Vaccination with chimeric protein induces protection in murine model against ascariasis

An estimated 400 million people are infected by parasites of the genus Ascaris and the existing control measures are inefficient. Vaccine development using B cell antigens is a promising strategy for increased protection against this parasite. The present study aimed at developing a chimeric protein capable of conferring protection against infection by Ascaris sp. For this purpose, we performed B-cell epitope predictions on previously described vaccine candidate proteins from Ascaris suum and the corresponding peptides were used to construct a chimeric protein. Female BALB / c mice were immunized subcutaneously in three doses at 10 day intervals with a vaccine formulation comprised of the chimeric protein together with monophosphoryl lipid A (MPLA). Control groups included protein alone, MPLA, or PBS. After challenge infection, animals vaccinated with chimeric protein plus MPLA showed a reduction of 73.54% of larval load in the lung compared to control group animals. Animals immunized with chimeric protein plus MPLA also display higher IgG response and a reduction in lung inflammation. Our study highlights how chimeric proteins containing more than one B cell epitope can enhance immune protection against helminthic infection and offer new approaches to the development of Ascaris vaccines.     

Effects of orthodox religious fasting versus combined energy and time restricted eating on body weight,lipid concentrations and glycaemic profile

Abstract

For seven weeks, 37 overweight adults followed a hypocaloric diet based on Orthodox Fasting (OF). A hypocaloric, time restricted eating (TRE) plan (eating between 08:00 to 16:00?h, water fasting from 16:00 to 08:00?h) was followed by 23 Body Mass Index (BMI)-matched participants. Anthropometric, glycaemic and inflammation markers and serum lipids were assessed before and after the diets. Both OF and TRE groups demonstrated reductions in BMI (28.54?±?5.45 vs 27.20?±?5.10?kg/m², p?<?0.001 and 26.40?±?4.11 vs 25.81?±?3.78?kg/m² p?=?0.001, respectively). Following the intervention, the OF group presented lower concentrations of total and low-density lipoprotein-cholesterol, compared with the pre-fasting values (178.40?±?34.14 vs 197.17?±?34.30?mg/dl, p?<?0.001 and 105.89?±?28.08 vs 122.37?±?29.70?mg/dl, p?<?0.001, respectively). Neither group manifested significant differences in glycaemic and inflammatory parameters. Our findings suggest that OF has superior lipid lowering effects than the TRE pattern.     

Tocopherol Succinate Reference Standard (Control 981) of National Institute of Health Sciences

The raw material of tocopherol succinate was tested for preparation of the "Tocopherol Succinate Reference Standard (Control 981)". The analytical data obtained were: infrared spectrum same as that of the Tocopherol Succinate Reference Standard (Control 8510); specific absorbance, E(1%)1 cm (286 nm) = 40.7; thin-layer chromatography, no impurities detected until 50.0 microgram; high-performance liquid chromatography (HPLC),three impurities detected and amount of tocopherol succinate estimated to be 98.2%, loss on drying, 0.19%, assay by HPLC, 101.7%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 981).     

Brain temperature modifies glutamate neurotoxicity in vivo

The purpose of this study was to examine the effects of mild hypothermia and hyperthermia on glutamate excitotoxicity. Glutamate-induced cortical lesions were produced in hypothermic (32 degrees C), normothermic (37 degrees C), and hyperthermic (40 degrees C) rats by perfusion of a 0.5 M glutamate solution via a microdialysis probe. The volume of the lesion 7 days after glutamate perfusion was quantified histologically by image analysis. This histological assessment was performed in two experiments; in one, each of the target temperatures was induced before glutamate perfusion, and in the other, each of the target temperatures was induced after stopping the glutamate perfusion. We also examined the effect of temperature on the diffusion of exogenously delivered material in the extracellular space using autoradiography of the perfused glutamate solution containing 14C-labeled sucrose. In the two experiments in which each of the target temperatures was induced before or after glutamate perfusion, the volume of damage was reduced by mild hypothermia and enlarged by mild hyperthermia. The volume of 14C diffusion also increased as brain temperature increased. These results provide evidence that small variations of brain temperature modify glutamate excitotoxicity. The results also suggest that the change in glutamate diffusion in the extracellular space is one mechanism by which mild hypothermia and hyperthermia exert their protective and harmful effects respectively.     

Childhood multiple sclerosis and allied demyelinative diseases

We report five cases of multiple sclerosis (MS) and three cases of allied demyelinative diseases starting during childhood. Three of the MS patients presented with atypical initial symptoms, such as acute encephalitis or myelitis, making an early clinical diagnosis difficult. Ophthalmologic symptoms were noted in four of MS children, and in two with allied demyelinative diseases. Therefore, if a child shows ophthalmologic symptoms (i.e. optic neuritis, ophthalmoplegia), brain magnetic resonance imaging (MRI) should be conducted for the differential diagnosis of MS and other demyelinative diseases. Cerebrospinal fluid analysis is not useful for the initial diagnosis of MS, because pleocytosis and increase of oligoclonal IgG band in cerebrospinal fluid are seen in both MS and other demyelinative disorders. However, neuron specific enolase (NSE) is slightly higher in the latter than in the former. T2-weighted MRI of multiple sclerosis showed multiple high intensity areas in the white matter of the cerebrum and cerebellum, capsula interna, and crus cerebri etc. Most of these lesions were clinically silent, being characteristic of MS. In two MS cases, however, initial MRI revealed no abnormal findings. Thus, the diagnosis of MS can not be made by initial MRI only.     

Two cases of asymptomatic epiglottic cyst confirmed by lateral cervical roentgenogram

Key words  complications - intubation - epiglottic cyst     

Histopathological grading and clinical features of patients with mucoepidermoid carcinoma of the salivary glands]

In the 22 years between March 1979 and February 2001, we treated 16 patients--10 men and 6 women aged 10-80 years (mean: 44 years)--with mucoepidermoid carcinoma (MEC) of the salivary gland, evaluating them clinically and histopathologically. Tumor sites included 12 at the parotid gland, 3 at the submandibular gland, and 1 at the minor salivary gland. All tumors were graded histopathologically based on the criteria of Goode et al. as follows: low grade (n = 10), intermediate grade (n = 1), and high grade (n = 5). Female gender was associated with low grade MEC and male gender with high grade MEC (P < 0.05). The age at onset in high grade MEC was older than that in low grade MEC (P < 0.005). Lymph-node metastasis was detected in 7 out of the 16 patients (44%) associated significantly with high grade MEC (P < 0.05). Distant metastasis was detected in 4 of 16 patients (25%). Distant metastasis was significantly associated with high grade MEC (P < 0.05). Local recurrence was detected in 3 of 15 patients undergoing surgery (20%). No difference was seen in local recurrence frequency between low and high grade MEC. Survival was calculated with Kaplan-Meier's method. In all 16, 5-year survival was 86% and 10-year survival 75%. Five-year survival in low grade MEC was 100%, whereas that in high grade MEC was 67% (P < 0.05). In MEC of the salivary gland, it was suggested that the histopathological MEC grade evaluated by Goode's criteria significantly correlated with gender, age, lymph-node metastasis, distant metastasis, and 5-year survival.     

Point mutations of ornithine decarboxylase gene are an infrequent event in colorectal cancer but a missense mutation was found in a replication error positive patient with hMSH2 germline mutation

BACKGROUND: Ornithine decarboxylase (ODC; EC 4.1.1.17) is the first rate-limiting enzyme in the biosynthesis of polyamines. ODC protein has a characteristic amino acid sequence, the PEST sequence, which is related to the enzyme's rapid degradation. ODC cDNA prepared from human hepatoma tissues has been reported to show nonsense or missense mutations. METHODS: We examined somatic mutations of ODC cDNA by RT-PCR-SSCP analysis and mRNA expressions by RT-PCR in 50 colorectal cancer tissues to investigate the involvement of ODC gene alterations in colorectal cancers. RESULTS: Increased expression of the ODC gene was observed in 36 cases (86%) out of the 42 examined by RT-PCR. In one case, a missense mutation was found in the cancer tissue but not in normal mucosa. The missense mutation from Asp to Asn at codon 424, in the PEST region, possibly stabilizes the ODC protein. In colorectal cancer, replication error and a germline mutation in hMSH2 gene were observed. CONCLUSIONS: The missense mutation at codon 424 is speculated to be a cause of stabilization and a passenger mutation owing to the mutator phenotype. Since only one of 50 colorectal cancers exhibited a missense mutation of the ODC gene, mutations in ODC gene are not frequent in colorectal cancer. The increased expression of the ODC gene was noted in 86% of colorectal cancer tissues by RT-PCR, however, it was not due to point mutations in ODC coding exons.