- On the Efficacy of Cardio-Pulmonary Resuscitation and Epinephrine Following Cyanide- and H2S Intoxication-Induced Cardiac Asystole. [Journal Article]
- CTCardiovasc Toxicol 2018 Apr 11
- This study was aimed at determining the efficacy of epinephrine, followed by chest compressions, in producing a return of spontaneous circulation (ROSC) during cyanide (CN)- or hydrogen sulfide (H2S)...
This study was aimed at determining the efficacy of epinephrine, followed by chest compressions, in producing a return of spontaneous circulation (ROSC) during cyanide (CN)- or hydrogen sulfide (H2S)-induced toxic cardiac pulseless electrical activity (PEA) in the rat. Thirty-nine anesthetized rats were exposed to either intravenous KCN (n = 27) or H2S solutions (n = 12), at a rate that led to a PEA within less than 10 min. In the group intoxicated by CN, 20 rats were mechanically ventilated and received either epinephrine (0.1 mg/kg i.v. n = 10) followed by chest compressions or saline (n = 10, "control CN") when in PEA. PEA was defined as a systolic pressure below 20 mmHg and a pulse pressure of less than 5 mmHg for 1 min. In addition, seven spontaneously breathing rats were also exposed to the same CN protocol, but infusion was stopped when a central apnea occurred; then, as soon as a PEA occurred, epinephrine (0.1 mg/kg IV) was administered while providing manual chest compressions and mechanical ventilation (CPR). Finally, 12 rats were intoxicated with H2S, while mechanically ventilated, and received either saline (n = 6, "control H2S") or epinephrine (n = 6) with CPR when in PEA. None of the control-intoxicated animals resuscitated (10 rats in the control CN group and 6 in the control H2S group). In contrast, all the animals intoxicated with CN or H2S that received epinephrine followed by chest compressions, returned to effective circulation. In addition, half of the spontaneously breathing CN-intoxicated animals that achieved ROSC after epinephrine resumed spontaneous breathing. In all the animals achieving ROSC, blood pressure, cardiac output, peripheral blood flow and [Formula: see text]O2 returned toward baseline, but remained lower than the pre-intoxication levels (p < 0.01) with a persistent lactic acidosis. Epinephrine, along with CPR maneuvers, was highly effective in resuscitating rodents intoxicated with CN or H2S. Since epinephrine is readily available in any ambulance, its place as an important countermeasure against mitochondrial poisons should be advocated. It remains critical to determine whether the systematic administration of epinephrine to any victims found hypotensive following CN or H2S intoxication could prevent PEA, decrease post-ischemic brain injury and increase the efficacy of current antidotes by improving the circulatory status.
- Assessing the efficacy of aqueous garlic extract, sodium nitrite and sodium thiosulfate against prolonged oral cyanide exposure in rabbits. [Journal Article]
- PJPak J Pharm Sci 2018; 31(2):411-419
- This study was aimed to compare the efficacy of aqueous garlic extract, sodium nitrite (SNT), sodium thiosulfate (STS) and hydroxocobalamin against oral cyanide exposure in rabbits. For this purpose,...
This study was aimed to compare the efficacy of aqueous garlic extract, sodium nitrite (SNT), sodium thiosulfate (STS) and hydroxocobalamin against oral cyanide exposure in rabbits. For this purpose, forty two adult male rabbits were divided randomly into 7 groups of 6 animals (A-G) each. Rabbits in group A were offered feed only and served as negative control, while the rabbits in group B received feed plus potassium cyanide (KCN) at 3mg/kg orally and were kept as positive control. Animals in group C received feed, KCN and intraperitoneal injection (IP) of aqueous garlic extract at 500mg/kg. Rabbits in group D were given feed, KCN and IP injection of STS at 600mg/kg. Members in group E received feed, KCN and IP injection of both aqueous garlic extract at 500mg/kg and SNT at 20mg/kg. Animals in group F were given feed, KCN and IP injection of both STS at 600mg/kg and SNT at 20mg/kg, while the rabbits in group G received feed, KCN and IP injection of hydroxocobalamin at 300mg/kg. The treatments were given to respective groups for 40 days. The efficacy of the antidotes was measured on the basis of changes in biochemical profile of rabbits in each group. In this study, hydroxocobalamin was found to be significantly more effective cyanide (CNI) antidote than garlic, STS, SNT plus garlic extract, or SNT and STS, either alone or in combination. A combination of SNT and garlic extract was the second most effective CNI antidote. The efficacy of garlic alone was significantly higher than STS alone or in combination with SNT. The efficacy of combined SNT and STS was superior to STS alone in treating rabbits with CNI toxicity. In conclusion, aqueous garlic extract alone or in combination with STS can effectively be used against cyanide toxicity.
- A Comparison of the Cyanide-Scavenging Capabilities of Some Cobalt-Containing Complexes in Mice. [Journal Article]
- CRChem Res Toxicol 2018 Apr 16; 31(4):259-268
- Four cobalt-containing macrocyclic compounds previously shown to ameliorate cyanide toxicity have been comparatively evaluated with an acute sublethal toxicity model in conscious (unanesthetized) adu...
Four cobalt-containing macrocyclic compounds previously shown to ameliorate cyanide toxicity have been comparatively evaluated with an acute sublethal toxicity model in conscious (unanesthetized) adult male Swiss-Webster mice. All of the compounds (the cobalt-corrins cobalamin and cobinamide, a cobalt-porphyrin, plus a cobalt-Schiff base macrocycle) given 5 min prior to the toxicant dose significantly decreased the righting-recovery time of cyanide-intoxicated mice, but the doses required for maximal antidotal effect varied. Additionally, all of the compounds tested significantly reduced the righting-recovery time when administered at either 1 or 2 min after cyanide intoxication, but none of the compounds tested significantly reduced the righting-recovery time when delivered 5 min after the toxicant dose. Using the lowest effective dose of each compound determined during the first (prophylactic) set of experiments, neuromuscular recovery following cyanide intoxication in the presence/absence of the cobalt-based antidotes was assessed by RotaRod testing. All the compounds tested accelerated recovery of neuromuscular coordination, and no persistent impairment in any group, including those animals that received toxicant and no antidote, was apparent up to 2 weeks postexposures. The relative effectiveness of the cobalt compounds as cyanide antidotes are discussed and rationalized on the basis of the cyanide-binding stoichiometries and stability constants of the Co(III) cyano adducts, together with consideration of the rate constants for axial ligand substitutions by cyanide in the Co(II) forms.
- Tacrolimus induced nephrotoxicity and pulmonary toxicity in Wistar rats. [Journal Article]
- JBJ Biol Regul Homeost Agents 2017 Oct-Dec; 31(4):1061-1066
- Transplantation has evolved into an accepted treatment for end-stage organ failure. The major limitation for solid organ transplantation is organ rejection, which is an adaptive immune response cause...
Transplantation has evolved into an accepted treatment for end-stage organ failure. The major limitation for solid organ transplantation is organ rejection, which is an adaptive immune response caused by the activation of T-cells. Immunosuppressant drugs are used to overcome this problem. Tacrolimus is a powerful immunosuppressive drug which is used to minimize the risk of organ rejection. The present study was designed to find the toxic effects of tacrolimus on lungs and kidneys. Wistar rats were divided into 4 experimental groups and one control group (n=9). Each rat of the experimental group was orally given the aqueous suspension of tacrolimus powder (3mg/ml) and dissected after 6, 12, 24 and 48 hours of tacrolimus suspension dose. Lungs and kidneys were excised and processed for histopathological and histochemical alterations. Kidney tissues presented signs of toxic potential on tissue architecture such as increased interstitial spaces, necrosis, especially acute tubular necrosis, glomerular shrinkage, dilated blood vessels and enlargement of Bowman’s capsule. Lung sections also confirmed the toxic potential, characterized by bronchiolar wall thickening, alveolar cells necrosis, collapsing of alveolar spaces and interstitial round cell infiltrate. Results of Prussian blue iron staining showed no iron deposition in kidney architecture while in lung sections, iron accumulation was evident. Taken together from these observations we can conclude that tacrolimus may induce toxicity to a certain extent with structural distortion of the kidneys and lungs.
- Mesoporous composite nanoparticles for dual-modality ultrasound/magnetic resonance imaging and synergistic chemo-/thermotherapy against deep tumors. [Journal Article]
- IJInt J Nanomedicine 2017; 12:7273-7289
- High-intensity focused ultrasound (HIFU) is a promising and noninvasive treatment for solid tumors, which has been explored for potential clinical applications. However, the clinical applications of ...
High-intensity focused ultrasound (HIFU) is a promising and noninvasive treatment for solid tumors, which has been explored for potential clinical applications. However, the clinical applications of HIFU for large and deep tumors such as hepatocellular carcinoma (HCC) are severely limited by unsatisfactory imaging guidance, long therapeutic times, and damage to normal tissue around the tumor due to the high power applied. In this study, we developed doxorubicin/perfluorohexane-encapsulated hollow mesoporous Prussian blue nanoparticles (HMPBs-DOX/PFH) as theranostic agents, which can effectively guide HIFU therapy and enhance its therapeutic effects in combination with chemotherapy, by decreasing the cavitation threshold. We investigated the effects of this agent on ultrasound and magnetic resonance imaging in vitro and in vivo. In addition, we showed a highly efficient HIFU therapeutic effect against HCC tumors, as well as controlled drug release, owing to the phase-transitional performance of the PFH. We therefore conclude that HMPB-DOX/PFH is a safe and efficient nanoplatform, which holds significant promise for cancer theranostics against deep tumors in clinical settings.
- Composite iron oxide-Prussian blue nanoparticles for magnetically guided T1-weighted magnetic resonance imaging and photothermal therapy of tumors. [Journal Article]
- IJInt J Nanomedicine 2017; 12:6413-6424
- Theranostic nanoparticles offer the potential for mixing and matching disparate diagnostic and therapeutic functionalities within a single nanoparticle for the personalized treatment of diseases. In ...
Theranostic nanoparticles offer the potential for mixing and matching disparate diagnostic and therapeutic functionalities within a single nanoparticle for the personalized treatment of diseases. In this article, we present composite iron oxide-gadolinium-containing Prussian blue nanoparticles (Fe3O4@GdPB) as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI) and photothermal therapy (PTT) of tumors. These particles combine the well-described properties and safety profiles of the constituent Fe3O4nanoparticles and gadolinium-containing Prussian blue nanoparticles. The Fe3O4@GdPB nanoparticles function both as effective MRI contrast agents and PTT agents as determined by characterizing studies performed in vitro and retain their properties in the presence of cells. Importantly, the Fe3O4@GdPB nanoparticles function as effective MRI contrast agents in vivo by increasing signal:noise ratios in T1-weighted scans of tumors and as effective PTT agents in vivo by decreasing tumor growth rates and increasing survival in an animal model of neuroblastoma. These findings demonstrate the potential of the Fe3O4@GdPB nanoparticles to function as effective theranostic agents.
- Oral Glycine and Sodium Thiosulfate for Lethal Cyanide Ingestion. [Journal Article]
- JCJ Clin Toxicol 2017; 7(3)
- CONCLUSIONS: Oral sodium thiosulfate with gastric alkalization rescued animals from lethal doses of ingested cyanide. The combination of oral glycine and sodium thiosulfate may have potential for treating high dose acute cyanide ingestion and merits further investigation. The combination of systemic and oral therapy may provide further options.
- Bactericidal activity of alpha-bromocinnamaldehyde against persisters in Escherichia coli. [Journal Article]
- PlosPLoS One 2017; 12(7):e0182122
- Persisters are tolerant to multiple antibiotics, and widely distributed in bacteria, fungi, parasites, and even cancerous human cell populations, leading to recurrent infections and relapse after the...
Persisters are tolerant to multiple antibiotics, and widely distributed in bacteria, fungi, parasites, and even cancerous human cell populations, leading to recurrent infections and relapse after therapy. In this study, we investigated the potential of cinnamaldehyde and its derivatives to eradicate persisters in Escherichia coli. The results showed that 200 μg/ml of alpha-bromocinnamaldehyde (Br-CA) was capable of killing all E. coli cells during the exponential phase. Considering the heterogeneous nature of persisters, multiple types of persisters were induced and exposed to Br-CA. Our results indicated that no cells in the ppGpp-overproducing strain or TisB-overexpressing strain survived the treatment of Br-CA although considerable amounts of persisters to ampicillin (Amp) and ciprofloxacin (Cip) were induced. Chemical induction by carbonyl cyanide m-chlorophenylhydrazone (CCCP) led to the formation of more than 10% persister to Amp and Cip in the entire population, and Br-CA still completely eradicated them. In addition, the cells in the stationary phase, which are usually highly recalcitrant to antibiotics treatment, were also completely eradicated by 400 μg/ml of Br-CA. Further studies showed that neither thiourea (hydroxyl-radical scavenger) nor DPTA (Fe3+ chelator to block the hydroxyl-radical) affected the bactericidal efficiency of the Br-CA to kill E. coli, indicating a ROS-independent bactericidal mechanism. Taken together, we concluded that Br-CA compound has a novel bactericidal mechanism and the potential to mitigate antibiotics resistance crisis.
- Correlation between serum ferritin and bone marrow iron stores. [Journal Article]
- TDTrop Doct 2017; 47(3):217-221
- Bone marrow aspirate examination is a gold standard to assess bone marrow iron stores. The correlation between serum ferritin and bone marrow iron has not been established in detail, as the cutoff va...
Bone marrow aspirate examination is a gold standard to assess bone marrow iron stores. The correlation between serum ferritin and bone marrow iron has not been established in detail, as the cutoff value for iron stores have not been uniformly established. Ours was a cross-sectional study. Perl's Prussian blue stain was used to stain bone marrow, assessed by Gale's grading. Receiver operating characteristic curve analysis and Spearman's correlation coefficient calculated. Gale's grading revealed iron store deficiency in 26 and sufficiency in 13. Spearman's correlation coefficient of 0.90 showed a significant relation between serum ferritin and bone marrow iron stores. A serum ferritin of 228 pmol/L had high sensitivity and specificity for iron deficiency; our study suggests that this level be taken as the cutoff value to predict iron store deficiency in bone marrow.
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- Design, Synthesis, and Antifouling Activity of Glucosamine-Based Isocyanides. [Journal Article]
- MDMar Drugs 2017 Jun 29; 15(7)
- Biofouling, an undesirable accumulation of organisms on sea-immersed structures such as ship hulls and fishing nets, is a serious economic issue whose effects include oil wastage and clogged nets. Or...
Biofouling, an undesirable accumulation of organisms on sea-immersed structures such as ship hulls and fishing nets, is a serious economic issue whose effects include oil wastage and clogged nets. Organotin compounds were utilized since the 1960s as an antifouling material; however, the use of such compounds was later banned by the International Maritime Organization (IMO) due to their high toxicity toward marine organisms, resulting in masculinization and imposex. Since the ban, there have been extensive efforts to develop environmentally benign antifoulants. Natural antifouling products obtained from marine creatures have been the subject of considerable attention due to their potent antifouling activity and low toxicity. These antifouling compounds often contain isocyano groups, which are well known to have natural antifouling properties. On the basis of our previous total synthesis of natural isocyanoterpenoids, we envisaged the installation of an isocyano functional group onto glucosamine to produce an environmentally friendly antifouling material. This paper describes an effective synthetic method for various glucosamine-based isocyanides and evaluation of their antifouling activity and toxicity against cypris larvae of the barnacle Amphibalanus amphitrite. Glucosamine isocyanides with an ether functionality at the anomeric position exhibited potent antifouling activity, with EC50 values below 1 μg/mL, without detectable toxicity even at a high concentration of 10 μg/mL. Two isocyanides had EC50 values of 0.23 and 0.25 μg/mL, comparable to that of CuSO₄, which is used as a fouling inhibitor (EC50 = 0.27 μg/mL).