The present study was undertaken to explore the protective effect of melatonin against isoproterenol bitartrate (ISO)-induced myocardial injury in rat. Treatment of rats with ISO increased the level of lipid peroxidation products and decreased the reduced glutathione levels in cardiac tissue indicating that this synthetic catecholamine induces oxidative damage following oxidative stress. Pretreatment of ISO-injected rats with melatonin at a dose of 10 mg/kg body weight, i.p. prevented these changes. Additionally, melatonin also restored the activities and the levels of antioxidant enzymes which were found to be altered by ISO treatment. Treatment of rats with ISO resulted into an increased generation of hydroxyl radicals with melatonin pretreatment significantly reducing their production. Finally, treatment of rats with ISO caused a lowering of systolic pressure with reduced cardiac output and diastolic dysfunction whereas melatonin pretreatment significantly restored many of these parameters to normal. The findings document melatonin's ability to provide cardio protection at a low pharmacological dose. Melatonin has virtually no toxicity which raises the possibility of this indole being a therapeutic treatment for ischemic heart disease.

The long terminal repeats of murine intracisternal A particles (IAPs) contain an IAP proximal enhancer (IPE) element that is inactive in murine F9 embryonal carcinoma cells and active in the parietal endoderm cell line PYS-2. The element binds efficiently to a 60-kDa IPE-binding protein (IPEB) present in PYS-2 cells but poorly to F9 proteins, suggesting a role for IPEB in regulating IAP expression. We have purified calf thymus IPEB, which binds to the IPE and transactivates a reporter gene in HeLa cell extracts. Based on the peptide sequence of the purified calf IPEB, we have cloned a 420-bp cDNA and showed that the encoded protein is the homolog of human p54 nrb and mouse NonO, which are characterized by the presence of two RNA recognition motifs. We show that p54 nrb is an IPE-binding transcription activator with its DNA-binding and activation domains in the N-and C-terminal halves, respectively. The activation domain of p54 nrb is active in HeLa, PYS-2, and F9 cells, whereas p54 nrb as a whole molecule is active in HeLa and PYS-2 cells but not in F9 cells. Thus, the lack of activity of p54 nrb in F9 cells is due to an ineffective DNA-binding domain. We demonstrate that p54 nrb also binds to a pre-mRNA. Based on the close sequence relatedness of this protein to PSF, which is required for pre-mRNA splicing in vitro, we discuss the possibility that p54 nrb has dual roles in transcription and splicing.Murine intracisternal A particles (IAPs) are defective endogenous retroviruses encoded by proviral elements that are reiterated 2,000 times and dispersed throughout the genome. IAPs are constitutively expressed at high levels in many mouse tumors and at basal levels in most normal adult mouse tissues (reviewed in references 21 and 22). In tumor cells where IAPs are actively expressed, these elements transpose and act as insertional mutagens via integration of actively synthesizing extrachromosomal viral DNA to new sites in the host genome. Such transpositions induce aberrant expression of target genes, contributing to augmented growth autonomy of the host cell and thus to the process of neoplastic transformation (21,22,25). Several germ line insertions contributing to mutagenesis have also been found (7,22). Thus, investigation of the mechanism of IAP transcriptional activation should ultimately lead to an understanding of the role of endogenous retroviruses in transposition-induced mutagenesis.IAP proviral elements contain in their long terminal repeats (LTRs) all of the cis-acting elements required for the enhancement of IAP gene transcription (8,23,26). The cis elements and their interacting transcription factors identified so far include the Enh1 and Enh2 elements located between nucleotides (nt) Ϫ164 and Ϫ110, which bind to EBP-80 of murine myeloma cells (13,14), and sites located at the 5Ј end of the LTR between nt Ϫ210 and Ϫ168, which bind to 28-and 46-kDa proteins of murine PCC3 embryonal carcinoma (EC) cells (40). In our analyses of the mechanism by which IAP expression becomes activated, we have found that...

The present study was undertaken to explore the protective effect of melatonin against isoproterenol bitartrate (ISO)-induced rat myocardial injury and to test whether melatonin has a role in preventing myocardial injury and recovery when the ISO-induced stress is withdrawn. Treatment for rats with ISO altered the activities of some of the key mitochondrial enzymes related to energy metabolism, the levels of some stress proteins, and the proteins related to apoptosis. These changes were found to be ameliorated when the animals were pretreated with melatonin at a dose of 10 mg/kg BW, i.p. In addition to its ability to reduce ISO-induced mitochondrial dysfunction, we also studied the role of melatonin in the recovery of the cardiac tissue after ISO-induced damage. Continuation of melatonin treatment in rats after the withdrawal of ISO treatment was found to reduce the activities of cardiac injury biomarkers including serum glutamate oxaloacetate transaminase (SGOT), lactate dehydrogenase (LDH), and cardio-specific LDH1 to control levels. The levels of tissue lipid peroxidation and reduced glutathione were also brought back to that seen in control animals by continued melatonin treatment. Continuation of melatonin treatment in post-ISO treatment period was also found to improve cardiac tissue morphology and heart function. Thus, the findings indicate melatonin’s ability to provide cardio protection at a low pharmacological dose and its role in the recovery process. Melatonin, a molecule with very low or no toxicity may be considered as a therapeutic for the treatment for ischemic heart disease.

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Oncocytes are epithelial cells with abundant, granular, eosinophilic cytoplasm due to presence of numerous large mitochondria of varied sizes. The presence of oncocytes in salivary glands can occur in a variety of conditions. Here, we present a rare case of a 68 year old male patient who presented with a 6 cm diameter swelling in the right parotid region. A fine needle aspiration cytology done from the lesion showed a cellular oncocytic lesion. A possibility of oncocytoma was entertained. Histopathology of the mass showed a rare entity called diffuse hyperplastic oncocytosis. Originally believed to be a metaplastic process, oncocytes can occur in various lesions ranging from hyperplastic conditions to malignant neoplasms. However, diagnosis on cytological smears can be very challenging for the cytopathologist.

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