L-carnitine and Acetyl-L Carnitine: A Possibility for Treating Alterations Induced by Obesity in the Central Nervous System.

Excessive consumption of nutrients, as well as obesity, leads to an inflammatory process, especially in adipose tissue. This inflammation reaches the systemic level and, subsequently, the central nervous system (CNS), which can lead to oxidative stress and mitochondrial dysfunction, resulting in brain damage. Thus, adequate treatment for obesity is necessary, including lifestyle changes (diet adequation and physical activity) and pharmacotherapy. However, these drugs can adversely affect the individual's health. In this sense, searching for new therapeutic alternatives for reestablishing metabolic homeostasis is necessary. L-carnitine (LC) and acetyl-L-carnitine (LAC) have neuroprotective effects against oxidative stress and mitochondrial dysfunction in several conditions, including obesity. Therefore, this study aimed to conduct a narrative review of the literature on the effect of LC and LAC on brain damage caused by obesity, in particular, on mitochondrial dysfunction and oxidative stress. Overall, these findings highlight that LC and LAC may be a promising treatment for recovering REDOX status and mitochondrial dysfunction in the CNS in obesity. Future work should focus on better elucidating the molecular mechanisms behind this treatment.

Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: A Phase 3B Trial Using a Novel Abdominal Scoring System.

INTRODUCTION: Linaclotide improves abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Patients report additional bothersome abdominal symptoms of bloating and discomfort. The intention of this study was to evaluate linaclotide's efficacy in relieving IBS-C-related abdominal symptoms (bloating, discomfort, and pain) using a novel multi-item Abdominal Score (AS). METHODS: Patients with IBS-C with abdominal pain ≥3 (0-10 scale) were randomized to linaclotide 290 µg or placebo daily for 12 weeks. The AS, derived from the Diary for IBS Symptoms-Constipation, is the average of abdominal bloating, discomfort, and pain at their worst (0 = none, 10 = worst possible). The primary end point was overall change from baseline (CFB) in AS. Secondary end points included CFB in 12-week AS evaluated using cumulative distribution function and 6-week/12-week AS responder (AS improvement ≥2 points for ≥6-week/12-week). RESULTS: Overall, 614 patients (mean age 46.7 years; 81% female) were randomized. All prespecified end points showed significant benefit of linaclotide vs placebo. The mean overall CFB AS reduction for linaclotide was -1.9 vs -1.2 for placebo (P < 0.0001); the 6-week/12-week AS responder rate was 40.5% for linaclotide vs 23.4% for placebo (odds ratio = 2.2 [95% confidence interval, 1.55-3.12; P < 0.0001]). Diarrhea was the most common treatment-emergent adverse event (linaclotide = 4.6%, placebo = 1.6%). DISCUSSION: Linaclotide significantly reduced multiple abdominal symptoms important to patients with IBS-C (bloating, discomfort, and pain) compared with placebo, as measured by a novel multi-item AS. The AS, derived from the Diary for IBS Symptoms-Constipation, should be considered for use in future IBS-C clinical studies to measure clinically meaningful improvements beyond traditional end points.

Psychometric Analysis of the Abdominal Score From the Diary for Irritable Bowel Syndrome Symptoms-Constipation Using Phase IIb Clinical Trial Data.

OBJECTIVES: The Diary for Irritable Bowel Syndrome Symptoms-Constipation (DIBSS-C) has been developed to assess the core signs and symptoms of irritable bowel syndrome with constipation (IBS-C). This article presents the psychometric evaluation of the DIBSS-C abdominal score. METHODS: Data for these analyses are from a multicenter phase IIb study in IBS-C patients (NCT02559206). Subjects completed a number of assessments via handheld electronic diary throughout the study. The analyses used the intent-to-treat population and were blinded to randomized treatment group. The analyses evaluated the reliability, validity, and responsiveness of the DIBSS-C abdominal score; identified an appropriate scoring algorithm; and determined thresholds for interpreting clinically meaningful changes at the individual level. RESULTS: The correlations between the DIBSS-C abdominal symptom items (ie, abdominal pain, discomfort, and bloating) were strong (>0.75). Cronbach's alpha for the abdominal symptom severity items was very strong (.94), indicating that the 3 abdominal symptom items produce a reliable score. The intraclass correlation coefficient for the abdominal score was 0.82, exceeding the threshold of 0.70 and indicating good test-retest reliability. Guyatt's responsiveness statistic values all exceeded the threshold for a large effect of 0.80, so the DIBSS-C abdominal score can be considered highly responsive to change. Triangulation across 3 sets of anchor-based analyses indicated that a threshold of -2.0 points on the abdominal score is an appropriate threshold for identifying meaningful change. CONCLUSIONS: Overall, this study provides evidence that the DIBSS-C abdominal score is valid, reliable, responsive to change, and interpretable for assessing treatment benefit in patients with IBS-C.

The Impact of Stool Consistency on Bowel Movement Satisfaction in Patients With IBS-C or CIC Treated With Linaclotide or Other Medications: Real-World Evidence From the CONTOR Study.

GOALS: This study aimed to characterize the impact of stool consistency on patient-reported bowel movement (BM) satisfaction in patients with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation, with a focus on linaclotide. BACKGROUND: As new medications for constipation become available, understanding patients' perceptions of treatment effects may help clinicians manage patient expectations and inform clinical decision-making. MATERIALS AND METHODS: Data were derived from the Chronic Constipation and IBS-C Treatment and Outcomes Real-world Research Platform (CONTOR) study from 2 patient-reported 7-day daily BM diaries to create a dataset of 2922 diaries representing 26,524 BMs for 1806 participants. Binary variables were created for: medication(s) used in the past 24 hours and categorization of BMs as loose or watery stools (LoWS), hard or lumpy stools (HoLS), or intermediate (neither LoWS nor HoLS). The relationship between stool consistency, medication use, and BM satisfaction was analyzed using logistic regression with SEs corrected for repeated observations. RESULTS: BMs characterized as intermediate stools and LoWS were satisfactory more often (61.2% and 51.2%, respectively) than HoLS (19.4%). Participants who reported taking linaclotide rated a similar proportion of BMs as satisfactory when described as LoWS (65.6%) or intermediate (64.1%). Linaclotide use was associated with higher odds of BMs being reported as satisfactory compared with nonlinaclotide use (odds ratio: 1.23, P<0.05). CONCLUSIONS: Overall, CONTOR participants were more likely to report BMs classified as LoWS or intermediate as satisfactory, versus HoLS. Participants taking linaclotide were more likely to be satisfied, particularly those reporting LoWS, versus those not taking linaclotide.

The impact of treatment with eluxadoline on health-related quality of life among adult patients with irritable bowel syndrome with diarrhea.

PURPOSE: Irritable bowel syndrome with diarrhea (IBS-D) significantly impacts health-related quality of life (HRQOL). This post hoc analysis of two phase III trials evaluated the effects of eluxadoline treatment on disease-specific HRQOL among patients with IBS-D. METHODS: Adult patients meeting Rome III criteria for IBS-D were randomized to oral eluxadoline (75 mg or 100 mg) or placebo twice daily in two phase III clinical trials for 52 weeks (IBS-3001) and 26 weeks (IBS-3002). The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire assessed disease-specific HRQOL throughout the study. Changes from baseline to Week 26 in IBS-QOL total and subscale scores were analyzed using an analysis of covariance model. Percentages of IBS-QOL responders with ≥ 14- and 20-point changes were evaluated for IBS-QOL total and subscale scores. A longitudinal mixed-effects model was fitted to evaluate mean IBS-QOL total scores. A cumulative distribution function for change from baseline to Week 26 in IBS-QOL total score was plotted. RESULTS: Mean changes from baseline to Week 26 for the IBS-QOL total and all subscale scores were significantly higher for patients treated with eluxadoline (both doses) compared to placebo. A significantly greater proportion of eluxadoline-treated patients were responders compared to placebo. Mean and mixed-effects model estimated mean IBS-QOL total scores were consistently higher for eluxadoline versus placebo over 52 weeks. CONCLUSIONS: Compared to placebo, twice-daily eluxadoline treatment significantly improved HRQOL among patients with IBS-D in two phase III trials.

Health Care Resource Use and Costs Pre- and Post-Treatment Initiation With Linaclotide: Retrospective Analyses of a U.S. Insured Population.

As expected, pharmacy costs increased with the introduction of this new treatment in a market dominated by over-the-counter and generic treatments. On the other hand, outpatient GI-related and irritable bowel disease health care resource use and costs substantially decreased among commercial and Medicare patients following linaclotide treatment initiation.

Leveraging sensor-based functional outcomes to enhance understanding of the patient experience: challenges and opportunities.

INTRODUCTION: Sensor-based digital health technology (DHT) has emerged as a promising means to assess patient functioning within and outside clinical trials. Sensor-based functional outcomes (SBFOs) provide valuable insights that complement other measures of how a patient feels or functions to enhance understanding of the patient experience to inform medical product development. AREAS COVERED: This perspective paper provides recommendations for defining SBFOs, discusses the core evidence required to support SBFOs to inform decision-making, and considers future directions for the field. EXPERT COMMENTARY: The clinical outcome assessment (COA) development process provides an important starting point for developing patient-centered SBFOs; however, given the infancy of the field, SBFO development may benefit from a hybrid approach to evidence generation by merging exploratory data analysis with patient engagement in measure development. Effective SBFO development requires combining unique expertise in patient engagement, measurement and regulatory science, and digital health and analytics. Challenges specific to SBFO development include identifying concepts of interest, ensuring measurement of meaningful aspects of health, and identifying thresholds for meaningful change. SBFOs are complementary to other COAs and, as part of an integrated evidence strategy, offer great promise in fostering a holistic understanding of patient experience and treatment benefits, particularly in real-world settings.

Nuxcell Neo® improves vaccine efficacy in antibody response.

Current vaccination protocols raise concerns about the efficacy of immunization. There is evidence that changes in the gut microbiota can impact immune response. The formation of the gut microbiota in newborns plays a crucial role in immunity. Probiotic bacteria and prebiotics present important health-promoting and immunomodulatory properties. Thus, we hypothesize that pro and prebiotic supplementation can improve the efficacy of vaccination in newborns. In this protocol, newborn mice were used and treated with a single-dose rabies vaccine combined with Nuxcell Neo® (2 g/animal/week) for 3 weeks. Samples were collected on days 7, 14, and 21 after vaccination for analysis of cytokines and concentration of circulating antibodies. Our results show an increased concentration of antibodies in animals vaccinated against rabies and simultaneously treated with Nuxcell Neo® on days 14 and 21 when compared to the group receiving only the vaccine. In the cytokine levels analysis, it was possible to observe that there weren't relevant and significant changes between the groups, which demonstrates that the health of the animal remains stable. The results of our study confirm the promising impact of the use of Nuxcell Neo® on the immune response after vaccination.

The combined treatment of gold nanoparticles associated with photobiomodulation accelerate the healing of dermonecrotic lesion.

Introduction: The search for fast and efficient treatment for dermonecrotic lesions caused by the venom of the spider from the Loxosceles simillis, is a demand in health. Prednisolone is one of the most used drugs, however it has side effects. In this context, addictionally gold nanoparticles (GNPs) have anti-inflammatory, antioxidant, and antibacterial properties. The use of photobiomodulation has show to be efficient in the process of tissue repair. Therefore, the purpose of this study was to investigate the anti-inflammatory effect of photobiomodulation and GNPs associated or not with a low concentration of prednisolone in animal models of dermonecrotic lesion.Methodology: For this, rabbits with venon-induced dermonecrotic lesion were subjected to topical treatment with prednisolone + laser or GNPs + laser or Pred-GNPs + laser. The area of edema, necrosis and erythema were measured. On the last day of treatment, the animals were euthanized to remove the organs for histopathological and biochemical analysis.Results: All treatments combinations were effective in promoting the reduction of necrotic tissue and erythema.Conclusion: With this results, we suggest that the use of laser and nanoparticles, associated or not with prednisolone, should be considered for the treatment of dermonecrotic injury.

Intravenous administration of recombinant Phα1ß: Antinociceptive properties and morphine tolerance reversal in a cancer-associated pain model.

Cancer-related pain is considered one of the most prevalent symptoms for those affected by cancer, significantly influencing quality of life and treatment outcomes. Morphine is currently employed for analgesic treatment in this case, however, chronic use of this opioid is limited by the development of analgesic tolerance and adverse effects, such as digestive and neurological disorders. Alternative therapies, such as ion channel blockade, are explored. The toxin Phα1ß has demonstrated efficacy in blocking calcium channels, making it a potential candidate for alleviating cancer-related pain. This study aims to assess the antinociceptive effects resulting from intravenous administration of the recombinant form of Phα1ß (r-Phα1ß) in an experimental model of cancer-related pain in mice, tolerant or not to morphine. The model of cancer-induced pain was used to evaluate these effects, with the injection of B16F10 cells, followed by the administration of the r-Phα1ß, and evaluation of the mechanical threshold by the von Frey test. Also, adverse effects were assessed using a score scale, the rotarod, and open field tests. Results indicate that the administration of r-Phα1ß provoked antinociception in animals with cancer-induced mechanical hyperalgesia, with or without morphine tolerance. Previous administration of r-Phα1ß was able to recover the analgesic activity of morphine in animals tolerant to this opioid. r-Phα1ß was proved safe for these parameters, as no adverse effects related to motor and behavioral activity were observed following intravenous administration. This study suggests that the concomitant use of morphine and r-Phα1ß could be a viable strategy for pain modulation in cancer patients.

Combination of Gold Nanoparticles with Carnitine Attenuates Brain Damage in an Obesity Animal Model.

Obesity causes inflammation in the adipose tissue and can affect the central nervous system, leading to oxidative stress and mitochondrial dysfunction. Therefore, it becomes necessary to seek new therapeutic alternatives. Gold nanoparticles (GNPs) could take carnitine to the adipose tissue, thus increasing fatty acid oxidation, reducing inflammation, and, consequently, restoring brain homeostasis. The objective of this study was to investigate the effects of GNPs associated with carnitine on the neurochemical parameters of obesity-induced mice. Eighty male Swiss mice that received a normal lipid diet (control group) or a high-fat diet (obese group) for 10 weeks were used. At the end of the sixth week, the groups were divided for daily treatment with saline, GNPs (70 µg/kg), carnitine (500 mg/kg), or GNPs associated with carnitine, respectively. Body weight was monitored weekly. At the end of the tenth week, the animals were euthanized and the mesenteric fat removed and weighed; the brain structures were separated for biochemical analysis. It was found that obesity caused oxidative damage and mitochondrial dysfunction in brain structures. Treatment with GNPs isolated reduced oxidative stress in the hippocampus. Carnitine isolated decreased the accumulation of mesenteric fat and oxidative stress in the hippocampus. The combination of treatments reduced the accumulation of mesenteric fat and mitochondrial dysfunction in the striatum. Therefore, these treatments in isolation, become a promising option for the treatment of obesity.

Therapeutic effects of the gold nanoparticle on obesity-triggered neuroinflammation: a review.

Introduction: Obesity is considered a chronic non-communicable disease characterised by excess body fat. In recent years the prevalence of obesity has grown a lot. Individuals with obesity store the excess of nutrients consumed in the form of fat in adipose tissue, and generate an imbalance of this tissue, where there is the secretion of adipocytokines, which contributes to a peripheral and central inflammatory picture, reaching the central nervous system (CNS), generating neuroinflammation. There is still no effective and safe therapy for the treatment of obesity, many of the drugs marketed has serious side effects. Therefore, there is a search for therapies aimed mainly at reducing inflammation.Objective: In this work the possibility of using a new therapeutic option for obesity will be explored, using nanotechnology. Nanotechnology has gained prominence in recent years for being a promising technology for treatment and as a molecule-in-the-light in inflammatory diseases. Gold nanoparticles (GNP) stand out among nanomaterials because they demonstrate anti-inflammatory characteristics by various pathways, and have been widely used in the treatment of inflammatory diseases, including in the CNS, demonstrating excellent results.Result: Thus, the use of GNP for the treatment of obesity is promising due to the inflammatory state of obesity, thus acting as anti-inflammatory at the peripheral and central levels.

Improved work productivity and health-related quality of life in patients with irritable bowel syndrome with diarrhea receiving eluxadoline following inadequate response to loperamide.

BACKGROUND: Irritable bowel syndrome with diarrhea (IBS-D) is a chronic disorder of gut-brain interaction that negatively affects work productivity and health-related quality of life (HRQOL). IBS-D therapeutic options are limited and include loperamide, an over-the-counter µ-opioid receptor agonist commonly used as an antidiarrheal agent, and eluxadoline, a mixed µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist approved in the United States for the treatment of IBS-D in adults. OBJECTIVE: To characterize the effect of eluxadoline on work productivity and HRQOL in patients with IBS-D with previous inadequate response to loperamide. METHODS: The Work Productivity and Activity Impairment Questionnaire for IBS-D (WPAI:IBS-D), Centers for Disease Control and Prevention Healthy Days Core Module (CDC HRQOL-4), and EuroQoL-5 Dimension (EQ-5D) instruments were administered at baseline and week 12 of a phase 4 clinical trial (RELIEF), assessing the efficacy and safety of eluxadoline treatment in adults with IBS-D reporting previous inadequate response to loperamide. Changes from baseline to week 12 for each assessment were evaluated using an analysis of covariance model. Indirect costs were calculated by converting overall work productivity losses into monetary values. RESULTS: A total of 346 patients were randomized to either eluxadoline (n = 172) or placebo (n = 174). From baseline to week 12, compared with placebo, twice-daily treatment with eluxadoline resulted in significantly greater reductions in absenteeism (2.6%; P = 0.046). Numerically greater decreases in presenteeism, overall work productivity loss, and daily activity impairment were also observed in patients receiving eluxadoline compared with those receiving placebo (P = not significant for each). Numerical reductions in overall work productivity loss from baseline to week 12 translate to approximately 2.4 hours per patient per week (123 hours annually) and correspond to an avoided overall work loss of $4,503 annually for an employee with IBS-D treated with eluxadoline. In addition, from baseline to week 12, treatment with eluxadoline led to a significantly greater reduction in the number of unhealthy days experienced (-1.7 days; P = 0.042), as well as numerical improvements in EQ-5D measures in comparison with placebo (P = not significant for each). CONCLUSIONS: In patients with IBS-D reporting inadequate response to loperamide, eluxadoline treatment was associated with significant reductions in absenteeism and the number of unhealthy days experienced. Eluxadoline treatment of IBS-D may lead to significant cost savings via mitigation of losses in work productivity. DISCLOSURES: This study was sponsored by Allergan plc (before acquisition by AbbVie, Inc.). Allergan plc and/or AbbVie, Inc., was involved in the study design, collection, analysis, interpretation of the data, writing of the report, and the decision to submit the report for publication. Abel and Burslem are employees of AbbVie, Inc., and own stock/stock options. Brenner has served as a consultant, speaker, and/or advisor for Allergan plc (before acquisition by AbbVie, Inc.), Alnylam, Alpha Sigma, Arena, Bayer, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Shire, Synergy, and Takeda Pharmaceuticals. He is also supported in research by an unrestricted gift from the Irene D. Pritzker Foundation. Sayuk has served as a consultant and speaker for Allergan plc (before acquisition by AbbVie, Inc.), Gi Health Foundation, Ironwood Pharmaceuticals, Salix Pharmaceuticals, and Synergy. Portions of the current work were presented at AMCP Nexus; October 22-25, 2018; Orlando, FL.

Lessons learned: Chronic idiopathic constipation patient experiences with over-the-counter medications.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a prevalent functional gastrointestinal disorder diagnosed based on patient-reported symptoms and the absence of structural gastrointestinal abnormalities. Individuals with CIC typically institute dietary changes and use stool softeners or over-the-counter (OTC) laxatives, possibly at the direction of a healthcare provider, before prescription medications for CIC are initiated. Although highly prevalent, there is limited information regarding CIC patient experiences with OTC medications. METHODS: This post-hoc analysis used patient-reported data from a questionnaire administered during patient screening for a prospective linaclotide Phase 3b clinical trial in patients with CIC (N = 1482 screened). The questionnaire asked patients to report their experiences with OTC CIC medications over the preceding 6 months. RESULTS: Among patients with screening responses (N = 1423), most were female (85%) and white (66%), with a mean age of 48.9 years. A high proportion of patients had used one or more OTC medications (70% had ≥1 OTC; 19% had ≥3 OTCs), with the majority being bisacodyl (33%) and polyethylene glycol (30%). The most commonly cited reason for stopping an OTC medication was insufficient symptom relief (17-40%). The majority of patients taking OTC medications reported no or little satisfaction with the medication's effect on their constipation (62%) and CIC-specific abdominal symptoms (78%). Many patients had little to no confidence in bowel movement (BM) frequency after taking OTC medications and their confidence in their ability to predict BM timing was also low (49-81% not at all confident). CONCLUSIONS: Treatment effects on individual CIC symptoms, predictability of bowel habits, and satisfaction with treatment are all important factors for healthcare providers and patients to consider when establishing an effective treatment regimen for CIC. TRIAL REGISTRATION NUMBER: NCT01642914.

Comprehensive assessment of patients with irritable bowel syndrome with constipation and chronic idiopathic constipation using deterministically linked administrative claims and patient-reported data: the Chronic Constipation and IBS-C Treatment and Outcomes Real-World Research Platform (CONTOR).

AIMS: To characterize a US population of patients with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) using CONTOR, a real-world longitudinal research platform that deterministically linked administrative claims data with patient-reported outcomes data among patients with these conditions. METHODS: Patients with IBS-C or CIC were identified using diagnosis and treatment codes from administrative claims. Potential respondents received a mailed survey followed by 12 monthly online follow-up surveys and 2 mailed diaries. Surveys collected symptom severity, treatment use, quality of life, productivity, and condition/treatment history. Comorbidities and healthcare costs/utilization were captured from claims data. Diaries collected symptoms, treatments, and clinical outcomes at baseline and 12 months. Data were linked to create a patient-centric research platform. RESULTS: Baseline surveys were returned by 2,052 respondents (16.8% response rate) and retention rates throughout the study were high (64.8%-70.8%). Most participants reported burdensome symptoms despite having complex treatment histories that included multiple treatments over many years. More than half (55.3%) were dissatisfied with their treatment regimen; however, a higher proportion of those treated with prescription medications were satisfied. LIMITATIONS: The study sample may have been biased by patients with difficult-to-treat symptoms as a result of prior authorization processes for IBS-C/CIC prescriptions. Results may not be generalizable to uninsured or older populations because all participants had commercial insurance coverage. CONCLUSIONS: By combining administrative claims and patient-reported data over time, CONTOR afforded a deeper understanding of the IBS-C/CIC patient experience than could be achieved with 1 data source alone; for example, participants self-reported burdensome symptoms and treatment dissatisfaction despite making few treatment changes, highlighting an opportunity to improve patient management. This patient-centric approach to understanding real-world experience and management of a chronic condition could be leveraged for other conditions in which the patient experience is not adequately captured by standardized data sources.

Antitumor activity associated with hyperthermia and 4-nitrochalcone loaded in superparamagnetic poly(thioether-ester) nanoparticles.

The combination of hyperthermia and chemotherapy has a potential synergic effect in antitumor activity. The development of new biocompatible and biodegradable polymers to simultaneously encapsulate magnetic nanoparticles (MNPs) and antitumoral drugs offer new cancer treatment opportunities. Here, biodegradable and biocompatible poly(thioether-ester) (PTEe) was used to encapsulate MNPs and 4-nitrochalcone (4NC) using miniemulsification and solvent evaporation. The resulting hybrid particles (MNPs-4NC-PTEe) had nanometer-scale diameters, spherical morphology, negative surface charge, high encapsulation efficiency, and superparamagnetic properties. Results showed that 4NC release occurred through diffusion. Free 4NC and MNPs + 4NC-PTEe did not have any cytotoxic effect on erythrocytes and mouse embryonic fibroblast (NIH3T3) cells. 4NC antitumor activity was verified on human cervical cancer (HeLa) and melanoma (B16F10) cells. Cellular uptake of MNPs + 4NC-PTEe nanoparticles was higher in HeLa cells compared to B16F10 and NIH3T3 cells. The hyperthermia application (115 kHz-500 Oe) potentiated the 4NC effects on HeLa and B16F10 cells when MNPs + 4NC-PTEe nanoparticles were used, indicating more effective antitumor activity. We concluded that the use of MNPs + 4NC-PTEe nanoparticles associated with hyperthermia is a promising form of treatment for some types of cancers.

Effects of gold nanoparticles administration through behavioral and oxidative parameters in animal model of Parkinson's disease.

Parkinson's disease (PD) is recognized as the second most common neurodegenerative disorder, after Alzheimer's disease. Reserpine administration to animals has been suggested as a PD model based on the effects of this monoamine-depleting agent on motor activity. Studies show that gold nanoparticles (GNPs) are effective for treating neurodegenerative diseases when used at certain concentrations. The objective of the present study was to evaluate the effects of GNPs administration under behavioral and oxidative stress conditions in an experimental model of PD. Fourty male C57BL/6 mice (20-30 g) were used, The animals were divided into four groups (N = 6): Sham; Sham and GNPs; Reserpine; Reserpine and GNPs. Three doses at the concentration of 0.25 mg/kg reserpine were administered subcutaneously at 48 h intervals. Treatment with GNPs was administered with 2.5 mg/kg GNPs (20 nm) for five consecutive days. Our results showed the therapeutic potential of GNPs, where the parameters observed in behavioral tests and oxidative stress were reverted in GNP-treated mice. It also partially improved neurotrophic factors, which are necessary for the survival of neurons. GNPs reversed the symptoms of PD caused by the use of alkaline reserpine in C57BL/6 mice, especially without toxicity. The results of this study suggest that GNPs could have clinical potential as an inhibitor of inflammation and oxidative stress in the CNS, thereby alleviating the secondary neurodegenerative processes and neuronal cell death caused by reserpine. These beneficial effects of GNPs provide support for new analyses to better understanding in the process of PD degeneration.

Cognitive profile of neurofibromatosis type 1.

General consensus has yet to be reached with regard to the exact cognitive profile of children with neurofibromatosis type 1 (NF1). The current overview seeks to provide a more comprehensive review of the literature by examining studies that have specifically compared individuals with NF1 to siblings, controls, and/or norms. We also examined results of studies that compared individuals with NF1 with various manifestations to each other. Consistent with previous reviews, no clear cognitive profile emerged; however, greater insight into patterns was obtained. Additionally, future directions for research on NF1 were suggested.