Deltamethrin and Its Nanoformulations Induce Behavioral Alteration and Toxicity in Rat Brain through Oxidative Stress and JAK2/STAT3 Signaling Pathway.

Deltamethrin (DM) is the most powerful synthetic pyrethroid that has toxicity to the central nervous system and results in behavioral changes in both animals and humans. This effect is mediated by inducing alterations in the action of neurotransmitters and brain pathological changes. Nanocarrier encapsulated pesticides may decrease the toxicity of pesticides. Thus, this study aimed to determine the effect of an inorganic metal carrier (silica Nps) and polymeric capsule (chitosan Nps) of deltamethrin nano-formulations on antioxidant levels and oxidative stress in the brain and on behavior of the male albino rat. Sixty male albino rats were equally divided into four groups. Group I: control group; group II given DM liquefied in corn oil at 3.855 mg/kg BW; group III receiving silica-loaded deltamethrin (S/DM Nps) at 8.795 mg/kg BW; and group IV: given chitosan encapsulated deltamethrin (CS/DM Nps) at 30.44 mg/kg BW. All treatments were given orally for four weeks. Following this, behavioral tests were conducted to record locomotor activity, anxiety like behaviors, exploration, and the short memory of rats. In addition, brain antioxidant/oxidant, serum neurotransmitters such as acetylcholine esterase (AchE) and monoamine oxidase (MAO), JAK2 and STAT3 gene and proteins expression were measured. The DM group showed a highly significant elevation in malondialdehyde content, MAO, AchE, vascular endothelial growth factor (VEGF) levels, and the expression level of neurogenic genes, JAK2 and STAT3, in comparison with the control group. Both S/DM Nps and CS/DM Nps significantly decreased MAO, AchE, and VEGF compared with the DM group. Moreover, both S/DM Nps and CS/DM Nps significantly decreased the gene and proteins expression of JAK2 and STAT3 compared with the DM group. These alterations were evidenced by the deficiency in memory and learning behaviors that were accompanied by histopathological findings of the hippocampus and the cortex. It was concluded that the nano formulations containing DM induced less neurobehavioral toxicity than free DM. Additionally, the use of nanocarriers reduced the damage to health and the environment.

Patterns and clinical outcomes of olfactory and gustatory disorders in six months: Prospective study of 1031 COVID-19 patients.

OBJECTIVE: This study aims to comprehensively evaluate olfactory and gustatory dysfunctions during the COVID-19 pandemic regarding onset, course, associated symptoms, prognosis and relation to patients' demographics, treatment received and other symptoms. PATIENTS& METHODS: This is a prospective study conducted on patients proven to be infected with COVID-19 and with olfactory/gustatory dysfunction symptoms. Detailed history was taken from each patient about the onset of this dysfunction, associated symptoms. Then follow-up survey was done after 6 months to evaluate the prognosis. RESULTS: 1031 patients were included in the study, aged 18 to 69 years old, with 31.8% were male. Olfactory/gustatory dysfunctions occurred after other COVID-19 symptoms in 43.5% of cases, occurred suddenly in 80.4% and gradually in 19.6%. These dysfunctions were anosmia & ageusia in 50.2%, hyposmia & hypogeusia in 23.3%, anosmia alone in 17.7%, phantosmia in 18%, Parosmia in 28.4%. In terms of recovery 6-month follow up, 680 patients (66%) recovered completely, 22.1% recovered partially while 11.9% did not recover. Most improvement occurred in the first two weeks. Headache, malaise, nasal obstruction and rhinorrhea were the commonest COVID-19 symptoms associated. CONCLUSION: Most recovery of olfactory/gustatory dysfunction in COVID-19 infection occurs at the first two weeks and is unrelated to patient demographics, treatment or olfactory training. Parosmia is an independent predictor for complete recovery, while phantosmia is significantly associated with lower probability of complete recovery.

Therapeutic effect of mesenchymal stem cells on histopathological, immunohistochemical, and molecular analysis in second-grade burn model.

BACKGROUND AND AIM: Deleterious cutaneous tissue damages could result from exposure to thermal trauma, which could be ameliorated structurally and functionally through therapy via the most multipotent progenitor bone marrow mesenchymal stem cells (BM-MSCs). This study aimed to induce burns and examine the effect of BM-MSCs during a short and long period of therapy. MATERIAL AND METHODS: Ninety albino rats were divided into three groups: group I (control); group II (burn model), the animals were exposed to the preheated aluminum bar at 100°C for 15 s; and group III (the burned animals subcutaneously injected with BM-MSCs (2×106 cells/ ml)); they were clinically observed and sacrificed at different short and long time intervals, and skin samples were collected for histopathological and immunohistochemical examination and analysis of different wound healing mediators via quantitative polymerase chain reaction (qPCR). RESULTS: Subcutaneous injection of BM-MSCs resulted in the decrease of the wound contraction rate; the wound having a pinpoint appearance and regular arrangement of the epidermal layer with thin stratum corneum; decrease in the area percentages of ADAMs10 expression; significant downregulation of transforming growth factor-ß (TGF-ß), interleukin-6 (IL-6), tumor necrotic factor-α (TNF-α), metalloproteinase-9 (MMP-9), and microRNA-21; and marked upregulation of heat shock protein-90α (HSP-90α) especially in late stages. CONCLUSION: BM-MSCs exhibited a powerful healing property through regulating the mediators of wound healing and restoring the normal skin structures, reducing the scar formation and the wound size.

Carcinogenic effect of potassium octatitanate (POT) fibers in the lung and pleura of male Fischer 344 rats after intrapulmonary administration.

BACKGROUND: Potassium octatitanate fibers (K2O•8TiO2, POT fibers) are used as an asbestos substitute. Their physical characteristics suggest that respirable POT fibers are likely to be carcinogenic in the lung and pleura. However, previous 2-year inhalation studies reported that respired POT fibers had little or no carcinogenic potential. In the present study ten-week old male F344 rats were left untreated or were administered vehicle, 0.25 or 0.5 mg rutile-type nano TiO2 (r-nTiO2), 0.25 or 0.5 mg POT fibers, or 0.5 mg MWCNT-7 by intra-tracheal intra-pulmonary spraying (TIPS), and then observed for 2 years. RESULTS: There were no differences between the r-nTiO2 and control groups. The incidence of bronchiolo-alveolar cell hyperplasia was significantly increased in the groups treated with 0.50 mg POT and 0.50 mg MWCNT-7. The overall incidence of lung tumors, however, was not increased in either the POT or MWCNT-7 treated groups. Notably, the carcinomas that developed in the POT and MWCNT-7 treated rats were accompanied by proliferative fibrous connective tissue while the carcinomas that developed in the untreated rats and the r-nTiO2 treated rats were not (carcinomas did not develop in the vehicle control rats). In addition, the carcinoma that developed in the rat treated with 0.25 mg POT was a squamous cell carcinoma, a tumor that develops spontaneously in about 1 per 1700 rats. The incidence of mesothelial cell hyperplasia was 4/17, 7/16, and 10/14 and the incidence of malignant mesothelioma was 3/17, 1/16, and 2/14 in the 0.25 mg POT, 0.5 mg POT, and MWCNT-7 treated groups, respectively. Neither mesothelial cell hyperplasia nor mesothelioma developed in control rats or the rats treated with r-nTiO2. Since the incidence of spontaneously occurring malignant mesothelioma in rats is extremely low, approximately 1 per 1000 animals (Japan Bioassay Research Center [JBRC] historical control data), the development of multiple malignant mesotheliomas in the POT and MWCNT-7 treated groups was biologically significant. CONCLUSION: The incidence of pleural mesotheliomas in male F344 rats administered POT fibers and MWCNT-7 was significantly higher than the JBRC historical control data, indicating that the incidence of pleural mesothelioma in the groups administered POT fibers and MWCNT-7 fibers via the airway using TIPS was biologically significant. The incidence of type II epithelial cell hyperplasia and the histology of the carcinomas that developed in the POT treated rats also indicates that respirable POT fibers are highly likely to be carcinogenic in the lungs of male F344 rats.

Pulmonary and pleural toxicity of potassium octatitanate fibers, rutile titanium dioxide nanoparticles, and MWCNT-7 in male Fischer 344 rats.

Potassium octatitanate (K2O·8TiO2, POT) fibers are used as an alternative to asbestos. Their shape and biopersistence suggest that they are possibly carcinogenic. However, inhalation studies have shown that respired POT fibers have little carcinogenic potential. We conducted a short-term study in which we administered POT fibers, and anatase and rutile titanium dioxide nanoparticles (a-nTiO2, r-nTiO2) to rats using intra-tracheal intra-pulmonary spraying (TIPS). We found that similarly to other materials, POT fibers were more toxic than non-fibrous nanoparticles of the same chemical composition, indicating that the titanium dioxide composition of POT fibers does not appear to account for their lack of carcinogenicity. The present report describes the results of the 3-week and 52-week interim killing of our current 2-year study of POT fibers, with MWCNT-7 as a positive control and r-nTiO2 as a non-fibrous titanium dioxide control. Male F344 rats were administered 0.5 ml vehicle, 62.5 µg/ml and 125 µg/ml r-nTiO2 and POT fibers, and 125 µg/ml MWCNT-7 by TIPS every other day for 2 weeks (eight doses: total doses of 0.25 and 0.50 mg/rat). At 1 year, POT and MWCNT-7 fibers induced significant increases in alveolar macrophage number, granulation tissue in the lung, bronchiolo-alveolar cell hyperplasia and thickening of the alveolar wall, and pulmonary 8-OHdG levels. The 0.5 mg POT- and the MWCNT-7-treated groups also had increased visceral and parietal pleura thickness, increased mesothelial cell PCNA labeling indices, and a few areas of visceral mesothelial cell hyperplasia. In contrast, in the r-nTiO2-treated groups, none of the measured parameters were different from the controls.

Potassium octatitanate fibers induce persistent lung and pleural injury and are possibly carcinogenic in male Fischer 344 rats.

Potassium octatitanate fibers (K2 O·8TiO2 , POT fibers) are widely used as an alternative to asbestos. We investigated the pulmonary and pleural toxicity of POT fibers with reference to 2 non-fibrous titanium dioxide nanoparticles (nTiO2 ), photoreactive anatase (a-nTiO2 ) and inert rutile (r-nTiO2 ). Ten-week-old male F344 rats were given 0.5 mL of 250 µg/mL suspensions of POT fibers, a-nTiO2 , or r-nTiO2 , 8 times (1 mg/rat) over a 15-day period by trans-tracheal intrapulmonary spraying (TIPS). Rats were killed at 6 hours and at 4 weeks after the last TIPS dose. Alveolar macrophages were significantly increased in all treatment groups at 6 hours and at 4 weeks. At week 4, a-nTiO2 and r-nTiO2 were largely cleared from the lung whereas a major fraction of POT fibers were not cleared. In the bronchoalveolar lavage, alkaline phosphatase activity was elevated in all treatment groups, and lactate dehydrogenase (LDH) activity was elevated in the a-nTiO2 and POT groups. In lung tissue, oxidative stress index and proliferating cell nuclear antigen (PCNA) index were elevated in the a-nTiO2 and POT groups, and there was a significant elevation in C-C motif chemokine ligand 2 (CCL2) mRNA and protein in the POT group. In pleural cavity lavage, total protein was elevated in all 3 treatment groups, and LDH activity was elevated in the a-nTiO2 and POT groups. Importantly, the PCNA index of the visceral mesothelium was increased in the POT group. Overall, POT fibers had greater biopersistence, induced higher expression of CCL2, and provoked a stronger tissue response than a-nTiO2 or r-nTiO2 .

Environmental life cycle assessment of seafood production: A case study of trawler catches in Tunisia.

The Gulf of Gabes is one of the most productive fishery areas in the southern Mediterranean Sea. It is archetypal of an ecosystem in which the effects of fisheries are most pronounced. Demersal trawling is the main fishing activity in the Gulf of Gabes. Life Cycle Assessment (LCA) was applied to assess the environmental performance landing 1t of seafood with wooden demersal trawlers in the Gulf of Gabes. Impact categories included in the study were abiotic depletion potential (ADP), acidification potential (AP), eutrophication potential (EP), global warming potential (GWP), ozone depletion potential (ODP), photochemical oxidant formation potential (POFP), human toxicity potential (HTP), marine eco-toxicity potential (METP), terrestrial eco-toxicity potential (TETP), land occupation potential (LOP), and total cumulative energy demand (TCED). Demersal trawlers were classified based on their impact intensity. Results showed that 70% of the vessels had relatively low impacts. Impact intensity was proportional to the amount of fuel consumed to land 1t of seafood. Ships that fished less had the highest impacts per ton, due to lower fishing effort and catch per unit effort. This is likely to typify vessels that target highly valuable species such as shrimp. Onboard vessel activities contributed most to different environmental impacts (AP, EP, GWP and POFP), related to the high energy use of this fishery. Several impacts (ADP, ODP, METP, LOP and TCED) were associated mainly with fuel and lubricating oil production. Therefore, improvements must focus on minimizing fuel consumption. LCA is a valuable tool for assessing how to increase environmental sustainability of demersal trawling and it can help stakeholders identify the main operational issues that require improvement.