In Vitro Evaluation of Cytotoxic Potential of Caladium lindenii Extracts on Human Hepatocarcinoma HepG2 and Normal HEK293T Cell Lines.

Data regarding the therapeutic potential of Caladium lindenii (C. lindenii) are insufficient. It becomes more important to explore plants as an alternative or palliative therapeutics in deadly diseases around the globe. The current study was planned to explore C. lindenii for its anticancer activity of ethanolic and hexane extracts of C. lindenii leaves against hepatic carcinoma (HepG2) and human embryonic kidney (HEK293T) cell lines. HepG2 and HEK293T cells were treated with 10, 50, 100, 200, and 400 µg/mL of ethanolic and hexane extracts of C. lindenii and were incubated for 72 h. Antiproliferative activity was measured by 3-(4,5-dimethylthiazol-2yl)-2,5-biphenyl tetrazolium bromide (MTT) assay, and percentage viability were calculated through crystal violet staining and cellular morphology by Floid Cell Imaging Station. The study showed ethanolic extract exhibiting a significantly higher antiproliferative effect on HepG2 (IC50 = 31µg/mL) in a concentration-dependent manner, while HEK293T (IC50 = 241µg/mL) cells showed no toxicity. Hexane extract exhibited lower cytotoxicity (IC50 = 150µg/mL) on HepG2 cells with no effect on HEK293T (IC50 = 550µg/mL). On the other hand, the percentage viability of HepG2 cells was recorded as 78%, 67%, 50%, 37%, and 28% by ethanolic extracts, and 88%, 80%, 69%, 59%, and 50% by hexane extracts at tested concentrations of both extracts. Toxicity assay showed significantly safer ranges of percentage viabilities in normal cells (HEK293T), i.e., 95%, 90%, 88%, 76%, and 61% with ethanolic extract and 97%, 95%, 88%, 75%, and 62% with hexane extract. The assay validity revealed 100% viability in the control negative (dimethyl sulfoxide treated) and less than 45% in the control positive (cisplatin) on both HepG2 and HEK293T cells. Morphological studies showed alterations in HepG2 cells upon exposure to >50 µg/mL of ethanolic extracts and ≥400 µg/mL of hexane extracts. HEK293T on the other hand did not change its morphology against any of the extracts compared to the aggressive changes on the HepG2 cell line by both extracts and positive control (cisplatin). In conclusion, extracts of C. lindenii are proved to have significant potential for cytotoxicity-induced apoptosis in human cancer HepG2 cells and are less toxic to normal HEK293T cells. Hence C. lindenii extracts are proposed to be used against hepatocellular carcinoma (HCC) after further validations.

Evaluation of In Vitro Cytotoxic Property Against Cholangiocarcinoma Cell Line and GC/MS Analysis from Leaf of Erythrophleum succirubrum Gagnep.

OBJECTIVE: Plants are valuable sources of new pharmaceuticals. Secondary metabolites of the genus Erythrophleum exhibit cytotoxicity and may have therapeutic value. The cytotoxic activity of ethanolic leaf extract of Erythrophleum succirubrum Gagnep. against a human cholangiocarcinoma cell line was assessed. METHODS: Crude extract of E. succirubrum was prepared by ethanol extraction. The ethanolic leaf extract of E. succirubrum was evaluated for cytotoxicity against the human cholangiocarcinoma cell line KKU-M213 using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assays. The chemical composition of E. succirubrum leaf extract was analyzed using GC/MS. RESULT: The ethanolic leaf extract of E. succirubrum reduced the viability of KKU-M213 cells in a dose- and time-dependent manner. It showed high cytotoxicity, with IC50 values of 65.22 ± 1.18 µg/mL and 1.19 ± 1.38 µg/mL at exposure times of 24 and 96 h, respectively. GC/MS analysis of the ethanolic leaf extract of E. succirubrum identified 22 components. The main constituents identified were Cyclohexanone, 2-[2-nitro-1-(2-naphthyl)ethyl]-(14.79%) followed by allomycin (14.65%), mome inositol (14.30%), campesterol (11.80%) and ethyl linolenate (10.83%), respectively. CONCLUSION: Five major groups of compounds were found, with lipids dominating, followed by carbohydrates, benzenoids, phenylpropanoids, polyketides and organoheterocyclic compounds. Many of the bioactive components discovered in the ethanolic leaf extract of E. succirubrum might be responsible for its cytotoxic properties.

In vitro Evaluation of Selective Cytotoxic Activity of Chaerophyllum macropodum Boiss. on Cultured Human SH-SY5Y Neuroblastoma Cells.

Neuroblastoma is the most common solid tumor in children. New treatment approaches are needed because of the harmful side effects and costs of the methods used in the treatment of neuroblastoma. Medicinal and aromatic plants are important for new treatment approaches due to their minimal side effects and economic advantages. Therefore, the present study was carried out to examine the cytotoxic effect of Chaerophyllum macropodum extract on human neuroblastoma (SH-SY5Y) and fibroblast (HDFa) cell lines. 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase release (LDH) assays were used to determine the cytotoxic effect of C. macropodum. The extracts were analyzed for their phenolic content by HPLC-PDA. Major components were determined as 63.600% o-coumaric acid, 15.606% catechine hydrate, 8.713% rosmarinic acid, 4.376% clorogenic acid, and 3.972% salicylic acid. The obtained results from cytotoxicity testing revealed that C. macropodum exerted a significant cytotoxic effect on human neuroblastoma cells at all tested concentrations (p < 0.05). But it did not lead to any cytotoxic potential on human fibroblasts. As a result, the obtained data clearly revealed C. macropodum exerted a selective cytotoxic action on neuroblastoma cells for the first time.

Two Patients With KCNT1-Related Epilepsy Responding to Phenobarbital and Potassium Bromide.

KCNT1 encodes a sodium-activated potassium channel highly expressed in the brain, regulating hyperpolarization following repetitive firing. Mutations in KCNT1 were originally implicated in autosomal-dominant nocturnal frontal lobe epilepsy and epilepsy of infancy with migrating focal seizures. It is now known that there is variability in phenotypic expression and incomplete penetrance. We describe 2 patients with KCNT1-related epilepsy, one with epilepsy of infancy with migrating focal seizures and one with multifocal epilepsy. As most patients with KCNT1 variants have treatment-resistant epilepsy, drugs that specifically target the KCNT1 channel have been of great interest. Quinidine, a broad-spectrum potassium channel blocker, has shown promise; however, clinical trial results have been variable. Our patient with epilepsy of infancy with migrating focal seizures did not respond to a trial of quinidine at 6 weeks of age-one of the earliest reported quinidine trials in the literature for KCNT1-related epilepsy. This indicates that timing of treatment and response may not be related. Both patients responded to high-dose phenobarbital. The patient with epilepsy of infancy with migrating focal seizures also had a significant reduction in seizures with potassium bromide (KBr). Our data suggest that alternative therapies to quinidine should be considered as a therapeutic option for patients with KCNT1-related epilepsy. Although improved seizure control led to parent-reported improvements in neurodevelopment, it is unknown if phenobarbital and KBr impact the overall developmental trajectory of patients with KCNT1-related epilepsy. Further multicenter longitudinal studies are required.

Effects of inhalation of thermal water on exhaled breath condensate in chronic obstructive pulmonary disease.

BACKGROUND: Inhalation of thermal water (TW) is traditionally used as part of the treatment of chronic obstructive pulmonary disease (COPD), but its benefit and mechanisms are controversial. We previously observed a reduced proportion of neutrophils in induced sputum after treatment with TW. OBJECTIVES: The aim of this study was to determine whether inhalation of TW in COPD patients is associated with biochemical changes of airway lining fluid, including a reduction in the neutrophil chemoattractant leukotriene B(4) (LTB(4)). METHODS: Thirteen COPD patients were randomly assigned to receive a 2-week course of TW and normal saline inhalation in a cross-over, single-blind study design. Exhaled breath condensate (EBC) was collected before and after treatments. LTB(4) concentrations in EBC were determined by ELISA, and EBC pH was measured before and after argon deaeration. RESULTS: No significant differences in LTB(4) concentrations in EBC were detected with either treatment. A significant decrease in pH of non-deaerated EBC was observed after a standard course of TW (median 7.45, interquartile range 6.93-7.66, vs. median 6.99, interquartile range 6.57-7.19; p = 0.05), which disappeared after argon deaeration. CONCLUSIONS: There is no evidence that TW treatment affects LTB(4) concentration in EBC. The results of EBC pH measurements suggest that TW inhalation induces an imbalance of volatile components of the buffer system in airway lining fluid.

Drug treatment of epilepsy in the century of the ILAE: the first 50 years, 1909-1958.

This paper provides a review of the drug treatment of epilepsy from 1909, the year of the foundation of the International League Against Epilepsy (ILAE), to 1958. It was during this period that modern approaches to the medicinal therapy of epilepsy were formulated and many new drugs were introduced. Of these, both phenytoin and phenobarbital continue to be widely used today. This was the period when scientific screening was also introduced into drug discovery. The leading figures in the ILAE played an important role in guiding the evolution of the treatment of epilepsy during this period.

[Muscular contrapulsation in rehabilitation of patients with osteoarthrosis].

Muscular contrapulsation (MCP) alone was used in osteoarthrosis patients as well as in combination with balneotherapy (radon and iodine-bromine baths). MCP of the lower limbs produced an analgetic and anti-inflammatory effect, improved the locomotor function, muscular tonicity, hemodynamics. MCP combination with radon and iodine-bromine baths potentiates the above positive effects. Thus, MCP can be recommended alone and in combination with radon and iodine-bromine baths for rehabilitation and outpatient treatment of lower limbs osteoarthrosis.

Improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent.

OBJECTIVE: To assess whether there is a change in seizure activity in dogs with refractory epilepsy that are receiving appropriate doses of phenobarbitone and/or potassium bromide, when gabapentin is added to the therapeutic regimen. DESIGN: A prospective study of 17 dogs with a refractory seizure disorder, 16 of which have idiopathic epilepsy. PROCEDURE: Patients were stabilised using phenobarbitone and/or potassium bromide to produce tolerable therapeutic serum concentrations and dosed additionally with gabapentin at 35 to 50 mg/kg/d (divided twice or three times daily) for 4 months. Owners recorded seizure activity and side effects during this period in a standardised diary. Patients underwent monthly physical examinations and venepuncture to assess selected serum biochemical analytes, as well as phenobarbitone and bromide concentrations. Patients were further monitored for long-term response to adjunctive gabapentin therapy. RESULTS: There was no significant decrease in the number of seizures over the study period for the entire cohort, however three dogs stopped seizuring completely. There was a significant increase in the number of patients who showed an increase in the interictal period (P > 0.001). Serum alkaline phosphatase activity and triglyceride concentrations were elevated at baseline. There were no significant changes in biochemical analytes during the course of the study period. Side effects observed initially on addition of gabapentin included sedation and hind limb ataxia. The former resolved spontaneously after a few days; the latter after a slight reduction in bromide dose. Long-term, a further two patients became seizure free and ten patients remained on gabapentin indefinitely. No long-term side effects have become apparent. CONCLUSION: Addition of gabapentin to phenobarbitone and/or potassium bromide increased the interictal period and shortened the post-seizure recovery in some canine epileptics. In some dogs, seizures were prevented completely, while in others there was an increase in interictal period. The short-half life of gabapentin has advantages for seizure control, however its present high cost may prohibit therapy in large dogs.

Iodine toxicity and its amelioration.

Iodine (I) toxicity is rare in animals and humans, but nuclear explosions that give off radioactive I and excessive stable I ingestion in parts of the world where seaweed is consumed represent specialized I toxicity concerns. Chronic overconsumption of I reduces organic binding of I by the thyroid gland, which results in hypothyroidism and goiter. Bromine can replace I on position 5 of both T(3) and T(4) with no loss of thyroid hormone activity. Avian work has also demonstrated that oral bromide salts can reverse the malaise and growth depressions caused by high doses of I (as KI) added as supplements to the diet. Newborn infants by virtue of having immature thyroid glands are most susceptible to I toxicity, whether of stable or radioactive origin. For the latter, the 1986 Chernobyl nuclear accident in Belarus has provided evidence that KI blockage therapy for exposed individuals 18 years of age and younger is effective in minimizing the development of thyroid cancer. Whether bromide therapy has a place in I toxicity situations remains to be determined.

Oral iodine toxicity in chicks can be reversed by supplemental bromine.

Four chick bioassays were conducted to quantify iodine (I) toxicity and its amelioration in young chicks. A supplemental I level from KI of 600 mg/kg depressed growth in chicks fed methionine-deficient diets but not in those fed methionine-adequate diets. An I dose level >or= 900 mg/kg was required to cause growth depression in chicks fed a methionine-adequate corn-soybean meal diet. Iodine intoxicated chicks also displayed neurological symptoms and extreme malaise, but dose levels up to 1200 mg I/kg had no effect on blood hemoglobin or hematocrit. Supplemental I levels of 1000-1500 mg/kg caused severe growth depressions that could be totally reversed by dietary addition of 50 or 100 mg/kg bromine provided as NaBr. Nuclear accidents or terrorist actions that result in I toxicity and thyroid cancer or goiter may benefit from use of NaBr as a therapeutic agent.

[Behavior of serum IgE and IgA in patients with allergic rhinitis treated with iodine bromide thermal water]. / Comportamento delle IGE e IGA sieriche in pazienti con rinite allergica trattata con acque salsobromoiodiche.

The aim of this study was to test the effects of the iodine bromide water of the thermal baths of Salsomaggiore on patients suffering from specific nonseasonal rhinitis (Dermatophagoides Farinae and Dermatophagoides Pteronyssinus). The patients, 80 in all, were divided in two groups (group A and group B). All of the patients underwent rhinoscopic examination, anterior rhinomanometry, prick test, rast screening, total IgE assay together with that of the other immunoglobulins (IgA, IgM, IgG), mucociliary clearance evaluation and were asked to evaluate their degree of nasal obstruction, before and after 30 days of treatment. Group A carried out the experiment by applying endonasal Acqua Sal spray seven times a day for 30 days; group B used oily drops for the same time and with the same frequency. At the end of the trial period, the patients in group A showed a 100% improvement in their subjective perception of their symptomatology, in comparison with a 33% improvement in the control group. A characteristic decrease in the IgE and increase in the IgA was observed in the serum of the patients who had been treated with Acqua Sal spray. Iodine bromide water has a general and local anti-inflammatory effect, which is also due to the activation of the corticosurrenal system (with a relative increase in cortisol). The cleansing action of hypertonic water in the nasal cavities must also be cited, as it minimizes contact between the mucosa and allergens.

Poisoning from a dietary supplement administered during hospitalization.

Increasing numbers of persons use dietary supplements (DS). Patients who believe in the effectiveness of DS may continue to take them on admission to a health care facility. We present the case of a child who received a DS on a daily basis as an outpatient, continued its use after admission to the hospital, and became poisoned by it during his hospitalization.

[A case of peculiar type of post-encephalitic/encephalopathic epilepsy: efficacy of bromide in the control of intractable seizures].

A 5-year-old boy with a peculiar type of post-encephalitic/encephalopathic epilepsy is reported. He had been healthy showing normal development before its onset. Five days after the onset of an upper respiratory infection, he had a severe generalized seizure, that evolved into intractable seizures. They were highly resistant to almost all anticonvulsants and occasionally resulted in status epilepticus. High-dose phenobarbital therapy successfully controlled the convulsions, but was discontinued because of drug-induced aplastic anemia. Alternative bromide therapy was markedly effective in controlling the seizures.

[The use of physical factors in the rehabilitative treatment of patients with stone fragments in the upper urinary tract after extracorporeal shockwave lithotripsy]. / Primenenie fizicheskikh faktorov v vosstanovitel'nom lechenii bol'nykh s fragmentami kamnia verkhnikh mochevyvodiashchikh putei posle distantsionnoi udarno-volnovoi litotripsii.

155 patients with fragments of the crushed stones in the upper urinary tract after lithotripsy were divided into 3 groups. 60 patients of group 1 received dynamic amplipulse therapy, oral mineral water, iodobromine baths. Elimination of the fragments was observed in 91.7% of the patients. Group 2 patients (n = 60) were exposed to local vibration, ultrasound and iodobromine baths. The effect occurred in 96.7% of the cases. 35 patients of group 3 were exposed to impulse low-frequency magnetic field and took iodobromine baths. The elimination of the fragments occurred in 62.9% of the cases after a single treatment course.

[The combined treatment of patients with chronic nonspecific salpingo-oophoritis using a low-frequency magnetic field and iodobromine water]. / Kompleksnoe lechenie bol'nykh khronicheskimi nespetsificheskimi sal'pingooforitami nizkochastotnym magnitnym polem i iodobromnoi vodoi.

The studies of 116 females with chronic nonspecific salpingo-oophoritis demonstrate that combination of low-frequency magnetic field with iodine-bromine water effectively corrects immunological indices, i.e. improves T- and B-cell immunity, production of IgM and IgA, proportion of immunoregulatory subpopulations of T-lymphocytes.

[The use of interference currents and iodobromine baths in the therapy of patients with chronic nonobstructive pyelonephritis]. / Primenenie interferentsionnykh tokov i iodobromnykh vann v terapii bol'nykh khronicheskim neobstruktivnym pielonefritom.

30 patients were exposed to interference currents (IC) alone (group 1) versus 34 patients treated with IC plus iodobromine baths (group 2). After IC action on the region of the kidney projection patients of group 1 experienced positive changes in cellular and humoral immunity providing an antiinflammatory effect. In group 2, the improvement was seen in renal and urinary functions, 24-h urinary excretion of oxalates and calcium diminished. Interference current proved beneficial in chronic pyelonephritis patients with latent inflammation. The combined therapy was effective in patients at high risk of lithogenesis.

[Bromide-iodide baths and magnetic-laser radiation in the correction of disorders of hemodynamics and of the adaptation processes in metallurgical workers]. / Bromiodnye vanny i magnitolazernoe izluchenie v korrektsii narushenii gemodinamiki i protsessov adaptatsii u rabochikh-metallurgov.

Positive changes in cardiovascular function and extracardiac regulation of cardiac rhythm in response to treatment by chloride-sodium bromine-iodine baths combined with magnetolaser radiation of the Zakhar'in-Ged zones suggest the conclusion on adaptogenic effects of the above physiobalneotherapeutic complex. The highest effect of magnetolaser therapy and bromine-iodine baths in metallurgists with adaptive disorders is achieved in early morning hours.

[The use of sinusoidal modulated currents and iodobromine baths in treating patients with the "stone pathway" of the upper urinary tract]. / Primenenie sinusoidal'nykh modulirovannykh tokov i iodobromnykh vann v lechenii bol'nykh s "kamennoi dorozhkoi" verkhnikh mochevykh putei.

After exposure to sinusoidal modulated currents and iodinebromine baths there was a decrease in serum levels of calcium, alanin aminotransferase, lactate dehydrogenase and urinary calcium, oxalates, leukocytes, red cells, acceleration of radiopharmaceutical accumulation (Tmax) and elimination from the kidneys (T1/2), urolith fragments (1-5 mm in size) elimination from the upper urinary tract in 21 (48.9%) out of 43 patients. The above physiotherapeutic complex is indicated for urolithiasis patients with associated diseases (hyperesthesia, causalgia).

[The use of an impulse magnetic field in the combined therapy of patients with stone fragments in the upper urinary tract]. / Primenenie impul'snogo magnitnogo polia v kompleksnoi terapii bol'nykh s fragmentami kamnia v verkhnikh mochevykh putiakh.

The paper covers the experiment's details and the results obtained at stimulation of the kidney projection region and upper ureter with remote-controlled impulse magnetic field (IMF). It was found that IMF activates impulse activity of ureteral smooth muscles in 100% of cases. The technique is detailed of managing ureterolith fragments using IMF combined with iodobromine baths. The results of the proposed treatment are given. A single therapeutic course produced effect in 62.9% of the patients.