Assessment of skin sensitization potential of zinc oxide, aluminum oxide, manganese oxide, and copper oxide nanoparticles through the local lymph node assay: 5-bromo-deoxyuridine flow cytometry method.

The advent of nanotechnology has significantly spurred the utilization of nanoparticles (NPs) across diverse sectors encompassing industry, agriculture, engineering, cosmetics, and medicine. Metallic oxides including zinc oxide (ZnO), copper oxide (CuO), manganese oxide (Mn2O3), and aluminum oxide (Al2O3), in their NP forms, have become prevalent in cosmetics and various dermal products. Despite the expanding consideration of these compounds for dermal applications, their potential for initiating skin sensitization (SS) has not been comprehensively examined. An in vivo assay, local lymph node assay: 5-bromo-2-deoxyuridine-flow cytometry method (LLNA: BrdU-FCM) recognized as an alternative testing method for screening SS potential was used to address these issues. Following the OECD TG 442B guidelines, NPs suspensions smaller than 50 nm size were prepared for ZnO and Al2O3 at concentrations of 10, 25, and 50%, and Mn2O3 and CuO at concentrations of 5, 10, and 25%, and applied to the dorsum of each ear of female BALB/c mice on a daily basis for 3 consecutive days. Regarding the prediction of test substance to skin sensitizer if sensitization index (SI)≥2.7, all 4 NPs were classified as non-sensitizing. The SI values were below 2.06, 1.33, 1.42, and 0.99 for ZnO, Al2O3, Mn2O3, and CuO, respectively, at all test concentrations. Although data presented were negative with respect to adverse SS potential for these 4 NPs, further confirmatory tests addressing other key events associated with SS adverse outcome pathway need to be carried out to arrive at an acceptable conclusion on the skin safety for both cosmetic and dermal applications.

Association of immunotoxicological indices with lung cancer biomarkers in poultry, grape, and rose farming workers.

Exposure to occupational hazards like dust, pesticides, diesel emission particles, or physical hazards in the agricultural sector is known to cause adverse health effects on farm workers. Our study aimed at addressing the association of immunomodulatory status with plasma levels of lung cancer biomarkers in farming population, attempting to recognition of vulnerable farming group. Blood samples from apparently healthy 51 chicken husbandry, 19 grape orchard, and 21 rose greenhouse workers were subjected to evaluate plasma levels of two representative lung cancer biomarkers, pro-gastrin releasing peptide (Pro-GRP) and cytokeratin fragment 19 (CYFRA 21-1). Peripheral blood mononuclear cells obtained from farmers were used for natural killer (NK) cell phenotyping and cytokines (interferon-gamma, IFN-γ and interleukin-13, IL-13) profiling in the culture supernatant. Compared to the rose greenhouse farmers, the grape orchard and chicken husbandry workers revealed a significantly upregulated plasma Pro-GRP and CYFRA 21-1 level. A low proportion of NK cells was observed among the female grape orchard workers and a lowered IFN- γ:IL-13 ratio was seen in the grape and chicken husbandry workers than the rose workers. Our findings imply that grape orchard and chicken husbandry workers have more disturbed immune homeostasis implicated with augmentation in the levels of lung cancer biomarkers than the rose greenhouse workers.

Primary retroperitoneal solitary fibrous tumor: A case report.

Primary retroperitoneal masses have numerous differential diagnoses, many of which are rare entities. These can be neoplastic or nonneoplastic. Among the rare conditions are solitary fibrous tumors, which can either be benign or malignant. It is a mesenchymal, spindle-cell tumor, reported first in 1931 as a pleural tumor by Klemperer et al. A 20-year-old lady, with abdominal pain for 6 months, was diagnosed with a retroperitoneal mass on the left lower abdomen on USG which was confirmed by an MRI scan of the abdomen. The patient underwent laparoscopy-assisted excision of the mass. The final histopathological reports and immunohistochemistry reports revealed a solitary fibrous tumor. Solitary fibrous tumors (SFTs) are rare tumors in the retroperitoneum. In our search, fewer than a hundred cases have been reported. It has a characteristic "patternless pattern" in a microscopic study. Adverse outcomes of SFTs are associated with atypical features in histology, such as nuclear pleomorphism, necrosis, increased cellularity, and mitoses >4/10 HPF and size more than 10 cm. The standard of care is surgical excision with clear margins. Open surgeries have been done traditionally; we present a case where we performed the excision laparoscopically.

Polytetrafluorethylene microplastic particles mediated oxidative stress, inflammation, and intracellular signaling pathway alteration in human derived cell lines.

Microplastics (MPs) are now widely distributed across the aerial, terrestrial, and aquatic environments. Thus, exposure to MPs via the oral, inhalation, or dermal routes is inevitable. Polytetrafluoroethylene (PTFE)-MPs is mainly used for manufacturing nonstick cookware, semiconductors, and medical devices; however, their toxicity has been rarely studied. In the present study, six different human cell lines, which are representative of tissues and cells that directly or indirectly come into contact with MPs, were exposed to two different sizes of irregular shape PTFE-MPs (with an average diameter of 6.0 or 31.7 µm). PTFE-MPs-mediated cytotoxicity, oxidative stress, and changes in proinflammatory cytokine production were then evaluated. We found that the PTFE-MPs did not induce cytotoxicity under any of the experimental conditions. However, PTFE-MPs (especially average diameter of 6.0 µm) induced nitric oxide and reactive oxygen species production in all the cell lines tested. Moreover, both sizes of PTFE-MPs increased the secretion of tumor necrosis factor alpha and interleukin-6 from the U937 macrophage cell line and the A549 lung epithelial cell line, respectively. In addition, PTFE-MPs activated the MAPK signaling pathways, especially the ERK pathway, in A549 and U937 cells, and in the THP-1 dendritic cell line. We also found that the expression of the NLRP3 inflammasome was reduced in the U937 and THP-1 cell lines following treatment with the PTFE-MPs sized 31.7 µm average diameter. Furthermore, expression of the apoptosis regulator, BCL2, was markedly increased in the A549 and U937 cell lines. Thus, although PTFE-MPs exert different effects on different cell types, our findings suggest that PTFE-MPs-associated toxicity may be specifically linked to the activation of the ERK pathway, which ultimately induces oxidative stress and inflammation.

A Rare Case Report of Giant Urinary Bladder Stone Causing Recurrent Dysuria in a Woman.

Background: Large urinary bladder stones are not common and even less common in females. We report a case of large bladder stone presented with acute retention of urine in a female patient. Case Report. A 62-year-old female presented in emergency department with retention of urine for 12 hours with history of recurrent UTIs for last 1 year. She was also complaining of mild dull lower abdominal pain for last 6 months. She had no history of incontinence of urine and fever. On physical examination, hard mass was palpable on suprapubic region on palpation of abdomen. Urine culture shows Escherichia coli for which antibiotics was given. An X-ray kidney ureter bladder showed a radio-opacity in the pelvic region measuring 9 × 8 cm in size. Ultrasonography revealed bilateral mild hydronephrosis with a large bladder stone. Open cystolithotomy was performed, and the stone was taken out. Stone biochemical analysis showed predominantly urate crystals. Patient had uneventful postoperative course, and she was discharged on 4th postoperative day and was followed up for 1 months after operation. Conclusions: Large urinary bladder stones are not common and even less common in females. Clinician should have think regarding large bladder stone as a cause of recurrent lower urinary tract symptoms like dysuria and should assess renal function for proper treatment. Open cystolithotomy is choice of operation in large bladder stone.

Prediction of the skin sensitization potential of didecyldimethylammonium chloride and 3,7-dimethyl-2,6-octadienal and mixtures of these compounds with the excipient ethylene glycol through the human Cell Line Activation Test and the Direct Peptide Reactivity Assay.

In commercial products such as household deodorants or biocides, didecyldimethylammonium chloride (DDAC) often serves as an antimicrobial agent, citral serves as a fragrance agent, and the excipient ethylene glycol (EG) is used to dissolve the active ingredients. The skin sensitization (SS) potentials of each of these substances are still being debated. Moreover, mixtures of DDAC or citral with EG have not been evaluated for SS potency. The in vitro alternative assay called human Cell Line Activation Test (h-CLAT) and Direct Peptide Reactivity Assay (DPRA) served to address these issues. On three independent runs of h-CLAT, DDAC and citral were predicted to be sensitizers while EG was predicted to be a non-sensitizer and also by the DPRA. Mixtures of DDAC or citral with EG at ratios of 7:3 and 1:4 w/v were all positive by the h-CLAT in terms of SS potential but SS potency was mitigated as the proportion of EG increased. Citral and its EG mixtures were all positive but DDAC and its EG mixtures were all negative by the DPRA, indicating that the DPRA method is not suitable for chemicals with pro-hapten characteristics. Since humans can be occupationally or environmentally exposed to mixtures of excipients with active ingredients, the present study may give insights into further investigations of the SS potentials of various chemical mixtures.

Optimizing the cutoff for the identification of skin sensitizers by the HaCaSens assay: Introducing an ROC-analysis-based cutoff approach.

The worldwide restricted use of animal testing makes it challenging to identify the skin sensitizing potentials of newly manufactured products. The HaCaSens assay has shown promise as an in vitro skin sensitizing assay comparable to existing assays, and is currently under pre-validation. However, there is little agreement on how to assess the results of the assay to discriminate sensitizers from non-sensitizers as the stimulation index (SI) cutoff value was arbitrarily chosen without appropriate statistical methods. Here, we investigated the SI cutoff values in identifying sensitizers to obtain the optimal value. Sensitivities and specificities were calculated for a set of 30 test substances, and plotted in receiver operator characteristics (ROC) curves. The SI cutoff values with the highest sum of sensitivity and specificity according to LLNA data were 2.2, 1.8 and 3.0 for interleukin 1α (IL-1α), interleukin 6 (IL-6), and the combination of the two cytokines respectively. Also, the same statistical analysis of human data demonstrated optimal SI cutoff values 2.0, 2.0 and 3.2 for the same respective parameters. When considering the predictive capacity of each possible SI cutoff value determined by ROC curves, the optimal value for HaCaSens is 3.0 for the combination of IL-1α and IL-6 as it had the highest sensitivity (90.9%), specificity (75.0%) and accuracy (86.7%) based on LLNA data. Thus, we recommend the wide use of the SI cutoff value of 3.0 to ensure consistent endpoints.

Association between endotoxin levels in dust from indoor swine housing environments and the immune responses of pigs.

Indoor animal husbandry environments are inevitably contaminated with endotoxins. Endotoxin exposure is associated with various inflammatory illnesses in animals. This cross-sectional study evaluated the relationship between the degree of endotoxin exposure and the cellular and humoral immune profiles of fattening pigs. Blood samples were taken from the jugular vein of 47 pigs from ten pig farms in Korea. Whole blood cell counts and plasma immunoglobulin (Ig) classes were determined. Peripheral-blood mononuclear cells were stimulated in vitro with concanavalin A for 48 h, and cytokines released into culture supernatants were measured. The barns in which the pigs lived were assessed for endotoxin levels in the total and respirable dust by using the limulus amebocyte lysate kinetic QCL method. Low and high endotoxin exposures were defined as ≤ 30 and ＞ 30 EU/m³, respectively. Compared to pigs with low endotoxin exposure (n = 19), highly exposed pigs (n = 28) had higher circulating neutrophil and lymphocyte (particularly B cells) counts, IgG and IgE levels, interferon-gamma (IFNγ) and interleukin (IL)-4 productions, and lower IgA levels and tumor necrosis factor-alpha (TNFα) production. The IL-4, IFNγ, and TNFα levels significantly correlated with endotoxin level and/or pig age. Constant exposure of pigs to high levels of airborne endotoxins can lead to aberrant immune profiles.