Application of a Live Varicella Vaccine to the Immunosuppressive Children and the Incibence of a Case of Herpes Zoster after Vaccination

A live varicella vaccine was applied to 13 susceptible children to varicella virus. Three were receiving steroid therapy, and one of them was treated with both steroid and anticancer drugs. Immunosuppressive therapy and anticancer medication were not suspended before and after vaccination. Serological responses were observed in 11 of 13 vaccinated children by fluorescent antibody to membrane antigen (FAMA) test 6 to 7 weeks after Vaccination. Mild rash appeared as only a clinical reaction in 3 of the vaccinated children. However, 3 and a half months later, a vaccinee with acute myeloblastic leukemia, developed herpes zoster. Our observation suggested a possibility of contracting zoster in immune compromised hosts after vaccination with a live varicella vaccine.     

Efficacy of Conventional Radiotherapy for Recurrent Meningioma

Results of radiation therapy for 20 patients with recurrent meningioma were analyzed. The patients included 8 men and 12 women, with a median age of 55 years. All of the patients had undergone at least one operation prior to the reoperation preceding radiotherapy. Ten patients had benign meningiomas, while 4 and 6 patients had atypical and malignant meningiomas, respectively, at the time of radiotherapy. The median radiation dose was 59.4Gy (range: 50–61.2Gy). The local control rate at 5 years was 36% for all 20 patients (41% for benign meningiomas and 30% for atypical or malignant meningiomas). The 5-year survival rate was 47%. Excluding 2 patients whose follow-up period was shorter than the preradiotherapy interval from the previous operation, the postradiation recurrence-free period was longer than the preradiotherapy interval in 50% (9/18) of the patients. No serious complications of radiotherapy were observed. Radiotherapy seemed to be effective in controlling the tumor or delaying recurrence in at least half of the patients. However, higher doses of radiation, using sophisticated radiation techniques, may be necessary to obtain higher control rates.     

Sex‐specific association between leptin receptor polymorphisms and leptin levels and BMI in healthy adolescents*

Aim: To examine the relationship of three common polymorphisms in the leptin receptor (LEPR) gene, implicated in the regulation of body weight, with leptin levels and obesity‐related phenotypes in a population‐based sample of healthy pubertal children in Spain. Methods: The study included 806 boys and girls aged 12–16 whose anthropometrical data and body composition were recorded. Serum leptin levels were determined by ELISA. The LEPR Q223R, K109R and K656N polymorphisms were determined by TaqMan® allelic discrimination assays. Results: When analysing the Q223R polymorphism, we observed that female carriers of the RR genotype had significantly higher plasma leptin levels (18.2 vs. 15.1 ng/mL p = 0.016) and significantly higher mean BMI values (22.5 vs. 21.3 Kg/m² p = 0.032) than QR carriers. Furthermore, the frequency of the RR genotype in overweight‐obese girls was significantly higher than that found in normal‐weight girls. No significant differences were observed in boys. Neither boys nor girls showed significant differences when comparing leptin levels, anthropometric variables or body composition by K109R or K656N genotype. Conclusion: The fact, that the Q223R polymorphism in the LEPR gene is significantly associated with leptin levels and BMI only in girls, suggests a sex‐specific influence of this polymorphism on these variables.     

Protective effect of alpha-lipoic acid in methotrexate-induced ovarian oxidative injury and decreased ovarian reserve in rats

To determine whether the possible oxidative effect of methotrexate (Mtx) on ovary and to evaluate the effectiveness of alpha lipoic acid (ALA), which may be useful in many oxidative stress models.

Thirty-two female Wistar-albino rats were randomly divided into four groups; control group, alpha lipoic acid group (ALA 100?mg/kg, 10?days), multiple dose Mtx group (Mtx 1?mg/kg 1, 3, 5, 7?days) and Mtx and ALA group (Mtx 1?mg/kg 1, 3, 5, 7?days and ALA 100?mg/kg, 10?days). Serum total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI), tumor necrosis factor-alpha (TNF-α), tissue malondialdehyde (MDA) and activities of glutathione peroxidase (GSH-Px) and catalase (CAT) and anti-Mullerian hormone (AMH) and total ovarian follicle count were evaluated.

Mtx administration caused a significant decrease in TAS, a significant increase in TOS and OSI, a significant increase in MDA levels and a decrease in GSH-Px and CAT activity. Moreover the proinflammatory cytokine (TNF-α) was increased in the Mtx group. And AMH values and total follicle count were significantly decreased in Mtx group. However, ALA treatment reversed biochemical results and AMH levels and total follicle count.

Alpha lipoic acid ameliorates methotrexate induced oxidative damage of ovarian in rats.     

Effect of vitamin E TPGS on immune response to nasally delivered diphtheria toxoid loaded poly(caprolactone) microparticles

The nasal mucosa has many advantages as a potential site for drug and vaccine delivery. The present study has sought to exploit this route of delivery using microparticles composed of D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a matrix material blended with poly(caprolactone) for nasal immunisation with diphtheria toxoid. Particles were prepared by a double emulsion method, followed by spray drying and the effect of TPGS on size, zeta potential, loading and release of antigen was assessed. Particles composed of TPGS-PCL blends were spherical, smooth and monodisperse, displaying increasing yields after spray drying with increasing concentrations of TPGS. The immune response to diphtheria toxoid loaded PCL-TPGS microspheres after nasal administration was shown to be higher than that achieved using PCL microspheres alone. We conclude that TPGS shows significant potential as a novel adjuvant either alone or in combination with an appropriate delivery system.     

Effects of long-term monounsaturated- vs polyunsaturated-enriched diets on lipoproteins in healthy men and women.

The effect of dietary-fat saturation on plasma lipoprotein concentrations was assessed in 46 men and 32 women placed on a diet enriched in polyunsaturated fatty acids (sunflower oil) for 12 wk and, under isocaloric conditions, on a diet enriched in monounsaturated fatty acids (olive oil) for the next 16 wk in men and 28 wk in women. Fat comprised 37% of the total energy intake in men and 36% in women. At the end of the monounsaturated fatty acid diet no change occurred in total cholesterol (TC) in men but it increased by 9% in women. High-density-lipoprotein (HDL) cholesterol increased by 17% in men and by 30% in women. The atherogenic index (TC:HDL cholesterol) fell significantly in both sexes. No significant changes occurred in plasma low-density-lipoprotein cholesterol or in total triglycerides values. These data show that when compared with polyunsaturates, monounsaturates increased HDL cholesterol and reduced the atherogenic risk profile in both sexes.     

2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine: an improved serotonin transporter imaging agent

Imaging serotonin transporters (SERT) is an emerging research tool potentially useful to cast light on the mechanisms of drug action as well as to monitor the treatment of depressed patients. We have prepared two new derivatives of 3, 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine (4) and 2-(2-(dimethylaminomethyl)benzyl)-5-iodophenylamine (5) (K(i) for SERT = 0.37 and 48.6 nM, respectively). Both [(125)I]4 and [(125)I]5 displayed excellent brain uptakes in rats, and they showed a highest uptake in hypothalamus (between 60 and 240 min), a region populated with the highest density of SERT. The specific uptake of [(125)I]4 in the hypothalamus resulted in a target to nontarget ratio ([hypothalamus-cerebellum]/cerebellum) of 4.3 at 2 h. Autoradiography of rat brain sections (ex vivo at 2 h) of [(125)I]4 showed an excellent regional distribution pattern consistent with known SERT localization. These data suggest that [(123)I]4 may be useful for imaging SERT binding sites in the brain by single photon emission computed tomography (SPECT).     

New PET imaging agent for the serotonin transporter: [(18)F]ACF (2-[(2-amino-4-chloro-5-fluorophenyl)thio]-N,N-dimethyl-benzenmethanamine)

A new F-18-labeled phenylthiophenyl derivative specific for imaging of serotonin transporters (SERT) in the brain by positron emission tomography (PET) is described. Fluorinated phenylthiophenyl derivative, ACF, 2-[(2-amino-4-chloro-5-fluorophenyl)thio]-N,N-dimethyl-benzenmethanamine, was prepared by first coupling 2,5-dichloro-4-nitroaniline with 2-mercapto-N,N-dimethylbenzamide. The amino group of the coupled adduct was converted to a fluoro group through a Schiemann reaction. Subsequently, a one pot reduction of both nitro and amide groups by BH(3)-tetrahydrofuran yielded the nonradioactive ACF (yield 25%). In vitro binding assays using cell membrane homogenates of LLC cells expressing SERT, dopamine transporters (DAT), or norepinephrine transporters (NET) showed excellent binding affinity and selectivity for SERT (K(i) = 0.05, 3020, and 650 nM for SERT, DAT, and NET, respectively). For preparation of the [(18)F]ACF, the NH(2) group of the initially coupled adduct was converted to the trimethylammonium salt, which was replaced by [(18)F]fluoride in the presence of Kryptofix 222 and potassium carbonate. The final product, [(18)F]ACF, was obtained after a borane and stannous chloride reduction reaction. The combined two step reaction gave a radiochemical yield of 10-15% (EOB) and a radiochemical purity of >99%. Synthesis of the novel PET tracer, [(18)F]ACF, as a probe for binding to SERT in the brain was successfully achieved. The new tracer [(18)F]ACF showed excellent brain penetration and selective localization after an iv injection in rats (brain uptake at 2, 30, 60, 120, and 240 min was 3.27, 1.28, 0.69, 0.21, and 0.06% dose/organ, respectively). The hypothalamus/cerebellum ratio at 60 min post iv injection was 3.55. This specific localization in the hypothalamus was blocked by pretreatment of (+)McN5652. This novel ligand is a potential PET tracer for in vivo evaluation of SERT in the brain.     

The development of polyplex-based DNA vaccines

DNA immunisation provides new possibilities for the development of effective vaccines for the prophylaxis and treatment of several diseases and infections. Application of such vaccines for mucosal (secretory or local) vaccination provides a powerful means to gain protection against local infection that enters and colonises the mucosa whilst inducing concomitant systemic immunity. This review examines the current and potential applications for polyplex-based mucosal vaccination strategies, notably those aimed at gaining expression of transgenes within dendritic cells, in order to gain both T-helper and cytotoxic T cell (CTL) responses. Emphasis is given to the development of polyplex-based oral vaccines in conjunction with microparticulate systems.