Purpose

The objective of this study is to evaluate the effects of heat and massage application on autonomic nervous system.

Materials and Methods

One hundred thirty-nine subjects volunteered and completed this study. Heat and massage was daily applied for 40 minutes, 5 days a week for 2 weeks. Primary-dependent measures included heart rate variability, sympathetic skin response, and serum cortisol and norepinephrine levels.

Results

Serum cortisol levels were significantly decreased at 2 weeks compared to baseline (p=0.003). Plasma norepinephrine levels at 4 weeks were significantly decreased compared to baseline (p=0.010). Heart rate, using the power spectra, increased significantly after 2 weeks compared to baseline. Of autonomic nerve conduction measures, latency was significantly increased at 2 and 4 weeks compared to baseline (p=0.023, 0.012), and amplitude was significantly decreased at 4 weeks compared to baseline (p=0.008). There were no serious adverse events such as burns or other major complications.

Conclusion

The results of this study suggest that heat and massage applications provide relaxation to the autonomic nervous system without serious adverse events.

Background

Women with gestational diabetes mellitus (GDM) are at high risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD); continuous life-style intervention, especially diet, is central to managing T2DM and CVD. However, little is known about the dietary patterns of women with GDM after delivery. The goal of this study was to compare the eating habits and food intakes of women diagnosed with GDM during the early postpartum period.

Methods

We performed a 75 g oral glucose tolerance test (OGTT) in 184 women with GDM between 6 and 12 weeks after delivery. Based on the results of the OGTT, the subjects were divided into three groups according to the American Diabetes Association criteria; normal glucose tolerance (NGT) (n=100), pre-diabetes (n=73), and diabetes mellitus (DM) (n=11). Eating habits and usual food intake after delivery were investigated using a questionnaire, based on 24 hour-recall, which was administered by a trained dietitian. The daily intake data were analyzed using CAN Pro 3.0. Blood tests were performed pre- and post-delivery.

Results

Eating habits were not significantly different among the three groups. However, animal fat consumption was significantly different among the three groups. The intake ratio of fat calories to total calories was also significantly higher in the pre-diabetes and DM groups.

Conclusion

Although diet in the period 6 to 12 weeks postpartum did not influence glucose level, it may be important to educate women with GDM about the risks of excessive animal fat intake during pregnancy and the postpartum period in order to prevent later onset of T2DM.

Purpose

The objective of this study is to define the clinical implications of consolidations in nodular bronchiectatic type Mycobacterium avium complex (NB-MAC) infection.

Materials and Methods

A total of 69 patients (M : F = 17 : 52; mean age, 64 years; age range, 41-85 years) with MAC isolated in the sputum culture and nodular bronchiectasis on the initial and follow-up CT scans were included. We retrospectively reviewed the incidence of consolidation and analyzed its clinical course by using radiographic changes with or without anti-MAC drug therapy.

Results

In 44 of the 69 cases (64%), focal consolidations were seen on the initial and follow-up CT images. In 35 of the 44 (80%) cases, consolidations completely regressed, and in 3 cases (7%), consolidations partially regressed within 2 months with only antibiotics. In 2 cases (5%), the consolidations remained stable for over 2 months without anti-MAC drug therapy. Only in 4 cases (9%) did the consolidations improve after anti-MAC drug therapy. In 11 of the 38 cases (29%) with responsiveness to antibiotics, non-mycobacterial micro-organisms were identified in sputum, including pseudomonas, hemophilus, staphylococcus, and others.

Conclusion

In NB-MAC, consolidations are commonly present on CT. In these conditions, most of consolidations result from pneumonia other than MAC.

The purpose of this study is to evaluate the clinical usefulness of the cervicogram as a primary screening test for cervical neoplasia. A total of 294 women who had undergone a cervicogram and a Pap test between January and July 2003, were selected. The diagnostic accuracy of the Pap test, cervicogram, and the Pap test combined with a cervicogram were compared with the histopathologic diagnosis. Among 294 women, the Pap test was negative in 130 cases and positive in 164 cases. Among patients with positive Pap test, cervicogram were negative in 101 cases (61.6%) and positive in 63 cases (38.4%). The diagnostic accuracy between cervicogram with positive Pap test and histology was as follows; sensitivity 44.9%, specificity 78.3%, positive predictive value 84.1%, negative predictive value 32.7%, false positive rate 15.9%, and false negative rate 67.3%. Although the adjunctive use of cervicogram with the Pap test in the initial screening of cervical neoplasia showed a higher specificity and higher positive predictive value compared to the Pap test alone, consideration in terms of lower sensitivity, lower positive predictive value, higher false positive rate and cost-effectiveness should be given in lieu of clinically applying cervicogram with the pap test as an initial screening test.

Purpose

Lamotrigine, a novel anticonvulsant, is a sodium channel blocker that is efficacious in certain forms of neuropathic pain. Recently, microglial and astrocytic activation has been implicated in the development of nerve injury-induced neuropathic pain. We have assessed the effects of continuous intrathecal administration of lamotrigine on the development of neuropathic pain and glial activation induced by L5/6 spinal-nerve ligation in rats.

Materials and Methods

Following left L5/6 spinal nerve ligation (SNL), Sprague-Dawley male rats were intrathecally administered lamotrigine (24, 72, or 240 µg/day) or saline continuously for 7 days. Mechanical allodynia of the left hind paw to von Frey filament stimuli was determined before surgery (baseline) and once daily for 7 days postoperatively. On day 7, spinal activation of microglia and astrocytes was evaluated immunohistochemically, using antibodies to the microglial marker OX-42 and the astrocyte marker glial fibrillary acidic protein (GFAP).

Results

Spinal-nerve ligation induced mechanical allodynia in saline-treated rats, with OX-42 and GFAP immunoreactivity being significantly increased on the ipsilateral side of the spinal cord. Continuously administered intrathecal lamotrigine (240 µg/day) prevented the development of mechanical allodynia, and lower dose of lamotrigine (72 µg/day) ameliorated allodynia. Intrathecal lamotrigine (72 and 240 µg/day) inhibited nerve ligation-induced microglial and astrocytic activation, as evidenced by reduced numbers of cells positive for OX-42 and GFAP.

Conclusion

Continuously administered intrathecal lamotrigine blocked the development of mechanical allodynia induced by SNL with suppression of microglial and astrocytic activation. Continuous intrathecal administration of lamotrigine may be a promising therapeutic intervention to prevent neuropathy.

Knowledge regarding the genetic risk loci for gestational diabetes mellitus (GDM) is still limited. In this study, we performed a two-stage genome-wide association analysis in Korean women. In the stage 1 genome scan, 468 women with GDM and 1,242 nondiabetic control women were compared using 2.19 million genotyped or imputed markers. We selected 11 loci for further genotyping in stage 2 samples of 931 case and 783 control subjects. The joint effect of stage 1 plus stage 2 studies was analyzed by meta-analysis. We also investigated the effect of known type 2 diabetes variants in GDM. Two loci known to be associated with type 2 diabetes had a genome-wide significant association with GDM in the joint analysis. rs7754840, a variant in CDKAL1, had the strongest association with GDM (odds ratio 1.518; P = 6.65 × 10−16). A variant near MTNR1B, rs10830962, was also significantly associated with the risk of GDM (1.454; P = 2.49 × 10−13). We found that there is an excess of association between known type 2 diabetes variants and GDM above what is expected under the null hypothesis. In conclusion, we have confirmed that genetic variants in CDKAL1 and near MTNR1B are strongly associated with GDM in Korean women. There seems to be a shared genetic basis between GDM and type 2 diabetes.

We examined the possible anti-inflammatory mechanisms of gabapentin in the attenuation of neuropathic pain and the interaction between the anti-allodynic effects of gabapentin and interleukin-10 (IL-10) expression in a rat model of neuropathic pain. The anti-allodynic effect of intrathecal gabapentin was examined over a 7-day period. The anti-allodynic effects of IL-10 was measured, and the effects of anti-IL-10 antibody on the gabapentin were assessed. On day 7, the concentrations of pro-inflammatory cytokines and IL-10 were measured. Gabapentin produced an anti-allodynic effect over the 7-day period, reducing the expression of pro-inflammatory cytokines but increasing the expression of IL-10 (TNF-α, 316.0 ± 69.7 pg/mL vs 88.8 ± 24.4 pg/mL; IL-1β, 1,212.9 ± 104.5 vs 577.4 ± 97.1 pg/mL; IL-6, 254.0 ± 64.8 pg/mL vs 125.5 ± 44.1 pg/mL; IL-10, 532.1 ± 78.7 pg/mL vs 918.9 ± 63.1 pg/mL). The suppressive effect of gabapentin on pro-inflammatory cytokine expression was partially blocked by the anti-IL-10 antibody. Expression of pro-inflammatory cytokines was significantly attenuated by daily injections of IL-10. The anti-allodynic effects of gabapentin may be caused by upregulation of IL-10 expression in the spinal cord, which leads to inhibition of the expression of pro-inflammatory cytokines in the spinal cords.

Glial cells play a critical role in morphine tolerance, resulting from repeated administration of morphine. Both the development and the expression of tolerance are suppressed by the analgesic lamotrigine. This study investigated the relationship between the ability of lamotrigine to maintain the antinociceptive effect of morphine during tolerance development and glial cell activation in the spinal cord. In a rat model, morphine (15 µg) was intrathecally injected once daily for 7 days to induce morphine tolerance. Lamotrigine (200 µg) was co-administered with morphine either for 7 days or the first or last 3 days of this 7 day period. Thermal nociception was measured. OX-42 and GFAP immunoreactivity, indicating spinal microglial and astrocytic activation were evaluated on day 8. Tolerance developed after 7 days of intrathecal morphine administration; however, this was completely blocked and reversed by co-administration of lamotrigine. When lamotrigine was coinjected with morphine on days 5-7, the morphine effect was partially restored. Glial cell activation increased with the development of morphine tolerance but was clearly inhibited in the presence of lamotrigine. These results suggest that, in association with the suppression of spinal glial cell activity, intrathecally coadministered lamotrigine attenuates antinociceptive tolerance to morphine.

Androgen receptor (AR) signaling is crucial for the genesis and progression of prostate cancer (PCa). We compared the growth responses of AR(+) LNCaP and LNCaP C4-2 vs. AR(−) DU145 and PC-3 PCa cell lines to galbanic acid (GBA) isolated from the resin of medicinal herb Ferula assafoetida and assessed their connection to AR signaling and cell cycle regulatory pathways. Our results showed that GBA preferentially suppressed AR(+) PCa cell growth than AR(−) PCa cells. GBA induced a caspase-mediated apoptosis that was attenuated by a general caspase inhibitor. Subapoptotic GBA down-regulated AR protein in LNCaP cells primarily through promoting its proteasomal degradation, and inhibited AR-dependent transcription without affecting AR nuclear translocation. Whereas docking simulations predicted binding of GBA to the AR ligand binding domain with similarities and differences with the AR antagonist drug bicalutamide, LNCaP cell culture assays did not detect agonist activity of GBA. GBA and bicalutamide exerted greater than additive inhibitory effect on cell growth when used together. Subapoptotic GBA induced G1 arrest associated with an inhibition of cyclin/CDK4/6 pathway, especially cyclin D1 without the causal involvement of CDK inhibitory proteins P21Cip1 and P27Kip1. In summary, the novelty of GBA as an anti-AR compound resides in the distinction between GBA and bicalutamide with respect to AR protein turnover and a lack of agonist effect. Our observations of anti-AR and cell cycle arrest actions plus the anti-angiogenesis effect reported elsewhere suggest GBA as a multi-targeting drug candidate for the prevention and therapy of PCa.

Preexcitation by accessory pathways (APs) is known to cause dyssynchrony of the ventricle, related to ventricular dysfunction. Correction of ventricular dyssynchrony can improve heart failure in cases of dilated cardiomyopathy (DCMP) with preexcitation. Here, we report the first case of a child with DCMP and Wolff-Parkinson-White (WPW) syndrome treated with amiodarone and radiofrequency catheter ablation (RFCA) in Korea. A 7-year-old boy, who suffered from DCMP and WPW syndrome, showed improved left ventricular function and clinical functional class after treatment with amiodarone to eliminate preexcitation. QRS duration and left ventricular ejection fraction (LVEF) were inversely correlated with amiodarone dosage. After confirming the reduction of preexcitation effects in DCMP, successful RFCA of the right anterior AP resulted in LVEF improvement, along with the disappearance of preexcitation. Our findings suggest that ventricular dyssynchrony, caused by preexcitation in DCMP with WPW syndrome, can worsen ventricular function and amiodarone, as well as RFCA, which should be considered as a treatment option, even in young children.

This study was performed to identify dietary behavior such as snack consumption, night-eating and nutrients intake associated with gestational diabetes mellitus (GDM). The study was conducted on 219 normal glucose tolerance (NGT) subjects and 44 GDM subjects by using a questionnaire including dietary behavior, food frequency and 3-day food record. The mean age, OGTT, and delivery weight of GDM subjects were statistically higher than those in NGT. A larger proportion of NGT subjects consumed black coffee (49.8%) while the majority of GDM subjects (61.4%) drank mixed coffee with sugar and cream. Dairy products were the most frequently consumed snack item in NGT subjects (40.7%), while fruits were most frequently consumed food item in GDM subjects (34.4%). Many of NGT subjects (49.8%) answered that they hardly took night-eating snacks whereas most of GDM subjects (61.4%) took night-eating snacks more than once a week. For change of taste preference, the proportion of NGT subjects who showed less preference for salty taste (33.3%) or greasy taste (16.9%) was higher than that of GDM subjects (11.4%). Nutrient intakes of energy, fat, cholesterol, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), carbohydrate, vitamin B1, vitamin B2, vitamin C, and vitamin E in GDM group were significantly higher than those in NGT group. Nutrient densities of SFA and vitamin C in GDM group were higher and nutrient density of calcium was lower than those in NGT group. Taken together, it is recommended to reduce night-eating snack and choose less salty and fatty foods, black-coffee rather than coffee with cream and sugar, and more dairy products to prevent GDM.

Although cryptotanshinone (CT) was known to exert antitumor activity in several cancers, its molecular mechanism under hypoxia still remains unclear. Here, the roles of AEG-1 and HIF-1α in CT-induced antitumor activity were investigated in hypoxic PC-3 cells. CT exerted cytotoxicity against prostate cancer cells and suppressed HIF-1α accumulation and AEG-1 expression in hypoxic PC-3 cells. Also, AEG-1 was overexpressed in prostate cancer cells. Interestingly, HIF-1α siRNA transfection enhanced the cleavages of caspase-9,3, and PAPR and decreased expression of Bcl-2 and AEG1 induced by CT in hypoxic PC-3 cells. Of note, DMOG enhanced the stability of AEG-1 and HIF-1α during hypoxia. Additionally, CT significantly reduced cellular level of VEGF in PC-3 cells and disturbed tube formation of HUVECs. Consistently, ChIP assay revealed that CT inhibited the binding of HIF-1α to VEGF promoter. Furthermore, CT at 10 mg/kg suppressed the growth of PC-3 cells in BALB/c athymic nude mice by 46.4% compared to untreated control. Consistently, immunohistochemistry revealed decreased expression of Ki-67, CD34, VEGF, carbonic anhydrase IX, and AEG-1 indices in CT-treated group compared to untreated control. Overall, our findings suggest that CT exerts antitumor activity via inhibition of HIF-1α, AEG1, and VEGF as a potent chemotherapeutic agent.

Though melatonin was known to regulate gap junctional intercellular communication (GJIC) in chick astrocytes and mouse hepatocytes, the underlying mechanism by melatonin was not elucidated in hydrogen peroxide- (H2O2-) treated HaCaT keratinocyte cells until now. In the current study, though melatonin at 2 mM and hydrogen peroxide (H2O2) at 300 μM showed weak cytotoxicity in HaCaT keratinocyte cells, melatonin significantly suppressed the formation of reactive oxygen species (ROS) in H2O2-treated HaCaT cells compared to untreated controls. Also, the scrape-loading dye-transfer assay revealed that melatonin enhances the intercellular communication by introducing Lucifer Yellow into H2O2-treated cells. Furthermore, melatonin significantly enhanced the expression of connexin 26 (Cx26) and connexin 43 (Cx43) at mRNA and protein levels, but not that of connexin 30 (Cx30) in H2O2-treated HaCaT cells. Of note, melatonin attenuated the phosphorylation of extracellular signal-regulated protein kinases (ERKs) more than p38 MAPK or JNK in H2O2-treated HaCaT cells. Conversely, ERK inhibitor PD98059 promoted the intercellular communication in H2O2-treated HaCaT cells. Furthermore, combined treatment of melatonin (200 μM) and vitamin C (10 μg/mL) significantly reduced ROS production in H2O2-treated HaCaT cells. Overall, these findings support the scientific evidences that melatonin facilitates gap junctional intercellular communication in H2O2-treated HaCaT keratinocyte cells via inhibition of connexin 26/43 and ERK as a potent chemopreventive agent.

Aggressive tumor growth, diffuse tissue invasion and neurodegeneration are hallmarks of malignant glioma. Although glutamate excitotoxicity is considered to play a key role in glioma-induced neurodegeneration, the mechanism(s) controlling this process is poorly understood. AEG-1 is an oncogene overexpressed in multiple types of human cancers including >90% of brain tumors. AEG-1 also promotes gliomagenesis particularly in the context of tumor growth and invasion, two primary characteristics of glioma. In the present study, we investigated the contribution of AEG-1 to glioma-induced neurodegeneration. Pearson correlation coefficient analysis in normal brain tissues and glioma patient samples indicated a strong negative correlation between expression of AEG-1 and a primary glutamate transporter of astrocytes EAAT2. Gain and loss of function studies in normal primary human fetal astrocytes and T98G glioblastoma multiforme cells revealed that AEG-1 repressed EAAT2 expression at a transcriptional level by inducing YY1 activity to inhibit CBP function as a coactivator on the EAAT2 promoter. In addition, AEG-1-mediated EAAT2 repression caused a reduction of glutamate uptake by glial cells, resulting in induction of neuronal cell death. These findings were also confirmed in glioma patient samples demonstrating that AEG-1 expression negatively correlated with NeuN expression. Taken together, our findings suggest that AEG-1 contributes to glioma-induced neurodegeneration, a hallmark of this fatal tumor, through regulation of EAAT2 expression.

Background

Elderly patients visiting pain clinic may be at greater risk of misunderstanding the explanation because of age-related cognitive decline. Video instruction may provide a consistent from of teaching in a visual and realistic manner. We evaluated the effect of educational video on the patient understanding and satisfaction in a group of geriatric patients visiting pain clinic.

Methods

Ninety two patients aged more than 60 years old who were scheduled for transforaminal epidural block were recruited. After exposure to either video or paper instruction process, each patient was asked 5-item comprehension questions, overall satisfaction and preference question. During follow-up period, number of outpatient referral-line call for further explanation was counted.

Results

We observed significantly better comprehension in the video education compared with paper instruction (P < 0.001). Patient satisfaction was also higher in the video group (P = 0.015), and patients visiting pain clinic were more preferred video instruction (P < 0.001). Proportion of referral-line call for further explanation were similar (P = 0.302).

Conclusions

Video approach to instruction process before consent improves treatment comprehension in geriatric patient visiting pain clinic.

Objective

The purpose of this study was to determine the efficacy of bone cement-augmented short segment fixation using percutaneous screws for thoracolumbar burst fractures in a background of severe osteoporosis.

Methods

Sixteen patients with a single-level thoracolumbar burst fracture (T11-L2) accompanying severe osteoporosis treated from January 2008 to November 2009 were prospectively analyzed. Surgical procedures included postural reduction for 3 days and bone cement augmented percutaneous screw fixation at the fracture level and at adjacent levels without bone fusion. Due to the possibility of implant failure, patients underwent implant removal 12 months after screw fixation. Imaging and clinical findings, including involved vertebral levels, local kyphosis, canal encroachment, and complications were analyzed.

Results

Prior to surgery, mean pain score (visual analogue scale) was 8.2 and this decreased to a mean of 2.2 at 12 months after screw fixation. None of the patients complained of pain worsening during the 6 months following implant removal. The percentage of canal compromise at the fractured level improved from a mean of 41.0% to 18.4% at 12 months after surgery. Mean kyphotic angle was improved significantly from 19.8° before surgery to 7.8 at 12 months after screw fixation. Canal compromise and kyphotic angle improvements were maintained at 6 months after implant removal. No significant neurological deterioration or complications occurred after screw removal in any patient.

Conclusion

Bone cement augmented short segment fixation using a percutaneous system can be an alternative to the traditional open technique for the management of selected thoracolumbar burst fractures accompanied by severe osteoporosis.

Fibroblast-like synoviocytes (FLS) colocalize with leukocyte infiltrates in rheumatoid synovia. Proinflammatory leukocytes are known to amplify inflammation by signaling to FLS, but crosstalk between FLS and regulatory T cells (Tregs) remains uncharacterized. To address this possibility, we cocultured FLS lines derived from arthritic mice with Tregs. FLS that expressed the ligand for glucocorticoid-induced TNF receptor family-related gene (GITR) decreased expression of Foxp3 and GITR in Tregs in a contact-dependent manner. This effect was abolished by blocking antibody to GITR. On the other hand, the Tregs caused the FLS to increase IL-6 production. These results demonstrate that inflamed FLS license Tregs to downregulate Foxp3 expression via the GITRL/GITR interaction while the Tregs induce the FLS to increase their production of IL-6. Our findings suggest that the interaction between FLS and Tregs dampens the anti-inflammatory activity of Tregs and amplifies the proinflammatory activity of FLS, thereby exacerbating inflammatory arthritis.

AIM: To assess the prognostic value of preoperative 18 fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) in patients with resectable colorectal cancer.

METHODS: One hundred sixty-three patients with resectable colorectal cancer who underwent FDG-PET/CT before surgery were included. Patient data including pathologic stage at presentation, histology, treatment, disease-free survival and the maximum standardized uptake value (SUVmax) of the primary tumor on FDG-PET/CT were retrospectively analyzed. Median follow up duration was 756 (range, 419-1355). The primary end point was disease-free survival.

RESULTS: Twenty-five of 163 patients (15.3%) had recurrences. The median SUVmax values of the recurrence and no-recurrence groups were 8.9 (range, 5-24) and 8.2 (range, 0-23, P = 0.998). Receiver operating characteristic (ROC) curve analysis showed no significant association between SUVmax and recurrence (area under the curve = 0.5, P = 0.998, 95% CI: 0.389-0.611). Because a statistically significant value was not found, SUVmax was dichotomized at its median of 8.6. The disease-free survival curve was analyzed using the median SUVmax (8.6) as the cut off. Univariate and multivariate analysis did not provide evidence that disease-free survival rates for the subgroups defined by the median SUVmax were significantly different (P = 0.52, P = 0.25).

CONCLUSION: Our study suggests that the high FDG uptake of primary mass in resectable colorectal cancer doesn’t have a significant relationship with tumor recurrence and disease-free survival.

Purpose

Many surgical patients are admitted to the intensive care unit (ICU), resulting in an increased demand, and possible waste, of resources. Patients who undergo liver resection are also transferred postoperatively to the ICU. However, this may not be necessary in all cases. This study was designed to assess the necessity of ICU admission.

Methods

The medical records of 313 patients who underwent liver resections, as performed by a single surgeon from March 2000 to December 2010 were retrospectively reviewed.

Results

Among 313 patients, 168 patients (53.7%) were treated in the ICU. 148 patients (88.1%) received only observation during the ICU care. The ICU re-admission and intensive medical treatment significantly correlated with major liver resection (odds ratio [OR], 6.481; P = 0.011), and intraoperative transfusions (OR, 7.108; P = 0.016). Patients who underwent major liver resection and intraoperative transfusion were significantly associated with need for mechanical ventilator care, longer postoperative stays in the ICU and the hospital, and hospital mortality.

Conclusion

Most patients admitted to the ICU after major liver resection just received close monitoring. Even though patients underwent major liver resection, patients without receipt of intraoperative transfusion could be sent to the general ward. Duration of ICU/hospital stay, ventilator care and mortality significantly correlated with major liver resection and intraoperative transfusion. Major liver resection and receipt of intraoperative transfusions should be considered indicators for ICU admission.

A 31-year-old man was admitted to our hospital due to hydrocephalus with neurosarcoidosis. Ventriculo-peritoneal shunting was performed in the right lateral ventricle with intravenous methylprednisolone. Subsequently, after 4 months, additional ventriculo-peritoneal shunting in the left lateral ventricle was performed due to the enlarged left lateral ventricle and slit-like right lateral ventricle. After 6 months, he was re-admitted due to upward gaze palsy, and magnetic resonance image showed an isolated fourth ventricle with both the inlet and outlet of fourth ventricle obstructed by recurrent neurosarcoidosis. Owing to the difficulty of using an endoscope, we performed neuronavigator-guided ventriculo-peritoneal shunting via the left lateral transcerebellar approach for the treatment of the isolated fourth ventricle with intravenous methyl prednisolone. The patient was discharged with improved neurological status.

Purpose

This treatment planning study was undertaken to evaluate the impact of beam angle configuration of intensity-modulated radiotherapy (IMRT) on the dose of the normal liver in hepatocellular carcinoma (HCC).

Materials and Methods

The computed tomography datasets of 25 patients treated with IMRT for HCC were selected. Two IMRT plans using five beams were made in each patient; beams with equidistance of 72° (Plan I), and beams with a 30° angle of separation entering the body near the tumor (Plan II). Both plans were generated using the same constraints in each patient. Conformity index (CI), homogeneity index (HI), gamma index, mean dose of the normal liver (Dmean_NL), Dmean_NL difference between the two plans, and percentage normal liver volumes receiving at least 10, 20, and 30 Gy (V10, V20, and V30) were evaluated and compared.

Results

Dmean_NL, V10, and V20 were significantly better for Plan II. The Dmean_NL was significantly lower for peripheral (p = 0.001) and central tumors (p = 0.034). Dmean_NL differences between the two plans increased in proportion to gross tumor volume to normal liver volume ratios (p = 0.002). CI, HI, and gamma indices were not significantly different for the two plans.

Conclusion

The IMRT plan based on beams with narrow separations reduced the irradiated dose of the normal liver, which would allow radiation dose escalation for HCC.

Pancreatic cancer is a devastating human malignancy and gain of functional mutations in K-ras oncogene is observed in 75%–90% of the patients. Studies have shown that oncogenic ras is not only able to promote cell growth or survival, but also apoptosis, depending upon circumstances. Using pancreatic cancer cell lines with or without expressing mutated K-ras, we demonstrated that the inhibition of endogenous PKC activity sensitized human pancreatic cancer cells (MIA and PANC-1) expressing mutated K-ras to apoptosis, which had no apoptotic effect on BxPC-3 pancreatic cancer cells that contain a normal Ras as well as human lung epithelial BAES-2B cells. In this apoptotic process, the level of ROS was increased and PUMA was upregulated in a p73-dependent fashion in MIA and PANC-1 cells. Subsequently, caspase-3 was cleaved. A full induction of apoptosis required the activation of both ROS- and p73-mediated pathways. The data suggest that PKC is a crucial factor that copes with aberrant K-ras to maintain the homeostasis of the pancreatic cancer cells harboring mutated K-ras. However, the suppression or loss of PKC disrupts the balance and initiates an apoptotic crisis, in which ROS and p73 appear the potential, key targets.

Objective

Alcoholic neuropathy is characterized by allodynia (a discomfort evoked by normally innocuous stimuli), hyperalgesia (an exaggerated pain in response to painful stimuli) and spontaneous burning pain. The aim of the present study is to investigate the effect of rolipram, a phosphodiesterase 4 inhibitor, against alcohol-induced neuropathy in rats.

Methods

Allodynia was induced by administering 35% v/v ethanol (10 g/kg; oral gavage) to Spraue-Dawley rats for 8 weeks. Rolipram and saline (vehicle) were administered intraperitoneally. Mechanical allodynia was measured by using von Frey filaments. Somatosensory evoked potential (SEP) was proposed as complementary measure to assess the integrity of nerve pathway.

Results

The ethanol-induced mechanical allodynia began to manifest from 3 week, and then peaked within 1 week. Beginning from 3 week, latency significantly started to increased in control group. In rolipram treated rats, the shorter latency was sustained until 8 weeks (p<0.05). The mechanical allodynia, which began to manifest on the 3 weeks, intraperitoneal injections of rolipram sustained statistical difference until 8 weeks, the final week of the study (p<0.05).

Conclusion

This study suggests that rolipram might alleviate mechanical allodynia induced by alcohol in rats, which clearly has clinical implication.

There is an urgent clinical need for chemotherapeutic and chemopreventive drugs for triple-negative breast cancer (TNBCa). Extending on our recent work, we hypothesize that the herbal compound 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) can inhibit the growth and metastasis of TNBCa xenograft and target Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) 3-signaling axis. Daily oral gavage of 10 mg PGG/kg body wt decreased MDA-MB-231 xenograft weight by 49.3% (P < 0.01) at 40 days postinoculation, whereas weekly intraperitoneal injections of Taxol at the same dosage resulted in a 21.4% reduction (P > 0.1). PGG treatment also decreased the incidence of lung metastasis. Immunohistochemical staining detected decreased Ki-67 (proliferation) index and increased terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (apoptosis) index in PGG-treated and Taxol-treated xenografts. However, the CD34 (angiogenesis) index was decreased only in PGG-treated xenografts along with decreased phospho-STAT3. In cell culture of MDA-MB-231 cells, PGG decreased pSTAT3 and its downstream target proteins, decreased its upstream kinase pJAK1 and induced the expression of SHP1, a JAK1 upstream tyrosine phosphatase, within as early as 1 h of exposure. The phosphatase inhibitor pervanadate reversed the PGG-induced downregulation of pSTAT3 and caspase activation. Orally administered PGG can inhibit TNBCa growth and metastasis, probably through anti-angiogenesis, antiproliferation and apoptosis induction. Mechanistically, PGG-induced inhibition of JAK1-STAT3 axis may contribute to the observed in vivo efficacy and the effects on the cellular processes.