Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

Assessment of heavy metals by ICP-OES and their impact on insulin stimulating hormone and carbohydrate metabolizing enzymes

Arsenic (As) and cadmium (Cd) have recently emerged as major health concerns owing to their strong association with diabetes mellitus (DM). We aimed to investigate the heavy metals exposure towards incidence of DM at various enzymatic and hormonal levels. Additionally, association of As and Cd with Zinc (Zn, essential metal) was also evaluated. Spot urine samples were collected to assess As, Cd and Zn through ICP-OES. Serum was analyzed by assay method for fasting blood glucose, liver and renal function biomarkers. ELISA was performed to investigate the impact of heavy metals on HbA1c, α-amylase, DPP-IV, IGF-1, leptin, GSH, MDA, SOD, HDL, FFA, TG and interleukin (IL)-6. Association of heavy metals with DM was measured by odds ratio (OR) and level of significance was assessed by Chi-squared test. Unpaired student's t-test was used to compare DM-associated risk factors in heavy metals-exposed and unexposed participants. As and Cd were detectable in 75.4% and 83% participants with mean concentration of 75.5 ppb and 54.5 ppb, respectively. For As exposure, OR in the third quartile was maximum ie 1.34 (95% CI, 0.80 to 2.23), however the result was not statistically significant (P > .05). For Cd exposure, OR in the fourth quartile was considerably high, 1.62 (95% CI, 1.00 to 2.61), with a significant probability value (P < .05). Urinary Cd was negatively associated with Zn. As and Cd exposure increases the incidence of DM in the general population. Impaired hormonal and enzymatic levels in diabetic and non-diabetic exposed participants reflect the multiple organ damage by heavy metal exposure.     

Antiseptic Compounds Still Active Against Bacterial Strains Isolated from Surgical Wound Infections Despite Increasing Antibiotic Resistance

The in vitro activities of povidone iodine, potassium peroxymonosulfate, and dimethyldidecylammonium chloride were investigated against 379 nosocomial isolates of Staphylococcus aureus and Pseudomonas aeruginosa responsible for surgical wound infections in patients operated on between July 1995 and June 2001. Overall, the isolates were inhibited by the antiseptics at concentrations below those used routinely. In spite of increasing resistance to the various antibiotics used to treat surgical wound infections, no significant variation in the susceptibility to antiseptics was demonstrated during this 6-year study. Electronic Publication     

Hypernephroma associated with multiple endocrine neoplasia type I: a case report

We report a case of multiple endocrine neoplasia type I and hypernephroma. Parathyroid hyperplasia, adrenocortical hyperplasia, a nodular goiter, multiple lipomas, a chromophobe adenoma of the pituitary and hypernephroma had all been diagnosed previously. All but the last are features consistent with the diagnosis of multiple endocrine neoplasia type I (Wermer's syndrome). The association of multiple endocrine neoplasia type I and hypernephroma may represent a new manifestation of this pleiotropic syndrome.     

Effect of long-term β2-agonist dosing on human cardiac β-adrenoceptor expression in vivo: Comparison with changes in lung and mononuclear leukocyte β-receptors

Background. Tachyphylaxis to the cardiac effects of β-adrenoceptor stimulation after long-term β₂-agonist administration is well recognized, but the influence on global cardiac β-adrenoceptor density has not been previously investigated in vivo. Positron emission tomography (PET) has made possible the noninvasive quantification of regional receptor density. This study assesses the effect of long-term β₂-agonist dosing on cardiac β-adrenoceptors.Methods and Results. β-Adrenoceptors in the hearts of 29 healthy male subjects aged 35 ± 8 years were imaged and quantified in vivo by means of PET and compared with the receptor density in the same subjects' lung tissue. Mononuclear leukocyte (MNL) β-receptor density was determined in vitro by means of a radioligand binding assay. β-Receptor density was 8.41 ± 2.03 pmol/gm tissue in heart, 10.81 ± 1.91 pmol/gm tissue in lung, and 38.0 ± 17.5 fmol/mg protein on MNLs. There was a weak relationship between cardiac and pulmonary β-receptor densities (r = 0.45, p < 0.02) but not between cardiac and MNL receptor density. In seven subjects, the measurements were repeated after 2 weeks of albuterol treatment (4 mg orally twice daily and 200 μg inhaled four times daily in the first week, with doubling of the dose during the second week). After the albuterol treatment, β-receptor density fell on average by 19% (p < 0.05) in the heart compared with 22% (p < 0.05) in the lung and 42% (p < 0.05) in MNLs. Correlations were found between the percentage changes in receptor density in heart and lung (r = 0.98, p < 0.001) and in heart and MNLs (r = 0.99, p < 0.002).Conclusions. Two weeks of high-dose albuterol results in equivalent downregulation of β-receptors in vivo, both in the lung and in the heart.     

Effect of fibronectin-rich human cryoprecipitate on fluid volume requirements in sheep during postoperative sepsis

Septic surgical patients often require fluid administration to maintain cardiovascular stability due, in part, to the sepsis-induced increase in vascular permeability and associated plasma volume depletion. Plasma fibronectin deficiency exists in such septic patients. We determined if maintenance of fibronectin levels by administration of fibronectin-rich human plasma cryoprecipitate would lower the resuscitative fluid volume needed for support of arterial pressure in septic postoperative sheep which were experimentally depleted of plasma fibronectin. Following a 2-hr postoperative baseline period, denatured collagen (gelatin, 8.7 mg/kg), which has a high affinity for fibronectin, was infused into both control and experimental sheep in order to acutely deplete plasma fibronectin. Sheep were then challenged both intraperitoneally and intravenously with live Pseudomonas (5 x 10(10) bacteria IP; 5 x 10(9) bacteria IV). Experimentals were given fresh plasma cryoprecipitate intravenously at a dose of 4 units bolus, followed by 3 units/hr for 5 hr. Controls received plasma cryoprecipitate selectively depleted of fibronectin by affinity chromatography. Bacterial challenge rapidly resulted in severe systemic hypotension. Ringer's lactate was infused intravenously into both groups at a rate sufficient to maintain a systemic arterial pressure of approximately 50 mm Hg with a maximum pulmonary artery wedge pressure of 15-18 mm Hg. Its rate of infusion was periodically adjusted to maintain this hemodynamic status. Comparison was made of the volume of Ringer's lactate required to maintain an arterial pressure of 50 mm Hg in both groups. Net fluid requirement was significantly (p less than 0.05) less in postoperative septic sheep (47.4 +/- 6.2 mg/kg/hr) treated with fibronectin-rich cryoprecipitate compared to the fluid requirement (71.7 +/- 4.7 mg/kg/hr) for postoperative septic sheep receiving fibronectin-deficient cryoprecipitate. Thus elevation of plasma fibronectin concentration lowers the fluid requirements needed for hemodynamic support in postoperative Gram-negative sepsis.     

The evaluation of putative tumor markers for malignant melanoma.

Biomarkers have long held out the promise that malignancies might be diagnosed early and that patients could be monitored more confidently during their clinical course to more reliably predict recurrence and the effect of therapy. Reliable tumor markers have been described for colon carcinoma, hepatomas, and other tumors, but no reliable marker has been identified to monitor the course of malignant melanoma. Recently, the plasma level of lipid-bound sialic acid (LASA-P) has been described as reflecting an alteration in the surface membrane of cancer cells. An attempt was made to correlate the LASA-P level, along with the serum level of neuron-specific enolase, a glycolytic enzyme specific to cells of neuroectoderm origin including melanocytes, with clinical disease activity with a follow-up to at least 2 years. Two hundred seventy patients had blood samples drawn at various times during their clinical course for assay of LASA-P and neuron-specific enolase. Eighty of the patients (30%) sampled developed a recurrence sometime during their clinical course, whereas another 10 patients had active disease noted at diagnosis with evaluative tumor markers. The sensitivity and specificity of neuron-specific enolase was 27% and 77%, respectively, and cannot be recommended as a marker for melanoma. LASA-P showed a sensitivity of 65%, with 55 patients recurring and having active disease with abnormally high markers and 35 patients recurring or having active disease with normal markers. Specificity of the LASA-P test was 76%. When recurrence was associated with elevated LASA-P levels, the elevated level preceded recurrence by a median of 9.3 months. LASA-P may be a useful marker to follow patients with malignant melanoma.     

The structure of the avian fast skeletal muscle troponin T gene: seven novel tandem-arranged exons in the exon x region

To elucidate the mechanism that produces enormous molecular diversity in troponin T (TnT) of fast skeletal muscle, we determined the 5-half genomic sequence of the chicken fast muscle TnT gene. The sequence of ca. 16 kb included seven exons (exons 1, 2, 3, 4, w, 5, and 6), which have been reported previously and presumed by sequencing TnT cDNAs. Additionally we found six 15 nt and one 18 nt sequences in the region between exons 5 and 6 (i.e. the exon x region). They were encompassed by consensus splice donor and acceptor sites and preceded by putative branch sites, and designated herein as exons xa to xg. Our result shows that the sequence derived from exons x1, x2, and x3, the exons presumed previously by cDNA sequencing, is actually encoded by the seven exons xa to xg, establishing the precise gene structure in the exon x region. Based on our data, together with that on the 3-half genomic sequence of the quail fast muscle TnT gene, we conclude that the avian fast skeletal muscle TnT gene includes 27 exons, 16 of which are alternatively spliced.