Occurrence Of Adverse Side Effects Research Articles

Current Perspectives on Proton Therapy: Techniques Shaping the Future of Cancer Treatment

Traditional Radiation Therapy (RT) predominantly comprises a targeted therapeutic strategy focused on improving localised tumour control and achieving a cure while minimising the occurrence of adverse side effects. It could be feasible to take advantage of the better dose distribution by enabling larger RT dosages to the malignancy while preventing a rise in the toxicity of RT-induced healthy tissue, or by reducing adverse reactions to manageable levels. Poor local disease control and important dose-limiting normal tissue, which prevent safe dosage increase with conventional photon RT, have been the key justifications for RT. Proton treatment, on the other hand, delivers therapeutic protons or positive particles using proton beams. The potential advantage of protons’ physical properties allows for more localised RT delivery. By increasing the dosage to equitoxic levels, it is also possible to take advantage of the potential improvement in normal tissue sparing to support local tumour management and, ideally, longevity. Proton treatment preserves more important structures than photon therapy because of its unique physics. Thus, there is a need for wide usage of Proton Therapy (PT) for successive cancer treatment. The present review focuses on PT based on tumour site, clinical studies, biological barriers, instrumentation of PT, significance, and limitations.

Nanoparticle-Mediated Drug Delivery to Cervical Cells: Harnessing the Potential of Liposomes for Enhanced Therapeutic Efficacy

Cervical cancer continues to pose a substantial worldwide health obstacle, requiring novel treatment approaches. This research investigates the capacity of Nanoparticle-Mediated Drug Delivery to augment the efficacy of cervical cancer therapy. Highlighting the significance of precise medication delivery, using nanoparticles, namely liposomes, appears viable. Introducing a new method called Nanoparticle-Based Drug Delivery to Cervical Cells (NP-DD-CC) utilizes liposomes to accurately deliver medicinal substances while minimizing adverse effects on the whole body. The NP-DD-CC has remarkable characteristics, such as attaching nanocarriers to ligands to achieve target selectivity. The simulation findings provide diverse metrics for distinct Nanoparticle Densities: Localized Drug Concentration (67.76%), Reduction in Side Effects (48.5%), Overall Patient Tolerance Increase (40.4%), and Nanoparticle Retention Improvement (73%). NP-DD-CC presents a promising advancement in the treatment of cervical cancer by enhancing the accuracy of medication administration and reducing the occurrence of adverse side effects.

Nanocomposite fibers based on cellulose acetate loaded with fullerene for cancer therapy: preparation, characterization and in-vitro evaluation

The current prevalence of cancerous diseases necessitates the exploration of materials that can effectively treat these conditions while minimizing the occurrence of adverse side effects. This study aims to identify materials with the potential to inhibit the metastasis of cancerous diseases within the human body while concurrently serving as therapeutic agents for their treatment. A novel approach was employed to enhance the anti-cancer properties of electrospun cellulose fibers by incorporating fullerene nanoparticles (NPs) into cellulose acetate (CA) fibers, resulting in a composite material called Fullerene@CA. This development aimed at utilizing the anti-cancer properties of fullerenes for potential therapeutic applications. This process has been demonstrated in vitro against various types of cancer, and it was found that Fullerene@CA nanocomposite fibers displayed robust anticancer activity. Cancer cells (Caco-2, MDA-MB 231, and HepG-2 cells) were inhibited by 0.3 and 0.5 mg.g−1 fullerene doses by 58.62–62.87%, 47.86–56.43%, and 48.60–57.73%, respectively. The tested cancer cells shrink and lose their spindle shape due to morphological changes. The investigation of the prepared nanocomposite reveals its impact on various genes, such as BCL2, NF-KB, p53, Bax, and p21, highlighting the therapeutic compounds' effectiveness. The experimental results demonstrated that the incorporation of NPs into CA fibers resulted in a significant improvement in their anti-cancer efficacy. Therefore, it is suggested that these modified fibers could be utilized as a novel therapeutic approach for the treatment and prevention of cancer metastasis.

Значення фармацевтичної опіки при відпуску лікарських засобів для профілактики та лікування вугрової хвороби у жінок

вугрова хвороба займає третє місце у структурі дерматологічних захворювань
 та є актуальною медико-соціальною проблемою. Захворювання часто є причиною психоемоцій-них розладів, сприяє погіршенню якості життя та соціальної активності пацієнтів. Разом з
 тим, лікування вугрової хвороби є комплексним та довготривалим. Мета даного дослідження:
 оцінити роль фармацевтичної опіки при відпуску лікарських засобів для профілактики та лі-кування вугрової хвороби у жінок. Проведено анонімне опитування 100 дівчат-підлітків та
 жінок різних вікових категорій за єдиною спеціально розробленою анкетою, враховуючи про-блеми лікування вугрової хвороби. Використано методи анонімного анкетного опитування,
 комп’ютерного опрацювання даних та графічний. Встановлено, що більшість (82 %) респон-дентів вважали лікування вугрового висипу проблемним. Окрім того, лише 36 % опитуваних
 зверталися за допомогою до лікаря, тоді як більшість вдалися до самолікування. Основнимипрепаратами вибору були: кислота саліцилова (42 %) та азелаїнова (38 %), кліндаміцин (24 %),бензоїл перкосид (11 %), ізотетиноїди (10 %). В більшості випадків (58 %) було використанокомплексну терапію. Окрім того, майже 60 % опитуваних, на час лікування вугрової хвороби,
 приймали сорбенти, майже 20 % – комбіновані оральні контрацептиви. Більшість респонден-тів відзначали покращення стану після завершення курсу лікування (57 %) та щонайменше
 через тиждень терапії (29 %). Важливо відмітити, що 38 % опитуваних відзначали появунесприятливих побічних реакцій при застосуванні противугрових засобів, найпоширенішимисеред яких були: сухість шкіри ( 68,7 %), її почервоніння (56,3 %), посилення висипу (25,0 %) та
 свербіж (20,8 %). Окрім того, більшість (80 %) респондентів не дотримувалися гігієни об-личчя та намагалися «видавлювати» вугрі. Разом з тим, лише половина опитуваних отримали
 рекомендації щодо режиму та правил застосування противугрових засобів від аптечних пра-цівників. Тоді як надання рекомендацій аптечними працівниками, сприяло вірогідному зменшен-ню частоти побічних реакцій, після застосування противугрових лікарських засобів (р<0,05).
 В межах фармацевтичної опіки, аптечні працівники визначають загрозливі стани що вимага-ють звернення до лікаря, надають рекомендації щодо правил та режиму застосування безре-цептурних лікарських засобів, здійснюють інформаційну та просвітницьку роботу щодо гігіє-ни обличчя, модифікації режиму харчування, здійснення немедикаментозних заходів. Отже, з
 урахуванням високої поширеності самолікування, використання декількох засобів, важливостідотримання правил гігієни шкіри обличчя, надання якісної фармацевтичної опіки є необхідноюумовою для досягнення максимально ефективної та безпечної терапії вугрової хвороби.

Phytotherapy in Integrative Oncology-An Update of Promising Treatment Options.

Modern phytotherapy is part of today’s conventional evidence-based medicine and the use of phytopharmaceuticals in integrative oncology is becoming increasingly popular. Approximately 40% of users of such phytopharmaceuticals are tumour patients. The present review provides an overview of the most important plants and nature-based compounds used in integrative oncology and illustrates their pharmacological potential in preclinical and clinical settings. A selection of promising anti-tumour plants and ingredients was made on the basis of scientific evidence and therapeutic practical relevance and included Boswellia, gingko, ginseng, ginger, and curcumin. In addition to these nominees, there is a large number of other interesting plants and plant ingredients that can be considered for the treatment of cancer diseases or for the treatment of tumour or tumour therapy-associated symptoms. Side effects and interactions are included in the discussion. However, with the regular and intended use of phytopharmaceuticals, the occurrence of adverse side effects is rather rare. Overall, the use of defined phytopharmaceuticals is recommended in the context of a rational integrative oncology approach.

Effects of trans-(±)-kusunokinin on chemosensitive and chemoresistant ovarian cancer cells.

Ovarian cancer ranks eighth in cancer incidence and mortality among women worldwide. Cisplatin-based chemotherapy is commonly used for patients with ovarian cancer. However, the clinical efficacy of cisplatin is limited due to the occurrence of adverse side effects and development of cancer chemoresistance during treatment. Trans-(±)-kusunokinin has been previously reported to inhibit cell proliferation and induce cell apoptosis in various cancer cell types, including breast, colon and cholangiocarcinoma. However, the potential effects of (±)-kusunokinin on ovarian cancer remains unknown. In the present study, chemosensitive ovarian cancer cell line A2780 and chemoresistant ovarian cancer cell lines A2780cis, SKOV-3 and OVCAR-3 were treated with trans-(±)-kusunokinin to investigate its potential effects. MTT, colony formation, apoptosis and multi-caspase assays were used to determine cytotoxicity, the ability of single cells to form colonies, induction of apoptosis and multi-caspase activity, respectively. Moreover, western blot analysis was performed to determine the proteins level of topoisomerase II, cyclin D1, CDK1, Bax and p53-upregulated modulator of apoptosis (PUMA). The results demonstrated that trans-(±)-kusunokinin exhibited the strongest cytotoxicity against A2780cis cells with an IC50 value of 3.4 µM whilst also reducing the colony formation of A2780 and A2780cis cells. Trans-(±)-kusunokinin also induced the cells to undergo apoptosis and increased multi-caspase activity in A2780 and A2780cis cells. This compound significantly downregulated topoisomerase II, cyclin D1 and CDK1 expression, but upregulated Bax and PUMA expression in both A2780 and A2780cis cells. In conclusion, trans-(±)-kusunokinin suppressed ovarian cancer cells through the inhibition of colony formation, cell proliferation and the induction of apoptosis. This pure compound could be a potential targeted therapy for ovarian cancer treatment in the future. However, studies in an animal model and clinical trial need to be performed to support the efficacy and safety of this new treatment.

A Prospective Study of the Relationship Between Clinical Outcomes After Enzalutamide and Serum Androgen Levels Measured via Liquid Chromatography-tandem Mass Spectrometry in Patients with Castration-resistant Prostate Cancer

BackgroundEnzalutamide (ENZ) is used to treat patients with castration-resistant prostate cancer (CRPC). However, the kinetics of serum androgens before and after ENZ treatment are unknown. ObjectiveTo elucidate the kinetics of serum androgens and explore the possibility of identifying a useful marker for predicting the effects of ENZ. Design, setting, and participantsWe conducted a prospective study from 2014 to 2018 at Gunma University Hospital and related facilities. Data were analyzed for 104 patients with CRPC treated with ENZ. Outcome measurements and statistical analysisWe measured serum androgen levels using liquid chromatography-tandem mass spectrometry. Relationships with outcomes were assessed using multivariable Cox regression and log-rank analyses. Results and limitationsThe median age of the patients was 73 yr. Median serum testosterone, dihydrotestosterone (DHT), androstenedione, and dehydroepiandrosterone sulfate levels were 49.0, 5.8, 222.2, and 326.3 pg/ml, respectively. We performed multivariate analysis using Cox regression to predict prostate-specific antigen progression–free survival (PSA-PFS) and overall survival (OS). Hemoglobin level (≥12.5 vs <12.5 g/dl), docetaxel treatment history (no vs yes), and DHT level (≥5.9 vs <5.9 pg/ml) were significant predictors of PSA-PFS (p < 0.05). Eastern Cooperative Oncology Group performance status (0 vs. 1–2), hemoglobin level (≥12.5 vs <12.5 g/dl), presence of visceral metastasis (no vs yes), amount of bone metastasis (extent of disease 0–2 vs 3–4), and docetaxel treatment history (no vs yes) were significant predictors of OS (p < 0.05). Binomial logistic analysis of the predictors of any grade of anorexia, malaise, and fatigue showed that the presence of visceral metastasis and a low DHT level (<5.9 pg/ml) were significant. ConclusionsOur results suggest that serum androgen levels before ENZ treatment may be useful for predicting efficacy, prognosis, and the incidence of adverse events. Patient summaryWe measured blood levels of testosterone and other male hormones before treatment with enzalutamide among men with prostate cancer resistant to castration. We found that the levels of these hormones may be useful for predicting the efficacy of enzalutamide treatment, prognosis, and the occurrence of adverse side effects.

The Integration of Olanzapine and Cognitive Behavioural Therapy for the Treatment of Schizophrenia: A Literature Review

Introduction: Schizophrenia is a serious psychiatric disorder that significantly impacts a person’s quality of life. This condition is characterized by three groups of symptoms: positive, negative and cognitive. There have been developments of new therapeutic methods for treating schizophrenia, both pharmacological and psychotherapeutic. Antipsychotic drugs such as the second generation antipsychotic olanzapine are often the first course of treatment, for the purpose of controlling symptoms. However, research has determined that using antipsychotics alone may limit its long-term effectiveness and produce adverse effects. Psychosocial interventions like cognitive behavioural therapy (CBT) aim to reduce psychotic symptoms and prevent relapse when used in conjunction with medication. This review aims to discuss the effectiveness of the integration of olanzapine and CBT, and how these treatments improve symptom reduction, reduce relapse and reduce the occurrence of adverse effects. Methods: A literature search between the years of 2010 to 2020 was conducted using PubMed and PsycInfo. Keywords included variations of “schizophrenia”, “treatment”, “olanzapine”, and “cognitive behavioural therapy”. Results: Olanzapine by itself was found to improve symptom reduction, yet showed adverse effects such as weight gain and extrapyramidal symptoms. CBT used as a lone treatment of schizophrenia showed less adverse effects than antipsychotics, yet was significantly less effective than both antipsychotics alone and the combinatorial treatment of CBT and olanzapine. The integration of olanzapine and CBT demonstrated an overall improvement in a schizophrenic patient’s health. Discussion: The integration of olanzapine and CBT show promise for symptom reduction, relapse prevention, reduced occurrence of adverse side effects, and the overall improvement of one’s health. Conclusion: Individuals diagnosed with schizophrenia experience emotional, physical and social hardships, thus it is imperative that physicians are aware of current treatments that can be tailored to best treat their patients.

Adverse effects and short-term developmental outcomes of infants exposed to atypical antipsychotics during breastfeeding.

Background:Postpartum period in women is vulnerable to the occurrence and exacerbation of psychiatric disorders. Mothers with postpartum psychosis or bipolar disorder need treatment with psychotropic medications, especially atypical antipsychotics. However, many mothers and families will have reservations about the use of psychotropics during the perinatal period, particularly during breastfeeding because of its presumed side effects and adverse developmental outcomes of the child. Since there are limited data in this area, the present study aimed to examine the adverse effects, if any, and the short-term developmental outcome of infants exposed to atypical antipsychotics during breastfeeding.Methods:The study involved infants of postpartum women (n = 28) who were admitted in the mother and baby inpatient psychiatry unit of a tertiary care center in India. The medication side effects were checked every alternate day for 1–2 weeks using a checklist based on common side effects that infants may experience due to lactation exposure of atypical antipsychotics. Developmental assessments of the infants were done using the Developmental Assessment Scales for Indian Infants and through anthropometric measurements such as weight, length, head circumference, and chest circumference in follow-up when they came as an outpatient after 1–3 month interval.Results:The occurrence of adverse side effects was quite low (17.85%). The main side effects directly attributable to atypical antipsychotics were constipation and sedation. Of the 17 infants who attended follow-up, 52.9% (n = 9) showed some form of developmental delay at the time of the first follow-up. However, low birth weight, higher maternal age (>35 years), and exposure to medications (quetiapine and phenytoin) during pregnancy may be confounding risk factors.Conclusions:The acute adverse effects of atypical antipsychotics such as sedation and constipation in the infant through breast milk were seen in less than a fourth of the sample. Developmental delay was noted in a proportion of infants; however, this may be due to other risk factors.

Practical pharmacogenetics for personalized management of glaucoma patients

At present, taking into account the widespread application of pharmacogenetics’ achievements to all branches of medicine, it has become possible to conduct such research in ophthalmology. At the moment, the studies on the most broadly used glaucoma medications have been carried out. The correlations between patients’ genotypes and the frequency of occurrence of adverse side effects have been found. The further exploration of the pharmacogenetics of the glaucoma medications and the introduction of pharmacogenetic testing will enable ophthalmologists to assign a rational, safe, and effective treatment in the short time, which will considerably improve the quality of provided aid.

Epidemiology of Oxytocin Administration in Out-of-Hospital Births Attended by Paramedics

Aim Primary postpartum hemorrhage (PPH) is a life-threatening obstetric emergency that can be mitigated through the administration of a uterotonic to actively manage the third stage of labor. This study describes the prehospital administration of oxytocin by paramedics following attendance of out-of-hospital (OOH) births. Methods A retrospective analysis was undertaken of all OOH births between the 1st January 2018 and 31st December 2018 attended by the Queensland Ambulance Service. The demographic and epidemiological characteristics of patients that were administered oxytocin and the occurrence of adverse side effects were described. Results In total, 350 OOH births were included in this study with the majority involving multigravidas women (94.3%) and all but two involving singleton pregnancies. Oxytocin was administered following 222 births (63.4%), while 67 patients (19.1%) declined administration preferring a physiological third stage of labor, and in 61 cases (17.4%) oxytocin was withheld by the attending paramedic. There were no documented adverse events or side effects following administration. Oxytocin administration occurred on average 14 minutes (interquartile range 9-25) following the time of birth. The median time from oxytocin administration to placenta delivery was 10 minutes (interquartile range 5-22). Conclusion Oxytocin is well accepted and safe treatment adjunct for the management of the third stage of labor in OOH births and should be considered for routine practice by other emergency medical services.

Culturing Periprosthetic Tissues in BacT/Alert® Virtuo Blood Culture Bottles for a Short Duration of Post-operative Empirical Antibiotic Therapy.

Introduction: A post-operative empirical antibiotic therapy (PEAT) is required in periprosthetic joint infections. It commonly uses broad-spectrum antibiotics to cover most Gram-positive cocci and Gram-negative bacilli. It is currently continued until first microbiological results are available, no less than five days later.Methods: We performed a retrospective study in order to evaluate duration of incubation required for surgical samples using the BacT/Alert® Virtuo blood culture bottles system.Results: Among 216 surgical interventions and 199 clinical strains (53.8% staphylococci, 22,1% streptococci and enterococci, 14,6% Gram-negative bacilli, 5,5% anaerobes), 90.5% of the strains were detected between day 0 and day 2; 15 infective strains are cultured from day 3 including 8 Cutibacterium sp., 4 staphylococci, 2 streptococci and 1 Enterococcus.Conclusions: We suggest that the duration of PEAT in patients operated for a periprosthetic joint infection may be shortened to three days as Gram-negative rods are unlikely to grow after three days of culture by using BacT/Alert® Virtuo blood culture bottles. This is likely to shorten the overall length of hospital stay, to diminish the occurrence of adverse side effects, and the emergence of antimicrobial resistance. However, coverage of Gram-positive cocci should be maintained for 14 days until the definite culture results are available.

Ginsenoside 3β-O-Glc-DM (C3DM) enhances the antitumor activity of Taxol on Lewis lung cancer by targeting the interleukin-6/Jak2/STAT3 and interleukin-6/AKT signaling pathways

Objective: Nonsmall-cell lung cancer (NSCLC) is an aggressive, highly chemoresistant disease. Taxol is an effective chemotherapeutic drug widely used for the treatment of NSCLC. However, the clinical use of Taxol is limited due to the occurrence of adverse side effects under high therapeutic doses. Therefore, it is desirable to explore combination therapy to reduce the dose of chemotherapeutic drugs and achieve excellent outcomes. A biosynthetic ginsenoside, 3-O-β-D-glucopyranosyl-dammar-24-ene-3β, 20S-diol (3β-O-Glc-DM, C3DM) is obtained from microbial fermentation by metabolic engineering. Based on previous study findings, we aimed to explore the mechanism of combination therapy with C3DM and Taxol and its increasing antitumor effect on Lewis lung cancer (LLC) in this study. Materials and Methods: A thiazolyl blue tetrazolium bromide (MTT) assay was performed to evaluate cell viability; the apoptotic effect was studied using cell apoptosis assay. The Lewis tumor xenograft experiment was performed to determine the effects of C3DM combined with Taxol on tumor growth in vivo, and western blotting was performed to analyze protein expressions. Results: C3DM effectively inhibited the proliferation of NSCLC cells. Moreover, C3DM increased the antiproliferative activity of Taxol and significantly enhanced cell apoptosis induced by Taxol in Lewis lung cancer cells. C3DM alone also suppressed Lewis tumor growth and enhanced the antitumor activity of Taxol in vivo. Western blot analysis revealed that the effects of the antiproliferation and apoptosis induction of C3DM treatment alone or in combination with Taxol on Lewis lung cancer were mediated by inhibiting the interleukin-6 (IL-6)/Jak2/STAT3 and IL-6/AKT signaling pathways. Conclusions: The results showed that C3DM has the potential to be used in combination therapy with Taxol against NSCLC.

Current understanding of pharmacogenetic implications of DNA damaging drugs used in osteosarcoma treatment

ABSTRACTIntroduction: DNA damaging drugs are widely used for the chemotherapeutic treatment of high-grade osteosarcoma (HGOS). In HGOS patients, several germline polymorphisms have been reported to impact on the development of adverse toxic events related to DNA damaging drugs treatment. Some of these polymorphisms, when present in tumor cells, may also influence treatment response and prognosis of HGOS patients.Area covered: In this review, the authors have focused on pharmacogenetic markers (mainly germline polymorphisms) described in patients with HGOS, which have proved or indicated to be related to the susceptibility to adverse toxic reactions and/or to influence response to DNA damaging drugs. The concordant and discordant results reported in different studies have also been discussed.Expert opinion: Response and toxicity predisposition to DNA damaging drugs are influenced by genes encoding proteins involved in their uptake, efflux, activation, inactivation, and in DNA repair, activity of which may vary according to specific gene variations. In HGOS, there is a substantial medical need for biomarkers predictive for individual response and toxicity predisposition to DNA-targeting drugs, which may be used to tailor therapy in order to decrease the occurrence of adverse side effects and increase treatment efficacy and safety.

&amp;lt;i&amp;gt;In Silico&amp;lt;/i&amp;gt; Pharmacological Analysis of a Potent Anti-Hepatoma Compound of Mushroom Origin and Emerging Role as an Adjuvant Drug Lead

Mushrooms are well-known to possess a continuum of anticancer metabolites that are vital in the development of anticancer adjuvant drug leads based on natural products. Owing to the fact that conventional cancer therapeutic methods were failed to lessen mortality caused by cancer to the estimated level with occurrence of adverse side effects, anticancer agents isolated from natural mushroom sources unarguably make an experimental research area worth mass focus today. The current study was targeted on in vitro cytotoxicity and in silico predictive pharmacological analysis of a flavonoid compound isolated from Fulvifomes fastuosus mushroom. Targeted compound was isolated from the mushroom using different chromatographic methods and identified by NMR spectrometry and mass spectrometry. Cytotoxicity experiments were carried out using MTT assay and apoptotic cells were identified by ethidium bromide/acridine orange staining. The SwissADME tool, BOILED-Egg construction model and Swiss target protein prediction software have been used to perform in silico predictive pharmacological analysis. The isolated compound has been identified as 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione by spectrometric methods. The result of MTT assay showed that 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has potent anticancer activity for hepatoma against Hep-G2 cell line (IC50 = 20.8 μg/ml) being less toxic to normal CC-1 epithelial cells (IC50 = 167.00 μM). The cells treated with compound ex-hibited apoptotic features such as cellular shrinkage, nuclear fragmentation and condensed cytoplasm. In summary, 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has shown potent anticancer properties against hepatoma with less cytotoxicity effect on normal cells. Furthermore, in silico study has revealed that properties of 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione may contribute to making a high absorption and clearance of the test compound as not interfering with the therapeutic failure of the compound. The properties of 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo-[3,2-c]pyran-3,2'-furan]-3',4-dione were compatible with well-known anticancer drug lapatinib. In conclusion, 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has a high tendency to act as a good anticancer adjuvant drug in the treatment of hepatoma.

An over-the-counter central sensitization therapy: a chronic back pain registry study of pain relief, medication use and their adverse effects.

Back pain, the most prevalent musculoskeletal chronic pain condition, is usually treated with analgesic medications of questionable efficacy and frequent occurrence of adverse side effects. The objective was to determine the effectiveness of the ActiPatch medical devices in reducing chronic back pain, document medication related adverse side effects and establish their impact on quality of life. Upon completing a 7-day trial, subjects were contacted via email with an assessment form using the Constant Contact email program. A total of 1394 responses were collected from subjects who used the device for back pain. Medication adverse effects are common and impact quality of life in the lay population. ActiPatch is an effective intervention for the majority of subjects for treating chronic back pain, although this requires further investigation in randomized clinical trials.

Phenolic compounds: Natural alternative in inflammation treatment. A Review

AbstractInflammation is a biological defense mechanism caused by the interruption of the tissue homeostasis caused by the presence of a biological, chemical, or physical agents in the body; immune system produces a series of pro-inflammatory mediators, however their overproduction, as occurs in chronic inflammation, might lead to the occurrence of several chronic diseases. For this reason, slowing down the inflammation process becomes very important, and with this purpose non-steroid anti-inflammatory drugs are generally used with the subsequent occurrence of adverse side effects. As an alternative in inflammation treatment, folklore medicine has used several plants and herbs with minimal or null side effects, with the phenolic compounds being one of their principal components. Phenolic compounds are able to inhibit either the production or the action of pro-inflammatory mediators, resulting in anti-inflammatory capacity.

Abstract 4627: Fasting reduces the systemic exposure to irinotecan and its active metabolite SN-38

Abstract Limitations to the use of chemotherapeutic agents are the often severe adverse side-effects which may lead to early discontinuation of treatment. Most anticancer agents have a narrow therapeutic index. In previous work we have shown that 72 hours of fasting prior to treatment with a high dose of irinotecan prevents the occurrence of adverse side effects in C26 colon carcinoma bearing mice, while the antitumor activity is not abrogated. To elucidate the mechanism of fasting induced resistance against adverse side effects, we have examined the pharmacokinetics of irinotecan in 72 hours fasted mice in plasma and liver. Male BALB/c mice were divided into four groups (n=18/group). Two groups were fasted for 72 hours and two groups were fed ad libitum. After the fasting period, mice were fed ad libitum again. One group of ad libitum and fasted animals was treated with 50 mg/kg and the other with 100 mg/kg irinotecan intraperitoneally. Plasma and liver were collected at 1,4,8,12,24 and 48 hours after irinotecan injection. Tissues were homogenized in lithium heparinized plasma and concentrations of irinotecan (CPT-11) and the active metabolite SN-38 were determined using a validated reversed-phase high-performance liquid chromatography (HPLC) system with fluorescence detection. Pharmacokinetic parameters, including peak concentration, area under the plasma concentration-time curve (AUC), clearance (CL), and the half-life of the terminal disposition phase were calculated. In the fasted group, plasma levels of SN-38 in the 50 mg/kg and 100 mg/kg group showed a 57% and 53% reduction, respectively, compared with ad libitum fed controls (AUC0-inf 5,149 vs. 2,242 ng*h/mL and 7,507 vs. 3,562 ng*h/mL). For CPT-11 the effects of fasting were smaller. An increase of 26% in the 50 mg/kg group and a reduction of 15% in the 100 mg/kg group were observed (AUC0-inf 9,715 vs. 12,235 and 37,360 vs. 31,924 ng*h/mL). In the liver, SN-38 levels in the 50 mg/kg and 100 mg/kg group showed a reduction of 51% and 30%, respectively, in the fasted animals (AUC0-inf 85.4 vs. 41.5 µg*h/g and 126 vs. 87.6 µg*h/g), while CPT-11 levels were reduced with 19% in the 50 mg/kg group and 28% in the 100 mg/kg group (AUC0-inf 218 vs. 177 µg*h/g and 712 vs. 512 µg*h/mg). Our data demonstrate that 72 hours of fasting prior to irinotecan administration induces an important change in its metabolism. Plasma and liver levels of the pro-drug CPT-11 were only slightly reduced in fasted animals. Levels of the active metabolite SN-38 were considerably lower in fasted animals compared to ad libitum fed animals. These data suggest that the reduction of side effects by fasting is due to the lower systemic exposure to SN-38, and may have important clinical implications if also found in humans. Citation Format: Sander A. Huisman, P de Bruijn, I.M. Ghobadi Moghaddam-Helmantel, J.N.M. IJzermans, E Wiemer, A.H.J. Mathijssen, R.W.F. de Bruin. Fasting reduces the systemic exposure to irinotecan and its active metabolite SN-38. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4627. doi:10.1158/1538-7445.AM2014-4627

Opioid-induced hyperalgesia

Opioids are a widely used pharmacological therapy for moderate-to-severe pain. Their use in the management of chronic non-cancer pain has escalated in recent years, particularly in North America. This escalation has posed many challenges for prescribers such as lack of longterm effectiveness, misuse and abuse, and the occurrence of adverse side-effects. The effectiveness of high-dose opioids can be diminished by two clinical occurrences, which are difficult to distinguish clinically: opioid tolerance and opioid-induced hyperalgesia (OIH). OIH is a phenomenon observed in patients treated with opioids who paradoxically demonstrate an increased sensitivity to painful stimulus. In contrast, opioid tolerance occurs when prolonged exposure to opioids results in a shift of the dose–response curve to the right; in other words, a larger dose of opioid is needed over time to produce the same level of analgesia. Chronic opioid exposure may lead to two interrelated outcomes; a desensitization process which leads to reduced clinical efficacy of opioids, and a sensitization process which can facilitate nociception, thereby counteracting the opioid’s analgesic effect.

The acute side effects of bright light therapy: a placebo-controlled investigation.

Despite the emergence of numerous clinical and non-clinical applications of bright light therapy (LT) in recent decades, the prevalence and severity of LT side effects have not yet been fully explicated. A few adverse LT effects—headache, eye strain, irritability, and nausea—have been consistently reported among depressed individuals and other psychiatric cohorts, but there exists little published evidence regarding LT side effects in non-clinical populations, who often undergo LT treatment of considerably briefer duration. Accordingly, in the present study we examined, in a randomized sample of healthy young adults, the acute side effects of exposure to a single 30-minute session of bright white light (10,000 lux) versus dim red light (< 500 lux). Across a broad range of potential side effects, repeated-measures analyses of variance revealed no significant group-by-time (Pre, Post) interactions. In other words, bright light exposure was not associated with a significantly higher incidence of any reported side effect than was the placebo control condition. Nevertheless, small but statistically significant increases in both eye strain and blurred vision were observed among both the LT and control groups. Overall, these results suggest that the relatively common occurrence of adverse side effects observed in the extant LT literature may not fully extend to non-clinical populations, especially for healthy young adults undergoing LT for a brief duration.