Renoprotective Effect of Taxifolin in Paracetamol-Induced Nephrotoxicity: Emerging Evidence from an Animal Model.

BACKGROUND: Taxifolin (TXF) is a flavonoid found abundantly in citrus/onion. Encouraging results on its renoprotective effect have been reported in a limited number of drug-induced nephrotoxicity animal models. The present study aimed to evaluate for the first time the potential renoprotective effects of TXF in a paracetamol (PAR)-induced nephrotoxicity rat model. METHODS: Rats were divided into three equal groups (n = 6 animals per group). Group 1 (PAR group, PARG) received PAR diluted in normal saline by gavage (1000 mg/kg). Group 2 (TXF group, TXFG) received TXF diluted in normal saline by gavage (50 mg/kg) one hour after PAR administration. Group 3 (control group, CG) received normal saline. Twenty-four hours after PAR administration, all animals were sacrificed using high-dose anesthesia. Blood samples were collected and kidneys were removed. RESULTS: The serum blood urea nitrogen, creatinine levels and serum malondialdehyde levels were significantly increased in the PARG. The serum glutathione peroxidase, glutathione reductase and total glutathione levels were significantly higher in the TXFG. At the same time, the kidneys of the PARG animals demonstrated tubular epithelium swelling, distension and severe vacuolar degeneration. The kidneys of the TXFG animals showed mildly dilated/congested blood vessels. CONCLUSIONS: The TXF renoprotective effects are promising in preventing PAR-induced nephrotoxicity, mainly through antioxidant activity, and warrant further testing in future studies.

Advancing athletic assessment by integrating conventional methods with cutting-edge biomedical technologies for comprehensive performance, wellness, and longevity insights.

In modern athlete assessment, the integration of conventional biochemical and ergophysiologic monitoring with innovative methods like telomere analysis, genotyping/phenotypic profiling, and metabolomics has the potential to offer a comprehensive understanding of athletes' performance and potential longevity. Telomeres provide insights into cellular functioning, aging, and adaptation and elucidate the effects of training on cellular health. Genotype/phenotype analysis explores genetic variations associated with athletic performance, injury predisposition, and recovery needs, enabling personalization of training plans and interventions. Metabolomics especially focusing on low-molecular weight metabolites, reveal metabolic pathways and responses to exercise. Biochemical tests assess key biomarkers related to energy metabolism, inflammation, and recovery. Essential elements depict the micronutrient status of the individual, which is critical for optimal performance. Echocardiography provides detailed monitoring of cardiac structure and function, while burnout testing evaluates psychological stress, fatigue, and readiness for optimal performance. By integrating this scientific testing battery, a multidimensional understanding of athlete health status can be achieved, leading to personalized interventions in training, nutrition, supplementation, injury prevention, and mental wellness support. This scientifically rigorous approach hereby presented holds significant potential for improving athletic performance and longevity through evidence-based, individualized interventions, contributing to advances in the field of sports performance optimization.

Health risk assessment of process-related contaminants in bread.

Bread constitutes a popular and even daily component of human diet world-wide, Iran included. However, there are concerns that various processing methods such as frying and baking could result in the production of potentially a source of known carcinogens such as acrylamide (AA) and benzo(a)pyrene (BaP). The present study tried to perform a risk assessment on seven categories of bread consumers, based on age and gender, calculating the Target Hazard Quotient (THQ), Incremental Lifetime Cancer Risk (ILCR), and Margin of Exposure (MOE) related to the dietary intake of AA and BaP. AA and BaP were analyzed in 87 bread samples using LC-MS/MS and GC-MS/MS, respectively. The results indicated that more than 94% (mean concentration: 25.9 ng/g) and about 20% (mean concentration: 1.98 ng/g) of the samples were contaminated with AA and BaP, respectively. The THQ of AA intake through bread consumption for seven categories was in the following decreasing order: semi-industrial Sangak bread of Shiraz (SIS-Sh)> traditional Sangak bread of Shiraz (TS-Sh)> traditional Sangak bread of Tehran (TS-Th)> commercial bread of Tehran (C-Th). The non-neoplastic and neoplastic MOE for AA (˂10,000) indicates a high risk of exposure for all people in Tehran and Shiraz through the consumption of all tested bread. Due to the consumption of TS, SIS, and C bread, the BaP MOE for all people in Tehran and Shiraz was >10 000, which shows a low health risk for consumers. Our findings showed that ILCR for AA in seven classes of people who had TS-Sh and TS-Th was remarkably higher than ILCR for all categories that consumed the C-Th. BaP ILCR for the people who ingested TS-Th, TS-Sh, SIS-Th, and SIS-Sh was about 2-4 times higher than people who had C-Th. This study indicates that bread is the main source of AA and BaP intake in Iran, which might elevate the cancer risk.

Cardiovascular adaptations and inflammation in marathon runners.

Long-distance running has become increasingly popular. Cardiovascular adaptations to exercise are relevant to the specific sports and this is also the case in long-distance running. Significant changes regarding inflammatory and endothelial markers along with indices of oxidative stress are observed in marathon and ultra-marathon runners. However, data linking inflammatory marker levels with cardiovascular adaptations to marathon running are limited. The aim of the present study was to describe the cardiovascular adaptations observed in a group of ultra-marathon runners and the association with a series of inflammatory and endothelial markers measured in their plasma. A total of 43 ultra-marathon runners were assessed by echocardiography and a treadmill exercise test. Blood samples were used for tumor necrosis factor-α (TNF-α), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, IL-10, C-reactive protein, creatine phosphokinase (CPK) and oxidative stress indice measurements. Ultra-marathon runners who presented augmented left ventricular (LV) end diastolic diameters >55 mm had higher ADMA values (1.07±0.07 vs. 0.99±0.08 µmol/ml, P<0.01) and lower CPK values (192.5±21.3 vs. 219.1±37.3 mg/dl, P<0.05) compared with those with normal LV diameters. Runners with a moderate and severe abnormal indexed LV mass >131 g/m2 had statistically significant higher TNF-α values compared with runners, with mildly elevated and a normal LV mass indexed (16.2±1.42 vs. 14.0+1.16 pg/ml, P<0.05). Runners with an abnormal left atrial volume index (LAVI; >29 ml/m2) had higher IL-6 values compared with runners with a normal LAVI (1.09+0.19 vs. 0.99±0.08 pg/ml, P<0.05). ROC curves analysis revealed that ADMA values were able to predict an abnormal LV diameter detected by echocardiography [P<0.05; area under the curve (AUC), 0.763], while TNF-α values could predict an abnormal LV mass in marathon runners (P<0.05; AUC, 0.78). On the whole, the present study demonstrates that, in ultra-marathon runners, cardiovascular adaptations to running are characterized by a specific pattern of changes in inflammatory and endothelial markers, which in turn can be used to predict the occurrence of the observed adaptations.

Cardiotoxicity of Chemical Substances: An Emerging Hazard Class.

(1) Background: Human health risks and hazards from chemical substances are well regulated internationally. However, cardiotoxicity, is not defined as a stand-alone hazard and therefore there are no defined criteria for the classification of substances as cardiotoxic. Identifying and regulating substances that cause cardiovascular adverse effects would undoubtedly strengthen the national health systems. (2) Methods: To overcome the aforementioned gap, a roadmap is proposed for identifying regulatory criteria from animal studies and endorse legislation in order to classify substances as cardiotoxic. The roadmap consists of: (i) the identification of the appropriate animal species and strains; (ii) the identification of the lines of scientific evidence (e.g., histopathological, biochemical and echocardiographic indices etc.) from animal studies with relevance to humans; (iii) the statistical analysis and meta-analysis for each line of scientific evidence after exposure to well-established cardiotoxicants to humans (e.g., anthracyclines) in order to identify threshold values or range of normal and/ or altered values due to exposure; (iv) validation of the above described lines of evidence in animals exposed to other alleged cardiotoxic substances (e.g., anabolic androgen steroids (AAS) and pesticides); (v) establishment of mechanisms of action based on information of either known or alleged cardiotoxicants; and (vi) introduction of novel indices and in silico methods. (3) Results: Preliminary results in rats indicate a clear distinction from normal values to values measured in rats exposed to anthracyclines regarding left ventricle (LV) fractional shortening (FS) and LV ejection fraction (EF). A distinctive pattern is similarly observed for Creatine Kinase-Myocardial Band isoenzyme (CK-MB) and cardiac tissue glutathione (GSH). These findings are encouraging and indicate that there is room for targeted research to this end, and that these specific indices and biochemical markers should be further investigated in order to be developed to regulatory criteria. (4) Conclusions: Further research should be conducted by both the scientific and regulatory community that aims to clearly define the cardiotoxicity hazard caused by chemicals and develop a full set of scientific criteria.

Moderately elevated lipoprotein (a) levels are associated with an earlier need for percutaneous coronary intervention in recurrent cardiovascular disease.

A significant number of cardiovascular disease (CVD) patients, with the target lipid levels, as set by the guidelines, achieved, continue to remain at risk. In this setting, lipoprotein (Lp) a role in CVD prognosis is regaining interest. Although Lp(a) is related to the arteriosclerotic process, there is not currently an adequate amount of data for the inclusion of Lp(a) levels as a primary therapeutic target in the treatment of coronary artery disease (CAD) patients. In this framework, the current retrospective study aims to investigate the association of Lp(a) levels with the adverse cardiovascular (CV) events presented in a 10 year follow-up of CVD patients with dyslipidemia and its association with the major CV risk factors. A statistically significant reduction in Lp(a) levels was observed during the follow-up period (72.8±45.6 vs. 68.3±41.8 mg/dl; McNemar test; P<0.001). The vast majority of patients who suffered a new acute myocardial infarction during the follow up period had Lp(a) levels >30 mg/dl (24/28 patients, mean ± standard deviation Lp(a), 83.1±36.6 mg/dl, P=0.001). Kaplan-Meier survival analysis did not find statistically significant differences in a percutaneous coronary intervention (PCI) time occurrence during the follow-up period between patients with low (≤30 mg/dl) and high (>30 mg/dl) Lp(a) levels (log-rank P=0.305). On the other hand, when a second and third PCI conducted during the monitoring period were included in the Kaplan Meier analysis as events, the mean time for a PCI was significantly shorter (7.2%; P=0.01) for patients with Lp(a) levels >30 mg/dl. In conclusion, the current study reported that patients with high Lp(a) values are more prone to the occurrence of new myocardial infarction, while the Lp(a) cut-off value of 30 mg/dl was linked in CVD patients to an earlier need for PCI, especially in the most vulnerable group of patients with more than one (recurrent) revascularizations.

The prognostic role of micronutrient status and supplements in COVID-19 outcomes: A systematic review.

Micronutrients constitute an adjuvant treatment for respiratory viral infections. Since there is no effective antiviral therapy for COVID-19 yet, adjuvant intervention for the survival of critically ill patients may be significant. Search of the PubMed, CINAHL and Cochrane databases was carried out to find human studies investigating the prognostic role of micronutrient status and the effects of micronutrient supplementation intervention in COVID-19 outcomes of adult patients. Patients with certain comorbidities (diabetes mellitus type 2, obesity, renal failure, liver dysfunction etc.) or pregnant women were excluded. 31 studies (27 observational studies and 4 clinical trials) spanning the years 2020-2021, pertaining to 8624 COVID-19 patients (mean age±SD, 61 ± 9 years) were included in this systematic review. Few studies provided direct evidence on the association of serum levels of vitamin D, calcium, zinc, magnesium, phosphorus and selenium to patients' survival or death. Vitamin D and calcium were the most studied micronutrients and those with a probable promising favorable impact on patients. This review highlights the importance of a balanced nutritional status for a favorable outcome in COVID-19. Micronutrients' deficiency on admission to hospital seems to be related to a high risk for ICU admission, intubation and even death. Nevertheless, evidence for intervention remains unclear.

Assessment of the combined effects of chromium and benzene on the rat neuroendocrine and immune systems.

This study assessed the hypothalamic-pituitary-adrenocortical (HPA) axis and lymphoid organs (thymus, spleen, and bone marrow) of Wistar rats treated with a mixture of chromium and benzene. Animals were assessed at three time-points (45, 90 and 135 days) following oral mixture exposure. The hypothalamus-pituitary system was examined in light and electron microscopy. Lymphoid organs underwent a morphological assessment and the immunophenotype of splenocytes was characterized immunohistochemically using monoclonal antibodies. Splenocytes cytokine production of was determined by ELISA after Con-A stimulation. Combined exposure to chromium and benzene in average doses of 20 mg Cr (VI)/kg body weight/day and 0.6 ml benzene/kg body weight/day impaired the responsiveness of the central compartment of the HPA axis, as evidenced by functional activation of the secretory activity of the hypothalamus and pituitary gland, which was not followed by a sufficient extrusion of nonapeptides at the neurohypophysis and hypothalamic median eminence. Chromium and benzene exposure reduced the thymus mass, thymocytes count, and caused a number of structural and functional changes indicative of transient thymus involution. In the spleen, exposure to both chemicals resulted in lymphoreticular hyperplasia and plasma cell-macrophage transformation (also observed in lymph nodes). Apoptosis of thymocytes and lymphocytes was also observed in T-zones of the spleen. Notably, the effects were similar to those observed earlier for the single agents, under the same experimental conditions, without evidence of additivity.

Children and Parents' Awareness Regarding Potential Hazards Derived from the Use of Chemical Products in Greece.

Over the last decades, human activities prompted the high production and widespread use of household chemical products, leading to daily exposure of humans to several chemicals. The objective of this study was to investigate the frequency of chemicals' use by children and parents in Greece and estimate the level of risk awareness and understanding among them. A total of 575 parents and children were asked to answer an anonymous, closed-ended, validated, and self-administered questionnaire. One-third of the children and almost half of the parents participating in the study believed that commonly used chemical products do not pose any risk to human health or to the environment, despite the product labelling. The majority of both children (61.8%) and parents (70.6%) were informed about product safety via the product labelling. Around 20% in both groups could not differentiate between systemic toxicity and acute lethal effects depicted by pictograms on the label and milder hazards, such as skin irritation. Moreover, the information on hazard and precautionary statements appearing on the label was very poorly perceived. Therefore, as both children and parents seem not to clearly identify the hazards and risks arising from the use of everyday chemical products, targeted awareness policies should be implemented to support the safe use of household products.

Exposure to multiple mycotoxins in domestic and imported rice commercially traded in Tehran and possible risk to public health.

Mycotoxins are secondary fungi metabolites that induce acute and chronic toxic effects in humans and animals. In the present study, nine mycotoxins including aflatoxins (AFB1, AFB2, AFG1 and AFG2), fumonisins (FB1 and FB2), Ochratoxin A (OTA), deoxynivalenol (DON), and zearalenone (ZEN) were determined in one hundred rice samples collected from Tehran using high performance liquid chromatography (HPLC) with fluorescence or photodiode array detector. In addition, possible risk to public health was investigated by assessing dietary exposure through rice consumption, the margin of exposure (MOE), respective risk of cancer and hazard index (HI) of the monitored mycotoxins in children and adults. The higher mean levels were determined for DON (102.22 µg.Kg-1), followed by FB1 (85.00 µg.Kg-1). For the rests of mycotoxins the levels did not exceed 20 µg.Kg-1. The estimated AFB1 intake for the adults and children through rice consumption exceeds the safe levels established for both carriers and non-carriers of hepatitis B virus. The mean and median determined exposure levels of OTA, DON ZEN and FB1, were found lower than the Provisional Maximum Tolerable Daily Intake (PMTDI) value for both adults and children of Tehran that consuming domestic and imported rice. The mean HI for adults and median HI for adults and children were below one, and mean HI for children was close to one. All the mean, median and maximum MoE values were <10,000 in adults and children, indicating a risk due to AFB1 exposure through rice consumption in Tehran. In addition, the calculated mean cancer risk in adult and child populations of Tehran were 0.27 and 0.64 cases per year per 105 individuals, respectively, that shows population in Tehran could be at risk of cancer due to AFB1 exposure through rice consumption as calculated. So further studies are necessary for the monitoring mycotoxins in rice and different food products as well as estimating average dietary exposure and cumulative exposure assessment of mycotoxins for main foods in IR Iran.

Updating the European Union's regulation on classification, labelling and packaging of substances and mixtures (CLP): A key opportunity for consumers, workers and stakeholders with interests in the legislation and toxicology of hazardous chemicals.

Recent advancements in toxicology and the European Union's Green Deal, with its Chemicals Strategy for Sustainability, have paved the way for major changes in EU legislation on the control of environmental chemicals for a cleaner and safer environment. Another substantial legislative advancement underway is the update of the "Regulation on Classification, Labelling and Packaging of Substances and Mixtures (CLP)," an ambitious piece of EU legislation with exceptional scientific toxicological background in identifying a hazard, aiming at better protecting its citizens and the environment from the risk of chemical substances and products, the occupational settings included. Update of CLP legislation additionally aims at facilitating the free exchange of chemicals in the European Internal Market, provided that proper labelling and packaging processes are implemented. Participation in the ongoing online public consultation on these issues, ending on November 15, 2021, is of key relevance to ensure a transparent and effective definition of such an important piece of legislation, fully compliant with current EU priorities in terms of human and environmental protection and animal welfare.

[Corrigendum] What is considered cardiotoxicity of anthracyclines in animal studies.

Subsequently to the publication of this paper, the authors have realized that the name of the seventh listed author, Dimitrios Stagos, was spelt incorrectly (it appeared as 'Stagkos' in print). The corrected author list is shown above. The authors regret that the name of the seventh author on the paper was spelt incorrectly, and apologize to the readers for any inconvenience caused.[the original article was published in Oncology Reports 44: 798-818, 2020; DOI: 10.3892/or.2020.7688].

Investigation of the health effects on workers exposed to respirable crystalline silica during outdoor and underground construction projects.

Chronic exposure of workers to powder containing crystalline silica (Silicon dioxide; SiO2) can lead to chronic lung diseases (lung cancer, silicosis, etc.). Aim of this study was to evaluate the exposure of Greek construction workers to SiO2 and describe their pulmonary function. The study involved 86 outdoor and underground workers. Medical and professional history was obtained, and breath samples were collected at morning hours through a mask for the determination of SiO2 levels. Pulmonary function tests, radiological examination and evaluation of radiographs were also performed. Pulmonary function examination showed that the majority of the workers were within normal range (61.4%) while the rest were diagnosed with mild (26.5%) and more severe impairment (7.24%). Working conditions (underground-outdoor) were statistically significantly related to the categorization of pulmonary function (P=0.038). During radiological examination, the type of working activity/ conditions (underground-outdoor) were statistically significantly related to the categorization of these findings (P=0.044). Of the 69 employees, 52 did not present findings (75.4%) and 5 were diagnosed with findings specific to occupational diseases (7.23%). Environmental exposure to respirable crystalline silica (RCS) was detected at 0.0125 mg/m3 in the workplace, which is not beyond the legal limits. Underground workers with more than 15 years of exposure to SiO2 are more likely to present chronic silicosis compared to the workers of outdoor activities.

Safe use of chemicals and risk communication among dentists and dental students in Greece.

Use of chemicals, most often classified for intrinsic hazards, is rather common among dentists. To date, no data have been recorded in the European Union (EU) on dentists' awareness regarding the safe use of chemicals. In the EU regulatory framework, two Regulations with wide applications, namely Regulations (EC) 1907/2006 (REACH) and 1272/2008 (CLP), have been introduced to protect human health and the environment and clearly communicate hazards posed by chemicals to workers and consumers. The aim of this study was to assess the extent of comprehension of hazard communication of chemicals among Greek dentists. For this, a closed-ended, anonymous and validated questionnaire was initially distributed to a total of 300 Greek dentists, both professionals and university students, over a period of 4 months. The collected data from 240 final responders were subjected to statistical analysis (frequencies, percentages, chi-square (χ2) and significance (p < 0.05)). The vast majority (90%) of the interviewed dentists are not aware of the CLP. Main sources of information regarding chemical hazard and safe use was the supplier through direct communication (90%), while some dentists also consulted the product labels (39%) and the material safety data sheets (54%). Regarding hazard communication, the perceived information from the pictograms is confusing to the vast majority of the dentists (86%), especially for systemic hazards (carcinogenicity and/or reproductive toxicity). In addition, 88% of the professional dentists have not noticed any changes in the labelling of chemical products, which also shows the low input of labels to hazard communication. On the other hand, 90% of the responders always utilize personal protective equipment (PPE), although it is not clear whether this PPE is adequate. In conclusion, rising awareness campaigns are needed, in collaboration with universities and dental care professional associations, to inform dentists about the safe use of chemicals not only to ensure protection of their own health but also to contribute to environmental sustainability.

Identifying early abdominal obesity risk in adolescents by telemedicine: A cross-sectional study in Greece.

Obesity and thus, lipotoxicity, is a major health risk factor. Modern exposure to environmental chemicals has contributed significantly to the obesity epidemic. The purpose of this study was to assess, via telemedicine and using bioelectrical impedance analysis (BIA) in schools, the levels of adiposity and other body composition parameters of Greek adolescents in relation with their metabolic syndrome (MetS) characteristics. A representative sample (1575 adolescents, 14.4 ± 1.7 years-old) of the Attica region population, underwent body composition assessment of fat mass (FM), fat-free mass (FFM), and total body water (TBW) and was evaluated for anthropometric and MetS characteristics. Males demonstrated higher FFM% and TBW% but lower FM% than females. Adolescents with abdominal obesity/MetS (n = 149/n = 40) demonstrated significantly (P < 0.001) higher body mass index (BMI 27.8 ± 3.8 kg/m2/30.2 ± 4.2 kg/m2) and FM (33.6 ± 9.7%/35.0 ± 10.5%) but significantly (P < 0.001) lower FFM (34.2 ± 5.7%/33.8 ± 6.2%) and TBW (45.6 ± 6.7%/44.6 ± 7.2%) than adolescents without abdominal obesity/MetS (BMI 20.9 ± 2.8 kg/m2/21.3 ± 3.2 kg/m2; FM 19.2 ± 6.9%/20.2 ± 8.0%; FFM 41.3 ± 4.4%/40.8 ± 4.8%; TBW 55.5 ± 4.8%/54.8 ± 5.5%). Findings suggest that early "osteosarcopenic" elements of abdominal obesity/MetS may exist even in adolescence. The application of BIA, incorporated in the new approach methodology of telemedicine in schools, identified adolescents at risk for obesity complications.

What is considered cardiotoxicity of anthracyclines in animal studies.

Anthracyclines are commonly used anticancer drugs with well­known and extensively studied cardiotoxic effects in humans. In the clinical setting guidelines for assessing cardiotoxicity are well­established with important therapeutic implications. Cardiotoxicity in terms of impairment of cardiac function is largely diagnosed by echocardiography and based on objective metrics of cardiac function. Until this day, cardiotoxicity is not an endpoint in the current general toxicology and safety pharmacology preclinical studies, although other classes of drugs apart from anthracyclines, along with everyday chemicals have been shown to manifest cardiotoxic properties. Also, in the relevant literature there are not well­established objective criteria or reference values in order to uniformly characterize cardiotoxic adverse effects in animal models. This in depth review focuses on the evaluation of two important echocardiographic indices, namely ejection fraction and fractional shortening, in the literature concerning anthracycline administration to rats as the reference laboratory animal model. The analysis of the gathered data gives promising results and solid prospects for both, defining anthracycline cardiotoxicity objective values and delineating the guidelines for assessing cardiotoxicity as a separate hazard class in animal preclinical studies for regulatory purposes.

Health risk assessment of aflatoxin M1 in infant formula milk in IR Iran.

In this study, two accurate, precise, selective and sensitive methods were developed for determining aflatoxin M1 (AFM1) in infant formula milk using immunoaffinity column clean-up followed by high performance liquid chromatography (HPLC) with fluorescence detection. The validated methods were used for determination of AFM1 in 29 samples of 6 different infant formula milk brands and the risk of AFM1 in infants aged zero to 6 months old was assessed using cancer risk, Margin of Exposure (MOE) and Hazard Index (HI). Only one sample (3.4%) was contaminated with AFM1. Although the results showed that MOE values for the mean and median exposure to AFM1 was <10,000 in infants, the additional cancer risk due to mean and median exposure to AFM1 in infant <6 months were 0.00010 and 0.00012 additional cases per year per 105 individuals, respectively, which indicates no health concern. In addition, HI values for the mean and median exposure to AFM1 for infants were quite below one which indicates no health concern. To the best of our knowledge, this is the first report on risk assessment of AFM1 in infant formula milk consumed by Iranian infants <6 months old, presenting a low risk for the evaluated groups.

Current Concepts on the Reno-Protective Effects of Phosphodiesterase 5 Inhibitors in Acute Kidney Injury: Systematic Search and Review.

Acute kidney injury (AKI) is associated with increased morbidity, prolonged hospitalization, and mortality, especially in high risk patients. Phosphodiesterase 5 inhibitors (PDE5Is), currently available as first-line therapy of erectile dysfunction in humans, have shown a beneficial potential of reno-protection through various reno-protective mechanisms. The aim of this work is to provide a comprehensive overview of the available literature on the reno-protective properties of PDE5Is in the various forms of AKI. Medline was systematically searched from 1946 to November 2019 to detect all relevant animal and human studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In total, 83 studies were included for qualitative synthesis. Sildenafil is the most widely investigated compound (42 studies), followed by tadalafil (20 studies), icariin (10 studies), vardenafil (7 studies), zaprinast (4 studies), and udenafil (2 studies). Even though data are limited, especially in humans with inconclusive or negative results of only two clinically relevant studies available at present, the results of animal studies are promising. The reno-protective action of PDE5Is was evident in the vast majority of studies, independently of the AKI type and the agent applied. PDE5Is appear to improve the renal functional/histopathological alternations of AKI through various mechanisms, mainly by affecting regional hemodynamics, cell expression, and mitochondrial response to oxidative stress and inflammation.

Role of anabolic agents in colorectal carcinogenesis: Myths and realities (Review).

Colorectal cancer (CRC) is one of the four leading causes of cancer­related mortality worldwide. Even though over the past few decades the global scientific community has made tremendous efforts to understand this entity, many questions remain to be raised on this issue and even more to be answered. Epidemiological findings have unveiled numerous environmental and genetic risk factors, each one contributing to a certain degree to the final account of new CRC cases. Moreover, different trends have been revealed regarding the age of onset of CRC between the two sexes. That, in addition to newly introduced therapeutic approaches for various diseases based on androgens, anti­androgens and anabolic hormones has raised some concerns regarding their possible carcinogenic effects or their synergistic potential with other substances/risk factors, predisposing the individual to CRC. Notably, despite the intense research on experimental settings and population studies, the conclusions regarding the majority of anabolic substances are ambiguous. Some of these indicate the carcinogenic properties of testosterone, dihydrotestosterone (DHT), growth hormone and insulin­like growth factor (IGF) and others, demonstrating their neutral nature or even their protective one, as in the case of vitamin D. Thus, the synergistic nature of anabolic substances with other CRC risk factors (such as type 2 diabetes mellitus, metabolic syndrome and smoking) has emerged, suggesting a more holistic approach.

A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse.

Drugs of abuse are associated with stroke, especially in young individuals. The major classes of drugs linked to stroke are cocaine, amphetamines, heroin, morphine, cannabis, and new synthetic cannabinoids, along with androgenic anabolic steroids (AASs). Both ischemic and hemorrhagic stroke have been reported due to drug abuse. Several common mechanisms have been identified, such as arrhythmias and cardioembolism, hypoxia, vascular toxicity, vascular spasm and effects on the thrombotic mechanism, as causes for ischemic stroke. For hemorrhagic stroke, acute hypertension, aneurysm formation/rupture and angiitis-like changes have been implicated. In AAS abuse, the effect of blood pressure is rather substance specific, whereas increased erythropoiesis usually leads to thromboembolism. Transient vasospasm, caused by synthetic cannabinoids, could lead to ischemic stroke. Opiates often cause infective endocarditis, resulting in ischemic stroke and hypereosinophilia accompanied by pyogenic arthritis, provoking hemorrhagic stroke. Genetic variants are linked to increased risk for stroke in cocaine abuse. The fact that case reports on cannabis-induced stroke usually refer to the young population is very alarming.