Investigation of the vaccine potential of an in silico designed FepA peptide vaccine against Shigella flexneri in mice model.

Background: Shigellosis is one of the significant causes of diarrhea in Bangladesh. It is a global health problem; approximately 1.3 million people die yearly from Shigellosis. The current treatment method, using different antibiotics against Shigellosis is ineffective. Moreover, it becomes a worrying situation due to the emergence of antibiotic-resistant pathogenic microbes responsible for these diarrheal diseases. Methodology: Previous immunoinformatics study predicted a potential peptide from the Ferric enterobactin protein (FepA) of Shigella spp. In this study, we have chemically synthesized the FepA peptide. As a highly immunogenic, FepA peptide conjugated with KLH has been tested in mice model with complete and incomplete adjuvants as a vaccine candidate. Results: Immunological analysis showed that all vaccinated mice were immunologically boosted, which was statistically significant (P-value 0.0325) compared to control mice. Immunological analysis for bacterial neutralization test result was also statistically significant (P-value 0.0468), where each ELISA plate was coated with 1 × 107S. flexneri cells. The Challenge test with 1 × 1012S. flexneri cells to each vaccinated and controlled mice showed that 37.5 % of control (non-vaccinated) mice died within seven days after the challenge was given while 100 % of vaccinated mice remained strong and stout. The analyses of the post-challenge weight loss of the mice were also significant (P-value 0.0367) as the weight loss percentage in control mice was much higher than in the vaccinated mice. The pathological and phenotypic appearances of vaccinated mice were also clearly differentiable compared with control mice. Thus all these immunological analysis and pathological appearances directly supported our FepA peptide as a potential immune booster. Conclusion: This study provides evidence that the FepA peptide is a highly immunogenic vaccine candidate against S. flexneri. Therefore, these findings inspire future trials for the evaluation of the suitability of this vaccine candidate against Shigellosis.

Inadequate sanitation in healthcare facilities: A comprehensive evaluation of toilets in major hospitals in Dhaka, Bangladesh.

BACKGROUND: Lack of access to functional and hygienic toilets in healthcare facilities (HCFs) is a significant public health issue in low- and middle-income countries (LMICs), leading to the transmission of infectious diseases. Globally, there is a lack of studies characterising toilet conditions and estimating user-to-toilet ratios in large urban hospitals in LMICs. We conducted a cross-sectional study in 10-government and two-private hospitals to explore the availability, functionality, cleanliness, and user-to-toilet ratio in Dhaka, Bangladesh. METHODS: From Aug-Dec 2022, we undertook infrastructure assessments of toilets in selected hospitals. We observed all toilets and recorded attributes of intended users, including sex, disability status, patient status (in-patient/out-patient/caregiver) and/or staff (doctor/nurse/cleaner/mixed-gender/shared). Toilet functionality was defined according to criteria used by the WHO/UNICEF Joint-Monitoring Programme in HCFs. Toilet cleanliness was assessed, considering visible feces on any surface, strong fecal odor, presence of flies, sputum, insects, and rodents, and solid waste. RESULTS: Amongst 2875 toilets, 2459 (86%) were observed. Sixty-eight-percent of government hospital toilets and 92% of private hospital toilets were functional. Only 33% of toilets in government hospitals and 56% in private hospitals were clean. A high user-to-toilet ratio was observed in government hospitals' outpatients service (214:1) compared to inpatients service (17:1). User-to-toilet ratio was also high in private hospitals' outpatients service (94:1) compared to inpatients wards (19:1). Only 3% of toilets had bins for menstrual-pad disposal and <1% of toilets had facilities for disabled people. CONCLUSION: A high percentage of unclean toilets coupled with high user-to-toilet ratio hinders the achievement of SDG by 2030 and risks poor infection-control. Increasing the number of usable, clean toilets in proportion to users is crucial. The findings suggest an urgent call for attention to ensure basic sanitation facilities in Dhaka's HCFs. The policy makers should allocate resources for adequate toilets, maintenance staff, cleanliness, along with strong leadership of the hospital administrators.

Antibody response to different COVID-19 vaccines among the migrant workers of Bangladesh.

Background: Due to the ongoing COVID-19 pandemic, various host countries such as Singapore, imposed entry requirements for migrant workers including pre-departure COVID-19 seroconversion proof. To combat COVID-19 worldwide, several vaccines have acquired conditional approval. This study sought to assess antibody levels after immunization with different COVID-19 vaccines among the migrant workers of Bangladesh. Methods: Venous blood samples were collected from migrant workers who were vaccinated with different COVID-19 vaccines (n=675). Antibodies to SARS-CoV-2 spike protein (S) and nucleocapsid protein (N) were determined using Roche Elecsys® Anti-SARS-CoV-2 S and N immunoassay, respectively. Results: All participants receiving COVID-19 vaccines showed antibodies to S-protein, while 91.36% were positive for N-specific antibodies. The highest anti-S antibody titers were found among the workers who completed booster doses (13327 U/mL), received mRNA vaccines Moderna/Spikevax (9459 U/mL) or Pfizer-BioNTech/Comirnaty (9181 U/mL), and reported SARS-CoV-2 infection in the last six months (8849 U/mL). The median anti-S antibody titers in the first month since the last vaccination was 8184 U/mL, which declined to 5094 U/mL at the end of six months. A strong correlation of anti-S antibodies was found with past SARS-CoV-2 infection (p < 0.001) and the type of vaccines received (p <0.001) in the workers.Conclusion: Bangladeshi migrant workers receiving booster doses of vaccine, vaccinated with mRNA vaccines, and having past SARS-CoV-2 infection, mounted higher antibody responses. However, antibody levels waned with time. These findings suggest a need for further booster doses, preferably with mRNA vaccines for migrant workers before reaching host countries.

Ecological risks of heavy metals on surficial sediment of Nijhum Dweep (Island), an important biodiversity area of Bangladesh.

Ten surficial sediment samples (up to a depth of 3 cm) were randomly collected during the pre-monsoon and analyzed for nine heavy metals using an atomic absorption spectrophotometer (AAS) to assess the distribution, contamination levels, and potential sources of heavy metals. The particle size distribution of the sediments was also investigated using a laser particle size analyzer. The mean concentration (mg/kg) of the analyzed metals followed a decreasing order of Fe (4706.24) > Mn (95.20) > Cu (36.97) > Zn (20.65) > Ni (9.26) > Cr (7.20) > Pb (5.63) > Co (5.52) > Cd (0.29). Surficial sediment of the Island was low to moderately contaminated by Cd and, to a laser extent by Cu in terms of enrichment factor (EF), geo-accumulation index (Igeo), and contamination factor. Ecologically, the Nijhum Dweep area was at low to moderate risk, where Cd was the most potential ecological risk factor. The Pearson correlation analysis revealed a significant positive correlation among Cr, Pb, Zn, Mn, Cd, Fe, Co, Ni, and silt particles, whereas a negative correlation with sand particles. No correlation was found with Cu and other metals except clay particles.

Development of an in silico multi-epitope vaccine against SARS-COV-2 by précised immune-informatics approaches.

The coronavirus family has been infecting the human population for the past two decades, but the ongoing coronavirus called SARS-CoV-2 has posed an enigmatic challenge to global public health security. Since last year, the mutagenic quality of this virus is causing changes to its genetic material. To prevent those situations, the FDA approved some emergency vaccines but there is no assurance that these will function properly in the complex human body system. In point of view, a short but efficient effort has made in this study to develop an immune epitope-based therapy for the rapid exploitation of SARS-CoV-2 by applying in silico structural biology and advancing immune information strategies. The antigenic epitopes were screened from the Surface, Membrane, Envelope proteins of SARS-CoV-2 and passed through several immunological filters to determine the best possible one. According to this, 7CD4+, 10CD8+ and 5 B-cell epitopes were found to be prominent, antigenic, immunogenic, and most importantly, highly conserved among 128 Bangladeshi and 110 other infected countries SARS-CoV-2 variants. After that, the selected epitopes and adjuvant were linked to finalize the multi-epitope vaccine by appropriate linkers. The immune simulation disclosed that the engineered vaccine could activate both humoral and innate immune responses. For the prediction of an effective binding, molecular docking was carried out between the vaccine and immunological receptors (TLRs). Strong binding affinity and good docking scores clarified the stringency of the vaccines. Furthermore, MD simulation was performed within the highest binding affinity complex to observe the stability. Codon optimization and other physicochemical properties revealed that the vaccine would be suitable for a higher expression at cloning level. So, monitoring the overall in silico assessment, we anticipated that our engineered vaccine would be a plausible prevention against COVID-19.

Phylogenetic Analysis and Genetic Diversity of Colletotrichum falcatum Isolates Causing Sugarcane Red Rot Disease in Bangladesh.

Colletotrichum falcatum Went causes red rot disease in sugarcane farming in the tropical and sub-tropical regions. This disease causes significant economic loss to the sugarcane production industry. Successful disease management strategies depend on understanding the evolutionary relationship between pathogens, genetic diversity, and population structure, particularly at the intra-specific level. Forty-one isolates of C. falcatum were collected from different sugarcane farms across Bangladesh for molecular identification, phylogeny and genetic diversity study. The four genes namely, ITS-rDNA, ß-tubulin, Actin and GAPDH sequences were conducted. All the 41 C. falcatum isolates showed a 99-100% similarity index to the conserved gene sequences in the GenBank database. The phylogram of the four genes revealed that C. falcatum isolates of Bangladesh clustered in the same clade and no distinct geographical structuring were evident within the clade. The four gene sequences revealed that C. falcatum isolates from Bangladesh differed from other countries´ isolates because of nucleotides substitution at different loci. The genetic structure of C. falcatum isolates were determined using ISSR marker generated 404 polymorphic loci from 10 selected markers. The percentage of polymorphic loci was 99.01. The genetic variability at species level was slightly higher than at population level. Total mean gene diversity at the species level was 0.1732 whereas at population level it was 0.1521. The cluster analysis divided 41 isolates into four main genetic groups and the principal component analysis was consistent with cluster analysis. To the best of our knowledge, this is the first finding on characterizing C. falcatum isolates infesting sugarcane in Bangladesh. The results of this present study provide important baseline information vis a vis C. falcatum phylogeny analysis and genetic diversity study.

Trends in Nanotechnology and Its Potentialities to Control Plant Pathogenic Fungi: A Review.

Approximately 15-18% of crops losses occur as a result of animal pests, while weeds and microbial diseases cause 34 and 16% losses, respectively. Fungal pathogens cause about 70-80% losses in yield. The present strategies for plant disease control depend transcendently on agrochemicals that cause negative effects on the environment and humans. Nanotechnology can help by reducing the negative impact of the fungicides, such as enhancing the solubility of low water-soluble fungicides, increasing the shelf-life, and reducing toxicity, in a sustainable and eco-friendly manner. Despite many advantages of the utilization of nanoparticles, very few nanoparticle-based products have so far been produced in commercial quantities for agricultural purposes. The shortage of commercial uses may be associated with many factors, for example, a lack of pest crop host systems usage and the insufficient number of field trials. In some areas, nanotechnology has been advanced, and the best way to be in touch with the advances in nanotechnology in agriculture is to understand the major aspect of the research and to address the scientific gaps in order to facilitate the development which can provide a rationale of different nanoproducts in commercial quantity. In this review, we, therefore, described the properties and synthesis of nanoparticles, their utilization for plant pathogenic fungal disease control (either in the form of (a) nanoparticles alone, that act as a protectant or (b) in the form of a nanocarrier for different fungicides), nano-formulations of agro-nanofungicides, Zataria multiflora, and ginger essential oils to control plant pathogenic fungi, as well as the biosafety and limitations of the nanoparticles applications.

First Report of Fusarium equiseti, Causing Fruit Rot Disease of Watermelon in Malaysia.

Watermelon (Citrullus lanatus) accounts for almost 13% of all tropical fresh fruit production in Malaysia. They are grown, mostly in Johor, Kedah, Kelantan, Pahang, and Terengganu areas of Malaysia on 10,406 ha and yielding 172,722 Mt. In 2019, a new fruit rot disease was observed in two major production areas in Peninsular Malaysia. Disease symptoms included water-soaked brown lesions on the fruit surface in contact with the soil. The lesions enlarged gradually and ultimately covered the whole fruit with white mycelium leading to internal fruit decay. Disease surveys were conducted in December 2019 and November 2020 in fields at Kuantan, Pahang and Serdang, Selangor. Disease incidence was 10% in 2019 and 15% in 2020. Infected fruits were collected and washed under running tap water to wash off adhering soil and debris. Fruit tissue sections 1 to 2 cm in length were surface sanitized with 0.6% sodium hypochlorite (NaOCl) for 3 min. and washed twice with sterile distilled water. The disinfected air-dried tissues were then transferred onto potato dextrose agar (PDA) media and incubated at 25±2℃ for 3 days. Fungal colonies with whitish mycelium and pink pigment isolated using single spore culture. The pure cultures were placed onto carnation leaf agar (CLA), and the culture plates were incubated at 25±2℃ for 15 days for morphological characterization. On CLA, macroconidia were produced from monophialides on branched conidiophores in orange sporodochia. Macroconindia were thick-walled, strong dorsiventral curvature, 5 to 7 septate with a tapered whip-liked pointed apical cell and characteristic foot-shaped basal cell, 21.9 to 50.98 µm long and 2.3 to 3.60 µm wide. Typical verrucose thick chlamydospores with rough walls were profuse in chains or clumps, sub-globose or ellipsoidal. Based on morphological characteristics they were identified as Fusarium equiseti (Leslie and Summerell 2006). Molecular identification of both U4-1 and N9-1 pure culture isolates were carried out using two primer pair sets; internal transcribed spacer (ITS) ITS-1/ ITS-4 and translation elongation factor 1 alpha (TEF1-α) (EF-1/EF-2). A Blastn analysis of the ITS gene sequence of U4-1(MW362286) and N9-1 (MW362287) showed >99% similarity index to the reference gene sequence of F. equiseti isolate 19MSr-B3-4 (LC514690). The TEF1-α sequences of U4-1 (accession no. MW839563) and N9-1 (accession no. MW839564) showed 100% identity; with an e-value of zero, to the reference gene sequence of F. equiseti isolate URM: 7561 (accession no. LS398490). Each isolate also had a >99% identity with isolate NRRL 34070 (accession no. GQ505642) in Fusarium MLST database that belongs to the F. incarnatum-equiseti species complex (O'Donnell et al. 2015). Based on phylogenetic analysis of the aligned sequences (TEF1-α) by the maximum likelihood method, the U4-1 and N9-1 isolates were confirmed to be F. equiseti as was reported in Georgia, USA (Li and Ji 2015) and in Harbin, Heilongjiang Province, China (Li et al. 2018). Finally, the two pure culture isolates of U4-1 and N9-1 were used to fulfill Koch's postulates. Stab inoculations of five healthy watermelon fruits (cv. 345-F1 hybrid seedless round watermelon) were performed with a microconidial suspension of individual isolates (4x106 spores/mL). Five control fruits were stabbed with double distilled water. The inoculated fruits were incubated under 95% relative humidity at a temperature of 25±2℃ for 48 h followed by additional incubation inside an incubator at 25±2℃ for 8 days. Ten days post-inoculation, the control fruits showed no disease symptoms. However, inoculated fruits exhibited typical symptoms of fruit rot disease like water-soaked brown lesions, white mycelium on the fruit surface and internal fruit decay, which is similar to the farmer's field infected fruits. The suspected pathogen was successfully re-isolated from the symptomatic portion of inoculated fruit and morphologically identified for verification. To our knowledge, this is the first report of F. equiseti causing fruit rot of watermelon in Malaysia. Malaysia exports watermelon year-round to many countries around the world. The outbreak of this new fruit rot disease could potentially pose a concern to watermelon cultivation in Malaysia.

Knowledge, awareness and preventive practices of dengue outbreak in Bangladesh: A countrywide study.

BACKGROUND: Dengue, the mosquito borne disease has become a growing public health threat in Bangladesh due to its gradual increasing morbidity and mortality since 2000. In 2019, the country witnessed the worst ever dengue outbreak. The present study was conducted to characterize the socio-economic factors and knowledge, attitude and practice (KAP) status towards dengue among the people of Bangladesh. METHOD: A cross-sectional study was conducted with 1,010 randomly selected respondents from nine different administrative regions of Bangladesh between July and November 2019. A structured questionnaire was used covering socio-demographic characteristics of the participants including their knowledge, awareness, treatment and practices regarding dengue fever. Factors associated with the knowledge and awareness of dengue were investigated separately, using multivariable logistic regression. RESULTS: Although majority (93.8%) of the respondents had heard about dengue, however, they had still misconceptions about Aedes breeding habitat. Around half of the study population (45.7%) had mistaken belief that Aedes can breed in dirty water and 43.1% knew that Aedes mosquito usually bites around sunrise and sunset. Fever indication was found in 36.6% of people which is the most common symptom of dengue. Among the socio-demographic variables, the level of education of the respondents was identified as an independent predictor for both knowledge (p<0.05) and awareness (p<0.05) of dengue. The preventive practice level was moderately less than the knowledge level though there was a significant association (p<0.05) existed between knowledge and preventive practices. Our study noted that TV/Radio is an effective predominant source of information about dengue fever. CONCLUSION: As dengue is emerging in Bangladesh, there is an urgent need to increase health promotion activities through campaigns for eliminating the misconception and considerable knowledge gaps about dengue.

First Report of Fusarium wilt disease on Watermelon Caused by Fusarium oxysporum f. sp. niveum (FON) in Malaysia.

Fusarium wilt disease incited by Fusarium oxysporum f. sp. niveum (FON) is the utmost devastating soil-inhabiting fungal pathogen limiting watermelon (Citrullus lanatus) production in Malaysia and globally. The field disease survey of fusarium wilt was carried out during December 2019 and November 2020, in three major production areas (3 farmer fields per location) in Peninsular Malaysia namely, Mersing, Serdang and Kuantan and disease incidence of 30 and 45%, was recorded for each year, respectively. Infected watermelon plants showed symptoms such as vascular discoloration, brown necrotic lesions to the soil line or the crown, one-sided wilt of a plant, or a runner or the whole plant. Infected root and stem tissues, 1-2 cm pieces were surface sterilized with 0.6% NaOCl for 1 minute followed by double washing with sterile water. The disinfected tissues were air-dried and transferred onto semi-selective Komada's medium (Komada 1975) and incubated for 5 days. The fungal colonies produced were placed on potato dextrose agar (PDA) to attain a pure culture and incubated at 25±2℃ for 15 days. The pure fungal colony was flat, round and light purple in color. Macroconidia were straight to slightly curved, 18.56-42.22 µm in length, 2.69-4.08 µm width, predominantly 3 septate and formed in sporodochia. Microconidia measured 6.16-10.86 µm in length and 2.49-3.83 µm in width, kidney-shaped, aseptate and were formed on short monophialides in false-heads. Chlamydospores were single or in pairs with smooth or rough walls, found both terminally or intercalary. To confirm their pathogenicity, two-week-old watermelon seedlings (cv. NEW BEAUTY) were dipped into spore suspension (1 ˟ 106 spores/ml) of representative isolates of JO20 (Mersing), UPM4 (Serdang) and KU41 (Kuantan) for 30 second and then moved into 10 cm diameter plastic pots containing 300 g sterilized soil mix. Disease symptoms were assessed weekly for one month. Control seedlings were immersed in sterile distilled water before transplanting. The inoculated seedlings showed typical Fusarium wilt symptoms like yellowing, stunted growth, and wilting, which is similar to the farmer field infected plants. However, the seedlings inoculated by sterile distilled water remained asymptomatic. The pathogen was successfully re-isolated from the infected seedlings onto Komada's medium, fulfilling the Koch's postulate. For the PCR amplification, primers EF-1 and EF-2 were used to amplify the tef1-α region. A Blastn analysis of the tef1-α sequences of the isolates JO20 (accession nos. MW315902), UPM4 (MW839560) and KU41 (MW839562) showed 100% similarity; with e-value of zero, to the reference sequences of F. oxysporum isolate FJAT-31690 (MN507110) and F. oxysporum f. sp. niveum isolate FON2 790-2 (MN057702). In Fusarium MLST database, isolates JO20, UPM4 and KU41 revealed 100% identity with the reference isolate of NRRL 22518 (accession no. FJ985265). Though isolate FJ985265 belongs to the f. sp. melonis, earlier findings had revealed Fusarium oxysporum f. sp. are naturally polyphyletic and making clusters with diverse groups of the Fusarium oxysporum species complex (O'Donnell et al. 2015). The isolates JO20, UPM4 and KU41 were identified as F. oxysporum f. sp. niveum based on the aligned sequences of tef1-α and molecular phylogenetic exploration by the maximum likelihood method. To the best of our knowledge, this is the first report of F. oxysporum f. sp. niveum as a causative pathogen of Fusarium wilt disease of watermelon in Malaysia. Malaysia enables to export watermelon all-year-round in different countries like Singapore, Hong-Kong, The United Arab Emirates (UAE), and Netherlands. The outburst of this destructive soil-borne fungal pathogen could cause hindrance to watermelon cultivation in Malaysia. Thus, growers need to choice multiple management tactics such as resistant varieties, cultural practices (soil amendments and solarization), grafting, cover crops and fungicide application to control this new pathogen.

T helper 2-driven immune dysfunction in chronic arsenic-exposed individuals and its link to the features of allergic asthma.

Limited information is available regarding the effects of arsenic exposure on immune function. We have recently reported that chronic exposure to As was associated asthma, as determined by spirometry and respiratory symptoms. Because T helper 2 (Th2)-driven immune responses are implicated in the pathogenesis of allergic diseases, including asthma, we studied the associations of serum Th1 and Th2 mediators with the As exposure markers and the features of asthma among individuals exposed to As. A total of 553 blood samples were selected from the same study subjects recruited in our previous asthma study. Serum levels of Th1 and Th2 cytokines were analyzed by immunoassay. Subjects' arsenic exposure levels (drinking water, hair and nail arsenic concentrations) were determined by inductively coupled plasma mass spectroscopy. Arsenic exposure levels of the subjects showed significant positive associations with serum Th2-mediators- interleukin (IL)-4, IL-5, IL-13, and eotaxin without any significant changes in Th1 mediators- interferon-γ and tumor necrosis factor-α. The ratios of Th2 to Th1 mediators were significantly increased with increasing exposure to As. Notably, most of the Th2 mediators were positively associated with serum levels of total immunoglobulin E and eotaxin. The serum levels of Th2 mediators were significantly higher in the subjects with asthma than those without asthma. The results of our study suggest that the exacerbated Th2-driven immune responses are involved in the increased susceptibility to allergic asthma among individuals chronically exposed to As.

Greyhound racing ideal trajectory path generation for straight to bend based on jerk rate minimization.

This paper presents methods for modelling and designing an ideal path trajectory between straight and bend track path segments for racing greyhounds. To do this, we numerically generate clothoid and algebraic curve segments for racing quadrupeds using a sequential vector transformation method as well as using a helper equation for approaching ideal clothoid segments that would respect greyhound kinematic parameters and boundary conditions of the track. Further, we look into the limitations of using a clothoid curve for racing dog track path design and propose a smooth composite curve for track transition design which roughly maintains G3 curvature continuity for smooth jerk to overcome limitations of a clothoid transition. Finally, we show results from race data modelling and past injury data, which provide a strong indication of clothoid curve segments improving the dynamics and safety of racing greyhounds while reducing injuries.

Association between chronic arsenic exposure and the characteristic features of asthma.

Widespread contamination of arsenic (As) has become a global public health concern. Exposure to As causes respiratory complications. Asthma, a major respiratory complication, is increasing worldwide. However, the effect of chronic As exposure on the risk of asthma remains to be clarified. This study aims to examine the associations between As exposure (water, hair and nail As) and the risk of asthma among 842 individuals exposed to a wide range of As concentrations through drinking water in Bangladesh. Subjects' As exposure levels were measured with ICP-MS. Lung function was examined by a handheld spirometer. Characteristic features of asthma were evaluated by bronchodilator-mediated reversibility in airway obstruction and asthma-like symptoms through a structured questionnaire. Total serum immunoglobulin E (sIgE) levels were measured by immunoassay. As exposure metrics showed inverse associations with lung function measures (FEV1, FEV6, and FEV1/FEV6 ratio) and positive associations with the risks of airway obstruction (AO), reversible airway obstruction (RAO), and asthma-like symptoms. The majority of AO patients (70 of 97) were RAO with one or more characteristic symptoms of asthma. Intriguingly, subjects' As exposure levels showed positive associations with total sIgE levels. Total sIgE in RAO patients was significantly (p < 0.001) higher than that in the control group. Thus the results revealed that chronic As exposure was associated with the risk of the characteristic features of asthma. Additionally the association between As exposure and subjects' total sIgE levels and an elevated level of total sIgE in RAO group suggested that As exposure-related asthma might be allergic in nature.

Study of a common azo food dye in mice model: Toxicity reports and its relation to carcinogenicity.

This study was conducted to evaluate the toxic effects of an azo dye carmoisine widely used in foods and to investigate its relation to carcinogenicity. Carmoisine administered into mice orally in four different doses as control, low, medium, and high equivalent to 0, 4, 200, and 400 mg/kg bw, respectively, for 120 days. The key toxicological endpoint was observed including animal body weight, organ weights, hematology, biochemistry, and molecular biology assessment. The body weights of medium- and high-dose carmoisine-treated mice group were significantly decreased as compared to the control mice group. Platelet, white blood cell and monocyte counts of treated group were considerably higher, while Hb and red blood cell counts were drastically lower than the control group. The biochemical parameters such as serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, globulin, urea, and creatinine level were significantly increased, while serum cholesterol level was decreased after treatment as compared to the control. RT-PCR results showed that expression of Bcl-x and PARP gene was intensively increased, whereas expression of p53 gene was decreased in the mouse liver tissues treated with carmoisine. This study revealed that high-dose (400 mg/kg bw) treatment of carmoisine was attributable to renal failure and hepatotoxicity. It also would be suspected as a culprit for liver oncogenesis.

Associations of total arsenic in drinking water, hair and nails with serum vascular endothelial growth factor in arsenic-endemic individuals in Bangladesh.

Arsenic exposure is associated with cancer and vascular diseases. Angiogenesis is an important step for the pathological development of cancer and vascular diseases. Vascular endothelial growth factor (VEGF) is a specific marker for angiogenesis. However, human study showing the association between arsenic exposure and serum VEGF levels has not yet been documented. This study was aimed to investigate the association between arsenic exposure and serum VEGF levels in the arsenic-endemic individuals in Bangladesh. A total of 260 individuals were recruited for this study. Arsenic exposure levels were measured by ICP-MS and VEGF levels were quantified using VEGF immunoassay kit. The study subjects were stratified into tertile (low, medium and high) groups based on the arsenic in water, hair and nails. Serum VEGF levels were correlated with water (rs = 0.363, p < 0.001), hair (rs = 0.205, p < 0.01) and nail (rs = 0.190, p < 0.01) arsenic. Further, VEGF levels showed dose-response relationships with water, hair and nail arsenic. Mean VEGF levels in ⩽ 10 µg L(-1), 10.1-50 µg L(-1) and > 50 µg L(-1) groups were 91.84, 129.54, and 169.86 pg mL(-1), respectively, however, significant (p < 0.01) difference in VEGF levels was only found in > 50 µg L(-1) versus ⩽ 10 µg L(-1) groups. Significant associations of arsenic exposure with VEGF levels were found even after adjusting with relevant covariates. Therefore, these results provide evidence that arsenic exposure has a pro-angiogenic effect on humans, which may be implicated in arsenic-induced tumorigenesis and vascular diseases.

Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh.

Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p<0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose-response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs.

Increases in oxidized low-density lipoprotein and other inflammatory and adhesion molecules with a concomitant decrease in high-density lipoprotein in the individuals exposed to arsenic in Bangladesh.

Elevated exposure to arsenic has been suggested to be associated with atherosclerosis leading to cardiovascular disease (CVD). However, biochemical events underlying the arsenic-induced atherosclerosis have not yet been fully documented. The aim of this study was to investigate the associations of circulating molecules involved in atherosclerosis with arsenic exposure in the individuals exposed to arsenic in Bangladesh. A total of 324 study subjects, 218 from arsenic-endemic areas and 106 from nonendemic areas in Bangladesh, were recruited. Drinking water, hair, nail, and blood samples were collected from the study subjects for analysis. Total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels were lower in arsenic-endemic subjects than those of nonendemic subjects. Oxidized LDL (Ox-LDL), C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) levels were significantly higher in arsenic-endemic subjects than those in nonendemic subjects. All these circulating molecules showed significant correlations with arsenic exposure (water, hair, and nail arsenic concentrations), and all these relations were significant before and after adjusting for relevant covariates. Among the circulating molecules tested in this study, HDL, Ox-LDL, and CRP showed dose-response relationships with arsenic exposure. Ox-LDL/HDL ratios were increased with the increasing concentrations of arsenic in the water, hair, and nails. Furthermore, non-HDL cholesterol and TC/HDL ratios were significantly correlated with arsenic exposure before and after adjusting for relevant covariates. Thus, all the observed associations may be the major features of arsenic exposure-related atherosclerosis leading to CVD.

Low-dose photon irradiation response of Ge and Al-doped SiO2 optical fibres.

We have investigated the thermoluminescent response and fading characteristics of germanium- and aluminium-doped SiO(2) optical fibres. These optical fibres were placed in a solid phantom and irradiated using 6 and 10 MV photon beams at doses ranging from 0.02 to 0.24 Gy delivered using a linear accelerator. In fading studies, the TL measurements were continued up to 14 days post-irradation. We have investigated the linearity of TL response as a function of dose for Ge-, Al-doped optical fibre and TLD-100 obtained for 6 and 10 MV photon irradiations. We have concentrated on doses that represent a small fraction of that delivered to the tumour to establish sensitivity of measurement for peripheral exposures in external beam radiotherapy.