Development of LC-MS/MS analytical method for the rapid determination of Diquat in water and beverages.

This study aimed to develop simple, fast, and sensitive methods for the determination of diquat (DQ) in various matrices such as water and beverages. For water, direct injection was tested first, however, the sensitivity of the incurred samples were too low and couldn't possibly achieve the targeted limit of quantification. Hence, dilution with "weaker" injection solvents were tested, and the final conditions involved the dilution of water with acetonitrile (0.4 % ammonium hydroxide) which increased the sensitivity by more than ten times. Nevertheless, the beverages samples needed further treatment to achieve acceptable spiked recovery. The final conditions involved extraction using the aforementioned solvent, followed by heating and partitioning. Both of the methods satisfied the validation requirements, with an average recovery ranging from 85.9 to115 % and associated relative standard deviation (RSD %) within the range 3-8. Further applications on real samples were done to test the levels of contamination.

Seroprevalence of Toxoplasma gondii, Neospora caninum and Trichinella spp. in Pigs from Cairo, Egypt.

Pork production is a niche economy in Egypt, and pigs are typically raised as backyard animals with no sanitary control, potentially exposing them to various pathogens. Commercially available ELISAs were used to detect specific antibodies to the food-borne zoonotic parasites Toxoplasma gondii and Trichinella spp., as well as to Neospora caninum, in serum samples of pigs slaughtered at Egypt's only licensed pig abattoir, the El-Bassatin abattoir in Cairo. Among the tested sera (n = 332), seroreactivity for T. gondii was 45.8% (95% confidence interval: 40.4-51.3), N. caninum was 28.0% (95% CI: 23.3-33.2), and Trichinella spp. was 1.2% (95% CI: 0.4-3.3). Mixed infection was only detected for T. gondii and N. caninum (18.7%; 95% CI: 14.7-23.4). The seroprevalence of T. gondii was significantly higher (p = 0.0003) in animals collected from southern Cairo (15 May city slum) than in eastern Cairo (Ezbet El Nakhl slum). Seroprevalence for N. caninum was higher in western (Manshiyat Naser slum; p = 0.0003) and southern Cairo (15 May city slum; p = 0.0003) than in that of eastern Cairo (Ezbet El Nakhl slum; p = 0.0003). Moreover, female pigs exhibited a higher rate of N. caninum antibodies than male ones (p < 0.0001). This study provides the first seroprevalence data for N. caninum in pigs in Egypt, and updates the prevalence of the zoonotic parasites Trichinella spp. and T. gondii.

Pleomorphic rhabdomyosarcoma of the liver in an adult: An extremely rare case report and review of literature.

INTRODUCTION AND IMPORTANCE: Primary hepatic sarcomas are one of the extremely rare malignant tumors representing less than 0.1 % of all primary malignant neoplasms. CASE PRESENTATION AND CLINICAL DISCUSSION: A known compensated cirrhotic HCV 60-year-old female lady MELD score 8 with a medical history of controlled diabetes and hypertension presented to our hepatobiliary clinic experiencing a chronic right hypochondrial pain that radiate to her right shoulder of 3 months duration. O/E there was right hypochondrial and epigastric tenderness. Pelvi-abdominal US was done then PET CT which revealed a large exophytic focal lesion measuring about 8 × 7 × 6 cm and achieving 12.4 SUV max on FDG uptake. Pre-operative US guided true-cut biopsy showed small oval rounded cells with focal spindling and the neoplastic cells showed hyperchromatic pleomorphic nuclei with little cytoplasm with a positive reaction of tumor cells stained with Desmin and Myogenin with a diagnosis of pleomorphic rhabdomyosarcoma. The patient was scheduled for neoadjuvant chemotherapy and then elective Right hemihepatectomy. Although many challenges were encountered during the resection of the tumor as the tumor was attached to the under surface of the diaphragm, the tumor was resected with a safety margin of 1 cm with frozen histopathological examination being negative for any malignant cells. The patient's postoperative course was uneventful apart from wound infection and was discharged on the postoperative sixth day. CONCLUSION: The percutaneous liver biopsy plays an important role in the diagnosis of liver's rhabdomyosarcomas. Neoadjuvant chemotherapy addresses the behavior of the tumor, together with early surgical intervention can lead to favorable outcomes and reduce the recurrence.

Multidrug-Resistant Enteropathogenic Escherichia coli Isolated from Diarrhoeic Calves, Milk, and Workers in Dairy Farms: A Potential Public Health Risk.

Enteropathogenic Escherichia coli (EPEC) is a leading cause of diarrhoeagenic diseases in humans and cattle worldwide. The emergence of multidrug-resistant (MDR) EPEC from cattle sources is a public health concern. A total of 240 samples (75 diarrhoeic calves, 150 milk samples, and 15 workers) were examined for prevalence of EPEC in three dairy farms in Egypt. Antimicrobial resistance (AMR) traits were determined by antibiogram and polymerase chain reaction (PCR) detection of ß-lactamase-encoding genes, plasmid-mediated quinolone resistance genes, and carbapenemase-encoding genes. The genetic relatedness of the isolates was assessed using repetitive extragenic palindromic sequence-based PCR (REP-PCR). EPEC isolates were detected in 22.7% (17/75) of diarrhoeic calves, 5.3% (8/150) of milk samples, and 20% (3/15) of worker samples. The detected serovars were O26 (5%), O111 (3.3%), O124 (1.6%), O126 (0.8%), and O55 (0.8%). AMR-EPEC (harbouring any AMR gene) was detected in 9.2% of samples. Among isolates, blaTEM was the most detected gene (39.3%), followed by blaSHV (32.1%) and blaCTX-M-1 (25%). The qnrA, qnrB, and qnrS genes were detected in 21.4%, 10.7%, and 7.1% of isolates, respectively. The blaVIM gene was detected in 14.3% of isolates. All EPEC (100%) isolates were MDR. High resistance rates were reported for ampicillin (100%), tetracycline (89.3%), cefazolin (71%), and ciprofloxacin (64.3%). Three O26 isolates and two O111 isolates showed the highest multiple-antibiotic resistance (MAR) indices (0.85-0.92); these isolates harboured blaSHV-12 and blaCTX-M-15 genes, respectively. REP-PCR genotyping showed high genetic diversity of EPEC, although isolates belonging to the same serotype or farm were clustered together. Two worker isolates (O111 and O26) showed high genetic similarity (80-95%) with diarrhoeic calf isolates of matched serotypes/farms. This may highlight potential inter-species transmission within the farm. This study highlights the potential high risk of cattle (especially diarrhoeic calves) as disseminators of MDR-EPEC and/or their AMR genes in the study area. Prohibition of non-prescribed use of antibiotics in dairy farms in Egypt is strongly warranted.

Improving the Functional Performance of Date Seed Protein Concentrate by High-Intensity Ultrasonic Treatment.

Date kernel is a plant-derived byproduct that has the potential to be converted into a high-value-added food ingredient, such as protein concentrate, in the food industry. Ultrasound, which is an alternative method for improving the functional properties of food proteins, is an effective physical treatment for modifying protein functionality. Solubility is the main criterion that primarily affects other functional properties of protein concentrates, such as emulsification, foaming, and water and oil binding. The aim of this study is to enhance the techno-functional performance of date seed protein concentrate (DSPC) by maximizing the solubility via a high-intensity ultrasound (HIUS) treatment at a fixed frequency of 20 kHz. The effect of ultrasonic homogenization under varying amplitudes and times (amplitude of 40, 60, and 80% for 5, 10, and 15 min, respectively) on the functional properties of the DSPC was investigated by using the response surface methodology (RSM). A face-centered central composite design (FC-CCD) revealed that the optimal process conditions of HIUS were at an amplitude of 80% for 15 min. The physicochemical and functional properties of the ultrasound-applied concentrate (DSPC-US) were determined under the optimum HIUS conditions, and then these properties of DSPC-US were compared to the native DSPC. The results showed that the solubility of all DSPC samples treated by HIUS was significantly (p < 0.05) higher than that of the native DSPC. In addition, emulsion activity/stability, foaming activity/stability, and oil-binding capacity increased after HIUS homogenization treatments, whereas the water-binding capacity decreased. These changes in the techno-functional properties of the DSPC-US were explained by the modification to the physicochemical structure of the DSPC (particle size, zeta potential, SDS-PAGE, SEM, FTIR, DSC, free SH content, surface hydrophobicity, and intrinsic emission). This work revealed that HIUS could be an effective treatment for enhancing the functional properties of date seed protein concentrate.

Prevalence and Prognostic Implications of PD-L1 Expression in Soft Tissue Sarcomas.

Background: PD-L1 expression differs from 19 to 92% in various cancer subtypes. Its expression carries a worse prognostic value in various malignancies and could also be used as a predictive marker for immune checkpoint inhibitor response. This study aimed to explore the prevalence of PD-L1 expression in soft tissue sarcomas and the correlation of PD-L1 expression with clinicopathological features. Patients and Methods: The tissue samples of 50 patients with STS were tested for PD-L1 expression using immunohistochemistry (IHC). We followed a 6-step proportional scoring system. The patients were treated at Ain Shams University Hospital from 2011 to 2017. We also explored the correlation of PD-L1 expression with different clinical features of the patients. The chi-square test was used to calculate the differences among variables. Results: Twelve cases (24%) showed positive PD-L1 expression with the highest prevalence in rhabdomyosarcoma and desmoid tumors (2/2 and 2/3 cases, respectively), followed by GIST in 2/4 cases and liposarcoma in 3/11 cases. Patients with positive PD-L1 expression showed a trend for worse survival, with a median overall survival of 11 months vs. 19 months for patients with negative PD-L1 expression (p-value = 0.1) and a mean PFS of 6 months vs. 11 months for patients with negative PD-L1 expression (p-value = 0.1). However, these findings did not reach statistical significance. Conclusion: Although the results did not reach statistical significance due to the small number of cases, PD-L1 expression could represent a prognostic factor for poor outcome. Larger clinical trials are recommended for the validation of PD-L1 as a poor prognostic biomarker.

Validation of real-time polymerase chain reaction versus conventional polymerase chain reaction for diagnosis of brucellosis in cattle sera.

BACKGROUND AND AIM: Different polymerase chain reaction (PCR) techniques have and are still being used for the direct detection of Brucella DNA in serum samples of different animal species and humans without being validated or properly validated, resulting in discrepancies. Thus, this study aimed to evaluate the diagnostic performance of the TaqMan Real-Time-PCR (RT-PCR) targeting the bcsp31 gene versus conventional PCR for the accurate diagnosis of brucellosis at the genus level in cattle sera. MATERIALS AND METHODS: One hundred and eighty-four serum samples were collected from bacteriologically positive and negative cows with ages ranging from 1 to 5 years old at some infected private farms in the Nile Delta under quarantine measures as well as brucellosis free farms. These samples were classified into four groups after serological diagnosis and investigated by TaqMan RT-PCR and conventional PCR targeting the IS711 gene for Brucella DNA detection. The diagnostic performance characteristics of both PCR techniques were estimated considering the bacteriological results as a gold standard. RESULTS: TaqMan RT-PCR revealed superiority over conventional PCR; it was able to detect Brucella DNA in 95% (67/70) and 89% (25/28) of the cattle sera samples belonging to Group 1 (serologically and bacteriologically positive) and Group 2 (serologically negative but bacteriologically positive), respectively. On evaluating the diagnostic performance, TaqMan RT-PCR showed superior diagnostic sensitivity (93.9%), diagnostic specificity (88.4%), performance index (182.3), almost perfect kappa agreement (0.825±0.042), strong positive correlation (r=0.826), high accuracy based on the receiver operating characteristic (ROC) curve, and area under the ROC curve (0.911) at p<0.05 and CI of 95%. CONCLUSION: A cattle serum sample is not the metric of choice for targeting Brucella genomic DNA by conventional PCR. The time-saving and rapid TaqMan RT-PCR method revealed a better diagnostic performance in the detection of Brucella DNA in cattle sera. Such performance offered by TaqMan RT-PCR may be considered a step toward the possibility of using such technology in the direct differentiation between Brucella-infected and -vaccinated cattle immunized by smooth vaccines from cattle sera using primers specific for such vaccines.

ß-Arrestin inhibition induces autophagy, apoptosis, G0/G1 cell cycle arrest in agonist-activated V2R receptor in breast cancer cells.

Non-visual arrestins (ß-arrestins) are endocytic proteins that mediate agonist-activated GPCRs internalization and signaling pathways in an independent manner. The involvement of ß-arrestins in cancer invasion and metastasis is increasingly reported. So, it is hypothesized that inhibition of ß-arrestins may diminish the survival chances of cancer cells. This study aimed to evaluate the in vitro impact of inhibiting ß-arrestins on the autophagic and/or apoptotic responsiveness of breast cancer cells. We used Barbadin to selectively inhibit ß-Arr/AP2 interaction in AVP-stimulated V2R receptor of triple-negative breast cancer cells (MDA MB-231). Autophagy was assessed by the microtubule-associated protein 1 light chain 3-II (LC3II), apoptosis was measured by Annexin-V/PI staining and cell cycle distribution was investigated based upon the DNA content using flow cytometry. Barbadin reduced cell viability to 69.1% and increased the autophagy marker LC3II and its autophagic effect disappeared in cells transiently starved in Earle's balanced salt solution (EBSS). Also, Barbadin mildly enhanced the expression of P62 mRNA and arrested 63.7% of cells in G0/G1 phase. In parallel, the drug-induced apoptosis in 29.9% of cells (by AV/PI) and 27.8% of cells were trapped in sub-G1 phase. The apoptotic effect of Barbadin was enhanced when autophagy was inhibited by the PI3K inhibitor (Wortmannin). Conclusively, the data demonstrate the dual autophagic and apoptotic effects of ß-ßArr/AP2 inhibition in triple-negative breast cancer cells. These observations nominate ß-Arrs as selective targets in breast cancer treatment.

Clinico-pathological relationship between androgen receptor and tumour infiltrating lymphocytes in triple negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with ill-defined therapeutic targets. Androgen receptor (AR) and tumour-infiltrating lymphocytes (TILs) had a prognostic and predictive value in TNBC. The relationship between AR, TILs and clinical behaviour is still not fully understood. METHODS: Thirty-six TNBC patients were evaluated for AR (positive if ≥1% expression), CD3, CD4, CD8 and CD20 by immunohistochemistry. Stromal TILs were quantified following TILs Working Group recommendations. Lymphocyte-predominant breast cancer (LPBC) was defined as stromal TILs ≥ 50%, whereas lymphocyte-deficient breast cancer (LDBC) was defined as <50%. RESULTS: The mean age was 52.5 years and 27.8% were ≥60 years. Seven patients (21.2%) were AR+. All AR+ cases were postmenopausal (≥50 years old). LPBC was 32.2% of the whole cohort. Median TILs were 37.5% and 10% (p = 0.1) and median CD20 was 20% and 7.5% (p = 0.008) in AR- and AR+, respectively. Mean CD3 was 80.7% and 93.3% (p = 0.007) and CD8 was 75% and 80.8% (p= 0.41) in AR- and AR+, respectively. All patients who were ≥60 years old expressed CD20. LDBC was found to be significantly higher in N+ versus N- patients (p = 0.03) with median TILs of 20% versus 50% in N+ versus N-, respectively (p = 0.03). LDBC was associated with higher risk of lymph node (LN) involvement (odds ratio = 6; 95% CI = 1.05-34.21; p = 0.04). CONCLUSIONS: AR expression was evident in older age (≥50 years). Median CD20 was higher in AR- TNBC, while mean CD3 was higher in AR+ tumours. LDBC was associated with higher risk of LN involvement. Larger studies are needed to focus on the clinical impact of the relation between AR and TILs in TNBC.

Pentoxifylline and vitamin E reduce the severity of radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients: a randomized, controlled study.

The purpose of this study was to assess the impact of pentoxifylline and vitamin E on the incidence and severity of radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients. This is a prospective, randomized, controlled study. Head and neck cancer patients receiving 30-35 radiotherapy fractions with or without concurrent chemotherapy excluding those intolerant to xanthines, with any bleeding tendency were included. Sixty patients were enrolled; 30 patients received radiotherapy (control group) and 30 patients received radiotherapy with pentoxifylline and vitamin E (intervention group). The incidence, severity, onset and duration of oral mucositis and/or dysphagia were assessed. Locoregional control, quality of life, need for hospitalization, radiotherapy breaks, and adverse events were recorded and compared between groups. Pentoxifylline and vitamin E combination did not affect the incidence or the onset of oral mucositis or dysphagia. After adjusting for age, the combination reduced the incidence of severe oral mucositis (p = 0.01) and dysphagia (p = 0.012). The combination decreased the duration of oral mucositis and dysphagia by 5 weeks (p = 0.002) and 4 weeks (p = 0.003), respectively. The study drugs reduced the need for hospitalization (p = 0.002) and for radiotherapy breaks (p = 0.002) with improvement of FOIS (p = 0.014), EQ-5D index (p = 0.009) and VAS score (p = 0.012). Pentoxifylline and vitamin E decreased the occurrence of dysgeusia (p = 0.026) and fatigue (p = 0.026) without compromising locoregional control. Pentoxifylline/vitamin E combination reduced the severity and duration of acute radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients.Trial registry ClinicalTrials.gov registration number: NCT02397486.

Tobacco smoking in Egypt: a scoping literature review of its epidemiology and control measures.

BACKGROUND: According to World Health Organization (WHO) reports, the prevalence of smoking is increasing in many developing countries, including Egypt. The aim of this study is to summarize the published data in the literature about tobacco smoking in Egypt. METHODS: A computerized literature search of PubMed and relevant Egyptian journals was conducted using the relevant keywords. The findings of retrieved studies were extracted and discussed in a narrative approach. RESULTS: Our search retrieved 44 relevant studies. The most updated prevalence of tobacco smoking in Egypt is 22% in 2010 and is increasing. Highly significant odds ratios were reported for sibling, parent, and peer smoking as risk factors for smoking. Cardiovascular disorders, malignant tumors, and erectile dysfunction are common complications of smoking in the Egyptian population. Efforts to control tobacco smoking are available, but inadequate. CONCLUSIONS: Tobacco smoking is a prevalent health problem in Egypt, associated with cardiovascular disorders and malignant tumors. Health education programmes should be delivered through mass media and school-based programmes to reach a large section of the Egyptian population.

Tobacco smoking in Egypt: a scoping literature review of its epidemiology and control measures

Background: According to World Health Organization [WHO] reports, the prevalence of smoking is increasing in many developing countries, including Egypt. The aim of this study is to summarize the published data in the literature about tobacco smoking in Egypt. Methods: A computerized literature search of PubMed and relevant Egyptian journals was conducted using the relevant keywords. The findings of retrieved studies were extracted and discussed in a narrative approach. Results: Our search retrieved 44 relevant studies. The most updated prevalence of tobacco smoking in Egypt is 22% in 2010 and is increasing. Highly significant odds ratios were reported for sibling, parent, and peer smoking as risk factors for smoking. Cardiovascular disorders, malignant tumors, and erectile dysfunction are common complications of smoking in the Egyptian population. Efforts to control tobacco smoking are available, but inadequate. Conclusions: Tobacco smoking is a prevalent health problem in Egypt, associated with cardiovascular disorders and malignant tumors. Health education programmes should be delivered through mass media and school-based programmes to reach a large section of the Egyptian population

Contexte : Selon les rapports de l'OMS, la prévalence du tabagisme est en augmentation dans de nombreux pays en développement, dont l'Égypte. La présente étude avait pour objectif de synthétiser l'ensemble des données publiées dans la littérature sur le tabagisme en Égypte. Méthodes : Une recherche documentaire sur ordinateur dans PubMed et d'autres revues égyptiennes pertinentes a été effectuée à l'aide de mots-clés. Les résultats des études extraites ont été compilés et discutés. Résultats : Notre recherche a permis d'extraire 44 études pertinentes. Des odds ratios hautement significatifs ont été rapportés pour le fait d'avoir des frères et sœurs, des parents et des amis fumeurs en tant que facteurs de risque. Les troubles cardio-vasculaires, les tumeurs malignes, et les dysfonctionnements érectiles sont des complications courantes du tabagisme dans la population égyptienne. Des mesures pour lutter contre le tabagisme sont disponibles, mais ne sont pas adaptées. Conclusions : Le tabagisme constitue un problème de santé prévalent en Égypte, associé aux troubles cardio-vasculaires et aux tumeurs malignes. Une éducation sanitaire devrait être dispensée à travers les médias de masse et dans le cadre de programmes menés dans les écoles afin d'atteindre une frange importante de la population égyptienne

معلومات أساسية: تشير تقارير منظمة الصحة العالمية إلى تزايد معدل انتشار التدخين في كثير من البلدان النامية، بما فيها مصر. وتهدف هذه الدراسةإلى تلخيص جميع البيانات المنشورة في الدراسات السابقة حول تدخين التبغ في مصر.والمجلات المصرية ذات الصلة باستخدام الكلمات PubMed طرق البحث: أُجري بحث باستخدام الحاسوب في الدراسات السابقة في موقعالرئيسية في هذا المجال. واستخلصت نتائج الدراسات المستخرجة ونوقشت بأسلوب سردي.النتائج: اعتمد البحث الذي أجريناه على 44 دراسة ذات صلة. وتبيّ وجود نسب أرجحية كبيرة للغاية لتدخين الأشقاء والآباء والأقران باعتبارهاعوامل خطر للتدخين. وتعدّ الاضطرابات القلبية الوعائية والأورام الخبيثة واضطراب الانتصاب من المضاعفات الشائعة للتدخين بين المصريين.وثمة جهود حالية لمكافحة تدخين التبغ، لكنها ليست كافية.الاستنتاجات: يمثل تدخين التبغ مشكلة صحية واسعة الانتشار في مصر، ترتبط بالاضطرابات القلبية الوعائية والأورام الخبيثة. وينبغي تقديمبرامج للتثقيف الصحي عبر وسائل الإعلام وفي المدارس للوصول إلى قطاع أوسع من المصريين

Do we need regional guidelines for breast cancer management in the MENA region? MENA Breast Cancer Guidelines project.

PURPOSE: Breast cancer is the most common cancer among females worldwide in general and in the Middle East and the North African region (MENA region) in particular. Management of breast cancer in the MENA region faces a lot of challenges, which include younger age at presentation, aggressive behaviour, lack of national breast screening programmes and lack of reliable data registries as well as socioeconomic factors. These factors make applying the international guidelines for breast cancer management very challenging. The aim of this project is to explore the need for a regional breast cancer guideline as well as to screen the clinical practice of breast cancer management in the MENA region. METHODOLOGY: Three web-based designed surveys were sent to more than 600 oncologists in the MENA region from the period of August 2013 to October 2014. Full descriptive data and information regarding the application of international breast cancer guidelines were collected. The software was using the IP address to prevent duplication of collected data. Descriptive analysis and results were shown as numbers and percentages. RESULTS: During the period of the survey, 104 oncologists responded, representing around an 11% response rate. The majority of replies came from Egypt (59 responses (59%)), followed by Saudi Arabia (ten responses (9.6%)). Fifty-one per cent of responders had more than ten years of experience, and further 31.7% had 5-10 years of experience. Seventy-four per cent were working in governmental hospitals, which is our target sector. There was a major defect in having a genetic counsel unit (78.8% declared an absence of this service), presence of a national breast screening programme (55.8% declared an absence of this service), performing sentinel lymph node biopsy (43.3% declared an absence of this service). The need for regional guidelines for the management of breast cancer was agreed upon by 90.6% of responders. CONCLUSION: There is a clear need to improve the management of breast cancer in the MENA region. Creating a national breast screening programme and a reliable database is essential. A regional guideline is required to establish the best possible management of breast cancer according to the patients and disease specification as well as the regional socioeconomic factors and facilities available. There is also a need to improve clinical research that meets the region's needs.

Curcumin improves the metabolic syndrome in high-fructose-diet-fed rats: role of TNF-α, NF-κB, and oxidative stress.

This study aimed to investigate effects of curcumin on high fructose diet (HFD)-induced metabolic syndrome (MetS) in rats and the possible mechanisms involved. MetS was induced in male albino rats (n = 20), over 8 weeks, by 65% HFD. For 8-week experiment period, rats were assigned to 2 equal groups: curcumin-treated rats received curcumin (200 mg/kg, p.o, once daily) along with HFD, and untreated rats were fed with HFD only. We evaluated body mass (BM), systolic blood pressure (SBP), homeostasis model assessment of insulin resistance (HOMA-IR), and serum levels of glucose, insulin, leptin, total cholesterol (TC), triglycerides (TGs), uric acid, malondialdehyde (MDA; lipid peroxidation product), and tumor necrosis factor-α (TNF-α; inflammatory cytokine), and serum catalase (endogenous antioxidant) activity and immunohistochemical expression of nuclear factor κB (NF-κB; inflammation-related transcription factor) in hepatocytes. HFD produced increases in BM, SBP, HOMA-IR, and serum levels of glucose, insulin, leptin, TC, TGs, uric acid, MDA, and TNF-α, a decrease in catalase activity, and strong positive expression of NF-κB in hepatocytes. Curcumin, in presence of HFD, produced significant improvements in all glucose and fat metabolism parameters, and in oxidative stress and inflammation biomarkers. Curcumin may potentially be useful in the treatment of MetS through its ability to modulate oxidation stress status and inflammation cascades.

Combination of Sitagliptin and Insulin against Type 2 Diabetes Mellitus with Neuropathy in Rats: Neuroprotection and Role of Oxidative and Inflammation Stress.

AIMS: The present study evaluated the effects of sitagliptin-insulin against type 2 diabetes mellitus with neuropathy in rats and possible neuroprotective mechanisms. METHODS: Diabetes was induced in 32 adult male albino rats by 6-week high-fat high-sugar diet followed by streptozotocin 30 mg/kg intraperitoneal injection. For 4 weeks thereafter, diabetic rats were divided into 4 groups, each group receiving one of the following daily: vehicle (untreated diabetic), insulin 10 IU/kg SC, sitagliptin 30 mg/kg PO or sitagliptin-insulin. We assessed systolic blood pressure (SBP), blood glucose, serum insulin and advanced glycation end-products (AGEs), thermal hyperalgesia and sciatic nerve tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) and sciatic histopathology. RESULTS: Compared to untreated and insulin-treated groups, sitagliptin decreased SBP, serum AGEs and sciatic MDA and TNF-α, and increased serum insulin and sciatic SOD, but insulin decreased blood glucose more. Sitagliptin-insulin (greater than sitagliptin or insulin alone) superiorly decreased and increased the above respective parameters, and ameliorated hyperalgesia and sciatic histopathological changes, but was similar to insulin in decreasing blood glucose, and similar to sitagliptin in rising serum insulin. CONCLUSIONS: Sitagliptin-insulin combination produced hypoglycemic and neuroprotective effect and ameliorated hyperalgesia, oxidative stress and inflammation more than either drug alone. This combination might have clinical efficacy in uncontrolled type 2 diabetes with neuropathy.

Protective effects of combined ß-caryophyllene and silymarin against ketoprofen-induced hepatotoxicity in rats.

Ketoprofen (Ket), widely utilized in treatment of many inflammatory disorders, is found to induce liver toxicity especially with overdose. This study aimed to evaluate the possible protective effects of concomitant ß-caryophyllene (Cary) and silymarin (Sily) against Ket-induced hepatotoxicity in rats. Forty adult male albino rats were divided into 5 groups (each n = 8): the control group received distilled water for 6 weeks; the Ket-treated group received distilled water for 5 weeks and Ket in a dose of 8 mg·kg(-1)·day(-1) p.o. for the 6th week; the Cary + Ket treated group received Cary in a dose of 200 mg·kg(-1)·day(-1) orally for 6 weeks and Ket for the 6th week; the Sily + Ket treated group received Sily in the dose of 150 mg·kg(-1)·day(-1) for 6 weeks and Ket for the 6th week; and the Cary + Sily + Ket treated group received Sily and Cary for 6 weeks and Ket for the 6th week. At end of the experiment, serum ALT, AST, and albumin and liver total antioxidant capacity (t.TAC) and malondialdehyde (t.MDA) were measured in all rats. Ket increased serum ALT and AST and t.MDA and decreased t.TAC. Cary and Sily improved these changes. Combined Cary and Sily restored these liver changes to nearly normal. Combined Cary and Sily is hepatoprotective, with the ability to scavenge oxidants against Ket-induced hepatotoxicity in rats.

Principles of a risk evaluation and mitigation strategy (REMS) for breast cancer patients receiving potentially cardiotoxic adjuvant treatments.

INTRODUCTION: The number of breast cancer long survivors has increased in the last few years. However, this increase in survival may be affected by the side effects of adjuvant breast cancer therapies. In this context cardiovascular toxicity is considered one of the most clinically important toxicities. AREAS COVERED: In this work we review the published clinical trials of adjuvant treatment on breast cancer, focusing on the trials which accurately mentioned the cardiotoxicity of the adjuvant treatments and those which underwent long term follow up of cardiac function. This article tries to summarize and evaluate the risk of cardiac toxicities associated with different adjuvant treatments for breast cancer (chemotherapy, radiotherapy, endocrine therapy and trastuzumab). EXPERT OPINION: In our opinion, each individual breast cancer patient should be meticulously evaluated before starting adjuvant treatment in order to basically asses cardiac function and to manage any predisposing risk factor which may increase the probability of treatment induced cardiotoxicity. Rigorous and frequent reassessment of cardiac function along with providing different mitigation strategies that can prevent or decrease the risk of such cardiovascular toxicities are inevitable methods to protect the patient from cardiac events which can mask the survival benefit associated with different adjuvant treatments.

Role of the antidiabetic drugs: Glibenclamide and metformin on the contractility of isolated rat uteri.

The current investigation has designed to study the role of two antidiabetics, glibenclamide and metformin on the spontaneous uterine contractions in the non-diabetic non-pregnant female rats. The rat uteri were isolated and allocated to two groups: 1)the glibenclamide group: After recording the normal spontaneous uterine contractions, the vehicle (ethanol) and glibenclamide molar concentrations (10(-7), 10(-6) and 10(-5) M) were analyzed on uterine contractions by recording on smoked paper on a rotating kymograph drum, and 2) the metformin group: After recording the normal spontaneous uterine contractions, the metformin concentrations (10(-7), 10(-6) and 10(-5) M) were analyzed on uterine contractions. Responses to the two drugs and vehicle control (ethanol) were recorded for 30 min. Glibenclamide has not significantly effected on the amplitude and frequency of spontaneous contractions of the isolated rat uteri. Metformin also has no significant effect on the amplitude and frequency of spontaneous contractions of the isolated rat uteri. In conclusion, the two oral antidiabetics glibenclamide and metformin have not changed both the amplitude and frequency of spontaneous uterine contractions in the non-pregnant non-diabetic female rats.

Systemic therapy options for malignant pleural mesothelioma beyond first-line therapy: a systematic review.

The aim of this systematic review is to assess the evidence for the available 2nd/3rd line systemic therapies for malignant pleural mesothelioma (MPM). Eligible studies were obtained through appropriate databases and meetings abstracts search. A total of 29 studies were considered eligible for this review and it includes three Phase III studies, eighteen phase II studies and eight retrospective studies. For the Phase III studies, none have achieved an overall survival benefit; while for the Phase II studies, the majority have not achieved sufficient satisfactory outcome to justify advancement to Phase III studies. We believe that the best salvage treatment for MPM would be inclusion into appropriately designed clinical trials. In the absence of a clinical trial, gemcitabine and/or vinorelbine-based regimens could be considered. Moreover, pemetrexed re-challenge can be considered in selected pemetrexed-sensitive patients.