Immobilized nuclide and leaching mechanism of zircon waste forms efficient synthesized by molten salt

Molten salt has rapid mass transfer and nucleation process, so it can synthesize ceramic solid solution of immobilized high-level radioactive waste at low temperature. The chemical stability in the process of interaction with groundwater determines the ability of matrix phase to prevent radionuclides from entering the biosphere and the release form of radionuclides. Nd-doped ZrSiO4 ceramics with different sintering temperature (1100-1500 ℃), sintering time (3-24 h) and molar ratio of salt to oxide (3:1, 7:1 and 10:1) were prepared by molten salt method. The sintered ceramic is Zr1−xNdxSiO4−x/2, where x is the solubility of Nd in ZrSiO4. The results show that the optimum molar ratio of molten salt to oxide is 10:1, which can quickly synthesize zircon waste form at low temperature. The chemical stability test shows that the normalized leaching rate of trivalent nuclides in zircon structure is in the order of ~10−5 g·m−1·d−1, and the surface layer is dissolved. The experimental results show that zircon structure is an excellent waste form.

Evaluation of immunotoxicity of the extended-release form of Afobazol

The research of immunotoxicity of extended-release form of Afobazol was conducted on male CBA, C57BL/6 and F1 hybrids (CBA×C57BL/6) mice. Afobazol was administered per os for 14 days in doses of 12 mg/kg and 120 mg/kg. Control group received a placebo. Weight of thymus, spleen and popliteal lymph nodes was not affected by the extended-release form of Afobazol in doses of 12 mg/kg and 120 mg/kg in F1 hybrids (CBA×C57BL/6) mice compared to the control group (p> 0.05). Cellularity of thymus was significantly increased by the extended-release form of Afobazol in dose of 12 mg/kg (p< 0.01 vs control group). Administration of the extended-release form of Afobazol in doses of 12 mg/kg and 120 mg/kg decreased spontaneous chemiluminescence activity of peripheral blood lymphocytes in 2.0 and 2.2 times, in dose of 120 mg/kg level integral chemiluminescence response S was decreased in 2.4 times (p< 0.05 vs control group). Phagocytic activity of peritoneal macrophages and antibody production in F1 hybrids (CBA×C57BL/6) mice were not affected by administration of the extended-release form of Afobazol in doses of 12 mg/kg and 120 mg/kg (p > 0.05 vs control group). 14 days of the extended-release form of Afobazol in doses of 12 mg/kg and 120 mg/kg did not cause any significant change to intensity of delayed-type hypersensitivity reactions (p> 0.05 vs control group). The results of the study allow us to conclude that administration of the extended-release form Afobazol in the range of studied doses does not induce immunotoxicity.

Fabrication, in vitro and in vivo Characterization of Solid Dispersion - Microsphere Controlled Release System for Lornoxicam

Background: Lornoxicam is widely used for its anti-inflammatory, analgesic and antipyretic properties. However, it suffers from the limitations of possessing a relatively short elimination half-life ranging from 3 to 5 h, thereby; leading to repeated dosing which in turn may cause local irritation and ulceration. In addition, LXM also exhibits pHdependent solubility. Effective management of inflammation in diseases such as arthritis requires the formulation of delivery systems that may be able to provide immediate release of drug for instant relief which shall be maintained for a prolonged period. Objective: The present research work was aimed to modify the release pattern of poorly water-soluble drug Lornoxicam by designing a biphasic tablet comprising of solid dispersion (immediate release form) and microspheres (controlled release form) for the effective management of inflammation. Methods: The solid dispersion (SD) was prepared by melting method using PEG 4000 and tween 80 and formation was confirmed by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD) studies. Polymeric microspheres loaded with Lornoxicam were prepared by ‘Emulsion Solvent-Evaporation’ method using Eudragit S-100 and Eudragit L-100. Microspheres (MS) were evaluated for drug entrapment efficiency, drug loading, drug content, particle size and in vitro release behaviour. Optimized microspheres (polymer concentration 0.5% w/v and drug concentration 0.1% w/v and solid dispersion (drug: PEG 4000: 4:6) were compressed in the ratio of 1:3 to produce biphasic tablet. The prepared tablets were evaluated for various pre-compression and post-compression parameters. Antiinflammatory activity of the F4, M6 and the combination of SD and Microspheres in a ratio of 1:3 was carried out by Carrageenan induced paw edema method in Wistar rats. Results: The solid dispersions prepared by melting technique showed an enhanced dissolution rate as compared to the pure drug. LXM microspheres exhibited a sustained drug release. In vitro release of lornoxicam from biphasic tablets showed that 20 % of the drug released at the end of first one hour, followed by 33% release at the end of 4th h and maximum release of 94.1 % at the end of 10 h. The prolonged effect continued till the end of 12 h. Results showed that the mixture of MS + SD exhibited 48 % inhibition in 30 min which is increased to 88.63% at the end of 4 h which can be explained by initial burst release from the soluble layer of SD (which gave initial required effective concentration of Lornoxicam) followed by sustained release from matrix of microspheres (which maintained required level of Lornoxicam in blood). Conclusion: A successful modification of the release pattern of LXM was achieved by designing a biphasic tablet comprising of solid dispersion for the effective management of inflammation.

Tmed2 regulates Smoothened trafficking and Hedgehog signalling

Hedgehog (HH) signalling plays a key role in embryonic pattering and stem cell differentiation. Compounds that selectively bind Smoothened (SMO) can induce cell death in mouse embryonic stem cells (ESCs). Here we perform a genetic screen in haploid ESCs and discover that SMO inhibits a cell death pathway that resembles dissociation induced death of human ESCs and Anoikis. In mouse ESCs, SMO acts through a G-protein coupled mechanism that is independent of GLI activation. Our screen also identifies the Golgi proteins Tmed2 and Tmed10. We show that TMED2 binds SMO and controls its abundance at the plasma membrane. In neural differentiation and neural tube pattering Tmed2 acts as a repressor of HH signalling strength. We demonstrate that the interaction between SMO and TMED2 is regulated by HH signalling suggesting SMO release form the ER-Golgi is critical for controlling G-protein and GLI mediated functions of mammalian HH signalling.

Epidemiological investigation and intergenerational clinical characteristics of 24 COVID-19 patients associated with supermarket cluster

ObjectiveTo analyze the epidemiological and intergenerational clinical characteristics of COVID-19 patients associated with cluster, so as to understand the rules of the patients associated with cluster of this outbreak and provide help for the prevention and control of COVID-19.MethodsAll close contacts of the patient were screened since the first supermarket employee with COVID-19 was identified. A retrospective analysis was made on the epidemiological and clinical characteristics of the confirmed cases admitted to the designated hospitals for centralized treatment. The patients were divided into two groups according to the first generation (supermarket employees, group A) and the second or third generation (family members or friends of supermarket employees, group B), and the similarities and differences between the two groups were compared.ResultsA total of 24 COVID-19 patients were diagnosed, with an average age of 48 ±1.73 years. The mean duration from onset to release form quarantine was 21.04± 6.77 days, and the onset time was concentrated in 5-11 days after the first patient was diagnosed. Among all the patients, 23 patients were moderate, among which 7 patients (29.17%) were asymptomatic. Symptoms of symptomatic patients were cough (75.00%), low fever (62.50%), shortness of breath (41.67%), sore throat (25.00%), gastrointestinal symptoms (25.00%), fatigue (20.83%), etc. Biochemical examination on admission showed that the white blood cell count < 4.0×109/L (29.17%) and the lymphocyte count <1.1×109/L (58.33%). The lymphocyte count of 50.00% of the patients was ≤ 0.6 × 109/L. On admission, chest CT showed pneumonia (100%) with bilateral infiltration (75.00%). Treatment: antiviral drug (100%), Chinese medicine (100%), common oxygen therapy (45.83%). There were 11 cases in group A (first generation, 11 cases) and 13 cases in group B (second generation, 11 cases; third generation, 2 cases). In group B, there were more males, from onset to admission later, more patients had underlying diseases, and more patients were treated with albumin (P<0.05). However, there was no statistical difference between the two groups in other clinical indicators, including the duration from onset to release form quarantine(P>0.05). There was no improvement in granulocyte count in all patients, as well as in groups A and B, between admission and release from quarantine(P>0.05).ConclusionThe clinical characteristics of COVID-19 patients associated with cluster were similar to those of other COVID-19 patients, but there were some special features. The severity of the disease was similar and there was intergenerational spread. There was no difference in clinical characteristics between generations. Asymptomatic infections occurred in a proportion of patients and could cause spread.

Evaluation of burst release and sustained release of pioglitazone-loaded fibrous mats on diabetic wound healing: an in vitro and in vivo comparison study

In order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, was investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl-pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation, but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-γ agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.

Synthesis of amide-spacered dimers of ursolic and oleanolic acid

Transdermal therapeutic systems can release drug substances slowly and in a controlled manner from a drug depot. To provide a slow-release form of ursolic and oleanolic acid amide-spacered dimers were synthesized from the parent acids and diamines of variable chain lengths. These dimers were assayed in sulforhodamine B (SRB) assays for their cytotoxicity since as a pre-requisite for their use in slow-release forms these substances must not exert any unfavorable side-effects such as cytotoxicity. As a result of long term incubation up to 96 hours, none of these compounds showed any significant cytotoxicity in sulforhodamine B assays.