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.     

Die Hallervorden-Spatz-Erkrankung Eine Differentialdiagnose des präsenilen Demenzsyndroms

We report the history of a 38 year old patient who began to develop mental deterioration at the age of 26. After a time of 7 years neurological signs like writing dystonia occurred. Hallervorden-Spatz-Disease (HSD) was diagnosed at the age of 36 in vivo with the clinical presentation of severe dystonia, rigidity, dementia, and typical signal loss in the globus-pallidus the reticular part of the substantia nigra, and the nucleus ruber in the T-2 weighted MRI. The "eye-of-the-tiger"-sign, a bilateral hyperintensity in the rostral globus pallidus, was not observed in follow-up examinations. HSD is a rare autosomal-recessive or sporadic disease of unknown etiology. In one third of the patients a dementing process is the first clinical sign of the disorder, and is a rare differential diagnosis of early onset dementia.     

DNA repair in human bronchial epithelial cells

The purpose of this investigation was to compare the responseof human cell types (bronchial epithelial cells and fibroblastsand skin fibroblasts) to various DNA damaging agents. Repairof DNA single strand breaks (SSB) induced by 5 krads of X-raywas similar for all cell types; 90% of the DNA SSB were rejoinedwithin one hour. During excision repair of DNA damage from u.v.-radiation,the frequencies of DNA SSB as estimated by the alkaline elutiontechnique, were similar in all cell types. Repair replicationas measured by BND cellulose chromatography was also similarin epithelial and fibroblastic cells after u.v.-irradiation.Similar levels of SSB were also observed in epithelial and fibroblasticcells after exposure to chemical carcinogens: 7,12-dimethylbenz[a]anthracene;benzo[a]pyrene diol epoxidle (BPDE); or N-methyl-N-nitro-N-nitrosoguanidine.Significant repair replication of BPDE-induced DNA damage wasdetected in both bronchial epithelial and fibroblastic cells,although the level in fibroblasts was 40% of that in epithelialcells. The pulmonary carcinogen asbestos did not damage DNA.DNA-protein crosslinks induced by formaldehyde were rapidlyremoved in bronchial cells. Further, epithelial and fibroblasticcells, which were incubated with formaldehyde and the polymeraseinhibitor combination of cytosine arabinoside and hydroxyurea,accumulated DNA SSB at approximately equal frequencies. Theseresults should provide a useful background for further investigationsof the response of human bronchial cells to various DNA damagingagents.     

Complications after laryngeal surgery: videofluoroscopic evaluation of 120 patients

AIM: Videofluoroscopic assessment of the spectrum and incidence of swallowing complications after state-of-the-art laryngeal cancer surgery. MATERIALS AND METHODS: We retrospectively studied videofluoroscopic examinations of 120 patients (94 men, 26 women; mean age, 58 years) with suspected complications after laryngeal resection (partial laryngectomy, 65; total laryngectomy, 55). Swallowing function (i.e., oral bolus control, laryngeal elevation and closure, presence of pharyngeal residue, aspiration) and structural abnormalities such as strictures, fistulas and tumour recurrence were assessed by videofluoroscopy. RESULTS: Abnormalities were found in 110 patients, including strictures in nine, fistulas in six and mass lesions in 13 patients. Aspiration was found in 63 patients overall (partial laryngectomy, 61/65; total laryngectomy, 2/55), occurring before swallowing in five, during swallowing in 34, after swallowing in nine and at more than one phase in 15 patients. Pharyngeal paresis was detected in three and pharyngeal weakness in 19 patients. Pharyngo-oesophageal sphincter dysfunction was observed in 10 cases. CONCLUSION: Aspiration is a very common complication after partial laryngeal resection. It is mainly caused by incomplete laryngeal closure, sphincter dysfunction or pharyngeal pooling. Videofluoroscopy is the only radiological technique able to identify both disordered swallowing function and structural changes after laryngeal resection. Detection of these complications is crucial for appropriate further therapy.Kreuzer, S. H. (2000). Clinical Radiology55, 775-781.     

Prognostic significance of molecular staging by PCR-amplification of immunoglobulin gene rearrangements in diffuse large B-cell lymphoma (DLBCL).

The prognostic value of the detection of peripheral blood (PB) and/or bone marrow (BM) involvement by polymerase chain reaction (PCR) amplification of rearranged immunoglobulin heavy chain (IgH) and immunoglobulin kappa light chain (Igkappa) genes was evaluated in 155 patients with diffuse large B-cell lymphomas (DLBCL). Immunoglobulin gene rearrangements (IgR) were detected in 35/155 (23%) patients. The presence of IgR in PB/BM was related to clinical stage (CS I-III vs CS IV; P<0.001), histopathological detection of BM involvement (P<0.001), and the International Prognostic Index (P<0.001). IgR-positive cases had a significantly lower complete remission (CR) rate (18/35, 51%) than IgR-negative patients (85/120, 71%; P=0.042), and a significantly poorer overall survival (OAS) at 5 years (25 vs 66%; P<0.001). There was a significant difference in the estimated OAS at 5 years between patients with negative BM histology and negative PCR results (66%), patients with negative BM histology but positive IgR (37%), and patients with positive BM histology (12%). Our results indicate that molecular methods improve the accuracy of staging in patients with DLBCL and define a group of patients with normal bone marrow histology who have a significantly poorer OAS due to molecular detection of PB/BM involvement.     

Impact of cytogenetics on the prognosis of adults with de novo AML in first relapse.

Karyotype is an important prognostic factor in patients with newly diagnosed acute myeloblastic leukaemia (AML). The prognostic value of cytogenetics on the outcome of patients with AML in relapse has not yet been well defined. We analysed the clinical outcome of 152 patients with de novo, chemotherapy-treated AML in first relapse according to the cytogenetic classification of the United Kingdom Medical Research Council. The rate of second complete remission (CR) (88, 64 and 36%) and the probability of survival at 3 years (43, 18 and 0%) were significantly different between the favourable, intermediate and adverse cytogenetic risk groups, respectively. Compared to the favourable group, the relative risk (RR) of death (multivariate analyses) was 2.6 (confidence interval (CI): 1.5-4.4, P<0.001) for the intermediate and 3.7 (CI: 1.7-7.9, P=0.001) for the adverse group. The prognostic value of the duration of first CR was confirmed (RR of death: 2.0 (CI: 1.0-4.0) for each additional year in first CR), whereas the FLT3 mutation obtained at diagnosis did not markedly influence the outcome of patients with AML in relapse. In conclusion, our results indicate that both karyotype and the duration of first CR are independent prognostic factors for patients with de novo AML in first relapse.     

Variation in the structure of Toxoplasma gondii and the roles of selfing, drift, and epistatic selection in maintaining linkage disequilibria.

Previous studies of Toxoplasma gondii, based on samples dominated by clinical isolates, have concluded that its population structure is clonal, despite the sexual reproduction that occurs in cats. To determine whether this applies to non-clinical isolates, we compared patterns of linkage disequilibrium (LD) among seven loci in samples of T. gondii from Brazil and the US. LD was detected in both locations, but it was substantially lower in Brazil. The lower LD in Brazil can be explained by a higher rate of sexual reproduction between different genotypes (outcrossing) because of a higher rate of transmission. The extent of LD between pairs of physically unlinked loci varied significantly in each location. Moreover, the magnitude of LD between corresponding locus pairs in Brazil and the US was correlated, despite minimal gene exchange between the continents (mean FST = 0.19). The heterogeneity among locus pairs and the correlation in LD between physically unlinked locus pairs from different continents suggests that locus-specific factors, such as epistatic selection are involved in maintaining LD in T. gondii. Possibly, the unique life cycle of T. gondii with its unpredictable transmission among diverse host species and distinct ecological habitats requires specific combinations of alleles from multiple loci. The usefulness of typing isolates based on physically unlinked loci is questioned not only by the geographic variation in the reproductive population structure, but mainly by the low overall predictability of the genotype of one locus based on the genotype in another (unlinked) locus. This predictability ranged between 23 and 45%, but was close to nil for a considerable fraction of locus pairs.     

两种不同方法经鼻盲探气管插管的临床观察

目的探讨两种不同方法经鼻盲探气管插管成功率。方法将25例需经鼻盲探气管内插管麻醉的手术患者随机分成观察组(13例)和对照组(12例)。采用镇静镇痛健忘法经鼻腔插入气管内导管,观察组当导管出鼻后孔达咽部时套囊充气10~15ml,对照组不充气。结果观察组13例盲探插管均成功,占100%;对照组12例,盲探成功5例,占42%;其中试验组一次插管成功11例,占85%,对照组为3例,占25%。两组对比有显著性(P<0.01)。结论咽部套囊充气法,可提高经鼻盲探插管的成功率。     

Synthesis, and antiprotozoal and antibacterial activities of S-substituted 4,6-dibromo- and 4,6-dichloro-2-mercaptobenzimidazoles.

The synthesis and some germicidal activities in vitro of two congener series of S-substituted 4,6-dihalogeno-2-mercapto-1H-benzimidazoles are reported. There was no substantial difference between antibacterial activities of corresponding 4,6-dichloro- and 4,6-dibromo-derivatives. The present results confirm lower susceptibility to substituted benzimidazoles of Gram-negative compared to Gram-positive bacteria. Minimum inhibitory concentrations (MICs) of a majority of the novel derivatives ranged between 25 and 100microg/ml for Gram-positive bacteria. The most active compounds (MICs for Gram-positive bacteria: 0.78-50microg/ml) were 4,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole and 4,6-dibromo-2-(4-nitrobenzylthio)-1H-benzimidazole that were 4-32 times more potent than nitrofurantoin against all Gram-positive bacteria utilized but Escherichia faecalis, against which they were, respectively, 2 and 4 times less potent than nitrofurantoin. Among Gram-negative bacteria used, Stenotrophomonas maltophilia and Bordetella bronchiseptica were most sensitive (as evidenced by a number of MICs 400microg/ml). All the new compounds were at least several times more active against Giardia intestinalis (IC(50): 0.006-0.053microg/ml), and a half of them were at least several times more active against Trichomonas vaginalis (IC(50): 0.0015-0.182microg/ml) than metronidazole (IC(50): 0.210 and 0.037microg/ml, respectively), the drug of choice in the treatment of G. intestinalis and T. vaginalis infections.