Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz

The present study investigated the effects of dietary oltipraz on cigarette smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats were exposed daily to sidestream cigarette smoke in a whole- body exposure chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained on control diet while another group received the same diet supplemented with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz, starting 1 week prior to initiation of smoke exposure until the end of the experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated 32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladder, respectively. Quantitative analysis revealed that the total adduct level was the highest in lungs (270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48 adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides) and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by >60%, while the reduction in lungs in the low-dose group was approximately 35%. In trachea, the effect of low and high dietary oltipraz on smoke DNA adduction was equivocal, while smoke-related DNA adducts in the heart were minimally inhibited by high-dose oltipraz. In a repeat experiment that employed a 3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the formation of DNA adducts in rat lungs and trachea by 80 and 65%, respectively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.      

Histopathologic parameters of prognosis in cervical cancer – a review

Apart from clinical stage and lymph node status, acknowledged to be among the most powerful predictors of outcome in cervical cancer, the determination of prognosis and thereby the need for adjuvant therapy in surgically treated patients currently relies on a variety of histopathologic factors. The role of many of these is controversial. This may be because histopathology is genuinely lacking in sensitivity for predicting tumor behavior in vivo. There is, however, wide variation in histopathologic definitions and criteria. This is probably the major reason for both the lack of reproducibility in the reporting of certain factors and in their diminished value in predicting behavior. Tumor type, grade, vascular invasion, pattern of invasion, and depth are all extremely important prognostic indicators when used individually or as a part of a scoring system.     

Maternal mortality rates in the last eight years: A university hospital-based study from Turkey.

OBJECTIVE: To analyze the cause of changing maternal mortality ratios (MMRs) in a tertiary women's health center in Turkey in the last eight years. MATERIALS AND METHODS: Charts of patients seen between 1998 and 2005 were retrospectively reviewed. Statistical analysis was performed using the Chi-square test. The results were accepted to be significant when the p value was <0.05. RESULTS: During this period, 27 pregnancy-related deaths were identified via hospital death records. The MMR was found to have decreased in rate by approximately 50% from 822.2/100,000 live births in the previous report including the years 1978-1997 to 412.0/100,000 during the last eight years (p < 0.01). Pregnancy-induced hypertension was still the most frequent cause of maternal death. The decrease in MMR was due to the decrease in the ratio of maternal infection (26.4% in 1978-1997 to 7.4% in 1998-2005, p < 0.01). CONCLUSION: Although treatment in the antenatal care and health service has decreased maternal deaths, it was discovered that the MMR has not reached the optimum levels found in developed countries in the last eight years. Also the percentage of direct obstetric deaths (with the exception of those caused by infection) showed no change and was similar to that found in the previous report (1978-1997).     

ROLE OF INTERMEDIARY BIOMARKERS IN DETERMINING THE ANTICANCER EFFICACY OF MARINE COMPOUNDS

In the present study, two of the probable an umor marine compounds, manzamine A and sarcophine, were screened using benzo[a]pyrene (BP)-derived DNA adduct formation in MCF-7 cells as intermediary biomarker. Briefly, MCF-7 cells were treated with the compounds for 24 h followed by treatment with BP (0.5 μM). After 24h incubation, cellular DNA was isolated and analyzed for BP-derived DNA adducts by ³²P-postlabeling technique. Manzamine A and sarcophine increased the BP-DNA adducts by 2 to 4-folds. Further, manzamine A (50 μM) substantially down regulated the expression of p53 while sarcophine (50 μM) slightly induced the level of p21. The residual DNA repair ability was almost completely abolished by manzamine A while sarcophine was ineffective. Based on our preliminary results, these compounds may be classified as potential genotoxic.     

Development and Characterizations of Pullulan and Maltodextrin-Based Oral Fast-Dissolving Films Employing a Box–Behnken Experimental Design

Migraine is a neurological disorder characterized by severe headaches, visual aversions, auditory, and olfactory disorders, accompanied by nausea and vomiting. Zolmitriptan (ZMT^®) is a potent 5HT1B/1D serotonin receptor agonist frequently used for the treatment of migraine. It has erratic absorption from the gastrointestinal tract (GIT), but its oral bioavailability is low (40–45%) due to the hepatic metabolism. This makes it an ideal candidate for oral fast dissolving formulations. Hence, the current study was undertaken to design and develop oral fast-dissolving films (OFDFs) containing ZMT for migraine treatment. The OFDFs were formulated by the solvent casting method (SCM) using Pullulan (PU) and maltodextrin (MDX) as film-forming agents and propylene glycol (PG) as a plasticizer. The strategy was designed using Box–Behnken experimental design considering the proportion of PU:MDX and percentage of PG as independent variables. The effectiveness of the OFDF’s was measured based on the following responses: drug release at five min, disintegration time (D-time), and tensile strength (TS). The influence of formulation factors, including percent elongation (%E), thickness, water content, moisture absorption, and folding endurance on ZMT-OFDFs, were also studied. The results showed a successful fabrication of stable ZMT-OFDFs, with surface uniformity and amorphous shape of ZMT in fabricated films. The optimized formulation showed a remarkable rapid dissolution, over 90% within the first 5 min, a fast D-time of 18 s, and excellent mechanical characteristics. Improved maximum plasma concentration (C max) and area under the curve (AUC 0–t) in animals (rats) treated with ZMT-OFDFs compared to those treated with an intra-gastric (i-g) suspension of ZMT were also observed. Copolymer OFDFs with ZMT is an exciting proposition with great potential for the treatment of migraine headache. This study offers a promising strategy for developing ZMT-OFDFs using SCM. ZMT-OFDFs showed remarkable rapid dissolution and fast D-time, which might endeavor ZMT-OFDFs as an auspicious alternative approach to improve patient compliance and shorten the onset time of ZMT in migraine treatment.     

Trimetazidine has Promising Preventive Effects on Experimental Chronic Pancreatitis Rat Model

Background: It was aimed to evaluate the preventive efficacy of trimetazidine in an experimental chronic pancreatitis rat model.Methods: Chronic pancreatitis model was accomplished with caerulein and alcohol administration. In the study, 40 female Sprague Dawley rats were randomized into 5 groups containing 8 animals in each. Group 1 (chronic pancreatitis); group 2 (chronic pancreatitis + low-dose trimetazidine group); group 3 (chronic pancreatitis + high-dose trimetazidine group); group 4 (placebo group (chronic pancreatitis + saline)); group 5 (sham group). 24 hours after the last injection, all animals were sacrificed. Tumor necrosis factor-alpha, transforming growth factor-β, malondialdehyde, and glutathione peroxidase levels were tested in blood samples. Histopathologic examinations were conducted by a senior pathologist who was unaware of the group allocations.Results: Results of biochemical parameters of the trimetazidine groups (groups 2 and 3) were significantly favorable compared with the chronic pancreatitis group (group 1) (P < .05). The difference between the low-dose- and the high-dose trimetazidine group (group 3) was significant in terms of blood tests (P < .05). The difference between the low-dose trimetazidine group and the chronic pancreatitis group was not significant in terms of histopathologic scores (P > .05); however, the difference was significant between the high-dose trimetazidine group and the chronic pancreatitis group (P < .05).Conclusions: To the best of our knowledge, this current research is the first study that evaluates trimetazidine’s efficacy in the chronic pancreatitis rat model. Trimetazidine has affirmative preventive properties in the chronic pancreatitis course.     

Investigation of antioxidant compounds in commercial pomegranate molasses products using matrix-solid phase dispersion extraction coupled with HPLC

Pomegranate is a well known fruit for its unique flavor, taste and health benefits. The medicinal properties of this fruits directly associated with the phenolic content present, with great anti-oxidant potential. The research is intended to develop matrix solid phase dispersion method (MSPD) and HPLC quantification of four major anti-oxidant marker constituents (vitamin C, gallic acid, rutin & ellagic acid) in pomegranate molasses samples. The effects of several important experimental parameters like type of dispersant, sample-dispersant ratio, solvents and its volume, time of extraction were investigated. A C₁₈ column with the specification (5?µm, 250?×?4.0?mm) was used for the separation. A gradient flow of mobile phase was selected after many trials containing 0.1%, v/v solution of orthophosphoric acid and acetonitrile. The flow rate was 1.0?mL/min; and the chromatograms were recorded at 254?nm. The validation parameters, like linearity (r²?=?0.9985, 0.9965, 0.9925 & 0.9986), accuracy (100.3, 99.5, 100.9 & 101.9%), intra-day precision (%RSD?=?1.09, 1.02, 1.26 & 0.97), inter-day precision (%RSD?=?1.32, 0.83, 1.07, & 1.15) LOD (0.07, 4.50, 0.45 & 0.40?µg/mL), LOQ (0.095, 9.50, 0.85 & 9.5?µg/mL) and robustness (% RSD?=?0.92, 0.76, 0.81 & 0.83) respectively for vitamin C, gallic acid, rutin & ellagic acid, were found satisfactory as per ICH guidelines.     

Expedient approach for trans-esterification of β-keto esters under solvent free conditions using silica supported boric acid (SiO2–H3BO3) as a recyclable catalyst

A highly efficient trans-esterification of β-keto methyl/ethyl esters with primary, secondary, allylic, benzylic and chiral alcohols has been carried out in excellent yields under solvent-free conditions using silica supported boric acid as a heterogeneous catalyst. The surface morphology of the silica-boric acid catalyst (fresh and recycled) has been characterized by SEM and EDX techniques. This sustainable protocol resulted in a remarkable enhancement in the synthetic efficiency (87–95% yield) with high purity and eliminating the use of an environmentally toxic solvent. The work up procedure is very simple and the catalyst has been successfully recovered and recycled. The present methodology is also applicable for trans-esterification with chiral alcohols on a multi-gram scale without compromising the yield. Noteworthy features of this protocol are simple operational procedure, minimizing production of chemical waste, mild reaction conditions, easy preparation of the catalyst and its recyclability up to five cycles without any appreciable loss of catalytic activity.

A simple, mild, high yielding and minimizing chemical waste procedure for trans-esterification of β-keto methyl/ethyl esters with alcohol groups was developed under solvent-free condition using silica-boric acid as recyclable heterogeneous catalyst.