Hyperglycemia, blood glucose levels above 2.0 g/L, is one of the major pathophysiological factors causing late complications in diabetes [1, 2]. Reactive Oxygen Species (ROS) are increased by hyperglycemia [3]. Oxidative damage in individual cells may reach a sufficient threshold to cause DNA strand breaks and induce cell death [4]. Therefore, hyperglycemia-induced oxidative stress is one of the responsible factors for the pathology of diabetic complications.
The COVID-19 pandemic is challenging world health authorities and researchers. WHO is supervising many clinical studies to ascertain whether some known drugs can be effective against the disease. Meanwhile, researchers around the globe are working on cellular and molecular mechanisms that are key steps of SARS-Cov-2 associated infection. Blood hemostasis dysfunction, inflammation, hypoxia and venous thrombotic events are reported to be involved in the pathophysiology of COVID-19 patients at early and late severe stages of the disease. It is of high relevance to understand how SARS-Cov-2 triggers negative cellular and biochemical events in infected persons. A large number of cell species and active molecules, such as blood and tissue enzymes, cytokines, and other active amines and lipid inflammatory molecular species, can be involved in immune reactions and host defense mechanisms upon human infectious diseases or other kinds of health issues such as trauma or snake envenomation. Possible physiopathology trends of COVID-19 and some therapeutic perspectives are discussed in the present minireview.
This paper would provide the analyst with an easy to use step-by-step guide to calculate the uncertainty of measurement in implementing a new analytical method.There are two main ways to attain such an achievement.The first is to consider all the possible sources of variability and then to sum up all of them in the final calculation.The second is taking part in a collaborative trial and processing the resulting statistics.Both methods imply different advantages and drawbacks.It is up the analyst to choose the one fits best his requirements.Anyway it is nearly inescapable providing, along with the test result, its own uncertainty.
It is nevertheless not easy to define the borders between Pharmacology and Toxicology too, because the side effects of commonly used therapies could be extremely toxic, the effects of the Drug of Abuse are also toxic, and toxic substances could be found in soil, water and air. It is well known that Medicine is “rapidly changing in rapidly changing world”, but the paramount progress in laboratory technology has positively influenced the whole Medicine diagnostic process and practice. For these reasons a rational diagnostic strategy is mandatory to optimize the resources. The aim of the toxicological analysis is firstly to detect the toxicant, and to fulfill this scope so that the toxicologist can take advantage of improved technology. Even if new screening methods are easy to perform, highly automated and fit not only for highly specialized laboratory staff, confirmation analysis needs more sophisticated and extremely expensive technology. It is well known indeed that confirmation tests should be performed only by chromatographic technology, both gas chromatographic and liquid chromatographic coupled with mass spectrometry, and these kinds of tests need highly specialized personnel.
Short residential rehabilitation in the treatment of alcohol dependence in Italy is becoming more widespread
Alcohol-related problems are typically associated with medical, economic and social issues. The reduction of the problem can only occur if effective strategies to prevent, diagnose and treat alcohol abuse are developed. Real help could come from laboratory tests that represent objective evidence of alcohol problems. Authors present new biomarkers as Carbohydrate-deficient transferrin (CDT), Ethyl Glucuronide and Ethyl Sulfate ( EtG and EtS)), Fatty Acids Ethyl Esters (FAEE) anf Phosphatidy ethanol (PEth) in differents biological samples.
Aflatoxicosis mostly leads to serious clinical signs of malnutrition, growth retardation, and impairment of utilization of nutrients, immunosupression, liver diseases and cancer.Detoxification or prevention of such toxicity is interesting to researchers in change field.In pursuit for an approach, the synthetic copper(I)-nicotinate complex has been evaluated against the traditional Butylated hydroxy toluene (BHT) for possible protective effects as a food additive in induced aflatoxicosed animals.Induction of toxicity in adult rats by AFB 1 60 µg/kg body weight divided on three times a week for consecutive five weeks resulted in marked hepatic necrosis, collagen fibers around portal tract and iron deposits as well as features of general cellular collapse and cirrhosis.The protective effects were tested on two animal groups by associate doses of BHT (0.05 mg / kg B.W.) in one group and copper (I) nicotinate complex (0.4 mg/kg B.W.) in the other.Results showed, in both groups, almost normal histological as well as biochemical markers especially those treated with the copper complex, which suggests that anti-inflammatory copper complex can be used as a protective agent against aflatoxicosis when used in doses resemble those used in pharmaceutical vitamin supplements.
In forensic toxicology the main relevant scope of toxicologist is to answer these following questions: which kind of drug is involved?Is the analytical result related to death?Which is the supposed lethal dose?Despite the technological improvement in laboratory medicine, the main questions are apparently unresolved, because the availability of new laboratory instrumentation has sometimes increased the complexity of the medical examiner task.In post mortem toxicology the medical examiner's and the toxicologist's role is constantly challenged by analytical, methodological, circumstantial problems, and only the single professional experience can help to find which drug is involved.In our experience the only way to avoid, or limit, mistakes is to follow strictly a Search Strategy, which combines single professional experience, circumstantial data and a correct and a punctual manner of sampling from corpses.The most complete and proper tissue sampling from autopsy is mandatory for the whole diagnostic process.This approach in synergy with the pathologist and toxicologist dialogue can help the medical examiner to avoid mistakes and positively infer the whole diagnostic process.
The organochlorine compound, pentachlorophenol (PCP), is classified as a hazardous substance.Its metabolite, tetrachloro-1,2-hydroquinone (TCHQ), has been detected in occupationally-exposed subjects and can readily be converted to tetrachloro-1,4-benzoquinone (TCBQ) under physiological conditions.Hazard characterization has previously identified the liver as the target organ of PCP toxicity in rats and dogs and as the liver is the major site of metabolism of the parent compound, this raises concern for the effects that the metabolites of PCP may have on the liver.Although the hepatotoxic effects of PCP have been described, less is known about the effects of its metabolites on hepatocyte function.Studying the effects of these metabolites on hepatocytes may provide valuable information regarding the effects that these compounds could exert on the liver itself and allude to the clinical manifestations of toxicity that can be expected.The aim of this study was therefore to assess the effect of PCP, TCHQ and TCBQ on the following cellular parameters: cell viability, mitochondrial membrane potential and intracellular ROS formation, as indicators of hepatocyte homeostasis.Both PCP and its metabolites, TCHQ and TCBQ decreased cell viability with IC 50 of 68.05, 129.40 and 144.00 µM, respectively.All three compounds caused mitochondrial depolarization, with the effect being more profound following exposure to TCHQ and TCBQ.PCP did not induce any ROS generation, whereas TCHQ and TCBQ produced extensive ROS.Findings from this study suggest that in hepatocytes the mechanism of toxicity of PCP differs from that of its metabolites, TCHQ and TCBQ.
Cocaine abuse is associated with multiple health problems including occasional hepatic failure and death. The mechanism of cocaine-induced hepatotoxicity (CIH) is not clear, although studies in mice have demonstrated that cocaine-induced liver injury may be mediated by nitric oxide and reactive oxygen species. Recently, we have found that cocaine increases poly (ADP-ribose) polymerase (PARP) activity in the liver. Therefore, inhibition of PARP may block CIH. A preliminary assessment of the PARP inhibitor 3,4-Dihydro-5-(4-(1-piperidinyl)butoxyl)-1(2H)-isoquinolinone (DPQ) in ICR mice failed to attenuate CIH. However, the PARP inhibitor 1,5-dihydroxyisoquinoline (DIQ) successfully attenuated CIH. Mean ALT activity of 569 IU caused by cocaine treatment alone, was limited to 79 IU in ICR mice concomitantly treated with DIQ (10 mg/kg, ip). The protective effect of DIQ was also associated with prevention of development of lipid peroxidation in liver tissue, reduced depletion of glutathione (GSH), and a reduced production of nitrites. Cocaine-induced TBARS was significantly decreased by DIQ from a mean of 5.7 nmol/mg protein to a mean of 2.5 nmol/mg protein, similar to untreated mice. Hepatic GSH was reduced more than 2 fold following cocaine administration but treatment with DIQ conserved GSH at the level of untreated mice. The protective effect of DIQ in attenuating CIH can potentially be explained by the dual inhibitory effect of DIQ that reduces induction of PARP and inducible nitric oxide synthetase (iNOS). The DIQ attenuation of CIH provides evidence for a PARP and iNOS modulated mechanism of action for this hepatocellular pathology.
Sidha medicines which are popular in Southern parts of India have significant quantity of heavy metals.It is claimed that mode of preparation of these drugs reduces their toxicities.However toxicity studies of Sidha preparations are seldom carried out.In the present study we have evaluated toxicity of Rasagandhi Mezhugu (RM), a Sidha preparation in Wistar rats.Drug was administered orally as single dose (acute) and sixty doses (chronic).Parameters checked were WBC count, haemoglobin and differential count, hepatic function tests such as SGOT, SGPT, ALP, bilirubin, creatinine, blood urea nitrogen, total protein, albumin, globulin and renal function tests such as blood urea nitrogen and creatinine, electrolytes such as sodium, potassium, bicarbonate and chloride.No impairment in hepatic, renal, haemopoietic functions were observed throughout the study.Histopathological analysis revealed that liver, kidney, spleen and thymus tissues of treated groups did not show any signs of toxicity.However, astrocytes showed mild hyperplasia, stroma showed oedema in the treated group.Cerebellum also shows stromal oedema.Rasagandhi Mezhugu (RM) administration for one year to HIV patients did not produce any toxicity as seen from liver function and renal function as well as analyzing haematological parameters.Analysis of the metal content in the tissues of RGM treated rats for one month indicated that there was significant accumulation of mercury and copper in the tissues, which indicate that RGM administration for long period of times can produce heavy metal toxicity which is also indicated in histopathological analysis.
In the present study, the kinetic characterization of leucurobin, a thrombin-like enzyme isolated from the venom of Bothrops leucurus was evaluated. This serpent is very common in the northeast of Brazil, but little is known about its venom. Leucurobin showed amidase activity against chromogenic substrates of the peptidyl-pNA type containing an Arg residue at P1. D-Phe-Pro-Arg-pNA was observed to be the best substrate of those tested. The amidase activity of leucurobin with this substrate was strongly inhibited by sodium and potassium ions and was weakly inhibited by calcium and magnesium ions. Leucurobin presented a high coagulating activity in vitro with citrated human plasma and with purified bovine fibrinogen. The coagulating activity with fibrinogen was inhibited by the presence of sodium and potassium ions, but not by calcium or magnesium ions. No interference in the amidase and coagulating activities by the glycoside fraction of native leucurobin was observed. The S1 site was found to be anionic, and the S2 and S3 sites are hydrophobic.
This work involves the evaluation of UV blocking efficiency of commercially available intraocular lens (IOL) materials using a retinal cell culture and a biological in vitro model that was developed in a previous study, as an effort to examine the sensitivity of this in vitro approach for evaluating toxicity of UV radiation on the retinal pigment epithelial cells. The human retinal pigment epithelial (RPE) cell line, ARPE-19, was cultured, and cells were irradiated with broadband UVB radiations at energy levels of 0.2 and 0.4 J/cm . Some treated cells were not shielded from the radiation while others were shielded using two thicknesses (0.9 and 1.5 mm) of IOL material. After irradiation, cellular viability, mitochondrial distribution, nuclei morphology, and phagocytotic activity were analyzed using the Alamar blue assay, Rhodamine 123 staining, the Hoechst assay, and a phagocytotic activity assay. The results demonstrate that UVB radiation can cause significant decreases in RPE cell viability as well as in phagocytotic activity. Also, the results show that UVB radiation can induce the degradation of DNA and mitochondria in cultured RPE cells. However, the two different thickness IOL material sheets (0.9 and 1.5 mm) showed very effective UV blocking ability, allowing no cellular damage at all. Thus, the finding suggest that these four assays together can be used as a sensitive, and meaningful in vitro biomarker method for evaluating toxicity of UV radiation on RPE cells, and also for examining IOL effectiveness.
Food products containing carrots were analyzed for benzene contamination using headspace gas chromatography with mass spectrometric detection. Of 82 commercial samples, 88% contained benzene above the detection limit of 0.04 µg/kg. Canned and jarred carrots contained 0.2 µg/kg of benzene on average. Higher levels were found in jarred baby foods containing carrots (0.9 µg/kg on average). The highest concentrations were found in carrot juices specifically intended for infants (2.0 µg/l on average). In contrast, freshly home-prepared carrot juices (n=8) and baby foods (n=30) were all benzene-free. The detection of the human carcinogen benzene at µg/kg levels in canned foods, jarred baby food and juices containing carrots proves that the level of exposure to benzene through food products is currently underestimated. The potential of this substance to pose a cancer hazard for consumers should be evaluated. Further research into the occurrence of benzene in food products, including formation mechanisms and mitigation measures, is necessary.
Sidha medicines which are popular in Southern parts of India have significant quantity of heavy metals. It is claimed that mode of preparation of these drugs reduces their toxicities. However toxicity studies of Sidha preparations are seldom carried out. In the present study we have evaluated toxicity of Rasagandhi Mezhugu (RM), a Sidha preparation in Wistar rats. Drug was administered orally as single dose (acute) and sixty doses (chronic). Parameters checked were WBC count, haemoglobin and differential count, hepatic function tests such as SGOT, SGPT, ALP, bilirubin, creatinine, blood urea nitrogen, total protein, albumin, globulin and renal function tests such as blood urea nitrogen and creatinine, electrolytes such as sodium, potassium, bicarbonate and chloride. No impairment in hepatic, renal, haemopoietic functions were observed throughout the study. Histopathological analysis revealed that liver, kidney, spleen and thymus tissues of treated groups did not show any signs of toxicity. However, astrocytes showed mild hyperplasia, stroma showed oedema in the treated group. Cerebellum also shows stromal oedema. Rasagandhi Mezhugu (RM) administration for one year to HIV patients did not produce any toxicity as seen from liver function and renal function as well as analyzing haematological parameters. Analysis of the metal content in the tissues of RGM treated rats for one month indicated that there was significant accumulation of mercury and copper in the tissues, which indicate that RGM administration for long period of times can produce heavy metal toxicity which is also indicated in histopathological analysis. Sidha medicine is being practiced in Southern part of India. Most medical practitioners caution against using Sidha medicines due to the extensive use of heavy metals like lead and mercury in the preparation. Drugs having these heavy metals more than their allowable limits are banned in many countries. Sidha practitioners claim that the heavy metals used in these medicines are completely transformed into inert compounds or ores through a 18-step process before being prescribed as medicine. However extensive research is necessary to solve such riddles of the transformation of these admittedly poisonous compounds. Recently Sidha system of medicare has been found to have useful in the management of HIV through scientific research involving viral load assays and CD4 + /CD8 + ratios (1). Rasagandhi Mezhugu (RGM) in the form of a capsule is being used for the treatment of HIV by some practitioners (2). This preparation contain 38 different botanicals, many of which have been shown to possess therapeutic efficacy, and 8 inorganic compounds such as mercury, sulphur, calomel (mercury chloride), yellow orpiment (arsenic sulphide), lodestone (iron), blue vitriol (copper sulfate), calamine (zinc oxide) and litharge (lead oxide), all prepared into a paste in palm sugar and hen's egg base. Composition of RGM is given elsewhere (3).
Occupational exposure to respirable crystalline silica has the ability to cause silicosis. Silica is also suspected of being associated with an increased risk of lung cancer, kidney disease, rheumatoid arthritis, and other diseases. The specific mechanism(s) of pathogenesis for silicosis and these other potential health concerns remains unclear. This investigation measured dissolution rates of silicon dioxide (SiO 2 ) particles in simulated lung fluid to determine the residence times of such particles within the intracellular or extracellular spaces. Silicon dioxide dissolution rates were determined as a function of fluid pH, particle size, and SiO 2 concentration and mass. Gamble's solution was used to simulate intracellular and extracellular lung fluids at pH 6.0, pH 6.5, and pH 7.5. Test samples were paired by pH, particle size, and SiO 2 concentration/mass. Sample aliquots of filtered solution were collected over a 28-day test period. Results revealed SiO 2 became soluble and the dissolution rate increased with increasing pH and decreasing particle size. SiO 2 concentration and mass also appeared to have some effect on the rate of dissolution. These solubility characteristics appear likely to impact the residence times of particles within biological systems, suggesting a model for exposure and subsequent pathogenesis for systemic silica-related diseases.
To analyze how toxic effects propagate from molecular to population level, a simple model of a circadian oscillator has been coupled with a cyanobacteria growth model. It has been assumed that the circadian oscillator synchronizes with light-dark environmental conditions and toxicants affect this synchronization reducing the population growth. Then dose-response curves have been developed. The results evidence that to understand toxic effects we have to focus our study on the interactions that a certain compound may have with proteins, and/or DNA, since the result of these interactions will determine the final mode of action at macroscopic level. Therefore an intermediate step for assessing toxic effects has been proposed.
The present study investigated safety/toxicity profile of fixed dose combination of Ofloxacin-Ornidazole injection in Mus musculus mice at three dose levels, ranging from asymptomatic to high dose.To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram positive bacteria, fixed dose combination of Ofloxacin and Ornidazole injection was introduced.It has been found highly effective as well as synergistic and has the potential of usage for empirical therapy because of extended spectrum.A 30 days repeat dose subchronic toxicity study was conducted on mice (male and female).Various physiological, hematological and biochemical parameters were studied.There were no signs of toxicity observed at any dose level used in this study.No mortality was seen in any of the treatment groups.Hematological as well as physiological parameters were unaltered at three dose levels in Ofloxacin-Ornidazole treatment groups.Results suggest that the fixed dose combination of Ofloxacin-Ornidazole injection is non toxic even at maximum dose level.
Cytochrome P4501A1 (CYP1A1), an enzyme known to metabolize polycyclic aromatic hydrocarbons, is regulated by the aryl hydrocarbon receptor (AhR).The involvement of protein kinase C (PKC) in the regulation of AhR signal transduction pathway, has been widely studied but the role of specific PKC isoform(s) involved in this process it is not well clarified.To study which PKC isoform(s) is implicated in the regulation of CYP1A1, in the poorly tumorigenic MH1C1 rat hepatoma cells, we examined the effects of some PKC pharmacological inhibitors, Calphostin C (CAL), Staurosporine (STA) and H7, and of 12-0-tetradecanoyl phorbol 13-acetate (TPA), a PKC activator, on basal and 3methylcholanthrene (MC)-induced CYP1A1 protein expression and mediated ethoxyresorufin O-deethylation (EROD) activity.In parallel, the activities of PKC-, -I, -and -isoforms, the most expressed in MH1C1 cells, were monitored.After pre-treatment with CAL, STA and H7, the MC-induced CYP1A1 protein and EROD activity were rapidly reduced with temporal profile similar to the profile of the activity of and 1 PKC isoforms.Moreover, TPA pre-treatment induced a biphasic effect on EROD activity, and a decline of PKC -I and -, in first instance, and -and -activities later on.These findings clearly show that, in MH1C1 cells, PKC is involved in CYP1A1 regulation and that and I classic PKC isoforms play an active role in modulating this process.
