Effect of Intraperitoneal Curcumin Instillation on Postoperative Peritoneal Adhesions

Objective

The aim of this study was to determine the effect of curcumin on adhesion formation in a rat cecum abrasion model.

Materials and Methods

Thirty Wistar rats were randomized into three groups; the control group received saline, the curcumin group received 10 mg/kg of curcumin after cecal abrasion, and in the sham group the abdominal wall was closed without any abrasion to the cecum. On day 15, adhesions were assessed blindly using a standardized scale, and histopathological samples were taken and examined.

Results

There were no incisional hernias or wound dehiscences in any animals of the three groups. A comparison of adhesion scores showed a significant difference between the curcumin (median = 1) and the control group (median = 2; p < 0.05). The grade of inflammation of the curcumin (median = 1) and the sham (median = 0) group was significantly lower than that of the control group (median = 3; p < 0.01 and p < 0.001, respectively). Hydroxyproline levels were significantly lower in the sham (48.3 ± 11.8 µg/mg) and the curcumin (63.8 ± 13.9 µg/mg) group compared to the control group (85.7 ± 22.1 µg/mg; p < 0.05).

Conclusion

These data suggest that curcumin, administered intraperitoneally, was effective in the prevention of peritoneal adhesion formation.Key Words: Curcumin, Intraperitoneal adhesion, Adhesion formation     

Locomotor differences in Mongolian gerbils with the effects of midazolam administration in the form of eye drops

Background

Midazolam is a sedative-hypnotic agent with amnestic and anticonvulsant properties that can be administrated to mammals through various routes, such as intravenous, intramuscular, oral, intrathecal, rectal, and buccal. Midazolam administration in the form of eye drops through the conjunctiva is not reported in the literature.

Aim

This study aims to demonstrate the possible central nervous system effects of midazolam administration as eyes drops in Mongolian gerbils.

Materials and Methods

Fourteen gerbils were randomly assigned to one of two equal sized groups. The active arm received 2 ml of 10 mg midazolam as eye drops in both eyes. Control group received a total of 2 ml of physiological saline (0.9% NaCl). We subjected the gerbils to an adapted “Open Field” to determine the possible effects on central nervous system of midazolam. Gerbils were allowed to move freely in the open field. Before and after the drug administration, locomotor activities of each gerbil have been recorded. Frequency of loss of righting reflex was quantified.

Results

Conjunctival midazolam administration resulted with the transient loss of righting reflex (p=0.017) and suppressed exploration motion (p=0.018) in the open field test compared to control subjects.

Conclusions

In the present study, administration of conjunctival midazolam as an eye drop may affect gerbil''s locomotor activities and open field behaviors. We argue that, using a sedative and anticonvulsive drug such as midazolam via conjunctival route may be useful in some clinical situations. Therefore, it could be beneficial to develop a new conjunctival formulation of midazolam. Also, there is a need for trials in humans with pharmacokinetic studies.     

Predictive factors for the development of brain metastases in patients with malignant melanoma: a study by the Anatolian society of medical oncology

Background

The development of brain metastases (BMs) was associated with poor prognosis in melanoma patients. Patients with BMs have a median survival of <6 months. Melanoma is the third most common tumor to metastasize to the brain with a reported incidence of 10–40 %. Our aim was to identify factors predicting development of BMs and survival.

Patients and methods

We performed a retrospective analysis of 470 melanoma patients between 2000 and 2012. The logistic regression analyses were used to identify the clinicopathological features of primary melanoma that are predictive of BMs development and survival after a diagnosis of brain metastases.

Results

There were 52 patients (11.1 %) who developed melanoma BMs during the study period. The analysis of post-BMs with Kaplan–Meier curves has resulted in a median survival rate of 4.1 months (range 2.9–5.1 months). On logistic regression analysis site of the primary tumor on the head and neck (p = 0.002), primary tumor thickness (Breslow >4 mm) (p = 0.008), ulceration (p = 0.007), and pathologically N2 and N3 diseases (p = 0.001) were found to be significantly associated with the development of BMs. In univariate analysis, tumor thickness and performance status had a significant influence on post-BMs survival. In multivariate analysis, these clinicopathologic factors were not remained as significant predictive factors.

Conclusions

Our results revealed the importance of primary tumor characteristics associated with the development of BMs. Ulceration, primary tumor thickness, anatomic site, and pathologic ≥N2 disease were found to be significant predictors of BMs development.     

Morphometry,asymmetry and variations of cerebral sulci on superolateral surface of cerebrum in autopsy cases

Background

The cerebral sulci are known as main microanatomical borders that serve as a gateway and surgical passage to reach the ventricles or to the deeper lesions. It is a matter of curiosity that whether there is a convergence between the morphological asymmetry and the functional asymmetry, and also its significance in surgery. The aim of this study is make morphometric measurements and evaluate asymmetry of several sulci on the lateral aspects of the cerebrum in regard to main sulci and related reference key points.

Methods

A total of 100 cerebral hemispheres from 50 autopsy cadavers were examined. The lengths of several sulci on the superolateral aspect of the hemispheres and the distances between the sulci and nearby sulci and the reference key points were measured. Encountered variations were examined and photographed.

Results

Evaluation of the variations: superior frontal sulcus (SFS), inferior frontal sulcus, superior temporal sulcus (STS), precentral sulcus and postcentral sulcus were found to be discontinuous in 60, 46, 41, 84 and 70 % of the hemispheres, respectively. Evaluation of the asymmetry: the distances between SFS posterior end and longitudinal fissure, STS posterior end and lateral sulcus posterior end, as well as lengths of external occipital fissure (EOF), and discontinuous course of STS were significantly different between left and right hemispheres.

Conclusions

There is usually a morphological partial asymmetry between the right and left hemispheres for any individual. Also, some of our measurements were found to be compatible with the ones in the literature, while others were incompatible.     

Influence of a single application of subgingival chlorhexidine gel or tetracycline paste on the clinical parameters of adult periodontitis patients

Abstract. The clinical effects of subgingivally placed 1% chlorhexidine gel (w/w) and 40% tetracycline (w/w) paste in periodontal pockets of 22 adult periodontitis patients were studied. The 2 agents were applied following scaling and root planing in pockets exceeding 4 mm. The patients were randomly divided into 3 groups: (a) scaling and root planing (SCRP) only, the control group; (b) corsodyl gel + SCRP; (c) Tetracycline paste + SCRP. Gel or paste were gently applied using a syringe with a blunt needle until the selected pocket was overfilled. Evaluations were made of clinical parameters including the plaque index (PI), gingival index (GI), bleeding index (GI-S), probing pocket depths, probing attachment levels and position of the gingival margin. The results suggested that all the treatment modalities were effective in producing statistically significant improvements in clinical parameters. It was concluded that the conventional treatment modalities were essential in the treatment of periodontal diseases, but in view of the structure of the periodontal pocket and adjacent complex root surface, subgingival drug application in certain cases, might also provide adjunctive improvement.     

Selective AKR1C3 inhibitors do not recapitulate the anti-leukaemic activities of the pan-AKR1C inhibitor medroxyprogesterone acetate

Background:

We and others have identified the aldo-keto reductase AKR1C3 as a potential drug target in prostate cancer, breast cancer and leukaemia. As a consequence, significant effort is being invested in the development of AKR1C3-selective inhibitors.

Methods:

We report the screening of an in-house drug library to identify known drugs that selectively inhibit AKR1C3 over the closely related isoforms AKR1C1, 1C2 and 1C4. This screen initially identified tetracycline as a potential AKR1C3-selective inhibitor. However, mass spectrometry and nuclear magnetic resonance studies identified that the active agent was a novel breakdown product (4-methyl(de-dimethylamine)-tetracycline (4-MDDT)).

Results:

We demonstrate that, although 4-MDDT enters AML cells and inhibits their AKR1C3 activity, it does not recapitulate the anti-leukaemic actions of the pan-AKR1C inhibitor medroxyprogesterone acetate (MPA). Screens of the NCI diversity set and an independently curated small-molecule library identified several additional AKR1C3-selective inhibitors, none of which had the expected anti-leukaemic activity. However, a pan AKR1C, also identified in the NCI diversity set faithfully recapitulated the actions of MPA.

Conclusions:

In summary, we have identified a novel tetracycline-derived product that provides an excellent lead structure with proven drug-like qualities for the development of AKR1C3 inhibitors. However, our findings suggest that, at least in leukaemia, selective inhibition of AKR1C3 is insufficient to elicit an anticancer effect and that multiple AKR1C inhibition may be required.