Increased prevalence of vitamin D deficiency in patients with alopecia areata: a systematic review and meta-analysis.

BACKGROUND: Alopecia areata (AA) is a hair follicle-specific autoimmune disorder. Vitamin D deficiency has been associated with various autoimmune disorders for its immunomodulatory effects. However, in previous studies, there had been inconsistent association found between AA and vitamin D deficiency. OBJECTIVE: To demonstrate the differences of the mean serum 25-hydroxyvitamin D level and prevalence of vitamin D deficiency between AA patients and non-AA population. METHODS: A systematic review and meta-analysis of observational studies on AA and serum vitamin D levels and/or prevalence of vitamin D deficiency was performed searching MEDLINE, Cochrane, Web of Science and Google Scholar databases. RESULTS: In all, 14 studies including a total of 1255 AA subjects and 784 non-AA control were analysed. The mean serum 25-hydroxyvitamin D level was significantly lower in AA subjects (-8.52 ng/dL; 95% confidential interval; -5.50 to -11.53). The AA subjects had higher odds of vitamin D deficiency (odds ratio of 3.89; 2.02 to 7.49, mean prevalence of 73.8%; 59.1 to 84.6%). However, it was difficult to find clear correlation between serum 25-hydroxyvitamin D level and extent of hair loss in AA subjects. CONCLUSION: The AA subjects had lower serum 25-hydroxyvitamin D level, and vitamin D deficiency was highly prevalent compared to non-AA controls. Hence, vitamin D deficiency should be assessed in AA patients. Furthermore, nutritional supplementation of vitamin D or topical vitamin D analogues can be considered for AA patients with vitamin D deficiency. The limitation of this study is the highly heterogeneity of the included studies.

Glechoma hederacea Suppresses RANKL-mediated Osteoclastogenesis.

Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-the-ground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca(2+) ([Ca(2+)]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrate-resistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca(2+)]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow-derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca(2+)]i while suppressing RANKL-induced [Ca(2+)]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca(2+)]i was dependent on extracellular Ca(2+) and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca(2+) channels (VGCCs), but was independent of store-operated Ca(2+) channels. Notably, after transient [Ca(2+)] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKL-induced [Ca(2+)]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis.

The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema.

Clostridium difficile infection (CDI) is one of the most frequent causes of healthcare-associated infections, and its rates are also increasing in the community. The management of CDI has become a major challenge, given growing rates of recurrences and failures with standard antibiotic therapy. Mounting evidence suggests that fecal microbiota transplantation (FMT) may be effective; however, as there is a paucity of data with regard to repeat FMT for primary non-response to this treatment, this study examined the outcome of multiple FMTs for recurrent CDI. Case records were reviewed for 94 patients who underwent FMT via retention enema for recurrent or refractory CDI during the period 2008-2012. Demographic information, treatment data, and clinical resolution rates were examined for single FMT and cumulative resolution was assessed for multiple FMTs in the context of ongoing symptoms. The cumulative clinical resolution following four or more FMTs was 86%. When antibiotic therapy was used between FMTs, the clinical resolution rate increased to 92%. There were no reported adverse events and no patients who were cured with FMT had further episodes of CDI at 6-24 months follow-up. Multiple FMTs administered through enemas is an effective, safe, and simple therapy for the management of recurrent or refractory CDI.

Salmonella induce autophagy in melanoma by the downregulation of AKT/mTOR pathway.

Salmonella have been demonstrated to inhibit tumor growth. However, the mechanism of Salmonella-induced tumor cell death is less defined. Autophagy is a cellular process that mediates the degradation of long-lived proteins and unwanted organelles in the cytosol. Tumor cells frequently display lower levels of basal autophagic activity than their normal counterparts and fail to increase autophagic activity in response to stresses. Autophagy is involved in the cell defense elimination of bacteria. The signaling pathways leading to activation of Salmonella-induced autophagy in tumor cells remain to be elucidated. We used autophagy inhibitor (3-Methyladenine) and apoptosis inhibitor (Z-VAD-FMK) to demonstrate that Salmonella may induce cell death via apoptosis and autophagic pathway. Meanwhile, we suggested that Salmonella induce autophagy in a dose- and time-dependent manner. The autophagic markers were increased after tumor cell infected with Salmonella. In addition, the protein express levels of phosph-protein kinase B (P-AKT), phosph-mammalian targets of rapamycin (P-mTOR), phosph-p70 ribosomal s6 kinase (P-p70s6K) in tumor cells were decreased by western analysis after Salmonella infection. In conclusion, our results point out that Salmonella induce the autophagic signaling pathway via downregulation of AKT/mTOR pathway. Herein, our findings that Salmonella in controlling tumor growth may induce autophagic signal pathway.

Octet-line node structure of superconducting order parameter in KFe2As2.

In iron-pnictide superconductivity, the interband interaction between the hole and electron Fermi surfaces (FSs) is believed to play an important role. However, KFe(2)As(2) has three zone-centered hole FSs and no electron FS but still exhibits superconductivity. Our ultrahigh-resolution laser angle-resolved photoemission spectroscopy unveils that KFe(2)As(2) is a nodal s-wave superconductor with highly unusual FS-selective multi-gap structure: a nodeless gap on the inner FS, an unconventional gap with "octet-line nodes" on the middle FS, and an almost-zero gap on the outer FS. This gap structure may arise from the frustration between competing pairing interactions on the hole FSs causing the eightfold sign reversal. Our results suggest that the A(1g) superconducting symmetry is universal in iron-pnictides, in spite of the variety of gap functions.

The effects of oral iron supplementation on the progression of anemia and renal dysfunction in patients with chronic kidney disease.

AIMS: Oral iron traditionally has been administered to patients with chronic kidney disease (CKD). However, there are limited data on the effect of oral iron in CKD patients. Here, we evaluate the effects of oral iron therapy on renal anemia and progression of renal disease in CKD patients. METHODS: Anemic patients with nondialytic CKD who were naive to erythropoiesis-stimulating agents (ESAs) were recruited for the prospective observational study. The participants were classified into oral iron or control group, and they were asked to keep their treatment status for 1 year. The primary outcomes were change in Hb and estimated glomerular filtration rate (eGFR). RESULTS: A total of 182 participants were enrolled and 138 completed a 12-month follow-up. No change in Hb level was observed during the follow-up period in the iron group, whereas a significant decrease in Hb was observed in the control group. Oral iron supplementation was effective, especially in patients with eGFR < 30 ml/min/1.73 m2. The changes in eGFR did not differ between the two groups. The incidences of drug-related adverse events were equivalent in two groups. CONCLUSIONS: Oral iron supplementation might attenuate the progression of anemia in nondialytic CKD patients without ESAs and not impact kidney function.

Noninvasive cutaneous blood flow as a response predictor for visible light therapy on segmental vitiligo: a prospective pilot study.

BACKGROUND: Visible light is a treatment option for segmental vitiligo (SV), and visible light-induced repigmentation is associated with normalization of sympathetic dysfunction. Currently, it is difficult to predict individual patients' response to visible light therapy. OBJECTIVES: To test whether cutaneous blood flow can serve as a response predictor for visible light on treating SV. METHODS: Fourteen patients with SV were recruited in this prospective pilot study. Laser Doppler flowmetry was used to evaluate the cutaneous blood flow over SV lesions and contralateral normal skin. The pretreatment blood flow evaluation consisted of two stages: stage 1, following cold stress without prior visible light irradiation, and stage 2, following cold stress with prior visible light irradiation. Subsequently, the patients received regular visible light treatment for 3months, and a comparison of the pretreatment blood flow patterns between the visible light responding and nonresponding groups was carried out at the end of the study period. RESULTS: The SV lesions showed different blood flow profiles as compared with the contralateral normal skin. At the end of the 3-month study period, seven (50%) patients showed clinical repigmentation of >25%. The visible light responding group showed a more consistent occurrence of increased blood flow after stage 2 of the pretreatment evaluation while the nonresponding counterpart showed no significant changes. CONCLUSIONS: Normalization of sympathetic dysfunction may account for the efficacy of visible light in treating SV. Evaluation of cutaneous blood flow with and without prior visible light irradiation on cold-stressed SV lesions may serve as a treatment response predictor.

Prescription pattern of traditional Chinese medicine for climacteric women in Taiwan.

BACKGROUND: Traditional Chinese medicine (TCM) has become more popular as a therapy for symptom relief among menopause-aged women. The aim of this study was to analyze the utilization of TCM for climacteric women in Taiwan. METHODS: The study analyzed frequency distributions among 19 379 women aged 45-55 years, recruited from a random-sampled cohort of 200 000 people from the National Health Insurance database. Data mining was conducted to explore the co-prescription patterns for finished herbal products (FHP). RESULT: There were 19 379 women aged 45-55 years in the sample; of these, 12 572 (64.9%) utilized TCM services at least once. A total of 4078 (21.0%) of the 19 379 climacteric women utilized 145 200 (79.2%) TCM visits. Of these, 39 802 (21.7%) visits were because of diseases of the musculoskeletal system and connective tissue, of which more than half were treated with acupuncture and traumatology manipulative therapies. There were 28 154 visits with FHP prescriptions because of non-specific symptoms and ill-defined conditions, and Jia-wei-xiao-yao-san was the most frequent formula. Nearly two-thirds of FHP contained more than two herbal formulae. CONCLUSIONS: Women of climacteric age in Taiwan utilized TCM more often than other age groups. To deal with multiple symptoms and/or diseases among climacteric women, new prescription patterns of combining two or more herbal formulae have evolved. Studies on safety issues and drug-herb interactions are warranted for future research.

Food protective effect of geraniol and its congeners against stored food mites.

The acaricidal activities of compounds derived from the oil of Pelargonium graveolens leaves against the storage food mite, Tyrophagus putrescentiae, were compared with the activity of a commercial acaricide, benzyl benzoate, in an impregnated fabric disk bioassay. Purification of the active constituent from P. graveolens was accomplished by silica gel chromatography and high-performance liquid chromatography. Structural analysis of the active constituent by 1H nuclear magnetic resonance (NMR), 13C-NMR, 1H-13C shift correlated spectroscopy NMR, and distortionless enhancement by polarization transfer NMR identified trans-3,7-dimethyl-2,6-octadien-1-ol (geraniol). Based on the 50% lethal dose values, the most toxic compounds against T. putrescentiae were geraniol (1.95 microg/cm3), which was followed by nerol (2.21 microg/cm3), citral (9.65 microg/cm3), benzyl benzoate (11.27 microg/cm3), and beta-citronellol (15.86 microg/cm3). Our results suggest that geraniol is more effective in controlling T. putrescentiae than benzyl benzoate is. Furthermore, geraniol, which is used as a flavoring for beverages, candies, ice creams, and baked goods and congeners (citral and nerol), may be useful for managing populations of T. putrescentiae.

Intra-articular magnesium sulfate (MgSO4) reduces experimental osteoarthritis and nociception: association with attenuation of N-methyl-D-aspartate (NMDA) receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes.

OBJECTIVE: To study the effects of intra-articular injection of magnesium sulfate (MgSO(4)) on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats. METHODS: OA was induced in Wistar rats with intra-articular injection of collagenase (500 U) in the right knee; the left knee was left untreated. In the OA+MgSO(4) group (n=7), the treated knee was injected with 500-microg (0.1-ml) MgSO(4) twice a week for 5 consecutive weeks starting at 1 week after collagenase injection; in the OA group (n=7), the same knee was injected with the same amount of physiological normal saline. In the MgSO(4) group (n=6), naïve rats received only MgSO(4) injections; in the control group (n=6), naïve rats received only physiological normal saline injections. Nociceptive behavior (mechanical allodynia and thermal hyperalgesia) on OA development was measured before and at 1, 2, 4, 6, and 8 weeks after collagenase injection, following which the animals were sacrificed. Gross morphology and histopathology were examined in the femoral condyles, tibial plateau, and synovia. Immunohistochemical analysis was performed to examine the effect of MgSO(4) on N-methyl-D-aspartate (NMDA) receptor subunit 1 phosphorylation (p-NR1) and apoptosis in the articular cartilage chondrocytes. RESULTS: OA rats receiving intra-articular MgSO(4) injections showed a significantly lower degree of cartilage degeneration than the rats receiving saline injections. MgSO(4) treatment also suppressed synovitis. Mechanical allodynia and thermal hyperalgesia showed significant improvement in the OA+MgSO(4) group as compared to the OA group. Moreover, MgSO(4) attenuated p-NR1 and chondrocyte apoptosis in OA-affected cartilage. CONCLUSIONS: Our results indicate that local intra-articular administration of MgSO(4) following collagenase injection in an experimental rat OA model (1) modulates chondrocyte metabolism through inhibition of cell NMDA receptor phosphorylation and apoptosis, (2) attenuates the development of OA, and (3) concomitantly reduces nociception.

Inhibition of cyclooxygenase 2 expression by diallyl sulfide on joint inflammation induced by urate crystal and IL-1beta.

OBJECTIVE: Investigation of the effects of diallyl sulfide (DAS), a garlic sulfur compound, on joint tissue inflammatory responses induced by monosodium urate (MSU) crystals and interleukin-1beta (IL-1beta). DESIGN: The HIG-82 synovial cell line was used to establish the experimental model and DAS regime. Primary cultures of articular chondrocytes and synovial fibroblasts obtained from patients undergoing joint replacement for osteoarthritis were used in experimental studies. Cyclooxygenase (COX) expression following MSU crystal and IL-1beta stimulation with/without DAS co-incubation was assessed by reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunocytochemistry and nuclear factor-kappa B (NF-kappaB) activation determined by electrophoretic mobility shift assay. Prostaglandin E2 (PGE(2)) production was measured by enzyme-linked immunosorbent assay (ELISA). DAS effects on COX gene expression in an MSU crystal-induced acute arthritis in rats were assessed by RT-PCR. RESULTS: MSU crystals upregulated COX-2 expression in HIG-82 cells and this was inhibited by co-incubation with DAS. DAS inhibited MSU crystal and IL-1beta induced elevation of COX-2 expression in primary synovial cells and chondrocytes. Production of PGE(2) induced by crystals was suppressed by DAS and celecoxib. MSU crystals had no effect on expression of COX-1 in synovial cells. NF-kappaB was activated by MSU crystals and this was blocked by DAS. Increased expression of COX-2 in synovium following intraarticular injection of MSU crystals in a rat model was inhibited by co-administration of DAS. CONCLUSIONS: DAS prevents IL-1beta and MSU crystal induced COX-2 upregulation in synovial cells and chondrocytes and ameliorates crystal induced synovitis potentially through a mechanism involving NF-kappaB. Anti-inflammatory actions of DAS may be of value in treatment of joint inflammation.

Red mold rice prevents the development of obesity, dyslipidemia and hyperinsulinemia induced by high-fat diet.

OBJECTIVE: To investigate the influences of red mold rice (RMR) on obesity and related metabolic abnormalities. METHODS AND RESULTS: The 3T3-L1 cell line was used to examine the effects of RMR extracts on preadipocytes and on mature adipocytes. Both water and ethanol extracts of RMR had inhibitory effects on 3T3-L1 preadipocyte proliferation and differentiation. Water extracts of RMR enhanced the lipolysis activity in mature adipocytes, which negatively correlated with the triglyceride content within cells. RMR treatment did not affect heparin-releasable lipoprotein lipase activity in mature adipocytes. Furthermore, animal studies were carried out to explore the antiobesity effects of RMR. The control group of male Wistar rats were fed regular laboratory feed, whereas the other groups were fed the high-fat (HF) diet supplemented with lovastatin, rice or RMR (0.4 and 2%, w w(-1)). The relative caloric intakes of the control and HF groups were 3.34 and 4.85 kcal g(-1), respectively. After 6 weeks, rats treated with RMR at the 0.4 and 2% doses had lower weight gain and less fat pads mass accompanied with smaller fat cells than did the HF-diet rats. These effects probably resulted from an increase in the lipolysis activity of adipose tissue and a reduction in food/energy consumption. On the other hand, the RMR supplement significantly reduced serum total cholesterol, serum low-density lipoprotein (LDL) cholesterol, the ratio of LDL to high-density lipoprotein (HDL) cholesterol and serum insulin in the HF group. Moreover, the 2% RMR treatment significantly increased serum HDL cholesterol. CONCLUSION: This study reveals for the first time that RMR can prevent body fat accumulation and improve dyslipidemia. The antiobesity effects of RMR mainly derive from the lipolytic activity and mild antiappetite potency of RMR. In addition, extracts of RMR suppressed the proliferation and differentiation in 3T3-L1 preadipocytes, which might have contributed to the inhibition of new adipocyte formation or hyperplasia in adipose tissue.

Involvement of the BLT2 receptor in the itch-associated scratching induced by 12-(S)-lipoxygenase products in ICR mice.

BACKGROUND AND PURPOSE: Recently, we reported that 12(S)-HPETE (12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid) induces scratching in ICR mice. We hypothesized that 12(S)-HPETE might act as an agonist of the low-affinity leukotriene B4 receptor BLT2. To confirm the involvement of the BLT2 receptor in 12(S)-HPETE-induced scratching, we studied the scratch response using the BLT2 receptor agonists compound A (4'-[[pentanoyl (phenyl) amino]methyl]-1,1'-biphenyl-2-carboxylic acid) and 12(S)-HETE (12(S)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid). EXPERIMENTAL APPROACH: A video recording was used to determine whether the BLT2 receptor agonists caused itch-associated scratching in ICR mice. Selective antagonists and several chemicals were used. KEY RESULTS: Both 12(S)-HETE and compound A dose dependently induced scratching in the ICR mice. The dose-response curve for compound A showed peaks at around 0.005-0.015 nmol per site. Compound A- and 12(S)-HETE-induced scratching was suppressed by capsaicin and naltrexon. We examined the suppressive effects of U75302 (6-[6-(3-hydroxy-1E,5Z-undecadienyl)-2-pyridinyl]-1,5-hexanediol, the BLT1 receptor antagonist) and LY255283 (1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]phenyl]-ethanone, the BLT2 receptor antagonist) on the BLT2 agonist-induced scratching. LY255283 suppressed compound A- and 12(S)-HETE-induced scratching, but U75302 did not. LY255283 required a higher dose to suppress the compound A-induced scratching than it did to suppress the 12(S)-HETE-induced scratching. One of the BLT(2) receptor agonists, 12(R)-HETE (12(R)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid), also induced scratching in the ICR mice. CONCLUSIONS AND IMPLICATIONS: Our present results corroborate the hypothesis that the BLT2 receptor is involved in 12(S)-lipoxygenase-product-induced scratching in ICR mice. We also confirmed that this animal model could be a valuable means of evaluating the effects of BLT2 receptor antagonists.

Percutaneous radiofrequency ablation of liver dome hepatocellular carcinoma invisible on ultrasonography: a new targeting strategy.

Targeting of index tumours is prerequisite to their radiofrequency ablation. However, small hepatocellular carcinomas (HCCs) in the liver dome are often invisible on ultrasonography, thus causing difficulty in their targeting. In cases with multinodular HCCs, adjacent HCC lesions with compact iodized oil retention can be used as anatomic landmarks to guide radiofrequency (RF) ablation of such nodules under fluoroscopy. We present two cases in which nodules that were difficult to target with conventional methods were successfully treated by RF ablation using this targeting strategy.

TRPV1 receptors in the CNS play a key role in broad-spectrum analgesia of TRPV1 antagonists.

Vanilloid receptor type 1 (TRPV1) is a ligand-gated nonselective cation channel that is considered to be an important integrator of various pain stimuli such as endogenous lipids, capsaicin, heat, and low pH. In addition to expression in primary afferents, TRPV1 is also expressed in the CNS. To test the hypothesis that the CNS plays a differential role in the effect of TRPV1 antagonists in various types of pain, the analgesic effects of two TRPV1 antagonists with similar in vitro potency but different CNS penetration were compared in vivo. Oral administration of either A-784168 (1-[3-(trifluoromethyl)pyridin-2-yl]-N-[4-(trifluoromethylsulfonyl)phenyl]-1,2,3,6-tetrahydropyridine-4-carboxamide) (good CNS penetration) or A-795614 (N-1H-indazol-4-yl-N'-[(1R)-5-piperidin-1-yl-2,3-dihydro-1H-inden-1-yl]urea) (poor CNS penetration) blocked capsaicin-induced acute pain with the same potency. In complete Freund's adjuvant (CFA)-induced chronic inflammatory pain, oral administration of either compound blocked thermal hyperalgesia with similar potency. Furthermore, intraplantar or intrathecal administration of A-784168 blocked CFA-induced thermal hyperalgesia, suggesting that both peripheral and CNS TRPV1 receptors may play a role in inflammatory thermal hyperalgesia. The effects of the two TRPV1 antagonists were further assessed in models presumably mediated by central sensitization, including CFA- and capsaicin-induced mechanical allodynia and osteoarthritic pain. In these models, the potency of the two compounds was similar after intrathecal administration. However, when administered orally, A-784168, with good CNS penetration, was much more potent than A-795614. Together, these results demonstrate that TRPV1 receptors in the CNS play an important role in pain mediated by central sensitization. In addition, these results demonstrate that significant CNS penetration is necessary for a TRPV1 antagonist to produce broad-spectrum analgesia.

Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro.

PURPOSE: The antimalarial agent, artemisinin, also confers cancer-specific cytotoxic effects by reacting with ferrous iron atoms to form free radicals. Here, we investigated the radiosensitizing effects of dihydroartemisinin on glioma cells and assessed some possible mechanisms for these effects. MATERIALS AND METHODS: U373MG glioma cells treated with various concentrations of dihydroartemisinin plus radiation, and efficiency of radiosensitization was assessed by clonogenic survival assay. Expression and activity of antioxidant enzymes, glutathione-S-transferase (GST) were quantified by western blot and enzymatic activity analyses, respectively. RESULTS: Dihydroartemisinin showed higher cytotoxicity in the glioma cell lines than in the liver, breast or cervical cancer cell lines. In clonogenic survival assays, treatment with dihydroartemisinin alone dose-dependently reduced the number of U373MG colonies, while treatment with dihydroartemisinin plus gamma-irradiation showed far lower clonal survival than cultures treated with radiation or dihydroartemisinin alone. The radiosensitizing effect of dihydroartemisinin was blocked significantly by the free radical scavengers, NAC and TIRON, indicating association with dihydroartemisinin-induced ROS generation. In addition, the radiation-induced expression of endogenous GST was suppressed by treatment with dihydroartemisinin. The radiosensitizing effect of dihydroartemisinin was also markedly enhanced by the addition of holotransferrin CONCLUSION: Taken together, our results strongly suggest that dihydroartemisinin triggers production of ROS and inhibits GST activity, leading to effective and therapeutically relevant radiosensitization of human glioma cells.

Improved treatment results for childhood acute myeloid leukemia in Taiwan.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.

Vertebral artery dissection and cerebellar infarction following chiropractic manipulation.

Vertebral artery dissection (VAD) associated with chiropractic cervical manipulation is a rare but potentially disabling condition. In this report, we present a young patient manifesting with repeated vertigo. Owing to the initial misdiagnosis, the patient later developed cerebellar stroke with inability to stand or walk. Vertigo and disequilibrium are the usual presenting symptoms of this condition, which can result from inner ear or vestibular nerve dysfunction, vertebrobasilar insufficiency, and even lethal cerebellar infarction or haemorrhage; these last two, although rarely seen in young adults, can be caused by traumatic or spontaneous arterial injury, including injury secondary to chiropractic cervical manipulation. A number of cases of VAD associated with chiropractic cervical manipulation have been reported, but rarely in the emergency medicine literature. We present a case of this rare occurrence, and discuss the diagnostic pitfalls.

Coenzyme q10 confers cardiovascular protection against acute mevinphos intoxication by ameliorating bioenergetic failure and hypoxia in the rostral ventrolateral medulla of the rat.

Coenzyme Q10 (CoQ10, ubiquinone) is a highly mobile electron carrier in the mitochondrial respiratory chain that also acts as an antioxidant. We evaluated the cardiovascular protective efficacy of CoQ10 at the rostral ventrolateral medulla (RVLM), a medullary site where sympathetic vasomotor tone originates and where the organophosphate poison mevinphos (Mev) acts to elicit cardiovascular intoxication. Experiments were carried out in adult male Sprague-Dawley rats that were maintained under propofol anesthesia. Microinjection bilaterally of Mev (10 nmol) into the RVLM induced progressive hypotension and minor bradycardia, alongside significant depression of the activity of NADH cytochrome c reductase (enzyme marker for Complexes I and III) or cytochrome c oxidase (enzyme marker for Complex IV) in the mitochondrial respiratory chain, reduction in ATP concentration, or tissue hypoxia in the RVLM. On the other hand, the activity of succinate cytochrome c reductase (enzyme marker for Complexes II and III) remained unaltered. The Mev-induced hypotension, bioenergetic failure, or hypoxia was significantly reversed when CoQ10 (4 microg) was coadministered bilaterally into the RVLM with the organophosphate poison. We conclude that CoQ10 confers cardiovascular protection against acute Mev intoxication by acting on the RVLM, whose neuronal activity is intimately related to the "life-and-death" process. We also showed that amelioration of the selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain, the reduced ATP level, and the induced tissue hypoxia in the RVLM are among some of the underlying mechanisms for the elicited protection.