A battery in the stenotic esophagus of a child with a congenital tracheoesophageal fistula

A case of a three-year-old male child who was admitted to our hospital with the suspicion that he had swallowed a battery approximately one hour before admittance. The parents believed that it was a button-shaped lithium battery approximately 12 mm in diameter. A chest X-ray was taken immediately, and a battery was identified in the esophagus at the fifth thoracic vertebra. By reviewing the child's medical history, we found that the child had had surgery the day after birth due to congenital atresia of the esophagus and a tracheoesophageal fistula type III b. An esophagoscopy was performed one hour after admittance, and the battery was found to be partially past the scar from the first surgery. Because of that, the battery was pushed further toward the stomach, out of fear that retrieving the battery through the scarred section of the child's esophagus could damage the stenotic wall. Upon the next X-ray of the abdomen, the battery was observed in the stomach. The child was monitored, and X-rays were taken over the next several days. The battery was evacuated in stool eight days after it had been ingested.     

Inhibition of human carbonic anhydrase isozymes I, II and VI with a series of bisphenol, methoxy and bromophenol compounds

Carbonic anhydrase inhibitors (CAI) are valuable molecules as they have several therapeutic applications, including anti-glaucoma activity. In this study, inhibition of three human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I, II and VI with a series of bisphenol and bromophenol derivatives was investigated. Molecular docking studies of a set of such inhibitors within CA I and II were also performed. K(I) values of the molecules 2-9 were in the range of 10.025-892.109 μM for hCA I, 1.437-59.107 μM for hCA II and 11.143-919.182 μM for hCA VI, respectively. Reported inhibitory activities of molecules 2-9 will assist in better understanding of structure-activity relationship studies of CAI.     

Efficacy of vitamin E,phosphatidyl choline,and pyruvate on buffering neuronal degeneration and oxidative stress in cultured cortical neurons and in central nervous tissue of apolipoprotein E-deficient mice

Oxidative stress is a pivotal factor in neuronal degeneration. However, vitamin E was only marginally effective in clinical trials. We examined whether or not a mixture of vitamin E (as alpha-tocopherol), sodium pyruvate and phosphatidyl choline (PC), a mixture that promotes wound healing in non-neuronal systems, would provide neuroprotection beyond that observed with vitamin E alone. Combined treatment with these agents improved survival and neuritic spouting of murine embryonic cortical neurons in culture, and provided neuroprotection against oxidative damage following treatment with hydrogen peroxide. Dietary treatment with these three agents also compensated for the diminished oxidative buffering capacity of brains of apolipoprotein E-deficient mice, while vitamin E alone failed to do so. These data underscore the possibility that critical nutritional deficiencies may modulate the impact of genetic compromise on neurodegeneration.     

Proteasome-associated cysteine deubiquitinases are molecular targets of environmental optical brightener compounds

The levels of organic pollutants, such as optical brightener (OB) compounds, in the global environment have been increasing in recent years. The toxicological effects and signal transduction systems associated with OB toxicity have not been thoroughly studied. The ubiquitin-proteasome system (UPS) plays a crucial role in regulating multiple essential cellular processes, and proteasome-associated cysteine deubiquitinases (DUBs), ubiquitin C-terminal hydrolase L5 (UCHL5) and USP14, are two major regulators for (de)ubiquitination and stability of many important target proteins. Therefore, potential inhibition of UCHL5 and USP14 activities by some environmental chemicals might cause in vivo toxicity. In the current study we hypothesize that electrophilic OB compounds, such as 4,4′-diamino-2,2′-stilbenedisulfonic acid(DAST), fluorescent brightener 28 (FB-28) and FB-71, can interact with the catalytic triads (CYS, HIS, and ASP) of UCHL5 and USP14 and inhibit their enzymatic activities, leading to cell growth suppression. This hypothesis is supported by our findings presented in this study. Results from in silico computational docking and ubiquitin vinyl sulfone assay confirmed the UCHL5/USP14-inhibitory activities of these OB compounds that have potencies in an order of: FB-71 > FB-28 > DAST. Furthermore, inhibition of these two proteasomal DUBs by OBs resulted in cell growth inhibition and apoptosis induction in two human breast cancer cell models. In addition, we found that OB-mediated DUB inhibition triggers a feedback reaction in which expression of UCHL5 and USP14 proteins is increased to compromise the suppressed activities. Our study suggests that these commonly used OB compounds may target and inhibit proteasomal cysteine DUBs, which should contribute to their toxicological effects in vivo.     

Impact of deltamethrin exposure on mRNA expression levels of metallothionein A, B and cytochrome P450 1A in rainbow trout muscles

Metallothioneins (MT) are widely utilized to identify specific responses to heavy metal pollution. In addition, there is evidence demonstrating that in vertebrates MT synthesis is stimulated by different endogenous and exogenous agents in particular compounds leading to production of ROS. Also, cytochrome P450 1A can enhance the generation of ROS. On this basis, MT and CYP 1A induction can be considered as biomarkers of oxidative stress. In the current study, we examined the influences of pesticide administration on the expression of MT-A, MT-B and CYP 1A. For this purpose, we produced muscle metallothionein-A, metallothionein-B and cytochrome P450 1A cDNAs and used quantitative RT-PCR to assay mRNAs in rainbow trout exposed to acute and long-term deltamethrin administration. We observed that deltamethrin exposure significantly (p<0.05) increased the expression levels of Cyp1A, MT-A and MT-B in a time dependent manner. Results of our study contributes to the identification of inducers of such biomarkers in addition to well known agents.     

The effects of mesenchymal stem cell mitochondrial transplantation on doxorubicin‐mediated nephrotoxicity in rats

The effect of dysfunctional mitochondria in several cell pathologies has been reported in renal diseases, including diabetic nephropathy and acute kidney injury. Previous studies have reported that mitochondrial transplantation provided surprising results in myocardial and liver ischemia, as well as in Parkinson's disease. We aimed to investigate the beneficial effects of isolated mitochondria transplantation from mesenchymal stem cells (MSCs) in vivo, to mitigate renal damage that arises from doxorubicin‐mediated nephrotoxicity and its action mechanism. In this study, a kidney model of doxorubicin‐mediated nephrotoxicity was used and isolated mitochondria from MSCs were transferred to the renal cortex of rats. The findings showed that the rate of isolated mitochondria from MSCs maintains sufficient membrane integrity, and was associated with a beneficial renal therapeutic effect. Following doxorubicin‐mediated renal injury, isolated mitochondria or vehicle infused into the renal cortex and rats were monitored for five days. This study found that mitochondrial transplantation decreased cellular oxidative stress and promoted regeneration of tubular cells after renal injury (P < .001, P = .009). Moreover, mitochondrial transplantation reduced protein accumulation of tubular cells and reversed renal deficits (P = .01, P < .001). Mitochondrial transplantation increased Bcl‐2 levels, and caspase‐3 levels decreased in injured renal cells (P < .015, P < .001). Our results provide a direct link between mitochondria dysfunction and doxorubicin‐mediated nephrotoxicity and suggest a therapeutic effect of transferring isolated mitochondria obtained from MSCs against renal injury. To our knowledge, this study is the first study in the literature that showed good therapeutic effects of mitochondrial transplantation in a nephrotoxicity model, which is under‐researched.     

In vitro inhibition of human erythrocyte glutathione reductase by some new organic nitrates

Glutathione reductase (GR), is responsible for the existence of GSH molecule, a crucial antioxidant against oxidative stress reagents. The antimalarial activities of some redox active compounds are attributed to their inhibition of antioxidant flavoenzyme glutathione reductase, and inhibitors are therefore expected to be useful for the treatment of malaria. Twelve organic nitrate derivatives were synthesized and treated with human erythrocyte GR. The molecules were identified as strong GR inhibitors and novel antimalaria candidates.     

Phosphorylation of Tau Alters Its Association with the Plasma Membrane

1. The potential functions of the microtubule-associated protein tau have been expanded by the recent demonstration of its interaction with the plasma membrane. Since the association of tau with microtubules is regulated by phosphorylation, herein we examine whether or not the association of tau with the plasma membrane is also regulated by phosphorylation.2. A range of tau isoforms migrating from 46 to 64 kDa was associated with crude particulate fractions derived from SH-SY-5Y human neuroblastoma cells, and were retained during the initial stages of plasma membrane purification. During the extensive washing utilized in purification of the plasma membrane, portions of each of these isoforms were depleted from the resultant purified membrane. Immunoblot analysis with phospho-dependent and -independent antibodies revealed selective depletion of phospho isoforms during membrane washing. This effect was more pronounced for the slowest-migrating (64-kDa) tau isoform.3. This putative influence of phosphorylation on the association of tau with the plasma membrane was further probed by transfection of SH-SY-5Y human neuroblastoma cells with a tau construct that could associate with the plasma membrane but not with microtubules. Treatment with phorbol ester or calcium ionophore, both of which increased phospho-tau levels within the cytosol and plasma membrane, was accompanied by the dissociation of this tau construct from the membrane.4. These data indicate that phosphorylation regulates the association with the plasma membrane. Dissociation from the membrane by phosphorylation may place tau at risk for hyperphosphorylation and ultimate PHF formation in a manner previously considered for tau dissociated from microtubules.     

Diagnosis of hepatocellular carcinoma by fine needle aspiration cytology. Cellular features

OBJECTIVE: To evaluate the importance of fine needle aspiration cytology (FNAC) in the diagnosis of hepatocellular carcinoma (HCC). STUDY DESIGN: We analyzed 17 cytologic and 5 architectural features in a series of 320 FNACs from HCC and compared them with 73 FNACs from benign lesions and with 705 FNACs from metastatic carcinomas. One thousand ninety-eight patients who were diagnosed by liver FNAC between December 1988 and July 1998 and had adequate follow-up were included in the study. The specimens were evaluated according to the presence or absence of the cytologic features and cellular arrangement. A stepwise logistic regression analysis was performed on the data to determine the variables predictive of HCC. RESULTS: Multinucleated tumor giant cells, cytoplasmic hyaline and central sinusoidal pattern were selected as the 3 most predictive parameters for differentiated reactive hepatocytes from HCC (P < .0001), while bile, centrally located nucleus in an atypical cell and intranuclear inclusion were selected as the 3 most predictive parameters for differentiated metastatic carcinoma from HCC (P < .0001-< .001) by stepwise logistic regression analysis. CONCLUSION: In the 1,098 patients suspected of having hepatic malignancy, a correct diagnosis was made by a combination of the above features. The sensitivity of this procedure for hepatic malignancy was 99.5%, and the specificity was 100%.