Assessing the Risk of Birth Defects Associated with Exposure to Fixed-Dose Combined Antituberculous Agents during Pregnancy in Rats

Due to the risks of disease progression and transmission to the newborn, treatment of tuberculosis is often pursued during pregnancy and fixed-dose combined antituberculous agents have been found to be beneficial. Unfortunately, there is paucity of data on the safety of the fixed-dose combined antituberculous drugs during pregnancy. This study intends to assess the teratogenic effect of fixed-dose combined antituberculous drugs on the organogenesis stage of fetal development and also investigate the possible roles of vitamin C in modulating the teratogenic effects of these agents on the fetus using animal model. Pregnant rats were divided into 3 groups with 12 animals per group: group 1 received distilled water (10 mL/kg) orally; group 2 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents orally; group 3 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents plus vitamin C (10 mg/kg/day) orally. Six rats in each group were randomly selected and sacrificed on day 20 by cervical dislocation prior to day 21 of gestation, and the foetuses were harvested through abdominal incision for physical examination. Blood samples were collected from the 1st filial rats of the remaining six animals for biochemical and hematological examination. The liver, kidney, heart, and brain of all the sacrificed animals were used for histopathological examination. There were significant (P ≤ 0.05) low birth weights of the foetuses of the animals that were treated with fixed-dose combined antituberculous agents. The haematological parameters also revealed a reduction in the platelets counts and neutrophiles at the first filial generation. Significant (P ≤ 0.05) elevations in the levels of aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the foetuses of the animals treated with fixed-dose combined antituberculous agents were also observed. However, the combination of vitamin C with fixed-dose combined antituberculous agents significantly (P ≤ 0.05) reduced the level of AST. Fixed-dose combined antituberculous agents have teratogenic potential as shown in low birth weight and mild liver damage in the first filial of the treated animals. As much as it is imminent to treat TB patients in pregnancy, there is need to always exercise caution and clinically weigh the risk-benefit ratio

Indoor environmental conditions of selected shopping malls in Nigeria: A comparative study of microclimatic conditions, noise levels, and microbial burdens

oai:repository.uel.ac.uk:8x3x4The activities of people and equipment used within shopping malls are major factors that contribute to air pollution and increased sound levels, thereby affecting indoor environmental quality and the well-being of mall operators. This study assessed indoor environmental quality through microbial characterization and measurement of environmental conditions present in selected shopping malls. Investigations were conducted at three shopping malls in Ibadan selected through convenience sampling technique. Environmental parameters such as noise level, relative humidity, temperature, PM₂.₅ levels, total volatile organic compound (TVOC) levels, microbial characterization, and quantity were determined. Microclimatic parameters (temperature and relative humidity) were measured using a 4-in-1 Precision Gold N09AQ multi-tester. Culturable airborne microbes were collected using the settle plate technique. PM₂.₅ and TVOC levels were measured using a Thermo Scientific MIE pDR-1500 PM monitor and sf200-TVOC meter respectively. Two bacteria species and five fungi species were isolated across the malls. The noise levels ranged from 61.27 to 81.20 dB. The mean temperatures (highest mean of 33.44 ± 1.42 °C), PM₂.₅ (highest mean of 114.06 ± 25.64 μg/m³), and TVOC (highest mean of 55.21 ± 8.28 ppm) concentrations were higher than the permissible limits stipulated by the WHO guidelines and NESREA standard limits across all the selected malls. A positive correlation was found to exist between particulate matter and TVOC (r = 0.174, p = 0.004). The total bacteria count was generally high with the highest mean of 1965.33 ± 368.56 CFU/m³, while the total fungi count was generally low with the highest mean of 579.82 ± 51.55 CFU/m³. Bacillus spp. and Candida spp. were found to the consistent from all sample points across the three malls. The bacteria isolated are Gram-positive bacteria associated with human skin which suggests a high rate of indoor pollution from humans. In conclusion, this research has demonstrated the necessity to monitor noise levels and indoor air quality in malls. Also, there is need for government policies to improve indoor air quality which must be enforced and regulated, especially within shopping malls

Biomacromolecules in Recent Phosphate-Shelled Brachiopods: Identification and Characterization of Chitin Matrix

Abstract: Phosphate-shelled brachiopods differ in filter-feeding lifestyle, with Lingula anatina an active infaunal burrower, and Discinisca tenuis a shallow marine epibenthic animal. The shells of these animals are built of organophosphatic constituents, the organic fibres/sheets reinforced with calcium phosphate to provide a sophisticated ultrastructural robustness. This investigation examined the nature of the organic fibres in order to improve understanding of how living organisms produce hierarchically structured biomaterials. Unlike powdered samples commonly used in previous studies, organic fibres were isolated for the first time and the shell fractions were purified, in order to study the content and nature of the biopolymer fibres. Biochemical methods including Calcofluor staining revealed a chitin matrix. Ultrastructural analysis, thermal gravimetric analysis, and spectroscopic analyses show that the core polysaccharide framework is composed of layers of β-chitin sheets and/or fibrils that are coated with a fibrous organic matrix. There is more chitin matrix in the L. anatina shells (26.6 wt.%) compared to the D. tenuis shells (12.9 wt.%). Taken together, the data show that the chitin matrix contributes to increased skeletal strength, making L. anatina highly adapted for life as an active burrower. In comparison, D. tenuis contains less chitin and lives as attached epibenthos in a shallow marine environment. Graphical abstract: [Figure not available: see fulltext.] First spectroscopic evidence of β-chitin sheets in recent organophosphatic brachiopods. © 2021, The Author(s).OBAA is grateful to Uppsala University for support through the VR Project number 2018-03390. The research for this paper was supported by the Swedish Research Council (VR Project no. 2018-03390 to LEH, GAB and SCG), by the National Natural Science Foundation of China (41720104002, 41621003 and 41890844 to NWU members), and by a Zhongjian Yang Scholarship to LEH from the Department of Geology, Northwest University, Xi’an. GAB’s research is also funded by a 1000 Talent Shaanxi Province Fellowship at Northwest University, Xi’an

11β-HSD1 inhibition in men mitigates prednisolone-induced adverse effects in a proof-of-concept randomised double-blind placebo-controlled trial

Glucocorticoids prescribed to limit inflammation, have significant adverse effects. As 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid, we investigated whether 11β-HSD1 inhibition with AZD4017 could mitigate adverse glucocorticoid effects without compromising their anti-inflammatory actions. We conducted a proof-of-concept, randomized, double-blind, placebo-controlled study at Research Unit, Churchill Hospital, Oxford, UK (NCT03111810). 32 healthy male volunteers were randomized to AZD4017 or placebo, alongside prednisolone treatment. Although the primary endpoint of the study (change in glucose disposal during a two-step hyperinsulinemic, normoglycemic clamp) wasn’t met, hepatic insulin sensitivity worsened in the placebo-treated but not in the AZD4017-treated group. Protective effects of AZD4017 on markers of lipid metabolism and bone turnover were observed. Night-time blood pressure was higher in the placebo-treated but not in the AZD4017-treated group. Urinary (5aTHF+THF)/THE ratio was lower in the AZD4017-treated but remained the same in the placebo-treated group. Most anti-inflammatory actions of prednisolone persisted with AZD4017 co-treatment. Four adverse events were reported with AZD4017 and no serious adverse events. Here we show that co-administration of AZD4017 with prednisolone in men is a potential strategy to limit adverse glucocorticoid effects

Organic biopolymers of venus clams : Collagen-related matrix in the bivalve shells with crossed-lamellar ultrastructure

Background: Biochemical studies and spectroscopic techniques have shown that chitin-silk fibroins are common in nacroprismatic bivalve shells. However, the nature of organic biopolymers in the less well studied shell architectures, such as crossed lamellar shells, remain unknown. Here, two venus shells, Callista disrupta and Callista kingii, with crossed lamellar ultrastructure have been studied. Methods: We employed thermal gravimetric analysis, optical-, confocal- and scanning electron-microscopes, gel-sodium dodecyl sulfate (gel-SDS), FTIR, ultra-performance liquid chromatography and high-performance anion-exchange chromatography system with pulsed amperometric detection to analyse organic macromolecules in the shells. Results: Thermal analysis showed a low concentration of organic macromolecules in C. disrupta (1.38 wt%) and in C. kingii (1.71 wt%). A combination of biochemical protocols, including Calcofluor White staining and FTIR spectroscopic assessment, indicate that amino-polysaccharide chitin together with proteins, are present in the organic scaffolding of the shells. Scanning electron microscope of insoluble acid biopolymer extracts as well as FTIR technique show that the hierarchical structural organizations of organic biopolymers consist collagen-related matrix. Our histochemical fixing and staining techniques reveal many discrete proteins and glycoproteins from soluble organic macromolecules on the gel-SDS. We show here 'singlet' and 'doublet' glycosaminoglycan bands that are far above 260 kDa. General significance/conclusions: The presence of collagen matrix in Callista shells shows promise for the new source of biomaterials. Most importantly, the structural organization of the proteinaceous motif is predominantly helical structures and not silk-fibroin unlike in nacreous bivalve shells

Characterization of organophosphatic brachiopod shells : spectroscopic assessment of collagen matrix and biomineral components

The shells of linguloid brachiopods such as Lingula and Discinisca are inorganic–organic nanocomposites with a mineral phase of calcium phosphate (Ca-phosphate). Collagen, the main extracellular matrix in Ca-phosphatic vertebrate skeletons, has not previously been clearly resolved at the molecular level in organophosphatic brachiopods. Here, modern and recently-alive linguliform brachiopod shells of Lingula and Discinisca have been studied by microRaman spectroscopy, Fourier transform infrared spectroscopy, field emission gun scanning electron microscopy, and thermal gravimetric analysis. For the first time, biomineralized collagen matrix and Ca-phosphate components were simultaneously identified, showing that the collagen matrix is an important moiety in organophosphatic brachiopod shells, in addition to prevalent chitin. Stabilized nanosized apatitic biominerals (up to ∼50 nm) permeate the framework of organic fibrils. There is a ∼2.5-fold higher wt% of carbonate (CO32−) in Lingula versus Discinisca shells. Both microRaman spectroscopy and infrared spectra show transient amorphous Ca-phosphate and octacalcium phosphate components. For the first time, trivalent moieties at ∼1660 cm−1 and divalent moieties at ∼1690 cm−1 in the amide I spectral region were identified. These are related to collagen cross-links that are abundant in mineralized tissues, and could be important features in the biostructural and mechanical properties of Ca-phosphate shell biominerals. This work provides a critical new understanding of organophosphatic brachiopod shells, which are some of the earliest examples of biomineralization in still-living animals that appeared in the Cambrian radiation

Biomacromolecules in recent phosphate-shelled brachiopods : identification and characterization of chitin matrix

Phosphate-shelled brachiopods differ in filter-feeding lifestyle, with Lingula anatina an active infaunal burrower, and Discinisca tenuis a shallow marine epibenthic animal. The shells of these animals are built of organophosphatic constituents, the organic fibres/sheets reinforced with calcium phosphate to provide a sophisticated ultrastructural robustness. This investigation examined the nature of the organic fibres in order to improve understanding of how living organisms produce hierarchically structured biomaterials. Unlike powdered samples commonly used in previous studies, organic fibres were isolated for the first time and the shell fractions were purified, in order to study the content and nature of the biopolymer fibres. Biochemical methods including Calcofluor staining revealed a chitin matrix. Ultrastructural analysis, thermal gravimetric analysis, and spectroscopic analyses show that the core polysaccharide framework is composed of layers of β-chitin sheets and/or fibrils that are coated with a fibrous organic matrix. There is more chitin matrix in the L. anatina shells (26.6 wt.%) compared to the D. tenuis shells (12.9 wt.%). Taken together, the data show that the chitin matrix contributes to increased skeletal strength, making L. anatina highly adapted for life as an active burrower. In comparison, D. tenuis contains less chitin and lives as attached epibenthos in a shallow marine environment