Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with 90Y and 111In for domestic radioimmunotherapy and radioscintigraphy of Non-Hodgkin’s Lymphoma

Background

On the basis of results of our previous investigations on ⁹⁰Y-DTPA-rituximab and in order to fulfil national demands to radioimmunoconjugates for radioscintigraphy and radioimmunotherapy of Non-Hodgkin’s Lymphoma (NHL), preparation and radiolabeling of a lyophilized formulation (kit) of DOTA-rituximab with ¹¹¹In and ⁹⁰Y was investigated.

Methods

¹¹¹In and ⁹⁰Y with high radiochemical and radionuclide purity were prepared by ¹¹²Cd (p,2n)¹¹¹In nuclear reaction and a locally developed ⁹⁰Sr/⁹⁰Y generator, respectively. DOTA-rituximab immunoconjugates were prepared by the reaction of solutions of p-SCN-Bz-DOTA and rituximab in carbonate buffer (pH = 9.5) and the number of DOTA per molecule of conjugates were determined by transchelation reaction between DOTA and arsenaso yttrium(III) complex. DOTA-rituximab immunoconjugates were labeled with ¹¹¹In and ⁹⁰Y and radioimmunoconjugates were checked for radiochemical purity by chromatography methods and for immunoreactivity by cell-binding assay using Raji cell line. The stability of radiolabeled conjugate with the approximate number of 7 DOTA molecules per one rituximab molecule which was prepared in moderate yield and showed moderate immunoreactivity, compared to two other prepared radioimmunoconjugates, was determined at different time intervals and against EDTA and human serum by chromatography methods and reducing SDS-polyacrylamide gel electrophoresis, respectively. The biodistribution of the selected radioimmunoconjugate in rats was determined by measurement of the radioactivity of different organs after sacrificing the animals by ether asphyxiation.

Results

The radioimmunoconjugate with approximate DOTA/rituximab molar ratio of 7 showed stability after 24 h at room temperature, after 96 h at 4°C, as the lyophilized formulation after six months storage and against EDTA and human serum. This radioimmunoconjugate had a biodistribution profile similar to that of ⁹⁰Y-ibritumomab, which is approved by FDA for radioimmunotherapy of NHL, and showed low brain and lung uptakes and low yttrium deposition into bone.

Conclusion

Findings of this study suggest that further investigations may result in a lyophilized (kit) formulation of DOTA-rituximab which could be easily radiolabeled with ⁹⁰Y and ¹¹¹In in order to be used for radioimmunotherapy and radioscintigraphy of B-cell lymphoma in Iran.     

The State of Starch/Hydroxyapatite Composite Scaffold in Bone Tissue Engineering with Consideration for Dielectric Measurement as an Alternative Characterization Technique

Hydroxyapatite (HA) has been widely used as a scaffold in tissue engineering. HA possesses high mechanical stress and exhibits particularly excellent biocompatibility owing to its similarity to natural bone. Nonetheless, this ceramic scaffold has limited applications due to its apparent brittleness. Therefore, this had presented some difficulties when shaping implants out of HA and for sustaining a high mechanical load. Fortunately, these drawbacks can be improved by combining HA with other biomaterials. Starch was heavily considered for biomedical device applications in favor of its low cost, wide availability, and biocompatibility properties that complement HA. This review provides an insight into starch/HA composites used in the fabrication of bone tissue scaffolds and numerous factors that influence the scaffold properties. Moreover, an alternative characterization of scaffolds via dielectric and free space measurement as a potential contactless and nondestructive measurement method is also highlighted.     

Structure‐Based Design and Synthesis of a Small Molecule that Exhibits Anti‐inflammatory Activity by Inhibition of MyD88‐mediated Signaling to Bacterial Toxin Exposure

Both Gram‐positive and Gram‐negative pathogens or pathogen‐derived components, such as staphylococcal enterotoxins (SEs) and endotoxin (LPS) exposure, activate MyD88‐mediated pro‐inflammatory cellular immunity for host defense. However, dysregulated MyD88‐mediated signaling triggers exaggerated immune response that often leads to toxic shock and death. Previously, we reported a small molecule compound 1 mimicking BB‐loop structure of MyD88 was capable of inhibiting pro‐inflammatory response to SEB exposure in mice. In this study, we designed a dimeric structure compound 4210 covalently linked with compound 1 by a non‐polar cyclohexane linker which strongly inhibited the production of pro‐inflammatory cytokines in human primary cells to SEB (IC₅₀ 1–50 μm ) or LPS extracted from Francisella tularensis, Escherichia coli, or Burkholderia mallei (IC₅₀ 10–200 μm ). Consistent with cytokine inhibition, in a ligand‐induced cell‐based reporter assay, compound 4210 inhibited Burkholderia mallei or LPS‐induced MyD88‐mediated NF‐kB‐dependent expression of reporter activity (IC₅₀ 10–30 μm ). Furthermore, results from a newly expressed MyD88 revealed that 4210 inhibited MyD88 dimer formation which is critical for pro‐inflammatory signaling. Importantly, a single administration of compound 4210 in mice showed complete protection from lethal toxin challenge. Collectively, these results demonstrated that compound 4210 inhibits toxin‐induced inflated pro‐inflammatory immune signaling, thus displays a potential bacterial toxin therapeutic.     

Development and validation of a questionnaire to assess socio-behavioural impact of COVID-19 on the general population

Background and aimThe aim of the study is to develop a valid and reliable tool to assess sociobehavioural changes due to COVID among the general population.MethodsThis mixed method study has two phases. Phase I for questionnaire development (literature review, focus group discussion, expert evaluation and pilot testing). Phase II for establishing construct validity via factor analysis and internal consistency via Cronbach’s ɑ by administering the questionnaire on 179 participants.ResultsA questionnaire comprising 33 questions and five domains was developed having Cronbach’s α of 0·82.ConclusionThe developed questionnaire is a concise, easy to administer and valid tool to assess socio-behavioural changes.     

Assessment of Circulating Biochemical Markers in Mice Receiving Cinnamon and Glycyrrhizin Under Carbon Tetrachloride Induced Hepatic Injury

The study evaluated the hepatoprotective activity of plant extracts of cinnamon and glycyrrhizin in distinct dosage ways to minimize the oxidative stress induced by carbon tetrachloride (CCl₄) in BALB/cJ inbred albino mice. Fifteen albino mice were divided into five groups, each group containing three mice. Group A was referred as positive control while group B, C, D and E were injected intraperitoneally with 1 mL/kg body weight of CCl₄ twice a week for 1 month. Group C and D were treated orally with isolated extracts of cinnamon @50 mg/kg and glycyrrhizin @50 mg/kg respectively on daily basis for 1 month. However, group E was treated orally with combination dose of cinnamon @50 mg/kg + glycyrrhizin @50 mg/kg body weight. The increase in the levels of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), triglyceride (TG), malondialdehyde (MDA) and glucose were recorded in CCl₄ induced liver injury in mice while there is decrease in the levels of total protein (TP), reduced glutathione (GSH), Superoxide dismutase (SOD) and catalase (CAT) in CCL₄ intoxicated mice. Isolated therapy of plant extracts of cinnamon and glycyrrhizin decreased the levels of ALT, AST, ALP, MDA, TG and glucose whereas increase in TP, GSH, SOD and CAT was observed in plant extracts treated mice. The best restoration of all the above said parameters near to control was observed in group of mice treated with combination dose of cinnamon and glycyrrhizin @50 mg/kg. Therefore, the present study declared the antioxidative, anti-inflammatory and hepatoprotective activity of standardized extracts of cinnamon and glycyrrhizin and their potent defensive property.

     

Pathogenesis of pleural infection

The pleura responds to the presence of infecting organisms with a vigorous inflammatory response associated with an exudation of white blood cells and proteins. The development and outcome of pleural infections is a function of a balance between the virulence of the invading microorganism and the immune reaction involving professional immune cells as well as the pleural mesothelial cells. Most commonly, pleural infection occurs after invasion through the lung parenchyma and a breach in the viscera pleura resulting in the formation of a parapneumonic process. Upon infection, the microorganisms are recognized by the pleural mesothelial cell, which remains the first line of defence. Pleural responses to infection include those of innate immunity as well as adaptive or acquired immunity. Innate and acquired immune responses are closely linked. In this review, we discuss the different virulence factors that allow microorganisms to infect the pleura and the role of the pleural mesothelial cells in bridging the innate and acquired immune responses.     

Successful aztreonam treatment of acute typhoid fever after chloramphenicol failure

Aztreonam treatment was successful in 4 cases of typhoid fever. The patients were seriously ill with growth of Salmonella typhi in blood cultures despite treatment with chloramphenicol. Aztreonam appears to be a useful alternative to standard therapy of typhoid fever.     

Benzene exposure among auto-repair workers from workplace ambience: A pioneer study from Pakistan

Objectives

In Pakistan, the reports on benzene exposure among workers in chemical industries are almost non-existing due to limited research work in the field of exposure science. This study aimed to investigate such exposure in a widely adopted occupation in Rawalpindi city.

Material and Methods

In this cross-sectional study, 60 blood samples (N = 20/group) of mechanics (MCs), spray painters (PNs) and control participants (CN) were analyzed. The socio-economic and demographic information of workers and that of workplaces was documented using a short questionnaire.

Results

We identified that the workers in spray-painting occupation are highly at risk of benzene exposure. The results showed that PNs were more at risk of exposure to benzene than MCs, and this exposure was significantly correlated with long working hours (r = 0.68, p < 0.001). Moreover, there are several limitations in workplace setups, which need to be addressed in order to mitigate workers health risk in this occupation. In addition to the reckless use of chemicals, other identified predictors of exposure included active and passive smoking, poor workplace hygiene and substandard ventilation.

Conclusions

To mitigate workplace exposure, it is necessary to reduce working hours and encourage regular use of self-protective equipments and adoption of proper hygiene in chemical workplaces.