FDG index from 1.39 +/- 1.23 to 0.53 +/- 0.59 (P < 0.0001) and carotid 18F-FDG index from 0.08 +/- 0.16 to 0.03 +/- 0.06 (P = 0.01) were shown. The whole-body 18F-FDG index correlated with total cholesterol (P < 0.05) and HDL level (P < 0.05), and the magnitude of reduction in the 18F-FDG index closely correlated to the amount of increase in plasma HDL level (P = 0.005). CONCLUSION: Our study demonstrated that vascular 18F-FDG uptake is reversed in response to atherogenic risk reduction by lifestyle intervention and that the magnitude of improvement correlates to increases in plasma HDL levels. Thus, serial 18F-FDG PET/CT may be useful for monitoring improvements in the inflammatory component of atherosclerotic lesions in response to risk modification.     

Inhibition of bone healing by pamidronate in calvarial bony defects.

OBJECTIVE: Pamidronate has been studied as a therapeutic drug for various osteopenic diseases. However, avascular osteonecrosis in the jawbone has been recently reported in patients receiving pamidronate. The objective of this study was to examine the effect of pamidronate on bone regeneration in a controlled animal model. MATERIALS AND METHODS: To determine the effect of parmidronate on bone healing in a local bony defect area, a rabbit calvarial bony defect model was used and poly L-lactide-co-glycolide (PLGA) used as a drug carrier material. Four defect groups were made in each rabbit calvaria and the defects were treated as follows: untreated bony defect (group 1), PLGA only (group 2), 2 mg of pamidronate with PLGA (group 3), and 3 mg of pamidronate with PLGA (group 4). Bone healing was evaluated by radiography and histology at 1, 2, 4, 6, and 8 weeks after surgery. RESULTS: In radiographic analysis, radiopacity was lower in pamidronate groups than non-operated rabbit calvarial bone at all observation points (P < .05). In histological analysis, the initial bone formation at 1 week was not different among groups, but it was much lower in the pamidronate groups than in the control or PLGA group after 2 weeks. Newly formed bone at 1 week underwent avascular necrosis after 2 weeks in both pamidronate groups. Avascular necrosis was not observed until 8 weeks in both topically applied pamidronate groups. CONCLUSION: Collectively, pamidronate inhibits bone healing in rabbit calvarial bony defect and it may explain the avascular necrosis of the jaws in patients receiving pamidronate.     

Antioxidant and antiinflammatory activity of pine pollen extract in vitro

To determine the medicinal properties of pine pollen, the antioxidant and antiinflammatory activities of the ethanol extract of pine pollen extract (PPE) were investigated. PPE displayed a strong free radical scavenger activity on 1,1‐diphenyl‐2‐picrylhydrazyl radical and hydrogen peroxide. It was observed also that the antioxidant activity, measured by the ferric thiocyanate method, increased with the addition of PPE to the linoleic acid emulsion system. PPE was also found to inhibit significantly the amount of malondialdehyde and protein carbonyls formed from liver homogenate. Like the antioxidant activity, the reducing power of PPE was excellent. Thereafter, the study investigated the effects of PPE in modulating the production of pro‐inflammatory mediators in lipopolysaccharide (LPS)‐activated RAW 264.7 macrophages, and the effect of PPE on interleukin (IL)‐1β‐induced matrix metalloproteinases (MMPs) production and mitogen‐activated protein kinases (MAPKs) activation in the human synovial sarcoma cell line, SW982. PPE was found to inhibit the production of nitric oxide, tumor necrosis factor‐α, IL‐1 and IL‐6 in LPS‐activated macrophages. Treatment with PPE at 10 µg/mL significantly (p < 0.05) inhibited IL‐1β‐induced MMPs (MMP‐1 and ‐3) production in SW982 cells. IL‐1β‐induced JNK activation was inhibited by PPE (10 µg/mL), whereas p38 and ERK1/2 were not affected. These findings suggest that pine pollen is a potential antioxidant and beneficial for inflammatory conditions through down‐regulation of JNK and MMPs. Copyright © 2008 John Wiley & Sons, Ltd.     

Scalarane sesterterpenes from the sponge Smenospongia sp

Ten new sesterterpene compounds (4-13) and seven known metabolites (1-3, 14-17) were isolated from the sponge Smenospongia sp. collected from Korean coastal waters. On the basis of combined spectroscopic analyses, the new compounds exhibited diverse functionalities on a common scalarane sesterterpene structure. The presence of a 23-aldehyde on compound 6 and a 20-carboxylic acid on 11 is unprecedented among sponge-derived scalarane sesterterpenes. Several of the new compounds showed significant cytotoxicity and antimicrobial activity, as well as moderate inhibitory activity against isocitrate lyase.     

Treatment failure in intracranial primary germinomas

Object A radiation dose of 40–50 Gy is able to produce a cure rate of more than 90% in intracranial pure germinoma. However, many attempts have been made to reduce the dose and volume of radiation without compromising the disease control rate because of the toxicity of irradiation. This retrospective study is intended to provide the physician with an appropriate therapeutic strategy. Materials and methods We reviewed a series of 10 recurrent germinomas among 117 germinomas diagnosed histologically or clinically between 1979 and 2002. These patients involved underwent three different treatment modalities; radiation alone (N = 71), chemotherapy alone (N = 9), and combined therapy (N = 37). The 10-year overall and relapse-free survival rates were 97 and 93% in the radiation alone group, 89 and 67% in the chemotherapy alone group, and 92 and 92% in the combined therapy group, respectively. As expected, both radiation therapy and combined therapy were effective in controlling the disease. Tumor recurrence was closely related to the volume of radiation but not to the dose of radiation. If the tumor bed and craniospinal axis were fully covered, the radiation dose might be reduced. Chemotherapy alone showed earlier recurrence and a higher tumor recurrence rate. In the case of combined therapy, chemotherapy was useful in reducing the radiation dose but revealed some toxicity (death of two patients). Conclusions The investigation of a possible further dose reduction seems worthwhile. Radiation therapy alone with a dose of less than 40 Gy should be compared with ongoing chemotherapeutic protocols combined with low-dose irradiation.