Toxic Manifestations Research Articles

The c-Fos/AP-1 inhibitor inhibits sulfur mustard-induced chondrogenesis impairment in zebrafish larvae

Sulfur mustard (SM, dichlorodiethyl sulfide) is a potent erosive chemical poison that can cause pulmonary lung, skin and eye disease complications in humans. Currently, there is no designated remedy for SM, and its operation's toxicological process remains unidentified. This work employed zebrafish as a model organism to investigate the toxic manifestations and mechanisms of exposure to SM, aiming to offer novel insights for preventing and treating this condition. The results showed that SM caused a decrease in the survival rate of the zebrafish larvae (LC50 = 2.47 mg/L), a reduction in the hatching rate, an increase in the pericardial area, and small head syndrome. However, T-5224 (a selective inhibitor of c-Fos/activator protein) attenuated the reduction in mortality (LC50 = 2.79 mg/L), the reduction in hatching rate, and the worsening of morphological changes. We discovered that SM causes cartilage developmental disorders in zebrafish larvae. The reverse transcription-quantitative polymerase chain reaction found that SM increased the expression of inflammation-related genes (IL-1β, IL-6, and TNF-α) and significantly increased cartilage development-related gene expression (fosab, mmp9, and atf3). However, the expression of sox9a, sox9b, and Col2a1a was reduced. The protein level detection also found an increase in c-fos protein expression and a significant decrease in COL2A1 expression. However, T-5224,also and mitigated the changes in gene expression, and protein levels caused by SM exposure. The results of this study indicate that SM-induced cartilage development disorders are closely related to the c-Fos/AP-1 pathway in zebrafish.

Mining Real-World Big Data to Characterize Adverse Drug Reaction Quantitatively: Mixed Methods Study.

Adverse drug reactions (ADRs), which are the phenotypic manifestations of clinical drug toxicity in humans, are a major concern in precision clinical medicine. A comprehensive evaluation of ADRs is helpful for unbiased supervision of marketed drugs and for discovering new drugs with high success rates. In current practice, drug safety evaluation is often oversimplified to the occurrence or nonoccurrence of ADRs. Given the limitations of current qualitative methods, there is an urgent need for a quantitative evaluation model to improve pharmacovigilance and the accurate assessment of drug safety. In this study, we developed a mathematical model, namely the Adverse Drug Reaction Classification System (ADReCS) severity-grading model, for the quantitative characterization of ADR severity, a crucial feature for evaluating the impact of ADRs on human health. The model was constructed by mining millions of real-world historical adverse drug event reports. A new parameter called Severity_score was introduced to measure the severity of ADRs, and upper and lower score boundaries were determined for 5 severity grades. The ADReCS severity-grading model exhibited excellent consistency (99.22%) with the expert-grading system, the Common Terminology Criteria for Adverse Events. Hence, we graded the severity of 6277 standard ADRs for 129,407 drug-ADR pairs. Moreover, we calculated the occurrence rates of 6272 distinct ADRs for 127,763 drug-ADR pairs in large patient populations by mining real-world medication prescriptions. With the quantitative features, we demonstrated example applications in systematically elucidating ADR mechanisms and thereby discovered a list of drugs with improper dosages. In summary, this study represents the first comprehensive determination of both ADR severity grades and ADR frequencies. This endeavor establishes a strong foundation for future artificial intelligence applications in discovering new drugs with high efficacy and low toxicity. It also heralds a paradigm shift in clinical toxicity research, moving from qualitative description to quantitative evaluation.

H-ras-targeted genetic therapy remarkably surpassed docetaxel treatment in inhibiting chemically induced hepatic tumors in rats

AimsHepatocellular carcinoma (HCC) is still a leading cause of cancer-related death worldwide. But its chemotherapeutic options are far from expectation. We here compared H-ras targeted genetic therapy to a commercial docetaxel formulation (DXT) in inhibiting HCC in rats. Main methodsAfter the physicochemical characterization of phosphorothioate-antisense oligomer (PS-ASO) against H-ras mutated gene, the PS-ASO-mediated in vitro hemolysis, in vivo hepatic uptake, its pharmacokinetic profile, tissue distribution in some highly perfused organs, its effect in normal rats, antineoplastic efficacy in carcinogen-induced HCC in rats were evaluated and compared against DXT treatment. Mutated H-ras expression by in situ hybridization, hep-par-I, CK-7, CD-15, p53 expression patterns by immunohistochemical methods, scanning electron microscopic evaluation of hepatic architecture, various hepatic marker enzyme levels and caspase-3/9 apoptotic enzyme activities were also carried out in the experimental rats. Key findingsPS-ASO showed low in vitro hemolysis (<3 %), and had a sustained PS-ASO blood residence time in vivo compared to DTX, with a time-dependent hepatic uptake. It showed no toxic manifestations in normal rats. PS-ASO distribution was although initially less in the lung than liver and kidney, but at 8 h it accumulated more in lung than kidney. Antineoplastic potential of PS-ASO (treated for 6 weeks) excelled in inhibiting chemically induced tumorigenesis compared to DTX in rats, by inhibiting H-ras gene expression, some immonohistochemical modulations, and inducing caspase-3/9–mediated apoptosis. It prevented HCC-mediated lung metastatic tumor in the experimental rats. SignificancePS-ASO genetic therapy showed potential to inhibit HCC far more effectively than DXT in rats.

Molecular mechanism of nanomaterials induced liver injury: A review.

The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications, spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics. Consequently, humans encounter nanomaterials through diverse exposure routes, giving rise to potential health considerations. Noteworthy among these materials are silica and specific metallic nanoparticles, extensively utilized in consumer products, which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver. This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity, drawing insights from both in vitro and in vivo studies. Primarily, the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation. Additionally, we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials, emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.

Side effects and efficacy of low-dose amiodarone in rhythm disorders

Amiodarone is one of the most widely used antiarrhythmic drugs, which is the most effective drug for maintaining sinus rhythm.&amp;nbsp;&amp;nbsp; Taking this drug correlates with side effects such as pulmonary toxicity, thyroid dysfunction, neurotoxicity, hepatotoxicity, and skin manifestations. In addition, in some cases, amiodarone remains as a first-line therapy to maintain sinus rhythm. The side effects of amiodarone depend on the dose and duration of the drug. Systematic reviews and meta-analyses have shown the safety profile of a low dose of amiodarone, defined as 200 mg and a very low dose of amiodarone 100 mg. Due to the use of catheter ablation, the use of a low dose of amiodarone is sufficient. In this literature review, we have cited the side effects of a low dose of amiodarone. In addition, although there is evidence of a safer low-dose spectrum, it is not free from side effects and needs to develop an algorithm for early detection of adverse events, as well as studying the effectiveness according to modern research methods, such as an implantable heart monitor, which in turn is of undoubted interest.

Podophyllotoxin via SIRT1/PPAR /NF-κB axis induced cardiac injury in rats based on the toxicological evidence chain (TEC) concept

BackgroundThe study of cardiotoxicity of drugs has become an important part of clinical safety evaluation of drugs. It is commonly known that podophyllotoxin (PPT) and its many derivatives and congeners are broad-spectrum pharmacologically active substances. Clinical cardiotoxicity of PPT and its derivatives has been raised, basic research on the mechanism of cardiotoxicity remains insufficient. PurposeIn present study, our group's innovative concept of toxicological evidence chain (TEC) was applied to reveal the cardiac toxicity mechanism of PPT by targeted metabolomics, TMT-based quantitative proteomics and western blot. MethodsThe injury phenotype evidence (IPE) acquired from the toxicity manifestations, such as weight and behavior observation of Sprague-Dawley rat. The damage to rat hearts were assessed through histopathological examination and myocardial enzymes levels, which were defined as Adverse Outcomes Evidence (AOE). The damage to rat hearts was assessed through histopathological examination and myocardial enzyme levels, which were defined as evidence of adverse outcomes.Overall measurements of targeted metabolomics based on energy metabolism and TMT-based quantitative proteomics were obtained after exposure to PPT to acquire the Toxic Event Evidence (TEE). The mechanism of cardiac toxicity was speculated based on the integrated analysis of targeted metabolomics and TMT-based quantitative proteomics, which was verified by western blot. ResultsThe results indicated that exposure to PPT could result in significant elevation of myocardial enzymes and pathological alterations in rat hearts. In addition, we found that PPT caused disorders in cardiac energy metabolism, characterized by a decrease in energy metabolism fuels. TMT-based quantitative proteomics revealed that the PPAR (Peroxisome proliferators-activated receptor) signaling pathway needs further study. It is worth noting that PPT may suppress the expression of SIRT1, subsequently inhibiting AMPK, decreasing the expression of PGC-1α, PPARα and PPARγ. This results in disorders of glucose oxidation, glycolysis and ketone body metabolism. Additionally, the increase in the expression of p-IKK and p-IκBα, leads to the nuclear translocation of NF-κB p65 from the cytosol, thus triggering inflammation. ConclusionThis study comprehensively evaluated cardiac toxicity of PPT and initially revealed the mechanism of cardiotoxicity,suggesting that PPT induced disorders of energy metabolism and inflammation via SIRT1/PPAR/NF-κB axis, potentially contributing to cardiac injury.

Expanding Predictive Capacities in Toxicology: Insights from Hackathon-Enhanced Data and Model Aggregation.

In the realm of predictive toxicology for small molecules, the applicability domain of QSAR models is often limited by the coverage of the chemical space in the training set. Consequently, classical models fail to provide reliable predictions for wide classes of molecules. However, the emergence of innovative data collection methods such as intensive hackathons have promise to quickly expand the available chemical space for model construction. Combined with algorithmic refinement methods, these tools can address the challenges of toxicity prediction, enhancing both the robustness and applicability of the corresponding models. This study aimed to investigate the roles of gradient boosting and strategic data aggregation in enhancing the predictivity ability of models for the toxicity of small organic molecules. We focused on evaluating the impact of incorporating fragment features and expanding the chemical space, facilitated by a comprehensive dataset procured in an open hackathon. We used gradient boosting techniques, accounting for critical features such as the structural fragments or functional groups often associated with manifestations of toxicity.

Establishment of stellate ganglion block in mice

BackgroundThere have been no reports on the successful implementation of stellate ganglion block (SGB) in mice.ObjectivesThis study aims to investigate a new method for implementing SGB in mice by placing them in a supine position with abducted upper limbs and touching the trachea and sternoclavicular joint with the hand.MethodsFifty BABL/C mice, 8–10 weeks, were selected and randomly divided into four groups: control group (n = 5); SGB-R group (n = 15); SGB-L group (n = 15); and SGB-L + R (group n = 15). SGB was administered with 0.15% ropivacaine solution in a volume of 0.1 mL. The control group received equal volumes of saline. Horner's syndrome, heart rate, and complications such as brachial plexus block, vascular injury, pneumothorax, local anesthetic toxicity, and death were observed.ResultsHorner's syndrome developed in 100% of SGB surviving mice; no difference was seen in the time to onset (100.4 ± 13.4 vs 96.7 ± 12.4, mean ± SD, seconds) and duration (264.1 ± 40.5 vs 296.3 ± 48.0, mean ± SD, min) of Horner's syndrome in the left and right SGB (P > 0.05). Compared with the control group (722 [708–726], median [IQR], bpm), the heart rate was significantly slowed down in the right SGB (475 [451.5–491], median [IQR], bpm) (P < 0.05). While the heart rate was slowed down after performing the left SGB, the difference was not statistically significant (P > 0.05). The overall complication rate was 18.4%, with a brachial plexus block rate of 12.3%, a vascular injury rate of 4.6%, and a mortality rate of 1.5%, as well as no local anesthetic toxicity (includes bilateral implementation of SGB) or pneumothorax manifestations were found.ConclusionsThis method allows for the successful implementation of SGB in a mouse model.

Metabolic effects of a submaximal dose of pink salt and monosodium glutamate in experimental rats

Background & objectivesPink salt and monosodium glutamate (MSG) are two typical food additives used in cooking to enhance flavour. However, excessive use of them has been associated to a variety of metabolic problems, including weight gain and hyperglycemia. The current study aimed to assess the metabolic changes caused by submaximal dosages of MSG and pink salt in experimental rats. MethodsTwenty-four 120–150 g Wister rats of both sexes were divided into three groups: control, pink salt-treated (0.8 g/kg daily for three weeks), and MSG-treated (3.6 g/kg daily for three weeks). The body weight, amount of food and water consumed, and blood glucose levels of animals were measured and recorded as indicators of their metabolic changes. Furthermore, after salt treatments at intervals such as week 1, week 2, and week 3, the survival rate and general toxicity manifestations were determined. The results were statistically analysed using one-way ANOVA, with p < 0.05 being considered significant. ResultsThe study found that the group given a submaximal dose of MSG gained significantly more weight (p < 0.05), consumed more food and water, and had higher blood glucose levels than the control. Ninety percent of the MSG therapy group survived by the end of the third week, however, they suffered from negative effects like abdominal distention, respiratory problems, ptosis, and subcutaneous swelling. On the other hand, the consumption of food and drink was significantly (p < 0.05) increased upon the administration of pink salt. Only little changes were observed in the body weight, blood sugar levels, and general features (such as subcutaneous swelling, change in bowel colour, and loose stools). Additionally, it was shown that the survival rate remained unchanged, particularly after week 3. ConclusionAccording to study findings, MSG may induce metabolic issues, increasing the chance of death. While there was no discernible metabolic aberration linked to pink salt. Further research is required to fully understand the mechanism and consequences of these taste enhancers on the host system before pink salt can be deemed safe.

Clinical, Histopathological, and Radiological Profile of Patients Presenting With Thyroid Malignancies Among the Kerala Population.

Thyroid cancer, though relatively uncommon among all cancer types, stands as the primary form of endocrine tumor. Over the last 20 years, there has been a significant uptick in its occurrence. Papillary thyroid carcinoma (PTC), which is well-differentiated, emerges as the dominant subtype,in regions where iodine levels are deemed adequate. The study aimed to study the clinicopathological profile of patients diagnosed with thyroid malignancies at the Muslim Educational Society (MES) Medical CollegePerinthalmanna. This is a retrospective study undertaken at the MES Medical College by the Department of General Surgery and Endocrine Surgery. The study focuses on patients who have been diagnosed with thyroid cancer through a biopsy. Case sheets of all those patients diagnosed with thyroid malignancy were referred from the Medical Records Library to collect the relevant medical and sociodemographic data. This data was entered in the proforma, which was transferred to the Excel sheet and processed inIBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York, United States). The study included predominantly middle-aged individuals (40-60 years), with 22 (55%) falling within this age range, followed by 14 (35%) aged between 20 and 40 years, and only four (10%) above 60 years. Female patients constituted 82.5% of the study group. Most cases presented with swelling lasting less than six months 23 (57.5%), while only four (10%) had swelling lasting more than five years. Compression symptoms were rare, with only three (7.5%) experiencing dysphagia or dyspnea. Pain was reported in two (5%) of the cases. Hypothyroidism, toxic manifestations, or hoarseness were observed in one (2.5%) of the patients. Regarding swelling characteristics, most were greater than 4 cm in size (29, 72%) and firm in consistency (25, 62.5%). Nodular surfaces were present in 19 (47.5%) of the cases, while 38 (95%) of the swellings were mobile. Palpable lymph nodes were noted in 13 (32.5%) of cases. Radiologically, hypoechoic lesions were observed in 26 (65%) of cases, with microcalcification in 29 (72.5%) and peripheral vascularity in 31 (77.5%). Papillary carcinoma was the most common histological type (34, 85%), with medullary and follicular carcinomas accounting for five (12.5%) and one (2.5%), respectively. An association was found between the duration of swelling and histological type (p = 0.05) and between the mobility of swelling and histological type (p < 0.05). However, no significant associations were observed between imaging findings and histological type (p > 0.05). The gender distribution did not show a statistically significant association with histological type. The findings of the study revealed a statistically insignificant association between age, gender, clinical features, and the histological type of thyroid malignancy. Additionally, there was no statistically significant association between the histological type of thyroid malignancy and the size or type of surface or consistency of thyroid swelling or ultrasonographic findings of the swelling like echogenicity, microcalcification, increased peripheral vascularity, or loss of peripheral halo.

Prediction of radiation complications by determining the blood oxidation processes in cervical cancer patients under chemoradiotherapy

Background. Radiotherapy (RT) is one of the principal methods in cancer management, and its administration in oncology practice is much wider nowadays because of the increased incidence of newly diagnosed cancer cases with wide spread and aggressive course of tumor process, and also in view of organ-sparing strategies in the combined treatment. However, the radiation reactions, especially local ones in rectum or bladder, can’t be completely avoided even using the most advanced radiotherapy facilities and dosimetry planning. Therefore, at present time not only technical modernization, but also the progress in radiobiology should be considered. Given the cytotoxic properties of some anticancer drugs, they are used in the combined therapy of cervical cancer (CC) to receive a radiosensitizing effect on the malignant cells. In particular, cisplatin inhibits reparative processes by affecting the enzymes involved in restoring the integrity of DNA or chromosome structure. Administration of the combined radiation and chemotherapy leads not only to an increase in the percentage of tumor regression, but also to an increase in the number of radiation injuries to healthy tissues. Therefore, prediction of such injuries, research and development of means of their prevention and treatment in the regimen of chemoradiotherapy (ChRT) of CC is extremely urgent and remains an unsolved problem to date. Purpose. Development of personalized approaches in ChRT in CC patients by studying its efficiency, assessing its toxicity, and predicting radiation injuries according to the data of blood oxidative processes in patients. Materials and methods. The combined radiotherapy (CRT) and ChRT were administered to the stage IIB–IIIB CC (T2b-3bN0-1M0) patients (n = 105) at the National Cancer Institute. Patients aged 25–75 years were divided into two groups: the study group and the comparison group. Complex clinical examination was conducted prior to treatment featuring the assay of tumor parameters, state of «critical organs». At the stage I of CRT regimen, conformal irradiation on pelvis minor was delivered at the electron linear accelerator «Clinac 2100 CD» with an energy of 6 MeV per area of pelvis minor with single radiation dose (SRD) of 2.0 Gy and total radiation dose (TRD) of up to 46 Gy. Patients in the study group received the CRT along with administration of chemoradiomodifying agent cisplatin 40 mg/m2 once a week intravenously (drip-feed), patients in the comparison group received no radiomodifier. At the stage II of CRT regimen, an intracavitary brachytherapy (ICBT) was administered to the CC patients at the gamma therapy equipment «AGAT-VU» using 60Co (high dose rate – HDR) sources in the mode of SRD of 5 Gy 2 times a week, 7–8 fractions, and TRD of 35–40 Gy at p. A. The TRD in total was 77–89 Gy at the p. A and 54–60 Gy at p. B. Administration of cisplatin 40 mg/m2 at the stage II of CRT was continued in the study group once a week intravenously (drip-feed), total dose of up to 200–300 mg. Radiobiological studies were performed on the peripheral blood samples from the CC patients (n = 39) before and after ChRT. The control group consisted of healthy women of the appropriate age. Blood was sampled into the special 6 ml Vacutainer type tubes with an anticoagulant according to the manufacturer’s instructions (BioReagent). Intensity of generation of О• 2– in PBL was evaluated by the chemiluminescence method using the lucigenin indicator, which, as a result of reacting with О• 2–, emits light quanta recorded by the device. Measurements were carried out on the AutoLumat LB 953 device (Germany) with appropriate corrections made to the methodology. Results and discussion. Effectiveness of CRT in CC patients was evaluated according to regression of the primary tumor focus (clinical, ultrasound, MRI or SCT data) and presence/absence of toxic manifestations of treatment following the criteria for evaluating the solid tumors regression according to the Response Evaluation Criteria in Solid Tumor (RECIST). Conclusions. The results of the study indicate that chemoradiotherapy contributes to pronounced regression of cervical tumors and does not increase toxicity of treatment due to timely correction of complications.

Cutaneous manifestations of systemic methotrexate toxicity

Cutaneous manifestations of systemic methotrexate toxicity

Black pepper (Piper nigrum L.) essential oil counteracts dexamethasone-induced hepatic injury via modulating PGC-1α/ PPAR-α pathway in rats

We previously characterized the volatile compounds of black pepper (Piper nigrum) essential oil (BPEO) and demonstrated its mitigating effect against dexamethasone-induced pancreatic damage. Herein, we investigated the protective effect of the oil against dexamethasone-induced hepatotoxicity in rats and pinned the possible underlying mechanisms. In the in vivo experiment, male Wistar rats were divided into five groups. The first group served as the normal control receiving a saline solution (Control). The second group was subjected to hepatic damage through dexamethasone exposure (Dexa) at 10 mg/kg. The third group received both dexamethasone and metformin (Met) at a dose of 50 mg/kg. The remaining two groups were exposed to dexamethasone along with black pepper oil administration at low and high doses (BPEO, 0.5 mL/kg and 1 mL/kg). We showed that BPEO offset toxicity manifestations, as indicated by reducing monocyte infiltration, hepatocyte degeneration and vacuolation, and reduction of ALT and AST levels. Moreover, relative to the dexamethasone-treated rats, BPEO declined the number of PGC-1α positive hepatocytes and activated the expression of PPAR-α in the liver. BPEO showed comparable hepatoprotective potency to the standard drug, metformin, especially at the higher dose tested (1 mL/kg). This study showcases the promising potential of BPEO in thwarting dexamethasone-induced adverse effects on the liver by alleviating hepatic biomarkers hikes and preventing histopathological changes and fibrosis. Finally, it opens a new avenue on the potential role of BPEO in modulating steroid-induced hepatic injury through the PGC-1α/ PPAR-α pathway.

Dermatological toxicity in the treatment of malignant tumors in children: A review

Modern antitumor drugs have high antitumor activity. But only a number of them realize their antitumor effect in a targeted manner with minimal manifestations of concomitant toxicity. Damage to the skin and mucous membranes as part of the toxic effects of chemotherapy not only reduces the quality of life of patients, but can lead to disruption of the patient’s nutritional status, infection, and generalization of the infectious process with the development of sepsis. This review describes the major drugs that have dermatological toxicity, the main clinical variants of dermatological toxicity, methods for their prevention and treatment.

Intracerebral hemorrhage in methanol toxicity patients during COVID-19 pandemic: case report and review of literature.

The aim of this study is to examine the clinical and imaging manifestations of methanol toxicity during the COVID-19 pandemic, as well as to review existing studies on this topic.The most common cause of methanol intoxication is methanol-adulterated liquor. The primary metabolite of methanol, formic acid, is responsible for pathological changes. Symptoms typically present within 6-24h of consumption and can include visual disturbances, acute neurological symptoms, and gastrointestinal issues. During the initial year of the COVID-19 pandemic, methanol poisoning cases increased significantly. In this study, We present six different patients with methanol intoxication and their clinical and imaging features. In the literature review, the most common clinical presentation was loss of consciousness and obtundation and the other was vision loss. CT scan findings showed bilateral putaminal necrosis and hemorrhage in 55% of methanol toxicity patients. Methanol intoxication, causing bilateral putaminal involvement and a 50% mortality rate in intracerebral hemorrhage patients, warrants urgent toxicological analysis due to potential putaminal hemorrhage.

Reaction Pathways of Oxidative Transformation of the Radioprotector Quercetin

Quercetin is one of the most promising natural polyphenolic radioprotective compounds. This property is based on its radical-scavenging activity and high antioxidant capacity, in the manifestation of which the products of oxidative degradation of quercetin play a significant role. The formation of specific metabolites during the oxidation of quercetin can determine not only its radioprotective properties, but also toxic manifestations. The purpose of this article is to summarize previously obtained data regarding the reaction pathways of oxidative transformation of quercetin. Materials and methods. We used publicly available scientific publications dedicated to the study of quercetin transformation processes. The method of analysis is descriptive. The discussion of the results. A review of scientific works dedicated to oxygen oxidation, radical-initiated oxidation, electrochemical and enzymatic oxidation is presented, possible transformation products of quercetin and the mechanisms of their formation are given. The most characteristic oxidation pathways of quercetin are determined by the chemical structure of the rings, which exhibit specific reactivity. The influence of the solvent composition on the oxidation products during the autoxidation of quercetin was revealed, while the radical and electrochemical models of oxidation differ in the presence of polymer adducts. Once in a living organism, quercetin can bind free radicals, thereby preventing the harmful effects of radiation, that is, it has the properties of a radioprotector. Conclusions. Quercetin can be considered as a potential radioprotector due to its ability to bind free radicals formed in the biological fluids of living organisms exposed to radiation.

Clinical, radiological varieties and diagnostic facilities of smear negative pulmonary tuberculosis in HIV uninfected patients, a retrospective analysis

Abstract Context Pulmonary tuberculosis (TB) is still one of the most common infectious diseases in the world. It is the second leading cause of death from an infectious disease worldwide, after the human immunodeficiency virus (HIV). WHO estimated TB incidence in Egypt in 2019 at 12 000. Purpose The aim of this study was to make a re-look at the epidemiological characteristics, clinical presentations, and radiological findings of patients with smear-negative pulmonary tuberculosis (SNPT) in non-HIV infected patients. Methods Retrospective analysis was performed including non-HIV patients with smear negative TB, with studying of demographics, symptoms, radiological patterns, and radiological distribution and the used diagnostic methods. Statistical analysis The demographic, clinical, and radiological data were gathered together, tabulated, and statistically analyzed. Data analysis was performed by Statistical Package for Social Science (SPSS – version 22). Results 74 smear-negative TB, non-HIV, age mean 47.17 ± 12.8 SD, 72.2% were males, DM was present in (39.2%), fever in (83.3%), weight loss in (61.1%), cough in (59.7%), consolidation pattern in (63.8%), cavities in (36.1%), an apical segment of right upper lobe in (41.9%), bronchoscopic lavage with Ziehl–Neelsen stain (BAL ZN) diagnosed (52.7%) of sputum negative cases. Conclusion Common variables among recorded cases were male sex, middle-aged individuals, Diabetes Mellitus (DM), toxic manifestation, an involved right apical segment of the upper lobe, consolidation and cavitary patterns, and most cases were diagnosed by bronchoscopic lavage with Ziehl–Neelsen.

Перспективные подходы неинвазивной диагностики субклинической кардиоваскулярной токсичности химиотерапии

Objective: to present data on available modern methods of diagnosis of subclinical cardiovascular toxicity of chemotherapy. Modern strategies of treatment of cancer allow to stable remission and increase life expectancy of patients, the success of which is balanced by increased mortality of cancer patients due to the development of side effects of chemotherapy, the most prognostically significant of which are cardiovascular complications. Early diagnosis of cardiovascular toxicity in cancer patients is a “new” priority for collaboration of oncologists and cardiologists, as the development or progression of an already existing heart disease has a significant impact on the duration and quality of life of cancer patients. This review, at the current level of development of medical science, presents methods of diagnosis and monitoring of subclinical cardiovascular toxicity against the background of chemotherapy. Use for the diagnosis of subclinical cardiotoxicity such modern methods of visualization as two- and three-dimensional echocardiography, echocardiography with the definition of global longitudinal deformation of the myocardium - spectrum-tracking echocardiography, myocardial work, magnetic resonance tomography, definition of diastolic dysfunction allows to identify manifestations of cardiovascular toxicity in earlier terms, thereby affecting the prognosis and quality of life in cancer patients receiving chemotherapy treatment.

Cardiovascular events after cancer immunotherapy as oncologic emergencies: Analyses of 610 head and neck cancer patients treated with immune checkpoint inhibitors.

Cardio-oncology and emergency medicine are closely collaborative, as many cardiac events in cancer patients require evaluation and treatment in the emergency department (ED). Immune checkpoint inhibitors (ICIs) have become a common treatment for patients with head and neck cancer (HNC). However, the immune-related adverse events (irAEs) from ICIs can be clinically significant. We reviewed and analyzed cardiovascular diagnoses among HNC patients who received ICI during the period April 1, 2016-December 31, 2020 in a large tertiary cancer center. Demographics, clinical and cancer-related data were abstracted, and billing databases were queried for cardiovascular disease (CVD)-related diagnosis using International Classification of Disease-version10 (ICD-10) codes. We recorded receipt of care at the ED as one of the outcome variables. A total of 610 HNC patients with a median follow-up time of 12.3 months (median, interquartile range = 5-30 months) comprised our study cohort. Overall, 25.7% of patients had pre-existing CVD prior to ICI treatment. Of the remaining 453 patients without pre-existing CVD, 31.5% (n = 143) had at least one CVD-related diagnosis after ICI initiation. Tachyarrhythmias (91 new events) was the most frequent CVD-related diagnosis after ICI. The time to diagnosis of myocarditis from initiation of ICI occurred the earliest (median 2.5 months, 1.5-6.8 months), followed by myocardial infarction (3.7, 0.5-9), cardiomyopathy (4.5, 1.6-7.3), and tachyarrhythmias (4.9, 1.2-11.4). Patients with myocarditis and tachyarrhythmias mainly presented to the ED for care. The use of ICI in HNC is still expanding and the spectrum of delayed manifestation of ICI-induced cardiovascular toxicities is yet to be fully defined in HNC survivors.

A case of successful treatment for pancreatic cancer (observation from practice)

Objective: In recent years, researchers are increasingly considering the possibility of using immunotherapeutic drugs as part of the antitumor treatment of such patients, which can potentiate the effectiveness of cytostatic therapy. Particular attention is drawn to the combination of interferon- and recombinant tumor necrosis factor-thymosin--1, which can activate an antitumor immune response, stimulate apoptosis of tumor cells, have a direct antiproliferative effect, cause destruction of neoplasm vessels, and stimulate tumor tissue necrosis.Methods: This paper presents the results of a follow-up of 24 patients with histologically confirmed pancreatic carcinoma. Some patients received combined immunotherapy as the only method of treatment, when the possibilities of standard therapy were exhausted, there were serious complications of anticancer treatment, severe concomitant pathology that did not allow the planned treatment to be carried out in full, or when the patient refused to use cytostatics. In other cases, the introduction of immunotherapeutic drugs was carried out against the background of other antitumor treatment of the 1st or 2nd line, prescribed in connection with the progression of the disease.Results: As a result of the use of a combination of interferon- and recombinant tumor necrosis factor-thymosin--1, patients noted an improvement in the tolerability of the main antitumor treatment, additional manifestations of toxicity from the use of immunodrugs were not observed. The existence of an average positive correlation (r=0.57, p=0.0004) between the level of TNF and the value of the Karnofsky index was revealed, indicating that an increase in the content of TNF is accompanied by an increase in the functional activity of patients. According to computed tomography data, in accordance with the RECIST 1.1 criteria, one patient had a partial response of the tumor to the treatment, in 9 - stabilization of the tumor process, in other cases, observation continues.Conclusions: The data presented are of a pilot nature. One of the available observations is presented in this paper as a clinical case.