Influence of seasonal exposure to grass pollen on local and peripheral blood IgE repertoires in patients with allergic rhinitis.

BACKGROUND: Previous studies of immunoglobulin gene sequences in patients with allergic diseases using low-throughput Sanger sequencing have limited the analytic depth for characterization of IgE repertoires. OBJECTIVES: We used a high-throughput, next-generation sequencing approach to characterize immunoglobulin heavy-chain gene (IGH) repertoires in patients with seasonal allergic rhinitis (AR) with the aim of better understanding the underlying disease mechanisms. METHODS: IGH sequences in matched peripheral blood and nasal biopsy specimens from nonallergic healthy control subjects (n = 3) and patients with grass pollen-related AR taken in season (n = 3) or out of season (n = 4) were amplified and pyrosequenced on the 454 GS FLX+ System. RESULTS: A total of 97,610 IGH (including 8,135 IgE) sequences were analyzed. Use of immunoglobulin heavy-chain variable region gene families 1 (IGHV1) and 5 (IGHV5) was higher in IgE clonotypic repertoires compared with other antibody classes independent of atopic status. IgE repertoires measured inside the grass pollen season were more diverse and more mutated (particularly in the biopsy specimens) and had more evidence of antigen-driven selection compared with those taken outside of the pollen season or from healthy control subjects. Clonal relatedness was observed for IgE between the blood and nasal biopsy specimens. Furthermore in patients with AR, but not healthy control subjects, we found clonal relatedness between IgE and IgG classes. CONCLUSION: This is the first report that exploits next-generation sequencing to determine local and peripheral blood IGH repertoires in patients with respiratory allergic disease. We demonstrate that natural pollen exposure was associated with changes in IgE repertoires that were suggestive of ongoing germinal center reactions. Furthermore, these changes were more often apparent in nasal biopsy specimens compared with peripheral blood and in patients with AR compared with healthy control subjects.

Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats.

For centuries, Berberine has been used in the treatment of enteritis in China, and it is also known to have anti-hyperglycemic effects in type 2 diabetic patients. However, as Berberine is insoluble and rarely absorbed in gastrointestinal tract, the mechanism by which it works is unclear. We hypothesized that it may act locally by ameliorating intestinal barrier abnormalities and endotoxemia. A high-fat diet combined with low-dose streptozotocin was used to induce type 2 diabetes in male Sprague Dawley rats. Berberine (100 mg/kg) was administered by lavage to diabetic rats for 2 weeks and saline was given to controls. Hyperinsulinemia and insulin resistance improved in the Berberine group, although there was no significant decrease in blood glucose. Berberine treatment also led to a notable restoration of intestinal villi/mucosa structure and less infiltration of inflammatory cells, along with a decrease in plasma lipopolysaccharide (LPS) level. Tight junction protein zonula occludens 1 (ZO1) was also decreased in diabetic rats but was restored by Berberine treatment. Glutamine-induced glucagon-like peptide 2 (GLP2) secretion from ileal tissue decreased dramatically in the diabetic group but was restored by Berberine treatment. Fasting insulin, insulin resistance index, plasma LPS level, and ZO1 expression were significantly correlated with GLP2 level. In type 2 diabetic rats, Berberine treatment not only augments GLP2 secretion and improves diabetes but is also effective in repairing the damaged intestinal mucosa, restoring intestinal permeability, and improving endotoxemia. Whether these effects are mechanistically related will require further studies, but they certainly support the hypothesis that Berberine acts via modulation of intestinal function.

Effect of functional yogurt NY-YP901 in improving the trait of metabolic syndrome.

BACKGROUND/OBJECTIVES: This study was aimed to assess the beneficial effects on metabolic syndrome of functional yogurt NY-YP901 (Namyang Dairy Product Co. Ltd and Nutra R&BT Inc., Seoul, Korea) supplemented with mixture of Streptococcus thermophilus, Lactobacillus acidophilus, Bifidobacterium infantis and extra-ingredients containing Bifidobacterium breve (CBG-C2), Enterococcus faecalis FK-23, fibersol-2 and so on. SUBJECTS/METHODS: This study was designed as an 8-week randomized, double-blind, placebo-controlled, parallel study. Treatment and control groups consumed a functional yogurt NY-YP901 (150 ml) and a placebo yogurt twice a day, respectively, for 8 weeks. Body weight and body mass index (BMI), blood pressure, lipid profiles, fasting glucose with HbA1C and waist circumference were measured before and after treatment. Inclusion criteria were healthy individuals between the ages 20-65 years old who submitted an informed consent. RESULTS: During the period August 2009 to December 2009, 101 healthy participants (31 males and 70 females) finished the study. Treatment group were 53 individuals, and the control group were 48 individuals. In the treatment group consuming NY-YP901, statistically significant beneficial changes were observed in body weight (treatment group vs control group=-0.24±1.50 vs +0.64±1.39 kg, P<0.05), BMI (-0.10±0.58 vs +0.24±0.50 kg/m(2), P<0.05 ) and low-density lipoprotein (LDL)-cholesterol (-7.71±14.14 vs -0.43±15.32 mg/dl, P<0.05) after 8 weeks. The change in other parameters was not different between the treatment and the control groups. CONCLUSIONS: The functional yogurt NY-YP901 reduced LDL-cholesterol, body weight and BMI in the subjects at a 300-ml consumption daily for 8 weeks. From these findings, regular intake of functional yogurt NY-YP901 may be consequently related to improve metabolic syndrome.

Self-complementary AAV-mediated gene therapy restores cone function and prevents cone degeneration in two models of Rpe65 deficiency.

To test whether fast-acting, self-complimentary (sc), adeno-associated virus-mediated RPE65 expression prevents cone degeneration and/or restores cone function, we studied two mouse lines: the Rpe65-deficient rd12 mouse and the Rpe65-deficient, rhodopsin null ('that is, cone function-only') Rpe65(-/-)::Rho(-/-) mouse. scAAV5 expressing RPE65 was injected subretinally into one eye of rd12 and Rpe65(-/-)::Rho(-/-) mice at postnatal day 14 (P14). Contralateral rd12 eyes were injected later, at P35. Rd12 behavioral testing revealed that rod vision loss was prevented with either P14 or P35 treatment, whereas cone vision was only detected after P14 treatment. Consistent with this observation, P35 treatment only restored rod electroretinogram (ERG) signals, a result likely due to reduced cone densities at this time point. For Rpe65(-/-)::Rho(-/-) mice in which there is no confounding rod contribution to the ERG signal, cone cells and cone-mediated ERGs were also maintained with treatment at P14. This work establishes that a self-complimentary AAV5 vector can restore substantial visual function in two genetically distinct models of Rpe65 deficiency within 4 days of treatment. In addition, this therapy prevents cone degeneration but only if administered before extensive cone degeneration, thus supporting continuation of current Leber's congenital amaurosis-2 clinical trials with an added emphasis on cone subtype analysis and early intervention.

"Cryoanalgesic preparation" before local anaesthetic injection for lid surgery.

INTRODUCTION: Lid surgery under local anaesthetic is commonplace in ophthalmic practise. The most distressing part of the surgery for the patient is often the injection of local anaesthetic into the sensitive lid skin. Various methods like pre-injection warming of the anaesthetic agent, buffering pH levels, varying agents used, and using thinner gauge needles have been tried to reduce pain levels. Cooling of tissue is known to have anaesthetic properties and has been proposed as a substitute to injection of local anaesthetic in certain surgical procedures. In this study we use the anaesthetic property of cooling, as a pre local anaesthetic injection procedure ("Cryo-preparation"). The anaesthetic injection induced discomfort with and without "cryo-preparation" was then assessed. METHODS: Thirty-nine patients aged 13-85 years (mean = 50, s.d. = 19) were randomly allocated and assessed. Twenty-two patients underwent local lid anaesthetic infiltration with "cryo-preparation," and 17 without. Pain monitoring was performed subjectively and objectively by scoring systems. Results were analysed using unpaired two tailed t-test on Microsoft Excel. RESULTS: Significant reduction in injection pain with cryo-preparation (24.6% reduction in score) was achieved (statistically significant p = 0.039). Surgical anaesthesia was complete in all cases. CONCLUSION: The study shows that "cryopreparation" by local ice application immediately prior to local anaesthetic injection reduces the sensitivity to the injection by a significant 24.6%. Thus while all the advantages of good analgesia are obtained from the injection, the distressing discomfort is reduced. This study serves as a pilot, in demonstrating a novel method of pain control for lid surgery.

Effects of lentinan on broiler splenocyte proliferation, interleukin-2 production, and signal transduction.

Lentinan (LEN) is an intensively studied beta-glucan that has been shown to have immunostimulating and antitumor functions. However, it currently is not used in veterinary practice and animal production. This study was conducted to investigate the impacts of LEN on broiler splenocyte proliferation, interleukin-2 (IL-2) production, and to explore its effects on receptor signal transduction by determining signaling molecules, including nitric oxide (NO), cytosolic-free Ca2+, cytosolic cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP). The results showed that compared to the control all three measured doses, including 40, 80, and 160 microg/mL LEN, increased splenocyte proliferation and IL-2 production (P < 0.05). Lentinan increased splenocyte NO production and cytosolic-free calcium concentration in a dose-dependent manner (P < 0.001). After incubating splenocytes for 20 min, LEN increased intracellular cAMP and cGMP concentrations at a dose of 80 and 160 microg/mL, respectively. However, after incubating the splenocytes for 60 min, LEN had no effect on cytosolic cAMP and cGMP concentration irrespective of the LEN dosage. Those results indicated that LEN had immunostimulatory effects on splenocytes by increasing splenocyte proliferation and IL-2 production and by activating splenocyte receptor signal transduction.

Decomposition of NO on the alkalized Pt/Al2O3.

Catalytic decomposition of NO on platinum catalysts at 873-1,173 K was investigated in the present work. The yield of N2 in the NO decomposition process was significantly increased on the alkalizing Pt/Al2O3 catalyst. The enhancement may be attributed to a trap of additional NO molecules by basic sites ofthe alkalized catalyst. The interstitially adsorbed species (NaOH(NO)Pt) might increase the NO adsorption strength during the catalytic NO reduction process. Pt on the high acidity HY was also active for catalytic decomposition of NO. Nevertheless, its activity decreased at higher temperatures (>1,073 K) because of the distortion of the HY framework. Combined results of XPS (X-ray photoelectron spectra) and TPR (temperature programmed reduction) showed that PtO and PtO2 were the main active species on the alkalized Al2O3 and HY during NO reduction.

Effects of Chinese herbal polysaccharides on the immunity and growth performance of young broilers.

Two trials were conducted to study the effects of two Chinese herbal polysaccharides [achyranthan (ACH), a low-molecular-weight polysaccharide, and astragalan (APS), a high-molecular-weight polysaccaride] on the immunity and growth performance of young broilers. Trial 1 was a 28-d growth assay, in which 7-d-old broilers (n = 240) were randomly allotted to one of three dietary treatments, with eight replicate pens per treatment and ten chickens per pen. Dietary treatments included a control corn-soy-fishmeal (Treatment 1), a diet with 200 mg/kg APS (Treatment 2), and a diet with 200 mg/kg ACH (Treatment 3). Blood samples were collected by cardiac puncture on Days 7, 14, 21, and 28 for determination of serum parameters, and chickens were killed on Day 28 to measure immune organ indexes. Trial 2 was an in vitro trial to study the effects of different concentrations of polysaccharides on broiler splenocyte functions. In Trial 1, feeding either APS or ACH had no significant effects on growth performance of broilers relative to the control. However, compared to the control, feeding ACH significantly increased microhemagglutination inhibition (HI) antibody titers, bursa of Fabricius index, serum albumin, serum calcium, and nitric oxide (NO) concentrations at Day 28 (P < or = 0.05). In Trial 2, both polysaccharides showed significant immunostimulating effects. They increased NO and interleukin-2 (IL-2) production of splenocytes and enhanced splenocyte proliferation in a dose-dependent manner (P < 0.05). Those results indicate that the immunostimulating effects of APS are not as pronounced as those of ACH. Achyranthan showed immunostimulating effects in both the growth assay and in vitro studies. Therefore, ACH may be a Chinese herbal polysaccharide that has the potential to be used as a feed additive to improve broilers' immunity.

Targeting superoxide dismutase to renal proximal tubule cells inhibits nephrotoxicity of cisplatin and increases the survival of cancer-bearing mice.

Because cis-diamminedichloroplatinum(II) (cisplatin) which generates reactive oxygen species induces renal dysfunction, administration of a large dose for killing cancer cells is highly limited. We recently synthesized a cationic superoxide dismutase (SOD) (hexamethylenediamine-conjugated SOD, AH-SOD) which rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury of the kidney. Treatment of Ehrlich ascites tumor cells (EATC)-bearing mice with cisplatin sufficient for killing tumor cells increased their motality. The motality of cisplatin-treated EATC-bearing mice was markedly decreased by AH-SOD. These results suggest that targeting SOD to renal proximal tubule cells might permit the administration of high doses of cisplatin and related anticancer agents without causing renal injury.

Intraocular pressure and pulsatile ocular blood flow after retrobulbar and peribulbar anaesthesia.

AIMS: This study investigated the effect of peribulbar and retrobulbar local anaesthesia on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF), as such anaesthetic techniques may adversely affect these parameters. METHODS: 20 eyes of 20 patients who were to undergo phacoemulsification cataract surgery were prospectively randomised to receive peribulbar or retrobulbar anaesthesia. The OBF tonometer (OBF Labs, Wiltshire, UK) was used to simultaneously measure IOP and POBF before anaesthesia and 1 minute and 10 minutes after anaesthesia. Between group comparisons of age, baseline IOP, and baseline POBF were performed using the non-parametric Mann-Whitney test. Within group comparisons of IOP and POBF measured preanaesthesia and post-anaesthesia were performed using the non-parametric Wilcoxon signed ranks test for both groups. RESULTS: There was no statistically significant IOP increase post-anaesthesia in either group. In the group receiving peribulbar anaesthesia, there was a significant reduction in POBF initially post-anaesthesia which recovered after 10 minutes. In the group receiving retrobulbar anaesthesia, there was a persistent statistically significant reduction in POBF. CONCLUSIONS: Retrobulbar and peribulbar injections have little effect on IOP. Ocular compression is not needed for IOP reduction when using local anaesthesia for cataract surgery. Conversely, POBF falls, at least for a short time, when anaesthesia for ophthalmic surgery is administered via a retrobulbar route or a peribulbar route. This reduction may be mediated by pharmacologically altered orbital vascular tone. It may be safer to use other anaesthetic techniques in patients with ocular vascular compromise.

Assays for angiotensin converting enzyme inhibitory activity.

A colorimetric method and a capillary electrophoresis procedure were developed for quantifying histidyl-leucine and hippurate, respectively. The colorimetric method is sensitive (extinction coefficient = 7.5 mM(-1) cm(-1)) and reproducible (CV = 1.7%, n = 5), which is based on a selective chromogenic reaction for histidyl-leucine (lambda(max) = 390 nm) using o-phthalaldehyde. For samples containing unusually high levels of histidine and/or histidyl peptides, the separation-based approach is preferable. The capillary electrophoresis method makes use of an in-capillary microextraction technique; complicated samples can be measured in less than 4 min without pretreatment. Protocols using both methods to measure angiotensin converting enzyme inhibitory activity were proposed.

Local anaesthetic techniques and pulsatile ocular blood flow.

AIM: To compare pulsatile ocular blood flow (POBF) and intraocular pressure (IOP) between eyes of patients receiving either peribulbar (with and without balloon compression) or subconjunctival local anaesthesia (LA). METHODS: 30 eyes of 30 patients undergoing cataract surgery by phacoemulsification were investigated in a study of parallel group design. Ten patients had peribulbar LA and 10 minutes compression with a Honan's balloon (group A). A further 10 patients who received peribulbar LA alone (group B) acted as controls for the effects of balloon compression. Ten other patients were given subconjunctival LA (group C). POBF and IOP were measured using a modified Langham pneumatonometer. Three measurements were made in each eye, the first recording immediately before LA, the second 1 minute after, and the third 10 minutes after LA. RESULTS: No significant change in POBF or IOP was recorded in eyes receiving subconjunctival LA. In the peribulbar groups (A and B), there was a drop in median POBF of 252 and 138 microl/min respectively 1 minute after LA, which was statistically significant in both groups (p<0. 01). By 10 minutes, POBF tended to return to baseline levels, but remained significantly reduced in group B (p<0.05). In addition, there was a significant (p<0.05) reduction in IOP (mean drop of 4.82 mm Hg) in group A following peribulbar LA with balloon compression. CONCLUSIONS: POBF was significantly reduced after peribulbar LA but was unchanged after subconjunctival LA. Balloon compression reduced IOP and improved POBF following peribulbar LA. The findings may have clinical implications in patients with compromised ocular circulation or significant glaucomatous optic neuropathy.

The role of religion/spirituality in coping with caregiving for disabled elders.

This study examined how religious/spiritual coping was related to specific conditions of caregiving and psychological distress among 127 informal caregivers to community-residing disabled elders. Support was found for the hypothesis that religious/spiritual coping influences caregiver distress indirectly through the quality of the relationship between caregiver and care recipient. Caregivers who used religious or spiritual beliefs to cope with caregiving had a better relationship with care recipients, which was associated with lower levels of depression and role submersion.

Antimicrobial activity of magnolol and honokiol against periodontopathic microorganisms.

Magnolol (1) and honokiol (2), main compounds from the stem bark of Magnolia obovata Thunb., were evaluated for an antimicrobial activity against periodontopathic microorganisms, Porphyromonas gingivalis, Prevotella gingivalis, Actinobacillus actinomycetemcomitans, Capnocytophaga gingivalis, and Veillonella disper, and a cytotoxicity against human gingival fibroblasts and epithelial cells. Our results indicate that magnolol and honokiol, although less potent than chlorhexidine, show a significant antimicrobial activity against these microorganisms, and a relatively low cytotoxic effect on human gingival cells. Thus, it is suggested that magnolol and honokiol may have a potential therapeutic use as a safe oral antiseptic for the prevention and the treatment of periodontal disease.

Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice.

PURPOSE: To characterize ocular abnormalities associated with iris atrophy in DBA/2J mice and to determine whether mice of this strain develop elevated intraocular pressure (IOP) and glaucoma. METHODS: Different approaches, including slit-lamp biomicroscopy, ophthalmoscopic examination, ultrasound backscatter microscopy, and histology were used to examine the eyes of DBA/2J mice ranging from 2 to 30 months old. IOP was measured in DBA/2J mice of different ages. RESULTS: DBA/2J mice were found to develop pigment dispersion, iris transillumination, iris atrophy, anterior synechias, and elevated IOP. IOP was elevated in most mice by the age of 9 months. These changes were followed by the death of retinal ganglion cells, optic nerve atrophy, and optic nerve cupping. The prevalence and severity of these lesions increased with age. Optic nerve atrophy and optic nerve cupping was present in the majority of mice by the age of 22 months. CONCLUSIONS: DBA/2J mice develop a progressive form of secondary angle-closure glaucoma that appears to be initiated by iris atrophy and the associated formation of synechias. This mouse strain represents a useful model to evaluate mechanisms of pressure-related ganglion cell death and optic nerve atrophy, and to evaluate strategies for neuroprotection.

Removal of the inferior olive abolishes myoclonic seizures associated with a loss of olivary serotonin.

Several lines of clinical evidence suggest that myoclonus is caused by a reduction of serotonin in the brain and hyperactivity of the inferior olive. We determined whether a change in serotonin content within the olivocerebellar system accompanied a predisposition to myoclonus and investigated the necessity of the inferior olive for a myoclonic seizure. The experiments employed the genetically epilepsy-prone rat that exhibits a profound myoclonic seizure in response to an auditory stimulus. We found that these animals demonstrated a significant reduction in the serotonergic innervation of the inferior olive without a significant change in the serotonergic innervation at any other level of the olivocerebellar circuit. The deficit in olivary serotonin was verified physiologically and pharmacologically by a reduced sensitivity of the genetically epilepsy-prone rat to the tremorogenic effect of harmaline, which is known to produce tremor through a mechanism that requires serotonergic innervation of the inferior olive. We quantified the timing of the myoclonic seizure of the genetically epilepsy-prone rat and found that its large amplitude 2-6 Hz clonus was always preceded by 9-10 Hz tremor that was synchronized among limbs. Ablation of the inferior olive by 3-acetylpyridine abolished the myoclonic seizure. The specificity of the deficit in olivary serotonin, the timing of the seizure, and the demonstration of the necessity of the inferior olive for myoclonus suggest that pathological inferior olivary activity contributes to the genesis of a myoclonic seizure.

[The effect of herbal medicine including astragalus membranaceus (fisch) bge, codonpsis pilosula and glycyrrhiza uralensis fisch on airway responsiveness].

OBJECTIVE: To study the effect of astragalus membranceus(fisch) bge, codonpsis pilosula and glycyrrhiza uralensis fisch on airway responsiveness. METHOD: FVC, FEV1 and PEF of twenty-eight asthmatic patients were measured before and six weeks after treated with Astragalus membranceus(fisch) bge, codonpsis pilosual and glycyrrhiza uralensis fisch; methacholine challenge test with 0.033 mumol and 1.98 mumol. RESULT: After 28 asthmatic patients received the treatment of those herbs, the results showed that FVC value increased obviously (t = 2.217, P < 0.05) and the value of FEV1 and PEF was all higher compared with before treatment of the herbs (P < 0.01). CONCLUSION: The herbal medicine including astragalus memberanaceus (fisch) bge, codonpsis pilosual and glycyrrhiza uralensis fisch can decrease the airway responsiveness of the patients with asthma.

Axial (HNF3beta) and retinoic acid receptors are regulators of the zebrafish sonic hedgehog promoter.

The signalling molecule Sonic hedgehog is involved in a multitude of distinct patterning processes during vertebrate embryogenesis. In the nascent body axis of the zebrafish embryo, sonic hedgehog is co-expressed with axial (HNF3beta in mammals), a transcription regulator of the winged helix family. We show here that misexpression of axial leads to ectopic activation of sonic hedgehog expression in the zebrafish, suggesting that axial is a regulator of sonic hedgehog transcription. The sonic hedgehog gene was cloned from zebrafish and its promoter was characterized with respect to activation by axial. Expression of axial or rat HNF3beta in HeLa cells results in activation of co-transfected sonic hedgehog promoter-CAT fusion genes. This effect is mediated by two Axial (HNF3beta) recognition sequences. We furthermore identified a retinoic acid response element (RARE) in the sonic hedgehog upstream region which can be bound by retinoic acid receptor (RAR) and retinoid X receptor (RXR) heterodimers in vitro and confers retinoic acid inducibility to the sonic hedgehog promoter in the HeLa cell system. Our results suggest that both Axial (HNF3beta) and retinoic acid receptors are direct regulators of the sonic hedgehog gene.

Enhanced potency of daunorubicin against multidrug resistant subline KB-ChR-8-5-11 by a pulsed magnetic field.

Tumor cell resistance to many unrelated anticancer drugs is a major obstacle during cancer chemotherapy. One mechanism of drug resistance is thought to be due to the efflux of anticancer drugs caused by P-glycoprotein. In recent years, magnetic fields have been found to enhance the potency of anticancer drugs, with favorable modulation of cancer therapy. In this study, KB-ChR-8-5-11, a multidrug resistant (MDR) human carcinoma subline, was used as a model to evaluate the ability of pulsed magnetic fields (PMF) to modulate the potency of daunorubicin (DNR) in vivo and to determine the appropriate order of exposure to drugs and PMF using an in vitro cytotoxicity assay. Solenoid coils with a ramped pulse current source were used at 250 pulses per second for both in vivo and in vitro experiments. For the in vivo study, KB-ChR-8-5-11 cells were inoculated into thymic Balbc-nu/nu female mice. Treatment was begun when the average tumor volume reached 250-450 mm3. Treatment consisted of whole body exposure to PMF for one hour, followed immediately by intravenous (i.v.) injection of 8 mg/kg DNR designated as day 0, and repeated on days 7 and 14. Among the various groups, significant differences in the tumor volume were found between PMF + saline and PMF + DNR groups (p = 0.0107) at 39 days and 42 days (p = 0.0101). No mice died in the PMF alone group, and no toxicity attributable to PMF was found during the experimental period. For the in vitro studies, the sulforhodamine blue (SRB) cytotoxicity assay was used to determine the effect of the sequence which cells are exposed to PMF and/or DNR. Cells were exposed to PMF either before (pre-PMF) or after (post-PMF) drug was added. Results showed that the IC50 was significantly different between controls and pre-PMF + DNR groups (P = 0.0096, P = 0.0088). The IC50 of the post-PMF + DNR group was not found to be significantly different from control groups. Thus, the data in this report demonstrates that PMF enhanced the potency of DNR against KB-ChR-8-5-11 xenograft in vivo, while the efficacy of DNR was potentiated in vitro by PMF exposure only when PMF exposure occurred in the presence of drug. The data in vitro suggest that the mechanism by which PMFs modulate DNR's potency may be by inhibition of the efflux pump, P-glycoprotein. Further work to determine conditions for maximum modulation of drug potency by PMFs is warranted.

A clinical study on severe hydroa vacciniforme.

OBJECTIVE: To describe a severe type of hydroa vacciniforme (HV) in order to provide basis for treatment and prevention of this disease. METHODS: Nine cases of HV were collected in our outpatient department, and clinical and laboratory examinations were performed. RESULTS: All the cases had erythemas, papules, bullae, erosions or ulcers on exposed sites, with recurrences, gradually resulting in deformation. Five patients suffered from hand deformation manifesting rigidity, flexor tetanus, or malposition of the first, second and third interphalangeal joints of hands. Two of the above mentioned patients manifested partial bone absorption of fingers. Five patients showed partial defect of auricle. Two patients showed saddle nose, and partial absorption of nasal cartilage. One patient displayed cicatricial contracture of lower lip, with incisor extrusion. Four patients showed opacity of cornea. Through laboratory examinations, porphyrinopathies were excluded. Phototests showed increased sensitivity to ultraviolet-A radiation (UVA). CONCLUSIONS: Based on the clinical features and laboratory examinations, these patients were diagnosed as having severe HV. It is believed that this condition belongs to a disease spectrum induced by ultraviolet light. Our analysis suggests that for children with severe type of HV, preventive measures and therapeutic agents should be taken as soon as possible in order to avoid deterioration of the disease and malformations.