Effect of a selective cyclooxygenase-2 inhibitor, nimesulide, on the growth of lung tumors and their expression of cyclooxygenase-2 and peroxisome proliferator- activated receptor-gamma.

PURPOSE: The objectives of this study were to evaluate the effect of a cyclooxygenase (COX)-2 inhibitor, nimesulide, on the growth inhibition of s.c. human lung A549 adenocarcinoma tumors and to assess the effect of nimesulide on the expression of COX-2 and peroxisome proliferator-activated receptor (PPAR)-gamma in lung tumors harvested from mice. EXPERIMENTAL DESIGN: Female nu/nu mice were xenografted with s.c. A549 lung tumors, and 1 day after tumor implantation, the mice were fed with a diet containing nimesulide at 250-1500 ppm doses. Tumor dimensions were monitored twice weekly, and tumor samples isolated from mice were used to determine prostaglandin E(2) (PGE(2)) levels by enzyme immunoassay, expression of COX-2 and PPAR-gamma by Western blotting and immunohistochemistry. Furthermore, the induction of apoptosis in tumor specimens was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling staining. RESULTS: Nimesulide treatment showed a dose-dependent growth-inhibitory effect of A549 tumors with a maximum of 77.7% inhibition at 1500 ppm of nimesulide. Western blotting experiments showed similar expression of COX-2 in both control and nimesulide (250-1500 ppm)-treated mice tumor tissues. PPAR-gamma was found to be overexpressed as a result of 1500 ppm nimesulide treatment and was not detected in tumors from control or 250-1000 ppm nimesulide-treated mice. Nimesulide (1500 ppm) significantly reduced intratumor PGE(2) levels (P < 0.001) and induced apoptosis in 25% of tumor cells as compared with control tumors. CONCLUSIONS: Nimesulide (1500 ppm) induced growth inhibition of A549 lung tumors is associated with the reduction of intratumor PGE(2) levels but without affecting the expression of COX-2. Nimesulide-induced enhancement of the expression of PPAR-gamma may also contribute to its antitumor effect, which needs to be further investigated.     

Expression of the CA1 determinant by carcinomas and by non-malignant epithelial cells in oral lesions

The expression of the Ca antigen was investigated in 5 groups of oral lesions comprising 7 squamous cell carcinomas, 2 pre-invasive carcinomas, 7 lesions of types believed to predispose to carcinoma, 19 lesions of types that do not predispose to carcinoma and 5 biopsies of normal oral mucosa. Using an indirect immunoperoxidase method, the neoplastic epithelium reacted positively with the Ca1 antibody in only 4 out of 7 oral squamous cell carcinomas and the reaction varied between the specimens as to the intensity and number of positively stained cells. Several benign oral lesions specifically bound the Ca1 antibody in areas of epithelium showing infiltration with inflammatory cells. These lesions comprised 5 fibrous epulides, 1 pyogenic granuloma, 1 denture-induced hyperplasia and 1 non-diagnostic ulcer. We conclude that the Ca1 antibody is not sufficiently specific for the carcinoma to be of value in the diagnosis of malignant and premalignant lesions of the oral mucosa.     

Melatonin exerts its analgesic actions not by binding to opioid receptor subtypes but by increasing the release of β-endorphin an endogenous opioid

The occurrence of systematic diurnal variations in pain thresholds has been demonstrated in human. Salivary melatonin levels change following acute pain when other factors that could explain the change have been removed or controlled. Melatonin-induced analgesia is blocked by naloxone or pinealectomy. By using selective radioligands [3H]-DAMGO, [3H]-DPDPE, [3-U69593, and 3H]-nociceptin, we have shown that the bovine pinealocytes contain delta and mu, but not kappa or ORL1 opioid receptor subtypes. In the present study, by using melatonin receptor agonists (6-chloromelatonin or 2-iodo-N-butanoyl-5-methoxytryptamine) or melatonin receptor antagonist (2-phenylmelatonin), we have shown that these agents do not compete with opioid receptor subtypes. However, we observed a time-dependent release of beta-endorphin an endogenous opioid peptide, by melatonin from mouse pituitary cells in culture. Hence, it is suggested that melatonin exerts its analgesic actions not by binding to opioid receptor subtypes but by binding to its own receptors and increasing the release of beta-endorphin.     

Copper complexes of some amino acid derivatives of substituted coumarilic acid

A series of copper complexes of some amino acid derivatives of 6-methoxy-3-methyl-coumarilic acid were prepared. The infrared, visible spectra and magnetic sus-ceptibility of these compounds were reported. All copper complexes were found to have antimicrobial activity against gram-positive bacteria only.     

Nifedipine induced gingival enlargement in an edentulous patient: a case report with one year follow up

Background

Gingival enlargement due to calcium channel blockers is a common complaint reported by patients. It can be localized or generalized and can range from mild to severe, affecting patients appearance and function. Nifedipine induced gingival enlargement is noticed only in 10 % of patients and very few cases of Nifedipine induced gingival enlargement in an edentulous patient have been documented in the literature.

Case presentation

Here in, we report a case of gingival enlargement in a 70?year old hypertensive edentulous patient who was on low dose Nifedipine therapy. Patient wanted complete dentures. We planned to excise the overgrowth and followed up for 1 year.

Conclusion

Nifedipine induced gingival enlargement noticed only in 10 % of patients. Hence, there is a need for physicians and dentist to make a coordinated treatment plan and practice care while prescribing these drugs which are associated with gingival overgrowth.

     

How Should We Investigate Breast Implant Rupture?

We aimed to examine a cohort of patients presenting with breast implant complications to establish the sensitivity and specificity of clinical examination, Ultrasound Scanning (US) and Magnetic Resonance Imaging (MRI) in the diagnosis of implant rupture, and to examine the correlation between US and MRI. We performed a 26-month retrospective review. Patients underwent US and MRI to exclude rupture. Results of US and MRI were compared prospectively for concordance, then retrospectively to clinical findings and surgical diagnosis. Thirty-four patients with 60 implants were reviewed. The sensitivities of clinical diagnosis, US, and MRI for rupture was 42%, 50%, and 83%, respectively, while the specificities were 50%, 90%, and 90%. The concordance between US and MRI was 87%. MRI is the investigation of choice for implant rupture. US is a valuable alternative with good concordance with MRI. When US is positive for implant rupture an MRI is not necessary to confirm the diagnosis. Knowledge of the sensitivity and specificity as well as the concordance between the two investigations is useful to ensure the appropriate use of available resources.     

Applications of Colon Capsule Endoscopy

Purpose of Review

This is a review of colon capsule endoscopy (CCE) with a focus on its recent developments, technological improvements, and current and potential future indications.

Recent Findings

Based on the current literature, CCE II demonstrates comparable polyp detection rates as optical colonoscopy and CT colonography, and improved cost-effectiveness. The main limitation to patient acceptance is the requirement of a rigorous bowel preparation. Preliminary studies show good correlation between CCE and optical colonoscopy for assessment of colonic disease activity in inflammatory bowel disease (IBD).

Summary

CCE II is currently FDA, approved as an adjunctive test in patients with prior incomplete colonoscopy, and in the evaluation of patients with suspected lower gastrointestinal bleeding. The test is approved in Europe as one of the options for average-risk colorectal cancer screening, and high-risk screening in patients with contraindications or unwilling to undergo colonoscopy. CCE has a potential role in the evaluation and monitoring of colonic disease activity in IBD. Future technological advances should focus on minimizing bowel preparation, improvement in reading times, and development of therapeutic capabilities.? With technological improvements, the second-generation colon capsule has a significantly higher sensitivity than the first-generation capsule for detection of colon polyps.? Colon capsule endoscopy has been approved in Europe as an option for average-risk colorectal cancer screening, and high-risk screening in patients with contraindications or unwilling to undergo colonoscopy.? Colon capsule endoscopy has received FDA approval as an option for colorectal cancer screening in patients with prior incomplete colonoscopy, and in evaluation of patients with suspected lower gastrointestinal bleeding.? Colon capsule endoscopy may have a role in evaluation and monitoring of inflammatory bowel disease.? Colon capsule endoscopy currently requires a bowel preparation that is more rigorous than colonoscopy.

     

Hair dye related acute kidney injury--a clinical and experimental study

We studied paraphenylenediamine (PPD)-related acute kidney injury (AKI) in 81 patients and also in albino rats experimentally. In the patients' group AKI was found in 32.7%. Of them, 81.4% needed dialysis support. The overall mortality was 25.9%. In experimental rats the renal lesions were noted in all and they were glomerular congestion, intertubular (interstitial) hemorrhages, acute tubular necrosis, mesangial proliferation, and intratubular casts. The severity of renal injury appears to be dose dependent.