Impact of Interleukin-28B gene polymorphism (rs12979860) on Egyptian patients infected with hepatitis C virus genotype-4.

Single nucleotide polymorphisms (SNPs) in the Interleukin (IL)-28B gene, namely rs12979860, could predict response to pegylated interferon-α-ribavirin (PR) therapy in hepatitis C virus genotype 1 (HCV-1)-infected patients. A similar role was investigated in a case-control study conducted on 93 Egyptian patients chronically infected with HCV-4 in comparison to 22 individuals with spontaneous HCV clearance and 70 healthy volunteers. The homozygous C allele genotype (CC) was associated with sustained viral response (SVR) to therapy compared with the homozygous T allele genotype (TT) and the heterozygous genotype (CT). In the SVR group, the response rate was statistically significantly higher in CC genotypes (58.6%) compared with CT/TT (20.3%). There was no correlation between SVR patients' genotypes and early response to therapy or HCV baseline viral load. Our findings describe how IL-28B SNP genotyping may guide appropriate selection of HCV-4-infected patients for PR therapy.

Impact of Interleukin-28B gene polymorphism (rs12979860) on Egyptian patients infected with hepatitis C virus genotype-4

Single nucleotide polymorphisms [SNPs] in the Interleukin [IL]-28B gene, namely rs12979860, could predict response to pegylated interferon-?-ribavirin [PR] therapy in hepatitis C virus genotype 1 [HCV-1]-infected patients. A similar role was investigated in a case-control study conducted on 93 Egyptian patients chronically infected with HCV-4 in comparison to 22 individuals with spontaneous HCV clearance and 70 healthy volunteers. The homozygous C allele genotype [CC] was associated with sustained viral response [SVR] to therapy compared with the homozygous T allele genotype [TT] and the heterozygous genotype [CT]. In the SVR group, the response rate was statistically significantly higher in CC genotypes [58.6%] compared with CT/TT [20.3%]. There was no correlation between SVR patients' genotypes and early response to therapy or HCV baseline viral load. Our findings describe how IL-28B SNP genotyping may guide appropriate selection of HCV-4-infected patients for PR therapy. We underscore IL28B genotyping as a tool that might increase PR cost-benefit in Egypt

Analysis of common MEFV mutations in Egyptian patients with familial Mediterranean fever: molecular characterisation of the disease.

Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder transmitted as an autosomal recessive trait. It predominantly affects people living in, or originating from, areas around the Mediterranean and was difficult to diagnose until mutations in the MEFV gene were identified. This study aims to analyse the five most common MEFV mutations in Egyptian patients diagnosed clinically as FME Thirty-eight unrelated patients were tested for the presence of the MEFV gene mutations V726A, M694V, M694I, M680I and E148Q, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the amplification refractory mutation system (ARMS). Twenty-three patients (60.5%) had one or more mutations, whereas no mutation was found in the remaining 15 patients (39.5%). The most common mutation was M694I (42.5%), followed by V726A (22.5%), M680I (17.5%) and E148Q (17.5%). The M694V mutation was not detected. The profile of MEFV gene mutations in this study suggests that the origin of FMF in Egypt is heterogeneous, a finding in concordance with that for other Arab populations; however, some differences were observed as M694V, the most common mutation reported in Arabs, was not detected in this study.

Evaluation of an existing screening tool for psoriatic arthritis in people with psoriasis and the development of a new instrument: the Psoriasis Epidemiology Screening Tool (PEST) questionnaire.

OBJECTIVE: To evaluate an existing tool (the Swedish modification of the Psoriasis Assessment Questionnaire) and to develop a new instrument to screen for psoriatic arthritis in people with psoriasis. DESIGN: The starting point was a community-based survey of people with psoriasis using questionnaires developed from the literature. Selected respondents were examined and additional known cases of psoriatic arthritis were included in the analysis. The new instrument was developed using univariate statistics and a logistic regression model, comparing people with and without psoriatic arthritis. The instruments were compared using receiver operating curve (ROC) curve analysis. RESULTS: 168 questionnaires were returned (response rate 27%) and 93 people attended for examination (55% of questionnaire respondents). Of these 93, twelve were newly diagnosed with psoriatic arthritis during this study. These 12 were supplemented by 21 people with known psoriatic arthritis. Just 5 questions were found to be significant predictors of psoriatic arthritis in this population. Figures for sensitivity and specificity were 0.92 and 0.78 respectively, an improvement on the Alenius tool (sensitivity and specificity, 0.63 and 0.72 respectively). CONCLUSIONS: A new screening tool for identifying people with psoriatic arthritis has been developed. Five simple questions demonstrated good sensitivity and specificity in this population but further validation is required.

IL-12p40-independent induction of protective immunity upon multiple Plasmodium berghei irradiated sporozoite immunizations.

Both IFN-gamma and IL-12 play critical roles in defence against malaria. In a previous study, using Plasmodium yoelii model, C57BL/6 IFN-gamma receptor deficient mice (IFN-gammaR-/-) failed to develop protective immunity after a single immunization with irradiated sporozoites, but were protected after multiple immunizations. In contrast, in another study, BALB/c IFN-gamma gene knockout mice (IFN-gamma-/-) and BALB/c IL-12-deficient mice (IL-12p40-/- and IL-12p35-/-) were unable to mount protective immune response even after multiple immunizations with the same irradiated parasites. To better define the role of IFN-gamma and IL-12p40 in sterile protection, we selected the C57BL/6 model. Wild-type and IL-12p40-/- mice were immunized with a single or multiple doses of P. berghei irradiated sporozoites. While the wild-type mice were able to rapidly produce IFN-gamma and mount a protective immune response after a single immunization with irradiated sporozoites, IL-12p40-/- mice were neither able to produce IFN-gamma nor were protected. However, both strains of mice were able to produce IFN-gamma and were protected after three doses of irradiated sporozoites. Protection was partially and largely mediated by CD4+ T cells and CD8+ T cells, respectively. Thus, IL-12p40 plays an important role in mediating early protection by irradiated sporozoite immunization but is dispensable for protective immunity induced by several immunizations with irradiated sporozoites. Moreover, treatment of hyperimmune IL-12p40-/- mice with rhIL-18 bp-Fc, an inhibitor of IL-18 activity, did not abrogate protection indicating that IL-18 is not required for the effector phase of the immune response; it remains possible, however, that IL-18 may compensate for the lack of IL-12p40 in the induction phase of the immune response.

Unexplained musculoskeletal pain in people of South Asian ethnic group referred to a rheumatology clinic - relationship to biochemical osteomalacia, persistence over time and response to treatment with calcium and vitamin D.

BACKGROUND: Hypovitaminosis D continues to be a problem for South Asian people living in the UK. This study investigates the association between widespread unexplained pain and biochemical osteomalacia in this group of people. METHODS: All South Asian patients attending with unexplained widespread pain (CWP) over a two-year period had biochemical tests for osteomalacia: calcium, phosphate, alkaline phosphatase, vitamin D (25OHD), and parathyroid hormone (PtH). For comparison, a control group consisted of patients in whom a specific rheumatic diagnosis (SRD) had been made. A follow up questionnaire was sent enquiring about pain, disability and dietary habits. A small proportion of the responders attended for a further set of biochemical tests for osteomalacia. RESULTS: The majority of patients in both groups had a raised PtH (124/220, 57%) and a low 25OHD (117/160, 73%). Where data on both PtH and 25OHD were available, 47% (64/137) had a combination of reduced 25OHD and raised PtH. Few of these patients had abnormal calcium, phosphate or alkaline phosphates. From the postal questionnaire the prevalence of disability and continuing pain was high in both groups, with the majority of respondents complaining of difficulty with activities and nearly half needing help. Pain was widespread, the same or worse and graded above 7/10 for 69% and 78% of respondents in the CWP and SRD groups respectively. Overall, sixty one percent of respondents thought their gait pattern had changed in the last year. No significant differences were seen between respondents based on diagnosis (CWP or SRD), initial or subsequent PtH levels, or current calcium and vitamin D consumption. At the time of the second blood test, 52% of those with an elevated PtH on the first test now had a normal PtH value but 31% of those with a normal PtH first time had an elevated PtH. CONCLUSION: This observational study conducted in a rheumatology clinic in the north of England has shown high levels of biochemical osteomalacia in people of South Asian origin and high levels of persistent pain and disability, unrelated to diagnosis, biochemical status or treatment with calcium and vitamin D.

Frações da parede celular e digestibilidade in vitro da matéria seca de três genótipos de girassol ensilados com aditivos / In vitro dry matter and cell wall fractions of three genotypes of sunflower ensiled with additives

Ensilaram-se três genótipos de girassol (M734, Rumbosol 91 e variedade V2000), enriquecidos no material original com: 0,5 por cento de uréia (U); 0,5 por cento de carbonato de cálcio (CC); 0,5 por cento de uréia mais 0,5 por cento de carbonato de cálcio (U+CC); inoculante bacteriano comercial (IB) comercial e sem aditivo que serviu como silagem testemunha (T). Foram utilizados silos de laboratório de PVC, abertos com 1, 3, 5, 7, 14, 28 e 56 dias de ensilados, sendo determinados fibra em detergente neutro (FDN), fibra em detergente ácido (FDA), lignina e digestibilidade in vitro da matéria seca (DIVMS). As silagens de Rumbosol 91 apresentaram valores superiores aos dos genótipos V2000 e M734 nos dias de abertura para FDN, FDA e lignina. Os aditivos não promoveram alterações nos constituintes da parede celular. A silagem T não apresentou diferenças entre os genótipos quanto à DIVMS no decorrer do processo fermentativo, sendo os valores do último dia de abertura (56) de 51,0 por cento, 49,1 por cento e 48,9 por cento de DIVMS para os genótipos M734, V2000 e Rumbosol 91, respectivamente. Não houve diferença entre as silagens com aditivos e a silagem testemunha com a evolução do processo fermentativo quanto à DIVMS. Os aditivos utilizados não melhoraram as silagens de girassol quanto às características avaliadas e, apesar de os genótipos apresentarem digestibilidade in vitro semelhantes, o Rumbosol 91 apresentou maiores teores de constituintes da parede celular.

Three sunflower genotypes (M 734, Rumbosol 91 and V2000 variety) enriched with 0.5 percent of urea (U); 0.5% of calcium carbonate (CC); 0.5 percent of urea plus 0.5 percent of calcium carbonate (U + CC); commercial bacterial inoculate (BI); and without any additive, used as control silage (T) were ensiled in PVC silos and opened after 1, 3, 5, 7, 14, 28 and 56 days to determine the neutral detergent fiber (NDF), acid detergent fiber (FDA), lignin and dry matter in vitro digestibility (DMIVD). The Rumbosol 91 genotype silage showed higher NDF, ADF and lignin than V2000 and M734 genotypes. The additives did not promote changes in the cell wall constituents. No statistical differences among silages of the genotypes for DMIVD were observed during the fermentative process. The DMIVD at 56 days were 51.0, 49.1 and 48.9 percent for silage of M734, V2000 and Rumbosol 91 genotypes, respectively. No difference between silages with additives and control (T), during the fermentative process for DMIVD was observed. The additives did not improve sunflower silages. The genotypes showed similar in vitro digestibility, and the Rumbosol 91 genotype showed high compound of cell wall constituent.

Estimating the prevalence among Caucasian women of primary Sjögren's syndrome in two general practices in Birmingham, UK.

OBJECTIVE: To establish the prevalence among women of primary Sjögren's syndrome (PSS) in Birmingham, UK. METHODS: Eight hundred and forty-six female Caucasians from two general practitioner lists were invited to complete a questionnaire that included a screening question on dry eyes and mouth. Individuals who responded positively were evaluated further. RESULTS: Overall, 65/% of individuals who were sent a questionnaire responded. Two had possible PSS, but were negative for anti-Ro/La antibodies. Our estimates of the prevalence of PSS ranged from < 0.1% up to 0.4%, depending on the assumptions used. CONCLUSION: Our data support previous studies suggesting a prevalence of PSS in the community of 0.1-0.6% rather than those suggesting a higher figure.

Cloning and characterization of a chitin synthase cDNA from the mosquito Aedes aegypti.

Characterization of the enzymes involved in the chitin biosynthetic pathway in mosquitoes is critical due to the importance of chitin in the formation of the peritrophic matrix [PM] and its potential impact on vector competence. Chitin is the homopolymer of the amino sugar N-acetyl-D glucosamine [GlcNAc]. The final step of incorporation of GlcNAc into the chitin polymer is catalyzed by the enzyme chitin synthase [CS]. CS is a membrane bound enzyme, but the mechanism of its action in the biosynthesis of the PM is not understood. We have isolated and sequenced a CS-encoding cDNA clone from the mosquito Aedes aegypti, compared its sequence with CS from other organisms and studied its RNA expression. The cDNA is 3.5 kb in length with an open reading frame of 2.6 kb that encodes a protein of 865 amino acids with a predicted molecular mass of 99.5 kDa. The putative translation product shares 90% similarity to two CS proteins from Caenorhabditis elegans and 50% similarity to Saccharomyces cerevisiae in the catalytic domain of CS enzymes. Data suggest that CS is a single copy gene. RT-PCR analysis shows CS message in whole non-blood-fed females, whole blood-fed females, non-blood-fed midguts and in midguts dissected at different time points post-blood-feeding. In situ hybridization studies of midgut samples revealed that CS mRNA increases following a bloodmeal and is localized to the periphery of the epithelial cells facing the midgut lumen.

A polymerase chain reaction-based assay for detection of Wuchereria bancrofti in human blood and Culex pipiens.

Human blood samples and indoor-resting Culex pipiens were collected in 33 randomly selected houses from different sectors of a village in the Nile Delta of Egypt which was endemic for Wuchereria bancrofti. Blood was also collected from subjects with no history of living in filarial endemic areas. Human blood samples were divided and assessed by both membrane filtration and polymerase chain reaction (PCR). Similarly, mosquito samples were assessed by both dissection and PCR. Blood pools representing each household were tested by PCR. If a pool gave a positive result, then individual blood specimens were also tested by PCR. Of the 33 houses tested, both membrane filtration and blood pools assayed by PCR identified 14 (42.4%) 'infected houses'. PCR detected parasite deoxyribonucleic acid (DNA) in blood pools from an additional 3 households that gave negative results by membrane filtration. Of 178 endemic blood samples tested by membrane filtration, 22 (12.3%) had microfilariae and all were individually positive by PCR. Although microfilaria counts were lower in blood collected during the day than in night-collected blood, the PCR results were consistent, regardless of time of collection. All non-endemic blood samples were negative by PCR. Among the 33 houses rested, mosquito pools assayed by PCR identified 17 (51.5%) as 'infected households'. Of these, 8 houses (47%) contained at least one microfilaraemic resident. One 'infected household' was identified by mosquito dissection. We concluded that PCR is a powerful epidemiological tool for screening villages for the prevalence of W. bancrofti. PCR detection of W. bancrofti DNA in blood-fed mosquitoes could be used initially to locate endemic areas with transmission of bancroftian filariasis. PCR detection of W. bancrofti DNA in blood collected during the day could then be used to assess W. bancrofti infection rates.