Felix Effah, Sadiya Bi Shaikh, David Chalupa
et al.
Electronic cigarettes (e-cigs) use electrical resistance (sub-ohm to above-ohm) to heat coils that vaporize e-liquids for the generation of aerosols, which are inhaled directly. The effect of varying coil resistances on the production of toxicants in e-liquid aerosols remains unclear. In this study, we examined how varying coil resistance (0.6 Ω (sub-Ohm), 0.9 Ω (intermediate-Ohm), or 1.4 Ω (above-Ohm)) affects the physicochemical properties of e-cig aerosols, including mass median aerodynamic diameter (MMAD), size distribution, heavy metals, acellular reactive oxygen species (ROS), and volatile organic compounds (VOCs) in PG/VG, PG/VG with nicotine, and commercially available menthol and tobacco-flavored e-liquids. Further, we examined how varying coil resistance affected cytotoxicity and inflammatory mediator (interleukin-6) release by normal human bronchial epithelial cells (NHBE) that were exposed to e-cig aerosols at the air-liquid interface (ALI), a unique non-animal new methodological approach for vaping studies. Sub-ohm coils led to increased MMAD, while above-ohm coils produced finer particles and contained higher levels of aluminium, lead, chromium, and nickel, depending on the e-liquid formulation. Additionally, above-ohm coils significantly increased ROS generation in aerosols from commercially available flavored e-liquids, which in turn led to greater cellular ROS production in ALI-cultured NHBE. Both sub-ohm and above-ohm coils induced similar interleukin-6 release. Conversely, for cytotoxicity, PG/VG and menthol aerosols from sub- and intermediate-Ohm coils significantly raised LDH release. Overall, sub-ohm coils produce larger aerosols, above-ohm coils contain higher concentrations of heavy metals and ROS, whose toxicological impacts are reflected by the physiologically relevant in vitro lung models at the air-liquid interface.
Hormesis, a biphasic dose–response phenomenon, occurs when a low dose of a substance stimulates biological activity of an organism while higher doses inhibit it. Glyphosate, the most widely used herbicide in the United States, has frequently been associated with hormetic effects in certain plant species. The objective of this study was to evaluate whether sublethal doses of glyphosate could enhance soybean growth and yield under field conditions. A two-year experiment was conducted using a split-plot design, with glyphosate applied in seven sublethal doses (0–324 g ae ha−1) at three soybean growth stages: second trifoliate (V2), beginning of flowering (R1), and beginning of pod formation (R3). Growth-related parameters, yield components, and soybean grain yield were evaluated. Exposure to glyphosate at the V2 and R1 stages resulted in hormetic responses, with increase of up to 23% in plant dry matter, 26% in leaf area index, and approximately 60% in the number of branches per plant. No stimulatory effects were observed following R3 exposure. The doses associated with hormesis ranged from 0.65 to 107 g ae ha−1, depending on the response and soybean growth stage. Despite increased growth and biomass accumulation, no enhancement in yield components or soybean grain yield was observed. This study provides field-based evidence of glyphosate hormesis in soybean, contributing to a broader understanding of its agronomic implications and highlighting the complex nature of hormetic responses in agricultural systems.
BackgroundWork-related musculoskeletal disorders (WMSDs) are considered to be one of the biggest health problems in the workplace, seriously affecting the productivity and quality of life of the working population. Long working hours may associate with WMSDs, and leisure-time physical activity (LTPA) is beneficial for WMSDs. However, the independent and combined effects of these two factors on WMSDs remain poorly understood. ObjectiveTo explore the independent and joint relationships between long working hours, leisure time physical activity (LTPA), and WMSDs, and to provide a basis for prevention and intervention of WMSDs. MethodsA cross-sectional survey was conducted among 1227 frontline workers from multiple secondary industry companies in Nanchong City in 2023 using cluster random sampling. Demographic characteristics information, weekly working hours, LTPA, personal health behaviors, and occupational factors were collected through questionnaires. The Chinese version of Musculoskeletal Disorders Questionnaire was used to assess WMSDs. χ2 test and logistic regression were used to analyze the relationships between long working hours and/or LTPA and WMSDs. ResultsA total of 1227 workers were surveyed with a mean age of (41.3±9.3) years and 855 (69.7%) were male and 372 (30.3%) were female. Among then, 855 (69.7%) workers reported working >40 h per week, and 254 (20.7%) reported working ≥ 55 h per week; 561 (45.7%) reported no LTPA and 192 (15.6%) reported high LTPA. The overall positive rate of WMSDs was 57.4%. The positive rate of WMSDs was 71.3% in those working ≥55 h per week, which was significantly higher than those in the other groups (51.3%-58.2%, P<0.05). Comparison among the positive rate of WMSDs in the weekly working 41-48 h group (54.4%), the 49-54 h group (58.2%), and the ≤40 h group (51.3%) showed no statistically significant difference (P>0.05). The positive rate of WMSDs was higher in workers with no LTPA (59.0%)/low LTPA (58.9%) than in those with high LTPA (49.0%) (P<0.05). The logistic regression models showed that after adjusting gender, age, work experience, income per month, night shift, industry, prolonged fixed posture, prolonged repetition, smoking and alcohol drinking, compared with weekly working ≤40 h, the risk of WMSDs was higher in those with extra-long working hours (≥55 h·week−1 ) (OR=2.155, 95%CI: 1.504, 3.088), whereas those with high LTPA had a lower risk of WMSDs (OR=0.614, 95% CI: 0.432, 0.874 ). The combination of no LTPA and extra-long working hours (≥55 h·week−1) and low LTPA and extra-long working hours (≥55 h·week−1) showed associations with WMSDs, with 2.360 and 2.049 times higher risk of WMSDs than that of the combination of no LTPA and standard working hours (≤40 h ·week−1) respectively (P<0.05), whereas the combination of high LTPA and long working hours was not observed statistical significance (P>0.05). ConclusionExtra-long working hours and/or LTPA show different associations with the risk of WMSDs. Extra-long working hours are significantly positively associated with the risk of WMSDs, whereas high LTPA is significantly negatively associated with the risk of WMSDs. The combination of extra-long working hours with no or low LTPA is associated with elevated risk of reporting WMSDs, whereas no statistical significance is observed for the high LTPA-long work hours combination.
Nihal Yaman Artunç, Anıl Yirün, Gizem Yıldıztekin
et al.
Speech delay is a common developmental concern. Environmental pollutants like phthalates, recognized as endocrine disruptors, may be a risk factor. We aimed to investigate the relationship between phthalates and speech delay. The study comprised 50 children with isolated speech delay and 40 healthy children of similar ages. Children were assessed for speech delay risk factors and phthalate exposure sources. High-pressure liquid chromatography examined plasma di-(2-ethylhexyl) phthalate (DEHP), mono-(2-ethylhexyl) phthalate (MEHP) and dibutyl phthalate (DBP) levels. DEHP, MEHP, and DBP levels varied between study and control groups: 0.377 (0.003–1.224 µg/ml), 0.212 (0.007–1.112 µg/ml) (p = 0.033), 0.523 (0.031–2.477 µg/ml), 0.152 (0.239–2.129 µg/ml) (p < 0.001), and 0.395 (0.062–1.996 µg/ml) and 0.270 (0.006–0.528) (p = 0.004). Multiple linear regression was used to adjust phthalate levels and speech delay risk factors. DEHP levels were did not differ significantly between the groups (p = 0.233), whereas MEHP and DBP levels were considerably higher in the study group (p < 0.001). The statistically significant rise in plasma phthalate levels in children with speech delay implies phthalate exposure may be a risk factor, but further epidemiological research is needed.
Abstract Background Tin mine dust (MD), a by-product of tin mining and rock drilling, is a significant contributor to miners’ pneumoconiosis. This aerosolized dust is a complex mixture of mineral components, including potentially toxic heavy metals such as arsenic, which may contribute to the development of pneumoconiosis and lung cancer. This study investigates the inhalation toxicity of tin MD samples on pulmonary cells using an Air-Liquid Interface (ALI) exposure model. Results MD-A was characterized by high arsenic content, exceeding 30%. In contrast, the elemental composition of MD-B and MD-C was predominantly composed of calcium, magnesium, and aluminum. In the toxicity study, key toxicological endpoints (cell viability, cytotoxicity, pro-inflammatory markers, and cell barrier function) were systematically assessed, and real-time monitoring of the cell-delivered MD particles (MD-A, MD-B, MD-C, and silica) concentrations was achieved using QCM. MD-A significantly enhanced the proliferation ability of 16HBE and Calu-3 cells compared to other particulate matters, indicating arsenic-containing MD promotes cell proliferation. MD-A resulted in an increase in IL-1β mRNA expression in 16HBE cells; elevations in IL-1β, IL-6, IL-8, TNF-α, and CCL2 mRNA were observed in Calu-3 cells. Additionally, treatment with four different particles significantly increased the mRNA expression of MUC5AC in both cell types. Immunofluorescence staining demonstrated alterations in the typical morphology of epithelial cells exposed to arsenic-containing MD and silica particles. In this study, it was shown that four types of particles delivered via suspension to the same in vitro model can induce differing levels of cytotoxicity and proinflammatory responses. The differences in results underscore the specific effects of the inherent physicochemical attributes of particles on biological interactions. Conclusions Under identical particle size conditions, in vitro studies on inhalation toxicity reveal that the chemical composition of particulate matter causes varying degrees of toxic damage to cells. This study utilizes an advanced in vitro method to assess the inhalation hazards of tin MD particles by integrating the ALICE system. The chemical complexity of tin MD, particularly its significant arsenic content, requires special attention and thorough evaluation.
Traditional medicine is the primary healthcare source for most people in developing nations, with herbal remedies used for disorders of metabolism. The study assessed how Andrographis paniculata aqueous extract affected male Wistar rats' cardiotoxicity caused by dichlorvos. Three groups consisting of eighteen rats were randomly assigned (n = 6). Group A was not exposed to dichlorvos, as it served as (control). Group B was exposed to dichlorvos (1 ml/day for 1 week) via inhalation. Group C was exposed to dichlorvos (as in B) and treated with Andrographis paniculata aqueous extract (500 mg/kg body weight) orally for 28 days. Exposure to dichlorvos caused alteration in cardiovascular variables and electrocardiac function (blood pressure, heart rate and electrocardiogram), cardiac injury (lactate dehydrogenase and creatine kinase), oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GPx)), cardiac inflammation (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and apoptosis (caspase 3). However, treatment with Andrographis paniculata aqueous extract improved the antioxidant defense system, attenuated electrocardiac impairment, and prevented damage to cardiac musculature. Andrographis paniculata aqueous extract exhibited cardioprotective potential.
Teratogenic and embryotoxic effect of diclofenac sodium (DS) on different developmental stages of the chick-embryos was investigated by examining different parameters such as its mortality rate, hatching, morphological measurements, weighing its internal organs and calculation of different indices. Experiment was divided into four trials with different dose (0.1 mL, 0.2 mL, 0.3 mL in groups A, B, and C, respectively and group D received 0.3 mL saline solution (0.9% NaCl) and group E remained un-injected) administration and observation. Results of first and second trial showed statistically (p<0.01) significant difference in bodyweight, body-length, forelimb and hindlimb length between experimental and control groups. In third trial, diclofenac sodium administration showed a statistically (p<0.01) significant difference in the bodyweight, body-length, forelimb, hindlimb length, liver weight, egg weight (EE ratio) and kidney somatic index (KSI). The beak-size, heart weight, kidney weight, cardiac somatic index (CSI) and hepato somatic index (HSI) were not significant (p>0.05) when compared with the control groups. In trial 4, forelimb, hindlimb length, heart weight, CSI and HSI were statistically (p<0.01) significant. Body-length and liver weight were significant (p<0.05). While bodyweight, beak size, kidney weight and KSI were non-significant (p>0.05). The mortality rate was increased with increase dose of DS and also affected the hatching. DS effect on chick embryos can be applied to humans because the early development of mammals and birds are closely related. So, it was concluded that DS should be used with caution during pregnancy especially during first trimester of pregnancy.
Chronic respiratory disease is among the most common non-communicable diseases, and particulate materials (PM) are a major risk factor. Meanwhile, evidence of the relationship between the physicochemical characteristics of PM and pulmonary toxicity mechanism is still limited. Here, we collected particles (CPM) from the air of a port city adjacent to a cement factory, and we found that the CPM contained various elements, including heavy metals (such as arsenic, thallium, barium, and zirconium) which are predicted to have originated from a cement plant adjacent to the sampling site. We also delivered the CPM intratracheally to mice for 13 weeks to investigate the pulmonary toxicity of inhaled CPM. CPM-induced chronic inflammatory lesions with an increased total number of cells in the lung of mice. Meanwhile, among inflammatory mediators measured in this study, levels of IL-1β, TNF-α, CXCL-1, and IFN-γ were elevated in the treated group compared with the controls. Considering that the alveolar macrophage (known as dust cell) is a professional phagocyte that is responsible for the clearance of PM from the respiratory surfaces, we also investigated cellular responses following exposure to CPM in MH-S cells, a mouse alveolar macrophage cell line. CPM inhibited cell proliferation and formed autophagosome-like vacuoles. Intracellular calcium accumulation and oxidative stress, and altered expression of pyrimidine metabolism- and olfactory transduction-related genes were observed in CPM-treated cells. More interestingly, type I-LC3B and full-length PARP proteins were not replenished in CPM-treated cells, and cell cycle changes, apoptotic and necrotic cell death, and caspase-3 cleavage were not significantly detected in cells exposed to CPM. Taken together, we conclude that dysfunction of alveolar macrophages may contribute to CPM-induced pulmonary inflammation. In addition, given the possible transformation of heart tissue observed in CPM-treated mice, we suggest that further study is needed to clarify the systemic pathological changes and the molecular mechanisms following chronic exposure to CPM.
The aim of this safety study in mice was to determine in vivo toxicity and biodistribution potential of a single and multiple doses of L-glutamic acid-g-p(HEMA) polymeric nanoparticles as a drug delivery system. The single dose did not cause any lethal effect, and its acute oral LD50 was >2.000 mg/kg body weight (bw). Multiple doses (25, 50, or 100 mg/kg bw) given over 28 days resulted in no significant differences in body and relative organ weights compared to control. These results are supported by biochemical and histological findings. Moreover, nanoparticle exposure did not result in statistically significant differences in micronucleus counts in bone marrow cells compared to control. Nanoparticle distribution was time-dependent, and they reached the organs and even bone marrow by hour 6, as established by ex vivo imaging with the IVIS® spectrum imaging system. In conclusion, L-glutamic acid-g-p(HEMA) polymeric nanoparticles appear biocompatible and have a potential use as a drug delivery system.
Abbas Ali, Farhan Mahmood Shah, Jane Manfron
et al.
Essential oils from five <i>Baccharis</i> species were screened for their toxicity and biting deterrence/repellency against yellow fever mosquito, <i>Aedes aegypti</i> (L.), and imported fire ants, including <i>Solenopsis invicta</i> Buren (RIFA), <i>Solenopsis richteri</i> Forel (BIFA) and their hybrids (HIFA). <i>Baccharis microdonta</i> DC. and <i>B. punctulata</i> DC. at 10 µg/cm<sup>2</sup> showed biting deterrence similar to DEET, <i>N</i>, <i>N</i>-diethyl-<i>meta</i>-toluamide at 25 nmol/cm<sup>2</sup>, whereas the repellency of <i>B. pauciflosculosa</i> DC., <i>B. sphenophylla</i> Dusén ex Malme and <i>B. reticularioides</i> Deble & A.S. Oliveira essential oils was significantly lower than DEET against mosquitoes. Two major compounds from the active essential oils, kongol and spathulenol, also exhibited biting deterrence similar to DEET against mosquitoes. The highest toxicity exhibited against mosquitoes was by <i>Baccharis punctulata</i> essential oil (LC<sub>50</sub> = 20.4 ppm), followed by <i>B. pauciflosculosa</i> (LC<sub>50</sub> = 31.9 ppm), <i>B. sphenophylla</i> (LC<sub>50</sub> = 30.8 ppm), <i>B. microdonta</i> (LC<sub>50</sub> = 28.6 ppm), kongol (LC<sub>50</sub> = 32.3 ppm), spathulenol (LC<sub>50</sub> = 48.7 ppm) and <i>B. reticularioides</i> essential oil (LC<sub>50</sub> = 84.4 ppm). <i>Baccharis microdonta</i> essential oil showed repellency against RIFA, BIFA and HIFA at 4.9, 4.9 and 39 µg/g, respectively. <i>Baccharis microdonta</i> essential oil also showed toxicity with LC<sub>50</sub> of 78.9, 97.5 and 136.5 µg/g against RIFA, BIFA and HIFA, respectively, at 24 h post treatment.
Abstract Background The objective of this article is to observe the expression of Wnt-induced secreted proteins-1 (WISP1) in paraquat (PQ)-induced pulmonary fibrosis (PF) to explore the role of WISP1. Methods Healthy individuals were included in the control group. Patients who had acute lung injury or PF were included in the PF group. Venous blood samples were collected from the patients on days 1 and 3 following PQ poisoning to detect the expression levels of the WISP1 gene and protein concentration. Any changes in the patients’ blood gas analysis index were reviewed. In addition, chest computed tomography (CT) and x-ray images were observed to evaluate the relationship between WISP1 expression and disease severity. Results The expression of the WISP1 gene and the serum WISP1 protein concentration were higher in patients with PQ poisoning combined with PF than in patients without PF (P < 0.01). Serum PQ concentration was positively correlated with WISP1 gene expression (r = 0.621, P < 0.01), and serum WISP1 protein concentration (r = 0.596, P < 0.01) was considered a risk factor [odds ratio (OR) = 4.356, P < 0.05] for PQ-induced PF. Concurrently, the results of the adjusted and non-adjusted OR value for WISP1 gene expression and WISP1 protein concentration on day 1 was, respectively, as follows: OR = 12.797, 95% confidence interval (CI) (2.478–66.076), P = 0.002, OR’ = 11.353, P = 0.005; and OR = 1.545, 95% CI (1.197–1.995), P = 0.001, OR’ = 1.487, P = 0.003. The CT scan of a 20-year-old male with PQ-induced PF (20 ml) was observed, and it showed a typical hyaline-like lesion in the lungs on day 22 after poisoning; on day 33 after poisoning, the lungs showed localised consolidation combined with air bronchography. Conclusion The expression of WISP1 was higher in the patients with PQ-induced PF compared with the patients without PF. Accordingly, WISP1 plays an important role in PQ-induced PF.
Gasem Mohammad Abu-Taweel, Hani Manssor Albetran, Mohsen Ghaleb Al-Mutary
et al.
Silver nanoparticles (Ag-NPs) can easily cross through the blood-testis barrier and encourage reproductive dysfunction. This study investigated the protective effects of yttrium oxide nanoparticles (YO-NPs) on sexual behavior and spermatotoxicity induced by Ag-NPs in male mice. Twenty-four male mice were separated into four groups and injected intraperitoneally once a week as the following: group I (Ag-NPs at the dose of 40 mg/kg), group II (YO-NPs at the dose of 40 mg/kg), group III (Ag + YO NPs at the doses of 40 mg/kg, each) and group IV (control; distilled water). After 35 days of the injections, the sexual behavior, oxidative parameters in testis, sperm parameters, serum testosterone, apoptotic germ cells and testicular histology were evaluated. Our findings showed that Ag-NPs decreased the weight of the reproductive organs, sexual behavior, oxidative defense parameters, sperm count and motility of male mice. In addition, the apoptotic cells in testicular cross-sections and TBARS level increased after Ag-NPs exposure when compared to other groups. However, the YO-NPs had protective effects in the studied parameters of testicles and minimized the Ag-NPs toxicity in male mice. In conclusion, the results revealed that the toxicity of Ag-NPS altered testicular functions in male mice that were effectively ameliorated by YO-NPs.
Durvanei A. Maria, Sonia Elisabete A.L. Will, Rosemary V. Bosch
et al.
Amblyomin-X, a Kunitz-type protease inhibitor, is a recombinant protein that selectively induces apoptosis in tumor cells and promotes tumor reduction in vivo in melanoma animal models. Furthermore, Amblyomin-X was able to drastically reduce lung metastasis in a mice orthotopic kidney tumor model. Due to its antitumor activity, Amblyomin-X potential to become a new drug is currently under investigation, therefore the aim of the present study was to perform preclinical assays to evaluate Amblyomin-X toxicity in healthy mice. Exploratory toxicity assays have shown that treatment with 512 mg/kg of Amblyomin-X lead to animal mortality, therefore two groups of treatment were evaluated in the present work: in the acute toxicity assay, animals were injected once with doses ranging from 4 to 256 mg/kg of Amblyomin-X, while in the subacute toxicity assay, animals were injected with 0.25, 0.57 and 1 mg/kg of Amblyomin-X daily, during 28 days. Following this treatment regimens, Amblyomin-X did not cause any mortality; moreover, toxicity signs were discrete, reversible and observed only at the higher doses, thus establishing a safety profile for administration in mice, which can be further used to determine the dose translation of this novel drug candidate for treatment in other species. Keywords: Amblyomin-X, Kunitz-type inhibitor, Toxicity, Preclinical
Koustav Ganguly, Dariusch Ettehadieh, Swapna Upadhyay
et al.
Abstract Background The death toll associated with inhaled ambient particulate matter (PM) is attributed mainly to cardio-vascular rather than pulmonary effects. However, it is unclear whether the key event for cardiovascular impairment is particle translocation from lung to circulation (direct effect) or indirect effects due to pulmonary particle-cell interactions. In this work, we addressed this issue by exposing healthy mice via inhalation and intra-arterial infusion (IAI) to carbon nanoparticles (CNP) as surrogate for soot, a major constituent of (ultrafine) urban PM. Methods Equivalent surface area CNP doses in the blood (30mm2 per animal) were applied by IAI or inhalation (lung-deposited dose 10,000mm2; accounting for 0.3% of lung-to-blood CNP translocation). Mice were analyzed for changes in hematology and molecular markers of endothelial/epithelial dysfunction, pro-inflammatory reactions, oxidative stress, and coagulation in lungs and extra-pulmonary organs after CNP inhalation (4 h and 24 h) and CNP infusion (4 h). For methodological reasons, we used two different CNP types (spark-discharge and Printex90), with very similar physicochemical properties [≥98 and ≥95% elemental carbon; 10 and 14 nm primary particle diameter; and 800 and 300 m2/g specific surface area] for inhalation and IAI respectively. Results Mild pulmonary inflammatory responses and significant systemic effects were observed following 4 h and 24 h CNP inhalation. Increased retention of activated leukocytes, secondary thrombocytosis, and pro-inflammatory responses in secondary organs were detected following 4 h and 24 h of CNP inhalation only. Interestingly, among the investigated extra-pulmonary tissues (i.e. aorta, heart, and liver); aorta revealed as the most susceptible extra-pulmonary target following inhalation exposure. Bypassing the lungs by IAI however did not induce any extra-pulmonary effects at 4 h as compared to inhalation. Conclusions Our findings indicate that extra-pulmonary effects due to CNP inhalation are dominated by indirect effects (particle-cell interactions in the lung) rather than direct effects (translocated CNPs) within the first hours after exposure. Hence, CNP translocation may not be the key event inducing early cardiovascular impairment following air pollution episodes. The considerable response detected in the aorta after CNP inhalation warrants more emphasis on this tissue in future studies.
Arsenic and nicotine exposure has been a major health concern globally. Individually both these toxicants increase the risk to various diseases including cancers. However, limited information exists on the co-exposure. In this study, we evaluate the effects of their individual and combined exposure and if co-exposure to these toxicants might have a synergism or antagonism. Male rats were exposed to a very low dose of arsenic (25 ppm in drinking water) or nicotine (0.25 mg/kg, sub-cutaneously) for a period of 5 months and post exposure various biochemical variables indicative of oxidative stress and apoptosis evaluated. Almost all glutathione linked enzymes showed marked alteration in individual as well as co-exposure treated groups. While serum creatinine and apoptosis indicator, lactate dehydrogenase (LDH) were significantly increased in both treatments, an additive effect was noted in co-exposure group. A similar trend was also seen in brain and liver but not in kidneys. Gene expression studies showed marked reduction in catalase, Cu-Zn SOD, GST, there was a significant up regulation in Bax, caspase 3 in various tissues along with urinary 8-OHdG levels, indicative of DNA damage and apoptosis. Interestingly, a decrease in liver arsenic concentration was noted in co-exposed group compared to arsenic alone exposed group. In conclusion, the present study suggests that arsenic and nicotine exhibited significant toxicity during individual exposure whereas co-exposure to these toxins showed variable conditions (indicative of both synergism and antagonism) in male rats.
Gabriele Riva, Simona Baronchelli, Laura Paoletta
et al.
Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common malignant brain tumor. Current therapies provide a median survival of 12–15 months after diagnosis, due to the high recurrence rate. The failure of current therapies may be due to the presence, within the tumor, of cells characterized by enhanced self-renewal capacity, multilineage differentiation potential and elevated invasive behavior, called glioma stem cells (GSCs). To evaluate the pharmacological efficacy of selected drugs on six GSC lines, we set up a multiple drug responsivity assay based on the combined evaluation of cytomorphological and functional parameters, including the analysis of polymorphic nuclei, mitotic index and cell viability. In order to understand the real pharmacological efficacy of the tested drugs, we assigned a specific drug responsivity score to each GSC line, integrating the data produced by multiple assays. In this work we explored the antineoplastic effects of paclitaxel (PTX), an inhibitor of microtubule depolymerization, utilized as standard treatment in several cancers, and of valproic acid (VPA), an inhibitor of histone deacetylases (HDACs) with multiple anticancer properties. We classified the six GSC lines as responsive or resistant to these drugs, on the basis of their responsivity scores. This method can also be useful to identify the best way to combine two or more drugs. In particular, we utilized the pro-differentiating effect of VPA to improve the PTX effectiveness and we observed a significant reduction of cell viability compared to single treatments.
The present study was aimed to study the acute and subacute toxicity studies with orally administered 50% ethanolic leaves extract of Ocimum sanctum Linn (OSE). In acute toxicity tests, four groups of mice (n=6/group/sex) were orally treated with doses of 200, 600, and 2000 mg/kg, and general behavior, adverse effects, and mortality were recorded for up to 14 days. In subacute toxicity study, rats received OSE by gavage at the doses of 200, 400, and 800 mg/kg/day (n=6/group/sex) for 28 days, and biochemical, hematological, and histopathological changes in tissues (liver, kidney, spleen, heart, and testis/ovary) were determined. OSE did not produce any hazardous symptoms or death and CNS and ANS toxicities in the acute toxicity test. Subacute treatment with OSE did not show any change in body weight, food and water consumption, and hematological and biochemical profiles. In addition, no change was observed both in macroscopic and microscopic aspects of vital organs in rats. Our result showed that Ocimum sanctum extract could be safe for human use.
Background: Caustic substance ingestion is known for causing a wide array of gastrointestinal and systemic complications. In Russia, ingestion of acetic acid is a major problem which annually affects 11.2 per 100,000 individuals. The objective of this study was to report and analyze main complications and outcomes of patients with 70% concentrated acetic acid poisoning. Methods: This was a retrospective study of patients with acetic acid ingestion who were treated at Sverdlovsk Regional Poisoning Treatment Center during 2006 to 2012. GI mucosal injury of each patient was assessed with endoscopy according to Zargar’s scale. Data analysis was performed to analyze the predictors of stricture formation and mortality. Results: A total of 400 patients with median age of 47 yr were included. GI injury grade I was found in 66 cases (16.5%), IIa in 117 (29.3%), IIb in 120 (30%), IIIa in 27 (16.7%) and IIIb in 70 (17.5%). 11% of patients developed strictures and overall mortality rate was 21%. Main complications were hemolysis (55%), renal injury (35%), pneumonia (27%) and bleeding during the first 3 days (27%). Predictors of mortality were age 60 to 79 years, grade IIIa and IIIb of GI injury, pneumonia, stages “I”, “F” and “L” of kidney damage according to the RIFLE scale and administration of prednisolone. Predictors of stricture formation were ingestion of over 100 mL of acetic acid and grade IIb and IIIa of GI injury. Conclusion: Highly concentrated acetic acid is still frequently ingested in Russia with a high mortality rate. Patients with higher grades of GI injury, pneumonia, renal injury and higher amount of acid ingested should be more carefully monitored as they are more susceptible to develop fatal consequences.
Andrew R. Humpage, Aurélie Ledreux, Stella Fanok
et al.
Abstract Paralytic shellfish poisons (PSPs) are produced by freshwater cyanobacteria and pose a threat to human and animal drinking-water supplies. The wide range of toxin analogues (and the likelihood that further analogues remain to be discovered) means that chromatographic methods are not always reliable indicators of toxicity. Although the mouse bioassay remains the method of choice in the seafood industry, its use is increasingly being questioned on ethical grounds. The cell-based Neuro-2A neuroblastoma toxicity assay is an alternative bioassay validated for testing shellfish extracts, so it was of interest to determine its applicability with the different suite of toxin analogues produced by cyanobacteria. Cyanobacterial bloom samples from Australia, Brazil, and France were assayed using the neuroblastoma assay, liquid chromatography—tandem mass spectrometry (LC-MS/MS), high-performance liquid chromatography with postcolumn derivatization and fluorescence detection, and the Jellett Rapid Test for PSP™. To assess interlaboratory variability, the neuroblastoma assay was set up in laboratories in Paris (France) and Adelaide (Australia). Neuroblastoma and chromatographic methods gave comparable results except in the case of the neurotoxic Brazilian samples: LC-MS/MS did not detect the putative new PSPs contained in these samples. Inter- and intralaboratory variability of the neuroblastoma assay was typical of biological assays but no greater than that found for interassay variability between different chromatographic determinations. The batch of Jellett Rapid Tests for PSP used did not yield quantitative results. Overall, the neuroblastoma assay was useful as a screening assay for determination of toxicity caused by saxitoxin neurotoxins in freshwater cyanobacteria, having the advantage of being sensitive to unidentified toxins that currently cannot be quantified by chromatographic means.