A study of the effects of therapeutic doses of ionizing radiation in vitro on Lactobacillus isolates originating from the vagina - a pilot study.

BACKGROUND: Ionizing radiation is used as a therapeutic option in the treatment of certain neoplastic lesions located, among others, in the pelvic region. The therapeutic doses of radiation employed often result in adverse effects manifesting themselves primarily in the form of genital tract infections in patients or diarrhea. The data available in the literature indicate disorders in the microbial ecosystem caused by ionizing radiation, which leads to the problems mentioned above. In the present study, we examined the influence of ionizing radiation on 52 selected strains of bacteria: Lactobacillus crispatus, L. fermentum, L. plantarum, L. reuteri, L. acidophilus L. amylovorus, L. casei, L. helveticus, L. paracasei, L. rhamnosus, L. salivarius and L. gasseri. This collection of Lactobacillus bacteria isolates of various species, obtained from the genital tract and gastrointestinal tract of healthy women, was tested for resistance to therapeutic doses of ionizing radiation. RESULTS: The species studied, were isolated from the genital tract (n = 30) and from the anus (n = 22) of healthy pregnant women. Three doses of 3 Gy (fractionated dose) and 50 Gy (total dose of the whole radiotherapy cycle) were applied. The greatest differences in survival of the tested strains in comparison to the control group (not subjected to radiation) were observed at the dose of 50 Gy. However, the results were not statistically significant. Survival decrease to zero was not demonstrated for any of the tested strains. CONCLUSIONS: Therapeutic doses of radiation do not affect the Lactobacillus bacteria significantly.

Cytisine inhibits the anticonvulsant activity of phenytoin and lamotrigine in mice.

BACKGROUND: Cytisine (CYT), the most commonly used drug for smoking cessation in Poland, was experimentally found to induce convulsions. There is a lack of studies on the influence of CYT on the anticonvulsant activity of antiepileptic drugs (AEDs). METHODS: The effects of CYT on the anticonvulsant activity of six AEDs were examined in maximal electroshock (MES)-induced seizures in mice. RESULTS: Single intraperitoneal (ip) administration of CYT in a subthreshold dose of 2 mg/kg antagonized the protective activity of ip phenytoin and lamotrigine against MES-induced seizures in mice. A dose of 1 mg/kg did not reverse the protective activity of phenytoin and lamotrigine. CYT in a dose of 2 mg/kg had no effect on the anticonvulsive activity of carbamazepine, oxcarbazepine, phenobarbital, and valproate magnesium. CONCLUSION: CYT ability to antagonize the anticonvulsive activity of phenytoin and lamotrigine can be of serious concern for epileptic smokers, who might demonstrate therapeutic failure to these drugs resulting in possible breakthrough seizure attacks.

Clinical approach to visceral pain in irritable bowel syndrome - pathophysiology, symptoms, and treatment.

Visceral pain has been defined as a pain resulting from activation of pain receptors localized in mucous membrane, serous membrane, and smooth muscles of hollow organs. The great majority of these organs are innervated by parasympathetic and sympathetic outflows. Afferent nerve fibres are involved in conduction of both acute and persistent pain and hyperalgesia. Visceral pain differs significantly from other types of pain in the way it originates and in clinical presentation. It can be misleading as a symptom, producing several problems in the diagnostic process. Sometimes, severe visceral pain is observed in the course of non-lifethreatening functional gastrointestinal disorders, while slight abdominal discomfort may be a first symptom of malignant tumours. For many years, the treatment of visceral pain has been considered as not satisfactory enough and covered a wide variety of pharmacological substances. For example, the complex therapy of pain and other manifestations associated with irritable bowel syndrome include psychotherapy/behavioural therapy, bulk-forming agents, probiotics, laxatives, antidiarrheals, antibacterial agents, antispasmodics, and antidepressants. The current knowledge about the pathogenesis of visceral pain gives a rationale for the development of new, more efficacious drugs with a positive benefit/risk ratio. Unfortunately, experience gained so far with the use of some agents affecting serotoninergic transmission in the gastrointestinal tract have shown a serious danger associated with their administration for patients with irritable bowel syndrome.

Low dose of bupropion significantly enhances the anticonvulsant activity of felbamate, lamotrigine and topiramate in mice.

Experimental evidence indicates that bupropion hydrochloride, an antidepressant and a first-line smoking cessation aid, exerts dose-dependently anticonvulsant and convulsant effects. In this study, chronic bupropion pretreatment intraperitoneally (i.p.) for 14 days in a dose of 5 mg/kg reduced the ED(50) (i.e. the dose protecting 50% of mice against electroconvulsions) of lamotrigine, topiramate, and felbamate from 4.58, 60.95, and 48.79 (antiepileptic+vehicle) to 3.01, 41.68, and 37.28 mg/kg (antiepileptic+bupropion), respectively, against maximal electroshock-induced seizures in mice. Bupropion significantly increased the plasma and brain concentrations of lamotrigine. Plasma concentration of topiramate was elevated, however, the brain concentration of the drug was not affected. Neither plasma nor brain concentrations of felbamate were elevated by bupropion administration. Bupropion did not exacerbate motor coordination impairment caused by the antiepileptic drugs in the rotarod test. Chronic administration of bupropion significantly potentiates the protective activity of lamotrigine, topiramate, and felbamate against maximal electroshock-induced seizures. A pharmacokinetic interaction is responsible for the effect of bupropion co-administered with lamotrigine.

[Androgens and epilepsy]. / Androgeny a padaczka.

Nowadays there are increasing experimental and clinical data indicating an important role of an endocrine system (especially its neuroendocrine part and sex hormones) in the pathogenesis of epilepsy. The relationships between patomechanisms of epilepsy and activity of hypothalamo-pituitary-ovarian axis in animals and humans are quite well recognized but the role of male sex hormones, i.e androgens, in seizure susceptibility processes is less known. Epidemiological data clearly show that adrogens-related disorders occur more frequently in epileptic men than in general male population. Usually, they appear in the form of hypogonadism associated with low levels of plasma free testosterone and with low excretion of its 17-ketosteroid metabolites in the urine. Reproductive and sexual disorders can be attributed to hypogonadism. Androgen abnormalities in epileptics men are often affected by chronically used anti-epileptic drugs. Antiepileptic drugs, particularly classical ones, substantially modify bioavailability of androgens and can inhibit the activity of hypothalamo-pituitary-testicular axis, and--in a consequence--aggravate hypogonadism. Since neuroactive androgens cross the blood-brain barrier and modify seizure susceptibility, changes in their plasma concentrations can affect the course and clinical outcome of epilepsy. Effects of testosterone on seizures seem to depend on its different metabolic pathways. Aromatization of testosterone leads to formation of 17beta-estradiol that is believed to have proconvulsive activity. Activation of 5alpha-reductase pathway leads to formation of ketosteroid metabolites, primarily andosterone and etiocholanolone that demonstrate the ability to prevent convulsions in majority of animal studies. Recently, it has been shown that androsterone enhances the antiepileptic activity of phenobarbital, carbamazepine, and gabapentin in animal model of epilepsy. Antiepileptic activity of testosterone and its metabolites encourage further investigation of androgens as promising candidates for treatment of epilepsy in men with androgens-related disorders.

Different effects of nitric oxide synthase inhibitors on convulsions induced by nicotine in mice.

Acute intraperitoneal (i.p.) administration of N(G)-nitro-L-arginine (NNA, 10, 20 and 40 mg/kg), a non-selective nitric oxide synthase (NOS) inhibitor, significantly and dose-dependently decreased the incidence of convulsions induced by i.p. nicotine (NIC) in mice, whereas 7-nitroindazole (7NI, 50 and 100 mg/kg i.p.), a selective neuronal NOS inhibitor, had a proconvulsant effect. Aminoguanidine (100 mg/kg ip), a specific inducible NOS inhibitor, remained without an effect on convulsive behavior. L-arginine, a nitric oxide (NO) precursor, which independently has no effect on convulsions, markedly reversed the anticonvulsant effect of NNA; yet only partially reversed the proconvulsant effect of 7NI when injected at 500 mg/kg i.p.. Convulsions evoked by intracerebroventricular injection of NIC were significantly suppressed by ip NNA(40 mg/kg i.p.) and enhanced by i.p. 7NI (100 mg/kg i.p.); however, these effects of NNA and 7NI were less potent than those seen when NIC was administered i.p.. The present study revealed essential differences in the action of NOS inhibitors in NIC-induced convulsions. It appears that only NO produced by constitutive NOS is involved in the mechanism of NIC-induced convulsions. The proconvulsant effect of 7NI may result from the mechanisms unrelated to NOS inhibition.

Bupropion-induced convulsions: preclinical evaluation of antiepileptic drugs.

Bupropion, a unique, non-nicotine smoking cessation aid and an effective antidepressant, is well known to produce seizures following overdosing in humans. However, the experimental background for the usefulness of antiepileptic drugs in the protection against bupropion-induced convulsions has not been established yet. Therefore, we tested if the antiepileptic drugs were able to protect mice against clonic convulsions induced by intraperitoneally (i.p.) administered bupropion in the CD97 dose (139.5 mg/kg). Among 13 tested drugs, clonazepam showed the greatest potency (dose-dependent full protection; ED50 = 0.06 mg/kg, i.p.). No signs of locomotor impairment were observed in the rotarod test after anticonvulsive doses of clonazepam, resulting in a broad therapeutic window and favorable protective index (PI) (33.3). Gabapentin produced dose-dependent protection against convulsions at nontoxic doses (up to 1000 mg/kg), having PI>29. Diazepam in a very high dose showed full protection but its PI (1.7) was much less favorable than that of clonazepam. The PI values for ethosuximide, phenobarbital and valproate were slightly higher than unity and lower than 2, and for topiramate and felbamate were lower than unity. Phenytoin, carbamazepine, and lamotrigine as well as tiagabine failed to block the convulsant effects of bupropion even at doses that caused severe motor impairment. Our results encourage clinical testing of clonazepam against seizures developing after bupropion overdose.