Prognostic factors in the decision-making process for sigmoid volvulus: results of a single-centre retrospective cohort study.

BACKGROUND: Sigmoid volvulus is a common cause of emergency surgical admission. Those patients are often treated conservatively with a high rate of recurrence. We wondered if a more aggressive management might be indicated. METHODS: We have reviewed data of patients diagnosed with acute sigmoid volvulus over a 2-year period. The primary endpoint was patient survival. RESULTS: We analysed 332 admissions of 78 patients. 39.7% underwent resection. Survival was 54.9 ± 8.8 months from the first hospitalization, irrespective of the treatment. Long-term survival was positively influenced by being female, having a low "social score", a younger age and surgery. Multivariate analysis showed that only being female and surgery were independently associated with better survival. CONCLUSION: Early surgery may be the best approach in patients with recurrent sigmoid volvulus, as it ensures longer survival with a better quality of life, regardless of the patient's social and functional condition.

COVID-19 infection risk by open and laparoscopic surgical smoke: A systematic review of the literature.

BACKGROUND: The current COVID-19 pandemic has greatly changed the way surgery is delivered. In particular, current guidelines and policies have highlighted the need to use high level Personal Protective Equipment to reduce the risk of viral infection during open and laparoscopic surgical procedures. In particular, it was felt that the laparoscopic approach was at higher risk of viral transmission due to the chimney effect of the smoke escape from the trocars during and after the procedure. However, with this being a new and largely unknown viral agent, guidelines have been based on speculation and extrapolation from previous studies conducted in completely different situations, and led to anxiety amongst surgeons and theatre staff. We decided to conduct a systematic review of the Literature to try to clarify whether inhalation of surgical smoke can increase the risk of COVID-19 infection. METHODS: A thorough search of the relevant Literature was performed following the PRISMA guidelines and the most relevant papers on this topic were selected for qualitative analysis. Duplicates, review, personal opinions and guidelines have been excluded. Quantitative analysis has not been performed due to the lack of homogeneous high-quality studies. RESULTS: Literature search identified 740 papers but only 34 of them were suitable for qualitative analysis. The quality of those studies is generally quite low. We were not able to find any evidence directly linking surgical smoke with viral transmission, other than in patients with active HPV infection. DISCUSSION: Inhalation of surgical smoke can be generally hazardous, and therefore the use of PPE during surgical operations must be recommended in any case. However, the present systematic review of the existent Literature did not identify any significant evidence of the risk of viral transmission with the surgical smoke, therefore the current guidelines restricting the use of laparoscopy and/or diathermy during the current Covid-19 pandemic may be considered excessive and non-evidence based.

Metabolomics of Type 1 and Type 2 Diabetes.

Type 1 and type 2 diabetes mellitus (DM) are chronic diseases that affect nearly 425 million people worldwide, leading to poor health outcomes and high health care costs. High-throughput metabolomics screening can provide vital insight into the pathophysiological pathways of DM and help in managing its effects. The primary aim of this study was to contribute to the understanding and management of DM by providing reliable evidence of the relationships between metabolites and type 1 diabetes (T1D) and metabolites and type 2 diabetes (T2D). Information for the study was obtained from the PubMed, MEDLINE, and EMBASE databases, and leads to additional articles that were obtained from the reference lists of the studies examined. The results from the selected studies were used to assess the relationships between diabetes (T1D and/or T2D) and metabolite markers-such as glutamine, glycine, and aromatic amino acids-in patients. Seventy studies were selected from the three databases and from the reference lists in the records retrieved. All studies explored associations between various metabolites and T1D or T2D. This review identified several plasma metabolites associated with T2D prediabetes and/or T1D and/or T2D in humans. The evidence shows that metabolites such as glucose, fructose, amino acids, and lipids are typically altered in individuals with T1D and T2D. These metabolites exhibit significant predictive associations with T2D prediabetes, T1D, and/or T2D. The current review suggests that changes in plasma metabolites can be identified by metabolomic techniques and used to identify and analyze T1D and T2D biomarkers. The results of the metabolomic studies can be used to help create effective interventions for managing these diseases.

Various soil amendments and environmental wastes affect the (im)mobilization and phytoavailability of potentially toxic elements in a sewage effluent irrigated sandy soil.

Contamination of long-term sewage effluent irrigated soils by potentially toxic elements (PTEs) is a serious concern due to its high environmental and health risk. Our scientific hypothesis is that soil amendments can cause contradictory effects on the element mobilization and phytoavailability depending on the type of element and amendment. Therefore, we aimed to assess the impact of the application (1%) of several low cost amendments and environmental wastes on the (im)mobilization, availability, and uptake of Al, Cd, Cr, Cu, Fe, Mn, Ni, and Zn by sorghum (Sorghum bicolor) in a long term sewage effluent irrigated sandy soils collected from Egypt. The used materials include activated charcoal (AC), potassium humate (KH), phosphate rock (PR), phosphogypsum (PG), triple superphosphate (TSP), phosphoric acid (PA), sulfur (S), sugar beet factory lime (SBFL), cement bypass kiln dust (CBD), egg shell (ES), bone mill (BM), brick factory residual (BFR), ceramic powder (CP), and drinking water treatment residual (WTR). The mobilization and availability of the elements in the soil were extracted using NH4NO3 and ammonium bicarbonate- diethylene triamine penta acetic acid (AB-DTPA), respectively. The above-ground biomass samples were analyzed for the elements studied. The results confirmed our hypothesis and concluded that although some amendments like S, PA, and TSP can be used for reducing the plant uptake of Al, Cr, and Fe, they might be used with KH for enhancing the phytoextraction of Cd, Cu, Mn, and Ni. Moreover, several wastes such as BFR and WTR might be used for enhancing the phytoextraction of Al, Cd, Cr, Cu, Fe, and Ni and reducing the uptake of Mn from the studied soil. Although SBFL decreased the plant uptake of Al, Fe, Mn, and Zn, it's increased the plant uptake of Cd, Cu, and Ni. Therefore, the amendments which reduce the plant uptake of an element might be suitable candidates for its immobilization, while the amendments which increase the plant uptake of an element might be used for enhancing its phytoextraction when using bioenergy crops like sorghum in similar contaminated sandy soils. The studied materials offered the potential for effective and low cost media for the treatment of PTEs contaminated sewage effluent irrigated sandy soils. These results should be verified in a field study.

Melperone but not bisoprolol or metoprolol is a clinically relevant inhibitor of CYP2D6: evidence from a therapeutic drug monitoring survey.

Cytochrome P450 enzymes (CYP) can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. The objective of the study was to analyze the in vivo inhibitory potential of the beta-blockers bisoprolol and metoprolol as well as the low-potency antipsychotic melperone on CYP2D6. By utilizing a large therapeutic drug monitoring database of 2874 samples, data from patients who had been treated with venlafaxine (VEN) either without (control group) or with a concomitant medication with bisoprolol, metoprolol or melperone were evaluated retrospectively to study the CYP2D6-catalyzed O-demethylation to O-desmethylvenlafaxine (ODVEN). Dose-adjusted serum levels (C/D) of VEN and ODVEN as well as the metabolic ratios (ODVEN/VEN) were computed for the four groups and compared using Kruskal-Wallis test. In total, 381 patients could be included for analysis. No significant difference was found in the median C/D (VEN), C/D (ODVEN) or C/D of the active moiety (VEN + ODVEN) in either the metoprolol (N = 103) or bisoprolol group (N = 101), compared to the control group (N = 108). In contrast, a significantly higher median C/D (VEN) (0.79 ng/ml/mg, range 0.13-5.73 ng/ml/mg) (P < 0.01) was found in the melperone group (N = 69), compared to the control group (0.46 ng/ml/mg, range 0.02-7.39 ng/ml/mg). A significant decrease (P < 0.01) was solely found in the median metabolic ratios of ODVEN/VEN between the melperone group (0.90, range 0.14-15.15), compared to the control group (2.39, range 0.06-15.31). The results of this study provided evidence that melperone but not bisoprolol or metoprolol has a clinically relevant inhibitory potential on CYP2D6.

Adherence to medication among outpatient adolescents with epilepsy.

BACKGROUND AND OBJECTIVE: The promotion of medication adherence is considered as an integral component of pharmaceutical care practice and patient healthcare. An approach which focuses on the choice and dose of antiepileptic drug will have limited success without medication adherence. This study sought to assess medication adherence for improvement among adolescents who are suffering from epilepsy. METHODS: A total of 116 patients affected with idiopathic epilepsy and fulfilled the inclusion criteria were recruited in the current study. Adherence to the treatment was evaluated during patients' hospitalization in the Department of Neurology at Riyadh National Hospital, Riyadh, Saudi Arabia, between December 2011 and January 2014. The medication adherence has been assessed during semi-structured interviews with each patient and/or his parents using a multiple choice graded questionnaire. RESULTS: From the selected group of patients, only 94 patients (81.0%) fulfilled the inclusion criteria within the study period. Thirty-six of respondents (38.3%) were non adherent to antiepileptic treatment. No statistical differences were found between males and females regarding their ages, age at diagnosis of epilepsy, mother age, epilepsy duration, family numbers, number of poor-adherents or seizure frequency. The most important factors that were significantly affecting patients' adherence to the prescribed medications were age of mother, family number, number of administered drugs, the stability of parents' marriage, family support, and seizure frequency as well as the regularity of the relationship between patients and their healthcare providers. Forgetfulness was the most common cause of non-adherence among this group of patients followed by inability to obtain medication and fear from side effects of drugs. Our results revealed also that the number of patients who felt to be stigmatized is significantly more in non-adherent group as compared to patients with a strong sense of normality (P < 0.05). A positive relationship between adherence and the necessity and benefit scales at which patients have a stronger belief in the necessity of medication for controlling illness was associated with good adherence. CONCLUSION: The assessment of medication adherence among epileptic patients should be a routine part of the management process to improve the health care and quality of lives of those patients.

The clinical outcomes of dapagliflozin in patients with acute heart failure: A randomized controlled trial (DAPA-RESPONSE-AHF).

AIMS: Dapagliflozin may confer additional decongestive and natriuretic benefits to patients with acute heart failure (AHF). Nonetheless, this hypothesis was not clinically examined. This study aimed primarily to investigate the effect of dapagliflozin on symptomatic relief in those patients. METHODS: This was a randomized, double-blind study that included 87 patients with AHF presenting with dyspnea. Within 24 h of admission, patients were randomized to receive either dapagliflozin (10 mg/day, N = 45) or placebo (N = 42) for 30 days. The primary outcome was the difference between the two groups in the area under the curve (AUC) of visual analogue scale (VAS) dyspnea score over the first 4 days. Secondary endpoints included urinary sodium (Na) after 2 h of randomization, percent change in NT-proBNP, cumulative urine output (UOP), and differences in mortality and hospital readmission rates. RESULTS: The results showed that dapagliflozin significantly reduced the AUC of VAS dyspnea score compared to placebo (3192.2 ± 1631.9 mm × h vs 4713.1 ± 1714.9 mm × h, P < 0.001). The relative change of NT-proBNP compared to its baseline was also larger with dapagliflozin (-34.89% vs -10.085%, P = 0.001). Additionally, higher cumulative UOP was found at day 4 (18600 ml in dapagliflozin vs 13700 in placebo, P = 0.031). Dapagliflozin decreased rehospitalization rates within 30 days after discharge, while it did not affect the spot urinary Na concentration, incidence of worsening of heart failure, or mortality rates. CONCLUSION: Dapagliflozin may provide symptomatic relief and improve diuresis in patients with AHF. Further studies are needed to confirm these findings. https://clinicaltrials.gov/study/NCT05406505.

Effect of cilostazol on preventing paclitaxel-induced neuropathy in patients with breast cancer: A randomized controlled trial.

STUDY OBJECTIVE: Paclitaxel-induced peripheral neuropathy is a significant clinical problem can markedly deteriorate patient's quality of life (QoL). Preclinical evidence exists about the preventive capacity of cilostazol against peripheral neuropathy. However, this hypothesis has not yet been clinically investigated. This proof-of-concept study evaluated the effect of cilostazol on the incidence of paclitaxel-induced peripheral neuropathy in patients with non-metastatic breast cancer. DESIGN: This is a parallel randomized placebo-controlled trial. SETTING: The Oncology Center at Mansoura University, Egypt. PATIENTS: Patients with breast cancer scheduled to receive paclitaxel 175 mg/m2 biweekly. INTERVENTIONS: Patients were randomized to either cilostazol group who received cilostazol tablets 100 mg BID, or to control group who received placebo instead. MEASUREMENTS: The primary endpoint was the incidence of paclitaxel-induced neuropathy evaluated through common terminology criteria for adverse event (NCI-CTCAE) version 4. Secondary endpoints included assessment of the patient's QoL by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTx) subscale. Exploratory outcome measures included changes in serum levels of biomarkers namely nerve growth factor (NGF), and neurofilament light chain (NfL). MAIN RESULTS: The incidence of grade 2 and 3 peripheral neuropathies were significantly lower in the cilostazol group (40%) compared to the control group (86.7%) (p < 0.001). The incidence of clinically significant worsening in neuropathy-related QoL was higher in control group compared to the cilostazol group (p = 0.001). A higher percent increase from baseline in serum NGF was observed in the cilostazol group (p = 0.043). The circulating levels of NfL deemed comparable between the two arms at the end of the study (p = 0.593). CONCLUSION: Adjunctive use of cilostazol is as a novel option that might reduce the incidence of paclitaxel-induced peripheral neuropathy and improve the patients' QoL. Future larger clinical trials are warranted to confirm these findings.

Fish oil improves lipid metabolism and ameliorates inflammation in patients with metabolic syndrome: impact of nonalcoholic fatty liver disease.

CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent in Egypt, in parallel with increasing obesity. NAFLD can lead to liver inflammation, fibrosis and cirrhosis. NAFLD appears tightly linked with metabolic syndrome (MetS). OBJECTIVE: Examine the impact of dietary fish oil on human patients with MetS and NAFLD. MATERIALS AND METHODS: One hundred and forty patients were enrolled in the current study and classified into two groups: patients with both MetS and NAFLD and patients with MetS alone. Sixty-four patients were treated with daily supplementation of 2 g of fish oil for 6 months. Markers of hyperlipidemia and oxidative stress, hydrogen peroxide (H(2)O(2)) and malondialdhyde (MDA), as well as proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were analyzed. RESULTS: Patients without fish oil exhibited significant increases in triglycerides (TGs), low-density lipoprotein (LDL), H(2)O(2) and MDA that were associated with significantly elevated TNF-α and IL-6 compared to controls. Furthermore, patients with both NAFLD and MetS showed significant increase in H(2)O(2), MDA, TNF-α and IL-6 levels compared with MetS group (p < 0.05). Treatment with fish oil reduced serum level of TG, LDL-cholesterol (LDL-C), H(2)O(2), MDA, TNF-α and IL-6 levels in patients and did not affect the control levels. DISCUSSION AND CONCLUSION: Patients with NAFLD had bad lipid profile through a mechanism that involved developed redox imbalance, characterized by boosted free-radical activity and lipid peroxidation enhancing the release of proinflammatory cytokines leading to increased MetS risk and liver damage. However, daily treatment of patients with fish oil for 6 months improved lipid profile and blocked the oxidative stress and cytokines release.

Efficacy of Nondiuretic Pharmacotherapy for Improving the Treatment of Congestion in Patients with Acute Heart Failure: A Systematic Review of Randomised Controlled Trials.

Diuretic therapy is the mainstay during episodes of acute heart failure (AHF). Diuretic resistance is often encountered and poses a substantial challenge for clinicians. There is a lack of evidence on the optimal strategies to tackle this problem. This review aimed to compare the outcomes associated with congestion management based on a strategy of pharmacological nondiuretic-based regimens. The PubMed, Cochrane Library, Scopus, and ScienceDirect databases were systematically searched for all randomised controlled trials (RCTs) of adjuvant pharmacological treatments used during hospitalisation episodes of AHF patients. Congestion relief constitutes the main target in AHF; hence, only studies with efficacy indicators related to decongestion enhancement were included. The Cochrane risk-of-bias tool was used to evaluate the methodological quality of the included RCTs. Twenty-three studies were included; dyspnea relief constituted the critical efficacy endpoint in most included studies. However, substantial variations in dyspnea measurement were found. Tolvaptan and serelaxin were found to be promising options that might improve decongestion in AHF patients. However, further high-quality RCTs using a standardised approach to diuretic management, including dosing and monitoring strategies, are crucial to provide new insights and recommendations for managing heart failure in acute settings.

Remediation of Cd and Cu contaminated water and soil using novel nanomaterials derived from sugar beet processing- and clay brick factory-solid wastes.

Producing nanomaterials from hazardous wastes for water and soil treatment is of great concern. Here, we produced and fully characterized two novel nanomaterials from sugar beet processing (SBR)- and brick factory-residuals (BFR) and assed their ability for Cd and Cu sorption in water and reducing metal availability in a contaminated soil. The SBR removed up to 99% of Cu and 91% of Cd in water, and exhibited a significantly faster and higher sorption capacity (qmax (g kg-1) = 1111.1 for Cu and 33.3 for Cd) than BFR (qmax (g kg-1) = 33.3 for Cu and 10.0 for Cd), even at acidic pH. Soil metal availability was significantly reduced by SBR (up to 57% for Cu and 86% for Cd) and BFR (up to 36% for Cu and 68% for Cd) compared to the unamended soil. The higher removal efficacy of SBR over BFR could be attributed to its higher alkalinity (pH = 12.5), carbonate content (82%), and specific surface area, as well as the activity of hydroxyl -OH and Si-O groups. The nano-scale SBR and BFR, the former particularly, are novel, of low cost, and environmental friendly amendments that can be used for the remediation of metal-contaminated water and soil.

Investigation of Er3+ Ions Reinforced Zinc-Phosphate Glasses for Ionizing Radiation Shielding Applications.

Melt quenching technique is used for preparing glasses with chemical formula (70P2O5)-(16 - x)CdO-(14ZnO)-(xEr2O3), (x = 1-6 mol%). These glasses were named Er1, Er2, Er3, Er4, Er5, and Er6, respectively. Photon buildup factors, fast neutron absorption, and electron stopping of the prepared glasses were examined. Glasses' density was varied from 3.390 ± 0.003 for the Er1 glass sample to 3.412 ± 0.003 for the Er6 glass sample. The Buildup factor (BUF) spectra have relatively higher values in the Compton Scattering (CS) dominated areas compared to both Photoelectric effect (PE), and Pair Production (PP) dominated energy regions. The highest BUF appeared at the Er atom K-absorption edge, whose intensity increases as the molar concentration of Er2O3 in the glasses increases. The photon absorption efficiency (PAE) of the glasses increases according to the trend (PAE)Er1 < (PAE)Er2 < (PAE)Er3 < (PAE)Er4 < (PAE)Er5 < (PAE)Er6. Fast neutron removal cross-section, FNRC (ΣR) values of the glasses obtained via calculation varied from 0.1045-0.1039 cm-1 for Er1-Er6. Furthermore, the continuous slowing down approximation mode (CSDA) range enhances the kinetic energy of electrons for all glasses. Generally, results revealed that the investigated glasses could be applied for radiation shielding and dosimetric media.

Collection, storage and use of blood samples for future research: views of Egyptian patients expressed in a cross-sectional survey.

OBJECTIVE: To determine the attitudes of Egyptian patients regarding their participation in research and with the collection, storage and future use of blood samples for research purposes. DESIGN: Cross-sectional survey. STUDY POPULATION: Adult Egyptian patients (n=600) at rural and urban hospitals and clinics. RESULTS: Less than half of the study population (44.3%) felt that informed consent forms should provide research participants the option to have their blood samples stored for future research. Of these participants, 39.9% thought that consent forms should include the option that future research be restricted to the illness being studied. A slight majority (66.2%) would donate their samples for future genetic research. Respondents were more favourable towards having their blood samples exported to other Arab countries (62.0%) compared with countries in Europe (41.8%, p<0.001) and to the USA (37.2%, p<0.001). CONCLUSIONS: This study shows that many individuals do not favour the donation of a blood sample for future research. Of those who do approve of such future research, many favour a consent model that includes an option restricting the future research to the illness being studied. Also, many Egyptians were hesitant to have their blood samples donated for genetic research or exported out of the Arab region to the USA and European countries. Further qualitative research should be performed to determine the underlying reasons for many of our results.

Measuring the rate of therapeutic adherence among outpatients with T2DM in Egypt.

BACKGROUND AND OBJECTIVE: The promotion of therapeutic adherence is considered as an integral component of pharmaceutical care practice and patient healthcare. It has been shown that despite effective methods of treatment, 50% of diabetic patients fail to achieve satisfactory glycemic control, which leads to accelerated development of complications and increased mortality. Clinical experience indicates that no improvement of metabolic control is possible without patients' adherence to medications. This study sought to examine the rate of medication adherence and different factors affecting it among Type 2 diabetic patients in Egypt. METHODS: A total of 226 Type 2 diabetic patients who fulfilled the inclusion criteria were recruited in the current study. Adherence to the treatment was evaluated during patients' hospitalization in the Outpatient Clinics of Internal Medicine Department at University of Mansoura, Egypt. The medication adherence has been assessed during a personal interview with each patient using a multiple-choice graded questionnaire. RESULTS: In the study population, the adherence rates to medication, dietary/exercise and appointment were observed to be suboptimal. The most important social factors that were significantly affecting adherence rate to the prescribed oral hypoglycemic agent(s) included marital status (P < 0.01), family support (P < 0.01), and socio-economical level (P < 0.01). Other patient factors that were significantly affecting therapeutic adherence were patient knowledge about the disease (P < 0.01), patients' beliefs and motivation about prescribed drugs (P < 0.01), and regularity of patients' self monitoring of blood glucose level (P < 0.01). Among drug factors which found to affect significantly the rate of medication adherence are the number of drugs taken (P < 0.05), complexity of drug regimen (P < 0.01), and the presence of drug side effects (P < 0.01). Economical factor played an equally important role. Direct and indirect care costs in relation to patients' income were significantly affecting the rate of adherence to medication (P < 0.01). CONCLUSIONS: An improvement with the adherence to oral hypoglycemic agent(s) may be achieved through continuing patient education about diabetes, improvement of patients' economical levels as well as a reduction in the cost of medication. Pharmaceutical companies have to be involved and pharmacists have to be payed for helping chronically ill patients to take their medicines correctly for improving clinical outcomes.

Predictive factors for gangrene complication in acute calculous cholecystitis.

BACKGROUNDS/AIMS: Gallbladder gangrene is a grave complication of acute calculous cholecystitis that is difficult to detect preoperatively. Ultrasound could show a gallbladder wall that is more thickened. In addition, other clinical measures were reported to be possible predictive factors. Therefore, we aim in this study to evaluate the gallbladder wall thickness measured by ultrasound and other clinical measures as predictive factors for gangrene complication in acute calculous cholecystitis. METHODS: A prospective cohort database analysis of the results of 674 patients diagnosed and treated for acute calculous cholecystitis between January 2010 and December 2014 was done. Patient's inclusion criteria were acute calculous cholecystitis in adults who were operated within three days of onset of symptoms. RESULTS: 117 (17.4%) patients had gangrene. Gallbladder sonographic wall thickness 5.1-6 mm, more than 6 mm, male gender, diabetes mellitus, leukocytosis >15,000 cells/ml, and age ≥40 years were found to be factors predisposing to gangrene complicated acute calculous cholecystitis that represented a statistically significant difference (p≤0.01). CONCLUSIONS: We conclude that gallbladder sonographic wall thickness 5.1-6 mm, more than 6 mm, male gender, diabetes mellitus, leukocytosis >15,000 cells/ml, and age ≥40 years were found to be factors predisposing to gangrene complicated acute calculous cholecystitis that represented a statistically significant difference. By implementing these risk factors, patients urgency for surgery can be decided in the emergency department. Other risk factors such as high alanine aminotransferase, elevated aspartate aminotransferase, and high alkaline phosphatase could be of help in the decision for early operation.

Thymoquinone therapy remediates elevated brain tissue inflammatory mediators induced by chronic administration of food preservatives.

Continuous exposure to preservatives such as nitrite salts has deleterious effects on different organs. Meanwhile, Nigella sativa oil can remediate such organ dysfunction. Here, we studied the effect of consumption of thymoquinone (TQ); the main component of Nigella sativa oil on the brain damage induced by sodium nitrite. Forty adult male rats were daily given oral gavage of sodium nitrite (80 mg/kg) with or without thymoquinone (50 mg/kg). Oxidative stress, cytokines of inflammation, fibrotic elements and apoptotic markers in brain tissue were measured. Exposure to sodium nitrite (SN) resulted in increased levels of malondialdehyde, TGF-ß, c-reactive protein, NF-κB, TNF-α, IL-1ß and caspase-3 associated with reduced levels of glutathione, cytochrome c oxidase, Nrf2 and IL-10. However, exposure of rats' brain tissues to thymoquinone resulted ameliorated all these effects. In conclusion, thymoquinone remediates sodium nitrite-induced brain impairment through several mechanisms including attenuation of oxidative stress, retrieving the reduced concentration of glutathione, blocks elevated levels of pro-inflammatory cytokines, restores cytochrome c oxidase activity, and reducing the apoptosis markers in the brain tissues of rats.

Author Correction: Thymoquinone therapy remediates elevated brain tissue inflammatory mediators induced by chronic administration of food preservatives.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Inflammation and psychotropic drugs: the relationship between C-reactive protein and antipsychotic drug levels.

RATIONALE: In psychiatric clinical practice, there is a need to identify psychotropic drugs whose metabolisms are prone to be altered with increased inflammatory activity in an individual patient. OBJECTIVES: The aim of this study was to find out whether elevated serum levels (≥5 mg/l) of C-reactive protein (CRP), an established laboratory marker of infection and inflammation, are associated with increased serum concentrations of the atypical antipsychotic drugs clozapine, quetiapine, and risperidone. METHODS: Therapeutic drug monitoring request forms of patients whose antipsychotic drug concentrations had been measured under conditions of normal (<5 mg/l) and pathological (>5 mg/l) levels of C-reactive protein were retrospectively screened. The serum concentrations in relation to the daily doses [concentration per dose (C/D) (ng/mL/mg)] and the metabolic ratios [ratio of concentrations (metabolite/drug)] were compared intraindividually by the Wilcoxon signed rank test. To the study effects of the intensity of infections on drug concentrations, C-reactive protein and C/D levels were submitted to Spearman's correlation analysis. RESULTS: Elevated levels of C-reactive protein were found in 105 patients. They were significantly associated with elevated values in C/D for clozapine (n = 33, P < 0.01) and risperidone (n = 40, P < 0.01). A trend for an increase was found for quetiapine (n = 32, P = 0.05). Median increases were 48.0 % (clozapine), 11.9 % (quetiapine), and 24.2 % (active moiety of risperidone), respectively. CONCLUSIONS: In patients who exhibit signs of inflammation or infection with increased C-reactive protein values during psychopharmacological treatment, especially under clozapine and risperidone, therapeutic drug monitoring is recommendable in order to minimize the risk of intoxications due to elevated drug concentrations.

Protective effects of arjunolic acid against cardiac toxicity induced by oral sodium nitrite: effects on cytokine balance and apoptosis.

AIMS: Sodium nitrite, a preservative used in meat products, helps in the production of free radicals, leading to increased lipid peroxidation, which plays a vital role in posing toxic effects in different body organs. On the other hand, arjunolic acid possesses antioxidant properties and plays protective roles against chemically induced organ pathophysiology. We investigated the effect of sodium nitrite on cardiac tissue in rats on the inflammatory cytokine balance and the type of induced apoptosis, and we analyzed the protective role of arjunolic acid. MAIN METHODS: Sixty adult male Sprague-Dawley rats were injected with 80mg/kg sodium nitrite in the presence/absence of arjunolic acid (100 and 200mg/kg). Cardiac pro-inflammatory cytokines (TNF-α and IL-1ß), c-reactive protein (CRP) and anti-inflammatory cytokines (IL-4 and IL-10) were measured by ELISA. Cardiac mitochondrial activity (cytochrome-C-oxidase), JNK activation and apoptosis (caspase-3, caspase-8 and caspase-9) were assessed. KEY FINDINGS: Sodium nitrite resulted in increased TNF-α (1.6-fold), IL-1ß (3.7-fold) and CRP (2.4-fold) levels accompanied by 52%, 59% and 40% reductions in IL-10, IL-4 and cytochrome-C-oxidase, respectively, as well as enhanced JNK, caspase-3, caspase-8 and caspase-9 activities. Arjunolic acid markedly ameliorated these effects. SIGNIFICANCE: Arjunolic acid attenuated sodium nitrite-induced cardiac damage in rats and restored the normal balance between pro- and anti-inflammatory cytokines. Moreover, arjunolic acid protected cardiac tissues from both extrinsic and intrinsic cell death pathways.