A 6-month randomized controlled trial for vitamin E supplementation in pediatric patients with Gaucher disease: Effect on oxidative stress, disease severity and hepatic complications.

Enzymatic deficiency in Gaucher disease (GD) may induce oxidative stress. Vitamin E is the nature's most effective lipid-soluble antioxidant. This prospective clinical trial assessed the oxidant-antioxidant status in Egyptian patients with GD and the efficacy and safety and of vitamin E as an adjuvant antioxidant therapy. Forty children and adolescents with GD on stable doses of enzyme replacement therapy (ERT) were enrolled. Abdominal ultrasonography and transient elastography were performed. Malondialdehyde (MDA), vitamin E, and antioxidant enzymes (reduced glutathione [GSH], superoxide dismutase [SOD], glutathione peroxidase [GPx], and peroxiredoxin 2 [PRDX2]) were assessed. Patients were compared with 40 age- and sex-matched healthy controls. Patients with GD were randomized either to receive oral vitamin E for 6 months or not. All patients with GD had significantly higher MDA levels with lower levels of vitamin E and antioxidant enzymes compared with healthy controls (p < 0.001). Vitamin E and PRDX2 were negatively correlated to severity score index (SSI), lyso GL1, and MDA. After 6 months of vitamin E supplementation, SSI and liver and spleen volumes and liver stiffness were significantly lower. Lyso GL1 and MDA were significantly decreased post-vitamin E therapy while antioxidant enzymes were significantly higher compared with baseline levels and with patients without vitamin E therapy. Oxidative stress is related to disease severity in pediatric patients with GD. A 6-month vitamin E supplementation for those patients represents a safe therapeutic adjuvant agent increasing the efficacy of ERT, reducing oxidative stress, and improving outcomes.

Nucleic acid vaccines-based therapy for triple-negative breast cancer: A new paradigm in tumor immunotherapy arena.

Nucleic acid vaccines (NAVs) have the potential to be economical, safe, and efficacious. Furthermore, just the chosen antigen in the pathogen is the target of the immune responses brought on by NAVs. Triple-negative breast cancer (TNBC) treatment shows great promise for nucleic acid-based vaccines, such as DNA (as plasmids) and RNA (as messenger RNA [mRNA]). Moreover, cancer vaccines offer a compelling approach that can elicit targeted and long-lasting immune responses against tumor antigens. Bacterial plasmids that encode antigens and immunostimulatory molecules serve as the foundation for DNA vaccines. In the 1990s, plasmid DNA encoding the influenza A nucleoprotein triggered a protective and targeted cytotoxic T lymphocyte (CTL) response, marking the first instance of DNA vaccine-mediated immunity. Similarly, in vitro transcribed mRNA was first successfully used in animals in 1990. At that point, mice were given an injection of the gene encoding the mRNA sequence, and the researchers saw the production of a protein. We begin this review by summarizing our existing knowledge of NAVs. Next, we addressed NAV delivery, emphasizing the need to increase efficacy in TNBC.

Prognostic significance of annexin A2 and tumor associated macrophages (TAMs) in metastatic renal cell carcinoma and their relation to Sunitinib resistance.

Sunitinib, an antiangiogenic tyrosine kinase inhibitor, is the main treatment for metastatic renal cell carcinoma (mRCC). Development of resistance is a major obstacle against therapy success. The aim of this study was to assess annexin A2 and CD163+ tumor associated macrophages (TAMs) immunohistochemical expression in 50 mRCC cases as regard to patients' prognosis and Sunitinib response. Also, to assess the correlation between annexin A2 and TAMs expression. High annexin A2 expression and TAMs density were associated with serum calcium level (P = 0.024 and 0.037, respectively), larger tumor size (P < 0.001), high tumor grade (P = 0.014 and <0.001, respectively), and the presence of tumor necrosis (P < 0.001). High annexin A2 and TAMs expressions were related to shorter patients' overall survival (P = 0.009 and 0.001, respectively) and progression-free survival (P = 0.003 and 0.001, respectively). Annexin A2 was correlated with TAMs density (r = 0.890). Annexin A2 and TAMs are associated with poor prognostic parameters in mRCC patients, including high nuclear grade, increased tumor size, and the presence of tumor necrosis, together with shorter patients' survivals and poor response to Sunitinib. Annexin A2 expression is correlated with TAMs density suggesting immunomodulatory role of annexin A2.

Rosuvastatin repurposing for prophylaxis against ethanol-induced acute gastric ulceration in rats: a biochemical, histological, and ultrastructural perspective.

Ethanol (EtOH) consumption is frequently associated with acute and chronic gastrointestinal disorders. Rosuvastatin (RSV), a third-generation statin, has demonstrated certain biological functions beyond its lipid-lowering properties. This study is designed to explore the gastroprotective impact of RSV in a rat model of EtOH-induced gastric ulceration in a dose-dependent manner through the evaluation of oxidant/antioxidant biomarkers, inflammatory myeloperoxidase (MPO) enzyme activity, and prostaglandin E2 (PGE2) levels in gastric tissues, along with histopathological examination of the gastric tissues. Therefore, 40 adult male rats were randomly divided into five equal groups as control, EtOH (gastric ulcer), RSV-low dose plus EtOH and RSV-high dose plus EtOH. The EtOH rat model of gastric ulceration was achieved by intragastric administration of a single dose of EtOH. Seven days before EtOH administration, rats were orally administered either omeprazole (20 mg/kg/day) or RSV (10 mg/kg/day or 20 mg/kg/day). RSV administration enhanced the antioxidant glutathione reduced, countered oxidative malondialdehyde, augmented cytoprotective PGE2, suppressed inflammatory MPO enzyme activity in gastric tissues, decreased ulcer index scoring, increased the percentage of ulcer inhibition, and reversed the associated histological and ultrastructural abnormalities, additionally, RSV treatment resulted in weak positive nuclear staining for the inflammatory nuclear factor kappa B in a dose-dependent manner. It is concluded that RSV demonstrates gastroprotective potential, attributable at least in part, to its antioxidant and anti-inflammatory properties, as well as its ability to promote ulcer protection through the maintenance of mucosal content and PGE2 levels. Thus, RSV therapy emerges as a safe option for patients with gastric ulcers.

Optimizing geriatric palliative care in Egypt: Comprehensive patient and family perspectives.

OBJECTIVES: In Egypt, palliative care for geriatric patients is understudied, necessitating exploration for service optimization. Amidst rising chronic illnesses and aging, understanding perspectives of geriatric patients and families is crucial for targeted improvements. This study aims to explore geriatric patients' and their families' perspectives on palliative care in Egypt, seeking opportunities to optimize service delivery for the elderly. METHODS: Employing a cross-sectional design with 110 geriatric patients and an equal number of family caregivers from the Damietta Oncology Institute and the pain treatment clinics for cancer patients at Zagazig University Hospital, the study focuses on a specialized pain clinic. Validated tools (Palliative Care Outcome Scale, Family Satisfaction with End-of-Life Care [FAMCARE] Scale, Edmonton Symptom Assessment System [ESAS], Caregiver Strain Index [CSI]) assess quality of life, family satisfaction, symptom severity, and caregiver strain. RESULTS: Geriatric patients (mean age: 65.0 ± 8.1 years; 45.5% male, 55.5% female) have diverse diagnoses (e.g., breast cancer 22%). Palliative care outcomes reveal challenges: low emotional well-being (2.6 ± 0.0) and alarming overall quality of life (1.8 ± 0.0). Family dissatisfaction (FAMCARE) is pervasive (total mean score 2.6 ± 0.5). Symptom severity (ESAS) is high, and caregiver strain (CSI) is notable (8.5 ± 2.2). SIGNIFICANCE OF THE RESULTS: The findings underscore the significance of the challenges faced by geriatric patients and caregivers in palliative care. Patients confront considerable symptom burdens and emotional distress, while caregivers experience notable strain. Urgently needed are targeted interventions designed to enhance patient well-being, alleviate caregiver burden, and elevate satisfaction. The critical importance of implementing these interventions promptly is highlighted, as they are instrumental in improving the overall care experience for geriatric patients and their caregivers. Moreover, the results underscore the imperative of developing comprehensive support mechanisms to address the intricate dimensions of palliative care, ultimately contributing to a more compassionate and effective care continuum.

Endothelin-1 gene polymorphism (G8002A) and endothelial monocyte-activating polypeptide II: Role in vascular dysfunction in pediatric patients with ß-thalassemia major.

BACKGROUND: Endothelin-1 (ET-1), a potent endogenous vasoconstrictor, stimulates production of reactive oxygen species. Endothelial monocyte-activating polypeptide-II (EMAP-II) is a multifunctional polypeptide. AIM: To assess ET-1 gene polymorphism (G8002A) in pediatric patients with ß-thalassemia major (ß-TM) as a potential genetic marker for vascular dysfunction and its possible relation to EMAP II, oxidative stress and vascular complications. METHODS: ß-TM patients (n = 95) without symptomatic cardiac or renal disease were compared with 95 healthy controls. Markers of hemolysis, serum ferritin, urinary albumin-to-creatinine ratio, serum EMAP II, malondialdehyde (MDA) and antioxidant enzymes; superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase and catalase were measured. ET-1 gene polymorphism (G8002A) was determined using polymerase chain reaction­restriction fragment length polymorphism. RESULTS: ß-TM patients had significantly higher EMAP II than healthy controls. EMAP II was significantly higher among patients with cardiac disease, pulmonary hypertension (PH) risk, nephropathy, poor compliance to therapy and ferritin ≥ 2500 µg/L. There were significant correlations between EMAP II and transfusion index, LDH, ferritin and oxidative stress markers. The AA genotype of ET-1 gene polymorphism (G8002A) was significantly higher among ß-TM patients than controls. The number of patients with cardiac disease, PH risk or nephropathy was significantly higher among AA genotype compared with GG and GA genotypes. Lactate dehydrogenase (LDH), serum ferritin, EMAP II, MDA, SOD and GPx were significantly higher in AA genotype. CONCLUSION: ET-1 gene polymorphism (G8002A) could be a possible genetic marker for prediction of increased susceptibility to cardiopulmonary and renal complications among pediatric patients with ß-TM.

The reversed De Ritis ratio for predicting in-hospital mortality among intensive care patients with organophosphate poisoning.

INTRODUCTION: The uncontrolled use of pesticides signifies a substantial health hazard. This study was designed to explore the prognostic role of on-admission hepatic aminotransferases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the reversed De Ritis ratio (ALT/AST)] in the prediction of in-hospital mortality among patients with acute organophosphate (OP) poisoning. PATIENTS AND METHODS: We conducted a retrospective study based on extracting the required information from the specific medical records for acutely OP-intoxicated patients admitted to the intensive care unit. RESULTS: A total of 49 acutely malathion-intoxicated patients were enrolled in the study. The in-hospital mortality rate was 32.7%. Patients were stratified into survivors and non-survivors. Compared to the survivors, the non-survivors had significantly lower Glasgow coma scale scores, mean arterial blood pressure, significantly higher reversed De Ritis ratio (ALT/AST), and ALT and AST activities. The reversed De Ritis ratio (ALT/AST) and ALT demonstrated good discrimination between the survivors and the non-survivors with an area under the curve (AUC) of 0.708 vs 0.781, respectively, however, AST showed satisfactory discrimination, AUC of 0.694. CONCLUSION: Hepatic aminotransferases are useful in predicting in-hospital mortality in acute OP poisoning. ALT is the most specific biomarker. However, the reversed De Ritis ratio (ALT/AST) is the most sensitive one.

Nano-crystallization of flubendazole for enhanced dissolution rate and improved in vivo efficacy against Trichinella spiralis.

The aim was to enhance the dissolution rate and in vivo efficacy of flubendazole against trichinella spiralis. Flubendazole nanocrystals were developed by controlled anti-solvent recrystallization. Saturated flubendazole solution was prepared in DMSO. This was injected into phosphate buffer (pH 7.4) containing Aerosil 200, Poloxamer 407 or sodium lauryl sulphate (SLS) while mixing using paddle mixer. The developed crystals were separated from DMSO/aqueous system by centrifugation. The crystals were characterized using DSC, X-ray diffraction and electron microscopy. The crystals were suspended in Poloxamer 407 solution and dissolution rate was monitored. Optimal formulation was administered to Trichinella spiralis infected mice. Administration protocol attacked the parasite in intestinal, migrating and encysted phases. The crystals were spherical nanosized with formulation employing 0.2% Poloxamer 407 as stabilizer being optimum with size of 743.1 nm. DSC and X-ray supported particle size reduction with partial amorphization. Optimal formulation showed fast dissolution to deliver 83.1% after 5 min. Nanocrystals provided complete eradication of intestinal Trichinella and reduced larval count by 90.27 and 85.76% in migrating and encysted phases compared with marginal effect in case of unprocessed flubendazole. The efficacy was clearer from improved histopathological features of the muscles. The study introduced nano-crystallization for enhanced dissolution and in vivo efficacy of flubendazole.

Effect of parental attitudes on the practice and medicalization of female genital mutilation: a secondary analysis of Egypt Health Issues Survey, 2015.

BACKGROUND: Despite the observed decrease in female genital mutilation (FGM) prevalence, it is increasingly being medicalized. We examined the attitudes of both parents towards the FGM practice in Egypt, and highlighted the effect of fathers' decision making and attitudes towards FGM and violence on FGM practice and medicalization. METHODS: This study is a secondary analysis of Egypt Health Issues Survey (EHIS), 2015. The 2015 EHIS involved a systematic random selection of a subsample of 614 Shiakhas/villages out of the 884 shiakhas/villages that had been chosen as Primary Sampling Units in the 2014 EDHS. Descriptive statistics of the study sample and parents' attitudes was performed. Three indices were created describing; mothers' and fathers' attitudes towards FGM, decision making and rejecting violence against women. Bivariate and multivariable analyses were conducted to identify predictors of FGM practice and medicalization. RESULTS: A considerable proportion of EHIS girls; 16.4% were circumcised and 36% of girls were expected to be circumcised. More than two thirds of circumcised girls were circumcised by a physician; namely 67% and 13.5% by nurses. The majority of mothers (88.4%) and fathers (84.8%) believed that FGM practice should continue. They believed that FGM is a religious obligation (72.3% of mothers and 73% of fathers). Parents believed that husbands prefer a circumcised wife (81.1% and 82.5% of mothers and fathers respectively). Being in the poorest wealth quintile (OR = 4.2, p < 0.001) and living in rural Upper Egypt (OR = 4.55, p < 0.001) were the predictors of FGM practice, while medicalization was more likely among the rich and educated parents. Parents' attitudes supporting FGM was significantly associated with its practice (OR = 1.97, p < 0.001, for mothers and OR = 1.27, p < 0.001, for fathers). Rejecting violence against women was associated with less likelihood of practicing FGM (OR = 0.89, p < 0.05) and more likelihood of its medicalization (OR = 1.25, p < 0.01). CONCLUSION: More attention should be paid to enforce the laws against FGM practice by health care providers. Raising the community awareness on girls' human rights and elimination of FGM practice which is a severe form of violence against women and gender inequality in sexual rights should be prioritized with targeting men in FGM programs.

Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats.

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF-MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract's effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF-MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2'-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress.

Possible protective effect of TNF-α inhibition and triad NO/cGMP/VEGF activation on gastric ulcer in rats.

Peptic ulcers are one of the world's major gastrointestinal disorders, embracing both gastric and duodenal ulcers, and affecting 10% of the world population. The current study aimed to investigate the possible protective effect of tadalafil and pentoxifylline (PTX) on indomethacin-induced peptic ulcers. Male albino rats were divided into five groups: control group; ulcerated group; Indomethacin + Tadalafil, in which animals were pretreated with tadalafil orally before indomethacin; Indomethacin+ PTX, in which animals were pretreated with PTX orally before indomethacin; and Indomethacin + Tadafil + PTX. Indomethacin treatment revealed histopathological changes and ulcer scoring and ulcer index were markedly increased. Serum levels of prostaglandin and heme oxygenase-1 were significantly decreased. The ulcerogenic also induced marked oxidative stress as evident from the increased malondialdehyde, decreased in gastric glutathione content and superoxide dismutase activity, while the gastric myeloperoxidase was increased. Gastric nitric oxide content was decreased and the expression of vascular endothelial growth factor was downregulated while the tumor necrosis factor α (TNF-α) level was dramatically increased. Pretreatment of the ulcerative group by either tadalafil or PTX or their combination improved all these pathological changes. Tadalafil or PTX may have a role in protecting gastric mucosa damage caused by indomethacin which may be useful in the future for the treatment of gastric ulceration.

Toxicity Profile and Pharmacokinetic Study of Antibiotic Mixtures, Gentamicin and Vancomycin, in Rat Plasma by Ecofriendly Liquid Chromatography Coupled Tandem Mass Spectrometry.

The global burden of bacterial infection and antimicrobial resistance increases the demand to associate more than one antibiotic to fight life-threatening bacteria. Therefore, there is a great necessity to develop simple and sensitive methods for routine analysis of clinical samples. Therapeutic drug monitoring, bioequivalence, and pharmacokinetic studies are essential to ensure drug efficiency and safety. Herein, therefore, the first ecofriendly liquid chromatography -tandem mass spectrometry (LC-MS/MS) method was developed and fully validated for simultaneous determination of a commonly combined antibiotic for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin (VCM) and gentamicin (GTM), in rat plasma after parenteral administration. VCM and GTM were extracted from plasma sample using acetonitrile (ACN)/0.1% TFA-induced protein precipitation followed by the separation on an Agilent Eclipse Plus ODS (3 mm × 100 mm, 3.5 µm) column using water-enriched mobile phase consisting of water containing 0.1% THF/ACN (85:15, v/v%) at flow rates of 0.30 mL min-1. The mass spectrometry parameters were optimized, and multiple reaction monitoring (MRM) in positive ion mode of two transitions was utilized for quantification of precursor to product ion at m/z 725.5 → 144 and 100.1 for VCM as [M + 2H]2+, 478.3 → 322.2 and 156.9 for GTM, and 586.3 → 162.9 and 425.3 for amikacin (AMK) internal standard, as [M + H]+. The current method has been validated as per U.S. FDA bioanalytical guidelines in terms of linearity, accuracy, precision, selectivity, recovery, matrix effects, and stability. The method was linear in the range of 1-2000 ng mL-1 and 1-1000 ng mL-1 with detection limits (S/N of 3) of 0.18 and 0.09 ng mL-1 for VCM and GTM, respectively. The selectivity and high sensitivity allow the current method to succeed in the study of pharmacokinetic parameters and drug-drug interaction between VCM and GTM after single-dose administration. VCM increased plasma clearance and elimination rate constant of GTM when coadministered and GTM also too. The change of serum chemistry analysis and significant elevation of creatinine and BUN indicate an alteration in kidney function in group III in those given the combined antibiotics. Our finding illustrated the nephrotoxicity of the two drugs when associated. The ecofriendly, simplicity, and rapidity of the current study made it a promising method for high-throughput biomonitoring in clinical samples.

Manganese-induced neurotoxicity and the potential protective effects of lipoic acid and Spirulina platensis.

Manganese (Mn) is essential for many physiological processes; however, its excessive accumulation in the brain causes severe dysfunctions in the nervous system. Oxidative stress is thought to be involved in Mn-induced neurotoxicity. The aim of this study was to evaluate the neurotoxic effects of Mn and the potential protective effects of alpha lipoic acid (ALA) and Spirulina platensis (SP), each alone and in combination. Sixty-four male albino rats were divided into eight equal groups: group 1 was used as control, group 2 received saline, which used as a vehicle, group 3 received ALA (50 mg/kg/day), group 4 received SP (300 mg/kg/day), group 5 received Mn (74 mg/kg, 5 days/week), group 6 received Mn + ALA, group 7 received Mn + SP, group 8 received Mn + ALA + SP. Groups 6, 7 and 8 received the same previously mentioned doses. All treatments were orally gavaged for 8 weeks. Mn administration caused neurobehavioral changes, increases of brain and serum Mn and malondialdehyde (MDA), with decreased glutathione peroxidase (GPx), dopamine and acetylcholine levels. The co-treatment with ALA and SP revealed their ability to protect against oxidative damage, neurobehavioral and biochemical changes induced by Mn.

Who knows best? A Q methodology study to explore perspectives of professional stakeholders and community participants on health in low-income communities.

BACKGROUND: Health inequalities in the UK have proved to be stubborn, and health gaps between best and worst-off are widening. While there is growing understanding of how the main causes of poor health are perceived among different stakeholders, similar insight is lacking regarding what solutions should be prioritised. Furthermore, we do not know the relationship between perceived causes and solutions to health inequalities, whether there is agreement between professional stakeholders and people living in low-income communities or agreement within these groups. METHODS: Q methodology was used to identify and describe the shared perspectives ('subjectivities') that exist on i) why health is worse in low-income communities ('Causes') and ii) the ways that health could be improved in these same communities ('Solutions'). Purposively selected individuals (n = 53) from low-income communities (n = 25) and professional stakeholder groups (n = 28) ranked ordered sets of statements - 34 'Causes' and 39 'Solutions' - onto quasi-normal shaped grids according to their point of view. Factor analysis was used to identify shared points of view. 'Causes' and 'Solutions' were analysed independently, before examining correlations between perspectives on causes and perspectives on solutions. RESULTS: Analysis produced three factor solutions for both the 'Causes' and 'Solutions'. Broadly summarised these accounts for 'Causes' are: i) 'Unfair Society', ii) 'Dependent, workless and lazy', iii) 'Intergenerational hardships' and for 'Solutions': i) 'Empower communities', ii) 'Paternalism', iii) 'Redistribution'. No professionals defined (i.e. had a significant association with one factor only) the 'Causes' factor 'Dependent, workless and lazy' and the 'Solutions' factor 'Paternalism'. No community participants defined the 'Solutions' factor 'Redistribution'. The direction of correlations between the two sets of factor solutions - 'Causes' and 'Solutions' - appear to be intuitive, given the accounts identified. CONCLUSIONS: Despite the plurality of views there was broad agreement across accounts about issues relating to money. This is important as it points a way forward for tackling health inequalities, highlighting areas for policy and future research to focus on.

l-Carnitine-induced amelioration of HFD-induced hepatic dysfunction is accompanied by a reduction in hepatic TNF-α and TGF-ß1.

In this study, we evaluated the possible mechanisms through which l-carnitine ameliorates the adverse effects from obesity in rats, induced with a high-fat diet (HFD). For this, 56 albino Wister rats were randomly assigned to 7 groups. The control group was fed a basal diet and injected with saline. The second group was fed the basal diet and injected with l-carnitine (200 mg/kg body mass, by intraperitoneal injection; i.p.). The third group were fed the HFD. The fourth group was fed the HFD and injected with l-carnitine (200 mg/kg body mass, i.p.) for 8 weeks. The fifth group was fed the HFD for 10 weeks. The sixth group were fed the HFD for 10 weeks and were also injected with l-carnitine (200 mg/kg body mass, i.p.) during the final 2 weeks. The seventh group was fed the HFD diet for 8 weeks then the basal diet for 2 weeks. The HFD induced significantly increased levels of hyperglycemia, lipid peroxidation, pathological changes, TNF-α and TGF-ß1 protein expression in hepatic tissue, food intake, body weight gain, serum levels of total and non-high-density lipoprotein cholesterol, ketone bodies, triacylglycerol, urea, creatinine, AST, and ALT. However, the HFD diet significantly decreased serum levels of high-density lipoprotein (HDL) and hepatic levels of reduced glutathione. l-Carnitine ameliorated the effects of the HFD on the above-mentioned parameters. This study indicated that l-carnitine had protective and curative effects against HFD-induced hepatosteatosis by reducing hepatic oxidative stress and protein expression of TNF-α and TGF-ß1.

The differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on seizure frequency in patients with drug-resistant epilepsy - A randomized, double-blind, placebo-controlled trial.

OBJECTIVES: The omega-3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to play an important role in maintenance and modulation of neuronal functions. There is evidence that omega-3 fatty acids may have anticonvulsant effects. The effect of DHA and EPA on seizure rate in patients with drug-resistant epilepsy (DRE) was investigated. METHODS: A double-blind, randomized, placebo-controlled clinical trial included ninety-nine (n = 99) subjects with DRE, aged 5-16 years (n = 85) and 17-45 years (n = 14). After randomization, subjects were given two, four, or six capsules per day of DHA (417.8 mg DHA and 50.8 mg EPA/capsule, n = 33), EPA (385.6 mg EPA and 81.2 mg DHA/capsule, n = 33), or placebo (high oleic acid sunflower oil, n = 33) for one year. The primary endpoint was the effect of treatment on rate of seizure. Random-effects negative binomial regression models were fitted to model the patients' total count of seizures per month. The treatment effects on seizure incidence rate ratio (IRR) were tested after controlling for the covariate effects of gender, age, rate of seizure per week at enrollment, type of seizure, and number of antiepileptic drug (AED) combinations used at enrollment. RESULTS: Fifty-nine subjects (n = 59) completed the study (59.6%). The average number of seizures per month were 9.7 ±â€¯1.2 in the EPA group, 11.7 ±â€¯1.5 in the DHA group, and 16.6 ±â€¯1.5 in the placebo group. Age, gender, and seizure-type adjusted seizure IRRs of the EPA and DHA groups compared with the placebo group were 0.61 (CI = 0.42-0.88, p = 0.008, 42% reduction) and 0.67 (CI = 0.46-1.0, p = 0.04, 39% reduction), respectively. There was no difference in IRR between the EPA and DHA groups (p = 0.56). Both treatment groups had a significantly higher number of seizure-free days compared with the placebo group (p < 0.05). SIGNIFICANCE: This study demonstrates that EPA and DHA are effective in reducing seizure frequency in patients with DRE.

Effect of bone marrow mesenchymal stem cells on healing of temporomandibular joints in rats with induced rheumatoid arthritis.

The healing capacity of bone marrow mesenchymal stem cells (BMMSCs) has been evaluated in various studies. This study aimed to evaluate the effect of BMMSCs on the healing of temporomandibular joints (TMJs) with induced rheumatoid arthritis. Fifty healthy male Sprague Dawley rats were divided into three groups: group I (n = 10), negative control; group II (n = 20), positive control (induction of arthritis by adjuvant followed by intravenous injection of 0.1 ml of PBS); and group III (n = 20), intervention (as for group II but injected intravenously with 1 × 106  cells ml-1 of BMMSCs suspended in PBS). Half of the rats in each group were euthanized 3 wk after the start of the experiment and the other half was euthanized after 5 wk. Group I revealed normal TMJ features. Group II showed thickening of disc, thinning of cartilage, disordered bone trabeculae, and decreased in mean % area staining positive of collagen fibers at 3 wk, while at 5 wk these effects were more aggravated. Group III showed nearly normal thickness of disc and condylar cartilage, nearly normal arrangement of bone trabeculae and regenerated collagen fibers at 3 wk, while after 5 wk the TMJ features were almost normal. Two-way anova revealed statistically significant differences between groups. Thus, treatment of induced rheumatoid arthritis with BMMSCs shows promising results that need to be further investigated in humans.

Role of vitamin C as an adjuvant therapy to different iron chelators in young ß-thalassemia major patients: efficacy and safety in relation to tissue iron overload.

BACKGROUND: Vitamin C, as antioxidant, increases the efficacy of deferoxamine (DFO). AIM: To investigate the effects of vitamin C as an adjuvant therapy to the three used iron chelators in moderately iron-overloaded young vitamin C-deficient patients with ß-thalassemia major (ß-TM) in relation to tissue iron overload. METHODS: This randomized prospective trial that included 180 ß-TM vitamin C-deficient patients were equally divided into three groups (n = 60) and received DFO, deferiprone (DFP), and deferasirox (DFX). Patients in each group were further randomized either to receive vitamin C supplementation (100 mg daily) or not (n = 30). All patients received vitamin C (group A) or no vitamin C (group B) were followed up for 1 yr with assessment of transfusion index, hemoglobin, iron profile, liver iron concentration (LIC) and cardiac magnetic resonance imaging (MRI) T2*. RESULTS: Baseline vitamin C was negatively correlated with transfusion index, serum ferritin (SF), and LIC. After vitamin C therapy, transfusion index, serum iron, SF, transferrin saturation (Tsat), and LIC were significantly decreased in group A patients, while hemoglobin and cardiac MRI T2* were elevated compared with baseline levels or those in group B without vitamin C. The same improvement was found among DFO-treated patients post-vitamin C compared with baseline data. DFO-treated patients had the highest hemoglobin with the lowest iron, SF, and Tsat compared with DFP or DFX subgroups. CONCLUSIONS: Vitamin C as an adjuvant therapy possibly potentiates the efficacy of DFO more than DFP and DFX in reducing iron burden in the moderately iron-overloaded vitamin C-deficient patients with ß-TM, with no adverse events.

Therapeutic antioxidant and anti-inflammatory effects of laser acupuncture on patients with rheumatoid arthritis.

BACKGROUND AND OBJECTIVE: The laser acupuncture has many potential therapeutic effects. Currently, they are not evaluated for their therapeutic effects on rheumatoid arthritis (RA) patients. The aim of this study was to investigate the effects of laser acupuncture on the oxidative and antioxidative markers, as well as the inflammatory markers and disease activity of RA patients. DESIGN/MATERIALS AND METHODS: The study was conducted on 30 RA patients and 20 healthy subjects. The patients were subjected to laser acupuncture (904 nm, 100 mW power output, 1 minute irradiation time, beam area of 1 cm(2) , total energy per point 6 J, energy density 6 J/ cm(2) , irradiance 0.1 W/cm(2) , frequency 10000 Hz, duty-cycle 100%) for 3 days/week for duration of 4 weeks. The acupuncture points of exposure were LI4, TE5, LI 11, DU 14, LIV3, SP6, GB34, and S36. The levels of oxidative and antioxidant markers were determined by spectrophotometric methods whereas the inflammatory markers were determined by ELISA methods. Lastly, using DAS28 scores the disease activity was assessed. RESULTS: After laser acupuncture, the study group revealed significantly increased plasma superoxide dismutase (SOD), glutathione reductase (GR), catalase activities, blood glutathione (GSH), and plasma ATP concentrations, compared to those before treatment (P < 0.0005). Moreover, the results revealed significantly reduced plasma malondialdehyde (MDA), serum nitrate and nitrite, serum C-reactive protein (CRP), plasma interleukin-6 (IL-6) levels and significantly reduced glutathione peroxidase (GPx) activity and erythrocyte sedimentation rate (ESR) in laser exposed patients, compared to those before treatment (P < 0.0005). The RA patients subjected to laser acupuncture showed highly significant reduction in disease activity (P < 0.0005) based on DAS28 score. CONCLUSION: Our study results confirmed the effectiveness of laser acupuncture in alleviating oxidative stress and inflammation, improving antioxidant and energy metabolic status, while also suppressing the disease activity in RA patients. Laser acupuncture is a promising treatment modality to reduce the pain and suffering of RA patients because of its efficiency in inhibiting most of the main factors involved in the pathogenesis of this disease. Lasers Surg. Med. 48:490-497, 2016. © 2016 Wiley Periodicals, Inc.