Evaluation of genotoxicity induced by exposure to antineoplastic drugs in lymphocytes of oncology nurses and pharmacists

ABSTRACT: The hazards of handling antineoplastic drugs have been raised and discussed in several studies. Introduction of new antineoplastics together with abuse of safety standards have contributed to the exposure risk for personnel who handle these substances. Interactions of antineoplastic drugs with biological structures vary according to the drug(s) and the individual's genetic susceptibility. This study was carried out to evaluate the genome damage induced by exposure to antineoplastic drugs in nurses (n = 20) and pharmacists (n = 18) working in the Oncology Department of Tanta Cancer Center. Thirty subjects matched in age, gender and smoking habit were selected as controls. Both chromosomal aberration analysis and micronucleus assay were used to evaluate genome damage in peripheral blood lymphocytes of the study subjects. The numbers of aberrant lymphocytes, as well as chromosomal aberration and micronuclei frequencies, were significantly increased in exposed personnel in comparison to matched controls. Compared with pharmacists, nurses showed notably higher level of chromosome damage. On the other hand, no significant difference in micronuclei frequency was observed between nurses and pharmacists. Correlation analyses pointed to the influence of age and duration of occupational exposure on the level of chromosome damage among exposed subjects. The results of this study confirmed that handling antineoplastic drugs without appropriate precautions imposed a genotoxic risk for exposed healthcare workers. These results address the need for regular biomonitoring of exposed personnel. In addition, they call attention to the need for proper implementation of intervention measures aiming to eliminate or significantly reduce worker exposure and prevent untoward biological effects

Association between genetic polymorphism, severity, and treatment response among COVID-19 infected Egyptian patients

Background: The world has been suffering from the Coronavirus Disease-2019 (COVID-19) pandemic since the end of 2019. The COVID-19-infected patients differ in the severity of the infection and the treatment response. Several studies have been conducted to explore the factors that affect the severity of COVID-19 infection. One of these factors is the polymorphism of the angiotensin converting enzyme 2 (ACE-2) and the type 2 transmembrane serine protease (TMPRSS2) genes since these two proteins have a role in the entry of the virus into the cell. Also, the ACE-1 regulates the ACE-2 expression, so it is speculated to influence the COVID-19 severity.Objective: This study investigates the relationship between the ACE-1, ACE-2, and TMPRSS2 genes single nucleotide polymorphism (SNPs) and the COVID-19 disease severity, treatment response, need for hospitalization, and ICU admission in Egyptian patients.Patients and Methods: The current study is an observational prospective, cohort study, in which 109 total COVID-19 patients and 20 healthy volunteers were enrolled. Of those 109 patients, 51 patients were infected with the non-severe disease and were treated in an outpatient setting, and 58 suffered from severe disease and required hospitalization and were admitted to the ICU. All 109 COVID-19 patients received the treatment according to the Egyptian treatment protocol.Results: Genotypes and allele frequencies among severe and non-severe patients were determined for ACE-1 rs4343, TMPRSS2 rs12329760, and ACE-2 rs908004. The GG genotype and the wild allele of the ACE-2 rs908004 and the mutant allele of the ACE-1 rs4343 were significantly more predominant in severe patients. In contrast, no significant association existed between the TMPRSS2 rs12329760 genotypes or alleles and the disease severity.Conclusion: The results of this study show that the ACE-1 and ACE-2 SNPs can be used as severity predictors for COVID-19 infection since also they have an effect on length of hospitalization

Automated image analysis system for renal filtration barrier integrity of potassium bromate treated adult male albino rat

Potassium bromate (KBrO3) is a potent nephrotoxic agent that leads to a significant decrease in the activities of renal antioxidant capacity, antioxidant loss and restoration of the renal dysfunction. Several measurements are used to examine the kidney status, including the base width of the foot, the slit pore diameter, and the glomerular basement membrane thickness of the kidney. In this work, morphometric analysis based on image processing is carried out to assess the filtration barrier integrity parameters, which indicates the degree of recovery against the nephrotoxic effect of the KBrO3 on the renal cortex of adult male albino rat and assesses the capability of the renal cortex to recover after its cessation. The morphometric methods based proposed image analysis system enabled the identification of the renal status of different groups, namely the control, potassium bromate affected, and the recovered groups, according to the variation of the measured parameters is a powerful tool. The proposed image analysis system provided a radical geometric morphometrics, which includes morphological operations and structuring element processes in order to identify the glomerular filtration barrier and the feet for further measurements in each case study. The results established that the average lengths of the feet in the histological microscopic images are 465.2397 nm, 278.189 nm, and 393.2347 nm for the control, KBrO3 affected rats and the recovered rats; respectively

Consensus evidence-based clinical practice recommendations for the diagnosis and treat-to-target management of osteoporosis in chronic kidney disease stages G4-G5D and post-transplantation: An initiative of Egyptian Academy of Bone Health

The aim of this study was to reach a consensus on an updated version of the recommendations for the diagnosis and Treat-to-Target management of osteoporosis that is effective and safe for individuals with chronic kidney disease (CKD) G4-G5D/kidney transplant. Delphi process was implemented (3 rounds) to establish a consensus on 10 clinical domains: (1) study targets, (2) risk factors, (3) diagnosis, (4) case stratification, (5) treatment targets, (6) investigations, (7) medical management, (8) monitoring, (9) management of special groups, (10) fracture liaison service. After each round, statements were retired, modified, or added in view of the experts' suggestions, and the percent agreement was calculated. Statements receiving rates of 7-9 by more than 75% of experts' votes were considered as achieving consensus. The surveys were sent to an expert panel ( = 26), of whom 23 participated in the three rounds (2 were international experts and 21 were national). Most of the participants were rheumatologists (87%), followed by nephrologists (8.7%), and geriatric physicians (4.3%). Eighteen recommendations, categorized into 10 domains, were obtained. Agreement with the recommendations (rank 7-9) ranged from 80 to 100%. Consensus was reached on the wording of all 10 clinical domains identified by the scientific committee. An algorithm for the management of osteoporosis in CKD has been suggested. A panel of international and national experts established a consensus regarding the management of osteoporosis in CKD patients. The developed recommendations provide a comprehensive approach to assessing and managing osteoporosis for all healthcare professionals involved in its management. [Abstract copyright: Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.

Investigation of the existence and uniqueness of extremal and positive definite solutions of nonlinear matrix equations

Abstract We consider two nonlinear matrix equations X r ± ∑ i = 1 m A i ∗ X δ i A i = I $X^{r} \pm \sum_{i = 1}^{m} A_{i}^{*}X^{\delta_{i}}A_{i} = I$ , where − 1 < δ i < 0 $- 1 < \delta_{i} < 0$ , and r, m are positive integers. For the first equation (plus case), we prove the existence of positive definite solutions and extremal solutions. Two algorithms and proofs of their convergence to the extremal positive definite solutions are constructed. For the second equation (negative case), we prove the existence and the uniqueness of a positive definite solution. Moreover, the algorithm given in (Duan et al. in Linear Algebra Appl. 429:110-121, 2008) (actually, in (Shi et al. in Linear Multilinear Algebra 52:1-15, 2004)) for r = 1 $r = 1$ is proved to be valid for any r. Numerical examples are given to illustrate the performance and effectiveness of all the constructed algorithms. In Appendix, we analyze the ordering on the positive cone P ( n ) ‾ $\overline{P(n)}$

AICAR Ameliorates Non-Alcoholic Fatty Liver Disease via Modulation of the HGF/NF-κB/SNARK Signaling Pathway and Restores Mitochondrial and Endoplasmic Reticular Impairments in High-Fat Diet-Fed Rats

Non-alcoholic fatty liver disease (NAFLD) is a global health problem characterized by altered lipid and redox homeostasis, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. The AMP-dependent kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) has been shown to improve the outcome of NAFLD in the context of AMPK activation, yet the underlying molecular mechanism remains obscure. This study investigated the potential mechanism(s) of AICAR to attenuate NAFLD by exploring AICAR’s effects on the HGF/NF-κB/SNARK axis and downstream effectors as well as mitochondrial and ER derangements. High-fat diet (HFD)-fed male Wistar rats were given intraperitoneal AICAR at 0.7 mg/g body weight or left untreated for 8 weeks. In vitro steatosis was also examined. ELISA, Western blotting, immunohistochemistry and RT-PCR were used to explore AICAR’s effects. NAFLD was confirmed by steatosis score, dyslipidemia, altered glycemic, and redox status. HGF/NF-κB/SNARK was downregulated in HFD-fed rats receiving AICAR with improved hepatic steatosis and reduced inflammatory cytokines and oxidative stress. Aside from AMPK dominance, AICAR improved hepatic fatty acid oxidation and alleviated the ER stress response. In addition, it restored mitochondrial homeostasis by modulating Sirtuin 2 and mitochondrial quality gene expression. Our results provide a new mechanistic insight into the prophylactic role of AICAR in the prevention of NAFLD and its complications

Upregulation of Toll-like receptor 2 and nuclear factor-kappa B expression in experimental colonic schistosomiasis

Role of different mediators was described in the development of the granulomatous response and fibrosis observed in intestinal schistosomiasis. However, both Toll-like receptor 2 (TLR2) and nuclear factor kappa B (NF-κB) have not yet been investigated in intestinal schistosomiasis. This study aimed to characterize the role of TLR2 and NF-κB in the pathogenesis of intestinal schistosomiasis. Experimental animals were divided into two groups; group I: non-infected control group and group II: mice infected subcutaneously with S. mansoni cercariae. Colon samples were taken from infected mice, every two weeks, starting from the 6th week postinfection (PI) till 18th week PI. Samples were subjected to histopathological and immunohistochemical studies. Colon of S. mansoni infected mice showed histopathological changes in the form of mucosal degeneration, transmural mononuclear cellular infiltration and granulomas formation. Immunostained sections revealed significant increase in TLR2 and NF-κB positive cells in all layers of the colon, cells of the granuloma and those of the lymphoid follicles 10 weeks PI. All these changes decreased gradually starting from 12 weeks PI onward to be localized focally at 18 weeks PI. In conclusion, recruitment and activation of inflammatory cells to the colonic mucosa in intestinal schistosomiasis are multifactorial events involving TLR2 that can trigger the NF-κB pathways. Hence, down-regulation of both TLR2 and NF-κB could be exploited in the treatment of colonic schistosomiasis

Histological and immunohistochemical study of the effect of gold nanoparticles on the brain of adult male albino rat

AbstractGold nanoparticles (GNPs) have numerous medical applications as in biological imaging, cancer treatment and in implants (pacemakers and stents). Many conflicting results about GNPs safety and its accumulation in liver, kidney and brain were recorded. This work was carried out to study the histological effect of long period exposure to gold nanoparticle on the brain of adult male albino rat. Twenty adult male albino rats were divided into two equal groups: The first one served as a control group and the second one received 400μg/kg/day GNPs by gastric tube once daily for eight weeks. Brain specimens were collected at the end of the experiment for histological and immunohistochemical studies using caspase-3 and glial fibrillary acidic protein (GFAP). GNPs treated group revealed wide spread histological alterations and deposition of gold nanoparticle aggregates in the neurons of cerebral cortex and hippocampus and also in the epithelium of choroid plexus with hyalinization of the wall of some blood vessels and disruption of the capillaries. All these changes were associated with localized positive caspase 3 reaction. Various degrees of astrogliosis were evidenced by astrocytic proliferation and increase size of their cell body with increase number and length of their processes. It could be concluded that repeated exposure of adult male albino rats to gold nanoparticles induced its deposition in the brain in association with histological alterations and various degrees of astrogliosis

Oxidative stress predominates apoptosis during experimental hepatocellular carcinoma

Objective Hepatocellular carcinoma ranks the third among cancer deaths in the globe. Despite the fact that many strategies for diagnosing liver cancer are possible, many factors, including apoptosis, arise to interfere with cell cycle control. We initiated this study to investigate the importance of free radicals during experimental hepatocarcinogenesis, triggered by diethyl nitrosamine, against an anti-apoptotic factor, belongs to a family of oncogenes (Bcl-2). Methods Eighteen female Wistar rats were classified into two equal groups, group 1 received intraperitoneal normal saline doses, group 2 was injected with one IP dose of diethyl nitrosamine (200 mg/kg bw), 2 weeks later, they were given a single CCl4 dose (2 ml /kg b.w., IP), blood and liver tissue samples were collected after 60 days of diethyl nitrosamine dose. The Graph pad prism program was used in statistical calculations. Results The results revealed that treatment with diethyl nitrosamine + CCl4 significantly up regulated the plasma liver functions tests: aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, total bilirubin and increased alpha fetoprotein with decreased level of Bcl-2. Liver tissue showed elevation of lipid peroxide, malondialdehyde, catalase enzyme activity, with significant reduction in body weight, decreased total protein content, tissue antioxidants like glutathione S-transferase, total thiol and total antioxidant capacity, compared to control. Histological examination of liver showed an increased nuclear/cytoplasm (N/C) ratio, mitotic figures and nuclear polymorphism and microacinar formation in diethyl nitrosamine + CCl4-treated group. Conclusions Disturbed hepatocellular anti-oxidant mechanisms suppress apoptosis, reflecting failure in combating chemical hepatocarcinogenesis. Keywords liver cancer; diethyl nitrosamine; lipid peroxidation; tumor markers; Bcl-2; apoptosis

Histopathology and electron microscopy evaluation of the sildenafil effect on diabetic rats' retinae

Purpose: Although there is increasing evidence that phosphodiesterase-5 (PDE-5) inhibitors modify the effect of diabetes on different tissues, its effect on diabetic retinopathy is not well studied. Methods: Forty male Sprague–Dawley (SD) rats were divided into four groups: group I = control group that received no treatment; group II (diabetic group), in which diabetes was induced by a single streptozotocin injection; group III (sildenafil small dose, SSD), in which diabetes was similarly introduced (however, rats received daily oral 1 mg/kg sildenafil citrate (SC) for 3 months); and group IV (sildenafil large dose, SLD), which was as in group 3, but SC was 2.5 mg/kg. After 3 months, globes were removed and retinae were dissected; one globe from each rat was examined by light microscopy (LM), and the other by electron microscopy (EM). Results: In contrast to the control group, diabetic rats in group II demonstrated well-established diabetic changes in the form of capillary congestion, decreased cell population, hyaline changes of capillary walls, and degenerated nerve fiber layer by LM. Similarly, EM demonstrated photoreceptor degeneration, mitochondrial cristolysis, and vacuolated depleted cells among other features in group II. These diabetic features were less prominent in group III and nearly absent in group IV. Conclusion: SC use in the early stages of DR may prevent/delay diabetic retinopathy development or progression in diabetic rat models, an effect that seems to be dose-related