Oxidative Stress in Xenograft Mouse Model Exposed to Dendrimers Decorated Polydopamine Nanoparticles and Targeted Chemo- and Photothermal Therapy.

Polydopamine (PDA)-based nanostructures are used for biomedical purposes. A hybrid drug nanocarrier based on a PDA decorated with polyamidoamine (PAMAM) dendrimers G 3.0 (DG3) followed by a connection with glycol (PEG) moieties, folic acid (FA), and drug doxorubicin (DOX) was used for combined chemo- and photothermal therapy (CT-PTT) of liver cancer. Oxidative stress plays a crucial role in the development of cancer, and PDA seems to have the ability to both donate and accept electrons. We investigated oxidative stress in organs by evaluating oxidative stress markers in vivo. In the liver, the level of reduced glutathione (GSH) was lower and the level of Trolox equivalent antioxidant capacity (TEAC) was higher in the group receiving doxorubicin encapsulated in PDA nanoparticles with phototherapy (PDA@DG3@PEG@FA@DOX + PTT) compared to the control group. The concentration of thiobarbituric acid reactive substances (TBARS) in livers, was higher in the group receiving PDA coated with PAMAM dendrimers and functionalized with PEG and FA (PDA@DG3@PEG@FA) than in other groups. Markers in the brain also showed lower levels of GSH in the PDA@DG3@PEG@FA group than in the control group. Markers of oxidative stress indicated changes in the organs of animals receiving PDA nanoparticles with PAMAM dendrimers functionalized with FA in CT-PTT of liver cancer under in vivo conditions. Our work will provide insights into oxidative stress, which can be an indicator of the toxic potential of PDA nanoparticles and provide new strategies to improve existing therapies.

Effect of Protoberberine-Rich Fraction of Chelidonium majus L. on Endometriosis Regression.

Endometriosis is a gynecological disease defined by the presence of endometrial tissue outside the uterus. To date, the effective treatment of this disease is still based on invasive surgery or laparoscopy. Chelidonium majus L. (Papaveraceae) belongs to medicinal, latex-bearing plants. Extracts from the plant are a rich source of pharmacologically active agents. Protoberberine compounds derived from C. majus possess anticancer and antiproliferative activities. In the present study of a rat model of endometriosis, we investigated the influence of the plant protoberberine-rich fraction (BBR) obtained from the medicinal plant C. majus on the development of endometriosis. To understand of BBR therapeutic potential for endometriosis, metabolomics has been applied to study. BBR was prepared from an ethanolic extract of dry plants C. majus. Rats (n = 16) with confirmed endometriosis were treated with BBR administered orally (1 g/kg) for 14 days. Blood serum samples were collected from all of the animals and metabolites were studied using the NMR method. The metabolomic pattern was compared before and after the protoberberine treatment. The performed analysis showed significant changes in the concentrations of metabolites that are involved in energy homeostasis, including glucose, glutamine, and lactate. Histopathological studies showed no recurrence of endometriosis loci after treatment with BBR. The results of the study found that BBR treatment prevents the recurrence of endometriosis in rats. Moreover, metabolomics profiling can be applied to better understand the mechanisms of action of these protoberberine secondary plant metabolites. Our findings provide new insights into the pharmaceutical activity of natural protoberberine plant compounds.

Is low radioiodine uptake a contraindication to radioiodine therapy in patients with benign thyroid disease?

BACKGROUND: Radioiodine therapy (131I) is a standard procedure in the treatment of hyperthyroidism in the course of Graves' disease or toxic nodules. However, the use of 131I in patients with low radioiodine uptake (RAIU) may be controversial. OBJECTIVES: To determine the influence of lithium carbonate (Li) on iodine kinetics. MATERIAL AND METHODS: Patients with hyperthyroidism and low RAIU (< 30%) were divided into 2 groups: a Li(-) group of 305 patients not receiving Li adjuvant therapy and a Li(+) group of 264 patients receiving adjuvant therapy. The serum concentrations of free triiodothyronine (fT3), free thyroxine (fT4) and thyroid stimulating hormone (TSH) were assessed at baseline, 24 h, 48 h, 72 h and 96 h, and 1, 6 and 12 months after 131I therapy. The RAIU was assessed after 5 h, 24 h, 48 h, 72 h, and 96 h. RESULTS: Levels of fT3 in the Li(+) group compared to the Li(-) group were significantly higher at baseline, lower after 48 h, 72 h, 96 h and 1 month, and did not differ significantly after 24 h, 6 months and 12 months. Levels of fT4 in the Li(+) group compared to the Li(-) group were significantly higher at baseline, lower after 24 h, 48 h, 72 h, 96 h and 1 month, and not differ significantly after 6 and 12 months. The RAIU in the hyperthyroidism Li(-) and Li(+) groups, respectively, was 11.9 ±5.6% compared to 23.9 ±10.1% (p < 0.001) after 5 h; 25.9 ±8.3% compared to 40.5 ±12.4% (p < 0.05) after 24 h; 7.8 ±8.1% compared to 40.9 ±13.7% (p < 0.05) after 48 h; 26.2 ±10.2% compared to 39.5 ±11.2% (p < 0.01) after 72 h; and 24.7 ±7.1% compared to 37.4 ±10.1% (p < 0.01) after 96 h. CONCLUSIONS: Adjuvant therapy with Li in patients with hyperthyroidism caused a significant increase in RAIU and positive changes in the fT3 and fT4 profiles. The use of lithium carbonate prior to the inclusion of 131I in hyperthyroid patients with low RAIU should be considered.

Two Ecdysteroids Isolated from Micropropagated Lychnis flos-cuculi and the Biological Activity of Plant Material.

Genetically uniform plant material, derived from Lychnis flos-cuculi propagated in vitro, was used for the isolation of 20-hydroxyecdysone and polypodine B and subjected to an evaluation of the antifungal and antiamoebic activity. The activity of 80% aqueous methanolic extracts, their fractions, and isolated ecdysteroids were studied against pathogenic Acanthamoeba castellani. Additionally, a Microtox® acute toxicity assay was performed. It was found that an 80% methanolic fraction of root extract exerts the most potent amoebicidal activity at IC50 of 0.06 mg/mL at the 3rd day of treatment. Both ecdysteroids show comparable activity at IC50 of 0.07 mg/mL. The acute toxicity of 80% fractions at similar concentrations is significantly higher than that of 40% fractions. Crude extracts exhibited moderate antifungal activity, with a minimum inhibitory concentration (MIC) within the range of 1.25-2.5 mg/mL. To the best of our knowledge, the present report is the first to show the biological activity of L. flos-cuculi in terms of the antifungal and antiamoebic activities and acute toxicity. It is also the first isolation of the main ecdysteroids from L. flos-cuculi micropropagated, ecdysteroid-rich plant material.

Separation and HPLC Characterization of Active Natural Steroids in a Standardized Extract from the Serratula coronata Herb with Antiseborrheic Dermatitis Activity.

Phytoecdysteroids are natural compounds with therapeutic benefits in both humans and animals. The effectiveness of natural products with health potential is based on the activities and potencies of their active ingredients. In this study, dominant ecdysteroids-ajugasterone C, 20-hydroxyecdysone and polypodine B-from the Serratula coronata (S. coronata) herb were separated by column chromatography, identified by spectroscopic data and quantified by high-performance liquid chromatography with a diode array detector (HPLC-DAD). The obtained concentration of ecdysteroids (approximately 23%) in the S. coronatae herb extract enhances the possibility of their use in pharmaceutical and cosmetic products with high levels of phytoecdysteroids. Moreover, this study has shown a positive effect of ecdysteroids-containing cream on changes in quality of life and a beneficial effect in reducing the symptoms of seborrheic dermatitis. It has been demonstrated that the application of the cream with phytoecdysteroids resulted in a statistically significant alleviation of symptoms (p < 0.05), especially in terms of itching, pain or burning sensations in the affected areas in comparison to previous symptoms.

The Anti-Serotonin Effect of Parthenolide Derivatives and Standardised Extract from the Leaves of Stizolophus balsamita.

The presence of dominant active compounds in standardised methanol extract from the leaves of Stizolophus balsamita (S. balsamita) was examined using HPLC with a diode-array detector. The extract and three dominant parthenolide derivatives were tested with Serotonin Research ELISA for their ability to inhibit the serotonin release from platelets. The antiserotonin effect of the extract was compared with that of parthenolide, a compound with proven antiserotonin and antimigraine effects. This study aimed to evaluate the ability of natural parthenolide derivatives to inhibit serotonin release from platelets. Izospiciformin, stizolin and stizolicin were analysed along with the standardised alcohol extract of S. balsamita leaves, which also contained four other parthenolide derivatives. All the analysed substances were found to inhibit serotonin release from platelets as compared with the control sample, which had 100% of serotonin released. Izospiciformin had the most significant impact (97.98% serotonin release inhibition). The effect of the methanol extract of S. balsamita on the serotonin release inhibition was also statistically significant.

Efficacy and safety of radioiodine therapy for mild Graves ophthalmopathy depending on cigarette consumption: a 6­month follow­up.

INTRODUCTION    Graves ophthalmopathy (GO) is an autoimmune disease associated with Graves disease. Its treatment is largely dependent on the severity and activity of ocular lesions. Particular attention should be given to radioiodine (RAI) therapy. Although its use is a valuable therapeutic option for hyperthyroidism, it may be followed by worsening of GO.  OBJECTIVES    The aim of the present study was to analyze how the severity of nicotine addiction affects the response to RAI treatment in patients with GO. PATIENTS AND METHODS    A total of 106 patients (58 smokers and 48 nonsmokers) with mild GO treated with 800 MBq of RAI were included to the study. We assessed the serum levels of thyroid­stimulating hormone (TSH), thyroid hormones, autoantibodies against thyroperoxidase, thyroglobulin, and TSH receptor (TSHR­Abs), as well as urinary cotinine levels and severity of ophthalmopathy. Analyses were conducted at baseline (before RAI treatment) and 2 and 6 months after the therapy. RESULTS    Significant differences in serum levels of TSHR­Abs were found between nonsmokers and smokers at 2 and 6 months after RAI therapy, whereas there were no differences at baseline. In smokers, there were significant differences in the severity of ophthalmopathy and the concentration of serum TSHR­Abs assessed at baseline and at 6 months of follow­up. Six months after RAI therapy, 46.2% of smokers and 4.3% of nonsmokers (P <0.001) progressed from mild to moderate GO.  CONCLUSIONS    High urinary cotinine levels in smokers were associated with the deterioration of ocular lesions after RAI treatment. A high dose of RAI did not induce an exacerbation of GO in nonsmokers who were administered oral steroid prophylaxis.

Portrayal of alcohol consumption in movies and drinking initiation in low-risk adolescents.

OBJECTIVES: To investigate the hypothesis that exposure to alcohol consumption in movies affects the likelihood that low-risk adolescents will start to drink alcohol. METHODS: Longitudinal study of 2346 adolescent never drinkers who also reported at baseline intent to not to do so in the next 12 months (mean age 12.9 years, SD = 1.08). Recruitment was carried out in 2009 and 2010 in 112 state-funded schools in Germany, Iceland, Italy, Netherlands, Poland, and Scotland. Exposure to movie alcohol consumption was estimated from 250 top-grossing movies in each country in the years 2004 to 2009. Multilevel mixed-effects Poisson regressions assessed the relationship between baseline exposure to movie alcohol consumption and initiation of trying alcohol, and binge drinking (≥ 5 consecutive drinks) at follow-up. RESULTS: Overall, 40% of the sample initiated alcohol use and 6% initiated binge drinking by follow-up. Estimated mean exposure to movie alcohol consumption was 3653 (SD = 2448) occurrences. After age, gender, family affluence, school performance, TV screen time, personality characteristics, and drinking behavior of peers, parents, and siblings were controlled for, exposure to each additional 1000 movie alcohol occurrences was significantly associated with increased relative risk for trying alcohol, incidence rate ratio = 1.05 (95% confidence interval, 1.02-1.08; P = .003), and for binge drinking, incidence rate ratio = 1.13 (95% confidence interval, 1.06-1.20; P < .001). CONCLUSIONS: Seeing alcohol depictions in movies is an independent predictor of drinking initiation, particularly for more risky patterns of drinking. This result was shown in a heterogeneous sample of European youths who had a low affinity for drinking alcohol at the time of exposure.

[Valproic acid concentration in the blood serum of pregnant women and umbilical cord blood in relation to the condition of the newborn--case studies]. / Stezenie kwasu walproinowego w surowicy krwi kobiet ciezarnych oraz krwi pepowinowej w odniesieniu do stanu noworodka--analiza przypadków.

Epilepsy is one of the most common neurological diseases in the world. One of the most difficult clinical problems associated with the disease is to treat pregnant women because the use of antiepileptic drugs increase the risk of birth defects in the fetus. The second most common use in pregnant women is an antiepileptic drug valproic acid. Its use is associated with an increased risk of serious birth defects such as neural tube defects, heart defects, cleft palate, urinary tract defects, limb defects, specific syndromes that cause dysmorfizm face or abnormalities of the reproductive organs and developmental disorders affecting cognitive and behavioral functions. To minimize the risk to the fetus can be through the use of contraception and planning for pregnancy, taking valproic acid monotherapy, at a dose of less than 1000 mg/day in 2-3 divided doses, folic acid supplementation, close monitoring during pregnancy and full cooperation with doctors: a gynecologist and neurologist. The aim of this study was to measure the concentrations of valproic acid in maternal serum and cord serum and a reference to the results of the newborn. The concentrations of valproic acid in the serum was performed using high performance liquid chromatography method with fluorometric detection. Valproic acid concentration in the blood serum of patients housed or slightly exceed the therapeutic concentration. In all samples of umbilical cord blood serum were detected, no drug found to have birth defects. Born children should remain under control in order to detect possible birth defects that cannot be detected immediately after birth.

[Development and validation of method for the determination of cynarin, luteolin in plasma]. / Opracowanie i walidacja metody oznaczania cynaryny, luteoliny w osoczu.

The aim of this study was to develop and validate the method of cynarin and luteolin, the main constituents of artichoke (Cynara scolymus L.) leaf extract, determination in plasma. The compounds were separated using the high-performance liquid chromatography technique with diode array detection (HPLC-DAD). The analysis was preceded by liquid-liquid extraction using as the extracting agent ethyl acetate. The HPLC separation was performed on C18 column under gradient conditions using a mobile phase - 0,05% trifluoroacetic acid in water and methanol. The detector was set at lambda=330 nm. The validation was related to linearity, sensitivity (LOD and LOQ), accuracy and repeatability. In the validated method the linearity was achieved within concentration range 1,5625 - 50,0 microg/cm3 for the cynarin (R2=0,9989) and 1,5625 - 200,0 microg/cm3 for the luteolin (R2=0998). The limits of detection for cynarin and luteolin was: 0,75 microg/cm3 and 0,1 microg/cm3 and the limits of quatification: 2,25 microg/cm3 and 0,2 microg/cm3, respectively. Coefficient of variation for the inter-day and the intra-day analysis, which is a precision and accuracy parameter, do not exceed 10%. Recovery was 67% for the cynarin and 96% for the luteolin. The practical application of this method was proved by analysis of plasma samples from rats. The animals were administrated artichoke leaf extract - orally and intraperitoneally at a dose of 3 g/kg body weight or pure substances - intraperitoneally at a dose 1 mg/kg of luteolin and 0,5 mg/kg of cynarin. The presence of investigated compounds was proved only in samples after intraperitoneal administration of pure substances. The developed method is used to determine simultaneously cynarin and luteolin, after intraperitoneal administration of pure compounds.

[Marihuana and cannobinoids as medicaments]. / Marihuana i kanabinoidy jako leki.

Biological activity of cannabinoids is caused by binding to two cannabinoid receptors CB1 and CB2. Psychoactive is not only tetrahydrocannabinol (THC) but also: cannabidiol, cannabigerol or cannabichromen. Formerly, the usefulness of hemp was assessed in the relation to temporary appeasement of the symptoms of some ailments as nausea or vomiting. Present discoveries indicates that cannabis-based drugs has shown ability to alleviate of autoimmunological disorders such as: Multiple sclerosis (MS), Rheumatoid arthritis (RA) or inflammatory bowel disease. Another studies indicates that cannabinoids play role in treatment of neurological disorders like Alzheimer disease or Amyotrophic lateral sclerosis (ALS) or even can reduce spreading of tumor cells. Cannabinoids stand out high safety profile considering acute toxicity, it is low possibility of deadly overdosing and side-effects are comprise in range of tolerated side-effects of other medications. In some countries marinol and nabilone are used as anti vomiting and nausea drug. First cannabis-based drug containg naturally occurring cannabinoids is Sativex. Sativex is delivered in an mucosal spray for patients suffering from spasticity in MS, pain relevant with cancer and neuropathic pain of various origin. Despite the relatively low acute toxicity of cannabinoids they should be avoid in patients with psychotic disorders, pregnant or breastfeeding woman. Cannabinoids prolong a time of reaction and decrease power of concentration that's why driving any vehicles is forbidden. Cannabis side-effects varies and depend from several factors like administrated dose, rout of administration and present state of mind. After sudden break from long-lasting use, withdrawal symptoms can appear, although they entirely disappear after a week or two.

[Artichoke--herbal drug]. / Karczoch zwyczajny--lek roslinny.

The liver is the gland most vulnerable to the toxic effects of xenobiotics, as responsible for their metabolism. Significant impact on the functioning of this gland has a style of life: alcohol consumption, diet with high fats ingredients and prooxidative substances and synthetic drugs. Very improtant aspect in herbal medicaments is protective properties on parenchymal organ-damaging. Concomitant intake of plant extracts containing cytoprotective compounds, may increase the efficacy of treatment and reduce side effects. One of the plants of the hepatoprotective action is artichoke (Cynara scolymus L.). Artichoke with multiple therapeutic properties and practically no side effects is recommended not only in disorders of the liver, but also in the prevention of atherosclerosis and hyperlipidemia or dyspeptic disorders.

[Artichoke--untapped potential of herbal medicine in the treatment of atherosclerosis and liver diseases]. / Karczoch zwyczajny- niewykorzystane mozliwosci leku roslinnego w terapii miazdzycy i chorób watroby.

Substances of natural origin are the subject of growing interest on the part of both researchers and doctors. One of the well known herbal medicines extensively examined in terms of clinical and pharmacological is artichoke (Cynara scolymus L.), which was used in European medicine from the 18th century. His multidirectional treatment is a documented fact and it is associated with treatment of dyspepsia, influence of active substances contained in artichoke on plasma lipid levels and with a strong antioxidant effect of the artichoke extract--due to this properties, artichoke compounds have a protective effect on liver cells.

[Speed drugs]. / Dopalacze.

Until recently "speed drugs" have not awake higher social emotions. Usually they associate with Red Bull, allowed driving long time, and workaholic from modern enterprise to regenerate before next task. Currently on the base of new regulation on the list of controlled substances benzylpyperazine, its related compounds and 17 plants products were added. The article discussed the sources and biological action of these psychoactive substances, which are illegal in Poland.

[Do calcification of placenta reveal only maternal cigarette smoking?]. / Zlogi wapnia w lozysku--czy swiadcza wylacznie o paleniu papierosów?

Maternal smoking during pregnancy is associated with not only obstetrical and pediatrician complications with fetus, newborn and child but also with placenta. The aim of the work was the estimation of placental calcification between maternal cigarette smoking and non-smoking pregnant women. All women have taken vitamin supplements during time of experiment. The study group consisted of 200 pregnant women (100 smokers and 100 non-smokers). All patients were admitted and delivered singleton births in the Gynecological and Obstetric Clinical Hospital in Poznan, between 2004-2007. A questionnaire was used as a study tool. s. The study groups were similar under age, education, obstetrical interview and cigarette smoking (5-10 cigarettes/day). Ultrasound investigations showed placental calcification in 36% vs 45% pregnancy at 30 +/- 2 weeks of gestation and in 52% vs 57% at 40 +/- 2 weeks of pregnancy as well as in 55% vs 58% placentas in macroscopic examination, between smoking and non-smoking women. Cigarette smoking should not be considered as exclusive factor leading to formation deposits of calcium in placenta. The consumption of vitamin supplements probably also involve calcification of placenta tissue.

Antepartum/postpartum depressive symptoms and serum zinc and magnesium levels.

In the present study, we investigated the relationship between depressive symptoms and serum zinc and magnesium level in antepartum and postpartum women. All women received standard vitamin, zinc and magnesium supplementation. Sixty-six pregnant women in the Czerwiakowski Hospital in Kraków were assessed for prepartum depressive symptoms using the Beck Depression Inventory (BDI). Sixty-two and fifty-eight women were also assessed for postpartum depressive symptoms (using Edinburgh Postnatal Depression Rating Scale, EPDRS) at 3 and 30 days after delivery, respectively. Serum zinc and magnesium levels were also determined at these time points, however, the number of examined subjects were diminished. A significantly higher EPDRS score (by 45%), indicating severity of depressive symptoms, was found on the 3rd day after childbirth compared with the 30th postpartum day. Moreover, the early post-delivery period (3rd day) was characterized by a 24% lower serum zinc concentration than that found on the 30th day after childbirth. BDI scores assessed a month before childbirth revealed mild depressive symptoms, which was accompanied by a serum zinc concentration similar to that found on the 3rd day after delivery. No significant alterations were found in the magnesium levels between these time points. The present results demonstrated a relationship between severity of depressive symptoms and decreased serum zinc (but not magnesium) concentration in a very specific type of affective disorder, the postpartum depression.

The role of laboratory examinations in medical toxicology.

Medical toxicology is a medical subspecialty focusing on the diagnosis, management and prevention of poisoning and other adverse health effects due to medications, occupational and environmental toxins, and biological agents. The medical toxicology laboratories operates an analytical facility for clinical toxicology (intentional or unintentional drug overdose), environmental medicine (occupational and environmental toxicology, workplace drug monitoring), drug of abuse management, therapeutic drug monitoring (TDM) and in some cases forensic toxicology. This article is focus on clinical toxicology, monitoring of drug abused patients and TDM. Still the most popular in medical toxicology is determination of xenobiotics in classic biological materials (blood/plasma, urine) however alternative materials (saliva, hairs) cause increasing attention. Alternative materials has special value in drug of abuse management (evaluation of drug abstinence), when collecting the blood create some problems and urine samples can be adulterated. For screening usually immunology based assays are applied and for some xenobiotics thin-layer chromatography (TLC) method. Conformation and quantitative analysis are carrying on using chromatographic method. In clinical toxicology chemical analysis are performed for diagnostic, therapeutic and some time for legal purposes. If results of toxicological analysis have direct influence on diagnosis or treatment they should be available during 2 hours other determination ought to be performed during 24 or 48 hours. Integral part of toxicological analysis is interpretation of results carried over by well-trained analyst with close co-operation with clinical toxicologist (physician).