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.     

Bacteria induce osteoclastogenesis via an osteoblast-independent pathway

Bacteria or their products may cause chronic inflammation and subsequent bone loss. This inflammation and bone loss may be associated with significant morbidity in chronic otitis media, periodontitis, endodontic lesions, and loosening of orthopedic implants caused by lipopolysaccharide (LPS)-contaminated implant particles. Currently, it is not clear how bacteria or endotoxin-induced bone resorption occurs and what cell types are involved. Here we report that Porphyromonas gingivalis, a periodontal pathogen, and Escherichia coli LPS induce osteoclastic cell formation from murine leukocytes in the absence of osteoblasts. In contrast, stimulation with parathyroid hormone had no effect. These multinucleated, tartrate-resistant acid phosphatase-positive cells were positive for receptor activator of NF-kappaB (RANK), the receptor for osteoprotegerin ligand (OPGL), also known as RANK ligand (RANKL). Blocking antibodies demonstrated that their formation was dependent upon expression of OPGL and, to a lesser extent, on tumor necrosis factor alpha. Mononuclear cells represented a significant source of OPGL production. In vivo, P. gingivalis injection stimulated OPGL expression in both mononuclear leukocytes and osteoblastic cells. Thus, these findings describe a pathway by which bacteria could enhance osteolysis independently of osteoblasts and suggest that the mix of cells that participate in inflammatory and physiologic bone resorption may be different. This may give insight into new targets of therapeutic intervention.     

Novel Marine Compounds: Anticancer or Genotoxic?

In the past several decades, marine organisms have generouslygifted to the pharmaceutical industries numerous naturallybioactive compounds with antiviral, antibacterial,antimalarial, anti-inflammatory, antioxidant, and anticancerpotentials. But till date only few anticancer drugs (cytarabine,vidarabine) have been commercially developed from marinecompounds while several others are currently in differentclinical trials. Majority of these compounds were tested in thetumor xenograft models, however, lack of anticancer potentialdata in the chemical- and/or oncogene-induced pre-initiationanimal carcinogenesis models might have cost some of the marineanticancer compounds an early exit from the clinical trials. Thisreview critically discusses importance of preclinicalevaluation, failure of human clinical trials with certainpotential anticancer agents, the screening tests used, and choiceof biomarkers.     

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.     

A Study on Sustainable Concrete with Partial Substitution of Cement with Red Mud: A Review

Every year, millions of tons of red mud (RDM) are created across the globe. Its storage is a major environmental issue due to its high basicity and tendency for leaching. This material is often kept in dams, necessitating previous attention to the disposal location, as well as monitoring and maintenance during its useful life. As a result, it is critical to develop an industrial solution capable of consuming large quantities of this substance. Many academics have worked for decades to create different cost-effective methods for using RMD. One of the most cost-effective methods is to use RMD in cement manufacture, which is also an effective approach for large-scale RMD recycling. This article gives an overview of the use of RMD in concrete manufacturing. Other researchers’ backgrounds were considered and examined based on fresh characteristics, mechanical properties, durability, microstructure analysis, and environmental impact analysis. The results show that RMD enhanced the mechanical properties and durability of concrete while reducing its fluidity. Furthermore, by integrating 25% of RDM, the environmental consequences of cumulative energy demand (CED), global warming potential (GWP), and major criteria air pollutants (CO, NO_X, Pb, and SO₂) were minimized. In addition, the review assesses future researcher guidelines for concrete with RDM to improve performance.     

Interobserver variability in ultrasound assessment of thyroid nodules

The first diagnostic tool for thyroid disease management is ultrasound. Despite its importance, ultrasound is an extremely subjective procedure that requires a high level of performance skill. Few studies have assessed thyroid ultrasound performance and its effectiveness, particularly the variability between observers in the assessment of ultrasound images. This study evaluated the variability in ultrasound assessments and diagnoses of thyroid nodules between 2 radiologists. In this retrospective study, 75 thyroid nodules in 39 patients were reviewed by 2 experienced radiologists. The nodule composition, margin, shape, calcification, and vasculitis were determined using echogenicity. The study evaluation included these 5 assessments and the final diagnosis. Interobserver variation was determined using Cohen kappa statistics. The interobserver agreements in the interpretation of echogenicity, shape, and margin were fair (κ = 0.21–0.40), whereas there were substantial agreements for vascularity and calcification (κ = 0.62–0.78). The agreements between the observers for individual ultrasound features in this study were the highest for vascularity and the presence/absence of calcification. The interobserver reproducibility for thyroid nodule ultrasound reporting was adequate, but the diagnostic evaluation ability of the observers was inconsistent. The variability in the interpretation of sonographic features could influence the level of suspicion of thyroid malignancy. This study emphasizes the need for consistency in the training of sonographic interpretation of thyroid nodules, particularly for echogenicity, shape, and margin.     

Pelvi-abdominal ACTINOMYCOSIS as a complication of long-term use of intrauterine device (IUD). The important role of imaging in diagnosis and follow-up

ACTINOMYCOSIS is a rare chronic granulomatous disease caused by anaerobic filamentous gram-positive bacteria, the most common of which is Actinomyces israelii. Actinomycetes are commensal inhabitants of the oral cavity and gastrointestinal tract, but they may become pathogenic through invasion of breached or necrotic tissue. Pelviabdominal ACTINOMYCOSIS is uncommon and can mimic a variety of disease processes, including abdominal mass mimicking malignancy, acute abdomen, asthenia, and weight loss. We describe a 38-year-old woman who presented with acute abdominal pain and tenderness, as well as constitutional manifestations and elevated inflammatory markers. On initial computerized tomography (CT) and MRI, a large fluid collection underlining the anterior abdominal wall at the false pelvic cavity, as well as parietal peritoneal enhancement and smudging of the mesenteric fat and a bulky fibroid uterus with an implanted IUD, were identified. The ultrasound guided aspiration and anaerobic culture revealed positive growth for Actinomyces bacteria. An exploratory laparoscopy revealed extensive adhesions between the abdominal wall and the small intestine, as well as hyperemic and thickened peritoneum, and peritoneal biopsy confirmed ACTINOMYCOSIS. After the diagnosis was established, the IUD was removed and the patient was given Ceftriaxone 2 gm once daily for 6 weeks before switching to oral doxycycline 100 mg twice daily for another 3 months. A significant regression of the suprapubic fluid collection, and peritoneal-mesenteric changes were confirmed on follow-up. The case is discussed, and the relevant literature reviewed and analyzed.     

Intraoperative blood transfusion in pediatric patients undergoing renal transplant—Effect of renal graft size

In pediatric RT, donor allograft size often exceeds the expected recipient norms, especially in younger recipients. An “oversize” graft might not only present a technical‐ and space‐related challenge, but may possibly lead to increased demands in perioperative volume requirements due to the disparity between donor and recipient in renal blood flow. We evaluated transfusion practices at a single tertiary institution with special consideration of kidney graft size, hypothesizing that oversize graft kidneys might lead to a quantifiable increased need of blood transfusion in smaller recipients. Retrospective analysis of all patients who underwent pediatric RT from January 2004 to June 2014 at a tertiary pediatric centre was performed. Variables analyzed included patient age, weight, pre‐ and postoperative Hb concentration, graft size, EBL, amount of intraoperative blood transfusion, and preoperative use of erythropoietin. Based on graft size in relation to patient's age, a SMR and an OvR were identified. A subcohort of age‐matched pairs was used to allow for comparison between groups. We calculated the expected procedure‐ and transfusion‐induced changes in Hb and compared these changes to the observed difference in pre‐ vs postoperative Hb to assess the influence of graft size on transfusion requirements. RT was performed in 188 pediatric recipients during the study period. In the matched cohort, percentage of transfused patients during transplantation in the OvR group was more than double compared with SMR (89% vs 39%, P < .001); similarly, the median number of transfused PRBC units in OvR was 1, while the median of SMR did not receive transfusion (P < .001). The difference between expected (calculated) and observed change in Hb was significantly higher in OvR with a median of 1.9 g/dL compared with SMR with a median of 1.0 g/dL (P = .026). Correspondingly, the calculated median volume taken up by a regular size kidney was significantly higher with 213 mL compared with 313 mL (P = .031) taken up by an oversize graft kidney. Median estimated intraoperative blood loss was significantly higher in OvR than in SMR (6.9 mL/kg, vs 5.3 mL/kg, respectively; P = .04). Median postoperative Hb was similar among groups (10.4 g/dL vs 10.6 g/dL for SMR vs OvR, respectively). Transplantation of an oversized kidney in pediatric RT recipients is associated with a quantifiable higher need for blood transfusion. This may be caused by a higher intraoperative EBL and/or greater blood volume sequestered by the larger renal allograft and requires further evaluation.     

Effect of sinapic acid on aripiprazole pharmacokinetics in rats: Possible food drug interaction

Dietary supplements and foods can interact with various drugs, leading to possible clinical concerns. This study aimed to investigate the effect of orally administered sinapic acid (SA) on the pharmacokinetics of aripiprazole (APZ) in rats and its possible modulatory effects on hepatic cytochrome P450 (CYP3A2 and CYP2D6) expression in the liver tissues. Single dose and multiple dose parallel groups of wistar rats were categorized into six groups (n = 6 each) which abstained from food for 12 h prior to the experiment, while water was allowed ad libitum. The investigation was carried out for single dose: Group I was treated with normal saline orally for 15 days (normal control). Group II was administered normal saline orally for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group III received SA (20 mg/kg p.o.) for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group IV was treated with SA (20 mg/kg p.o.) for 15 days. For the multiple dose study, Group I was treated with normal saline orally for 15 days (normal control); Group II received APZ (3 mg/kg p.o.) daily for 15 days; Group III was administered with SA (20 mg/kg p.o.) and APZ (3 mg/kg p.o.) for 15 days and Group IV received SA (20 mg/kg p.o.) for 15 days. The group I and IV were kept common in single and multiple dose groups. After last APZ dose, plasma samples were collected and APZ concentrations were determined using an UPLC-MS/MS technique. The pharmacokinetic parameters were calculated using a non-compartmental analysis. The concomitant administration of APZ with SA (as single or multiple dose) resulted in an increase in APZ absorption and a decrease on its systemic clearance. This was associated with a reduction in CYP3A2 and CYP2D6 protein expressions by 33–43% and -71–68% after the single and multiple co-administration, which are two enzymes responsible of the metabolism of APZ. Therefore, a reduction in the metabolic clearance appears to be the mechanism underlying the drug interaction of dietary supplement containing SA with APZ. Therefore, the concomitant administration of SA and APZ should be carefully viewed. Further investigations are required to assess the clinical significance of such observations in humans.     

Agreement analysis of sleep patterns between self-reported questionnaires and actigraphy in adults

Purpose

To investigate the agreement in sleep pattern recording by self-reported sleep questionnaires and actigraphy in adults.

Methods

This is a cross-sectional study. Men and women who met inclusion criteria were recruited for this study. The inclusion criteria were apparently healthy Omani nationals ages 19 to 50 years. Sleep questionnaires were randomly distributed in Muscat either directly or via electronic and paper announcements. Data were collected from the participants using the self-reported questionnaires with four piloted questions for sleep pattern identification and through the actigraphy wristband given to subjects to wear for a week. Cohen’s kappa test was performed for agreement analysis.

Results

A total of 964 Omani subjects between ages 18 and 59 years of both genders were recruited and completed the questionnaires successfully. Out of these, only 321 subjects wore the actigraphy wristband for 1 week (response rate = 33%). Agreement analysis reported a mild level of agreement for the monophasic (41%), moderate level for biphasic (59%), and good level for polyphasic (70%) sleep patterns. The overall agreement level of sleep patterns between the two methods was 57%. There is a low specificity of self-reported assessment in reporting sleep pattern.

Conclusion

The average agreement level of subjective versus objective assessments of sleep patterns was moderate at 57% and self-reported sleep pattern is not specific. The study recommends the use of actigraphy along with sleep questionnaires for accurate assessment of sleep patterns in cohort studies.