Effects of transcranial focal electrical stimulation via tripolar concentric ring electrodes on pentylenetetrazole-induced seizures in rats.

PURPOSE: To study the effects of noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE) on the electrographic and behavioral activity from pentylenetetrazole (PTZ)-induced seizures in rats. METHODS: The TCREs were attached to the rat scalp. PTZ was administered and, after the first myoclonic jerk was observed, TFS was applied to the TFS treated group. The electroencephalogram (EEG) and behavioral activity were recorded and studied. RESULTS: In the case of the TFS treated group, after TFS, there was a significant (p=0.001) decrease in power compared to the control group in delta, theta, and alpha frequency bands. The number of myoclonic jerks was significantly different (p=0.002) with median of 22 and 4.5 for the control group and the TFS treated groups, respectively. The duration of myoclonic activity was also significantly different (p=0.031) with median of 17.56 min for the control group versus 8.63 min for the TFS treated group. At the same time there was no significant difference in seizure onset latency and maximal behavioral seizure activity score between control and TFS treated groups. CONCLUSIONS: TFS via TCREs interrupted PTZ-induced seizures and electrographic activity was reduced toward the "baseline." The significantly reduced electrographic power, number of myoclonic jerks, and duration of myoclonic activity of PTZ-induced seizures suggests that TFS may have an anticonvulsant effect.

[Vascular dental anaesthesias and their mechanism].

By their mechanism of action local anaesthesia methods were divided into diffused and vascular. Intraosseous, intraseptal and intraligamental anesthaesias are vascular ones at capillary-venous system level. Circulatory mechanism besides effectiveness increased more than 2-fold and also promotes enhancement of cardiovascular system responses.

[Results of three-year clinical study of prostamol uno efficacy and safety in patients with initial symptoms of prostatic adenoma and risk of its progression].

Prostamol Uno (PU) efficacy and safety were studied in a multicenter, open-population, randomized and comparative trial. PU was given in a single daily dose 320 mg for 36 months to 50 patients with initial symptoms of prostatic adenoma (PA) in comparison with 50 matched controls. The trial evaluated PU action on the symptoms progression and quality of life with application of questionnaires IPSS and QoL (BS). It was found that PU treatment relieved PA symptoms by IPSS, while these symptoms progressed in the controls. QoL improved in the study group and deteriorated in the control one. Administration of PU significantly increased urinary flow rate though in the controls urinary flow rate decreased, size of the prostate diminished and increased, respectively. Changes in the PSA were not seen and were insignificant, respectively. The results of the study say that prostamol Uno in a dose 320 mg/day can prevent PA progression without side effects.

[Efficacy and safety of prostamol-UNO in the treatment of patients with initial symptoms of prostatic adenoma and risk of progression: 2 years of investigations].

The article presents 2-year pilot results of a multicenter, randomized, controlled trial of prostamol-UNO effects on symptoms progression, quality of life, tolerance and safety in patients with early prostatic adenoma. The drug was used in a single dose 320 mg/day for 36 months. Prostamol-UNO efficacy in arrest of the symptoms progression and quality of life was assessed with the use of IPSS and QoL (BS) questionnaires. Measurements were also made of changes in Qmax, urine volume, residual urine, size of the prostate.

[Results of a multicenter trial of serenoa repens extract (permixon) in patients with chronic abacterial prostatitis].

Chronic prostatitis (CP) morbidity now makes up 8 to 35% in males aged 20-40 years (N.A. Lopatkin et al., 1998; O.L. Tiktinsky, 1999). In general population CP incidence rate is 5 to 8% (J.C. Nickel, 1999). Phytotherapy is now widely practiced in CP. A multicenter trial conducted by the authors demonstrates high efficacy ofpermixon in the treatment of chronic prostatitis/chronic pelvic pain syndrome. The results of 6-month follow-up are presented.

[Combined extract of Sabal palm and nettle in the treatment of patients with lower urinary tract symptoms in double blind, placebo-controlled trial].

A multicenter, prospective clinical trial was performed to study efficacy and tolerance of a compound drug PRO 160/120 in the elderly men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). A total of 257 patients were randomized into two groups. Group 1 of 129 patients received PRO 160/120; group 2 of 128 patients received placebo. In 2-week induction blind phase of placebo the patients received for 24 weeks 1 capsule of the drug or placebo twice a day in conditions of double blind study. The double blind phase was followed by an open control period for 24 weeks when all the patients received PRO 160/120. Treatment efficacy evaluation was based on I-PSS, quality of life index, urodynamic and ultrasonography evidence. PRO 160/120 was superior to placebo by attenuating LUTS assessed by I-PSS, improved obstructive and irritative symptoms, was effective in patients with moderate and severe symptoms. Tolerance of the plant extract was good.

Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms--a placebo-controlled, double-blind, multicenter trial.

The efficacy and tolerability of a fixed combination of 160 mg sabal fruit extract WS 1473 and 120 mg urtica root extract WS 1031 per capsule (PRO 160/120) was investigated in elderly, male patients suffering from lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia in a prospective multicenter trial. A total of 257 patients (129 and 128, respectively) were randomized to treatment with PRO 160/120 or placebo (127 and 126 were evaluable for efficacy). Following a single-blind placebo run-in phase of 2 weeks, the patients received 2 x 1 capsule/day of the study medication under double-blind conditions over a period of 24 weeks. Double-blind treatment was followed by an open control period of 24 weeks during which all patients were administered PRO 160/120. Outcome measures for treatment efficacy included the assessment of the patients' LUTS by means of the I-PSS self-rating questionnaire and a quality of life index as well as uroflow and sonographic parameters. Using the International Prostate Symptom Score (I-PSS), patients treated with PRO 160/120 exhibited a substantially higher total score reduction after 24 weeks of double-blind treatment than patients of the placebo group (6 points vs 4 points; P=0.003, one tailed) with a tendency in the same direction after 16 weeks. This applied to obstructive as well as to irritative symptoms, and to patients with moderate or severe symptoms at baseline. Patients randomized to placebo showed a marked improvement in LUTS (as measured by the I-PSS) after being switched to PRO 160/120 during the control period (P=0.01, one tailed, in comparison to those who had been treated with PRO 160/120 in the double-blind phase). The tolerability of PRO 160/120 was comparable to the placebo. In conclusion, PRO 160/120 was clearly superior to the placebo for the amelioration of LUTS as measured by the I-PSS. PRO 160/120 is advantageous in obstructive and irritative urinary symptoms and in patients with moderate and severe symptoms. The tolerability of the herbal extract was excellent.

[Morphological changes in prostatic tissue of patients with benign prostatic hyperplasia treated with permixon]. / Morfologicheskie izmeneniia v tkani predstatel'noi zhelezy bol'nykh s dobrokachestvennoi giperplaziei predstatel'noi zhelezy pri lechenii permiksonom.

A pilot trial has been performed to assess effects of permixon on prostatic tissue in patients with benign prostatic hyperplasia (BPH). A total of 49 BPH and control patients entered the trial. 36 patients of the study group were randomized into 3 subgroups of 12 patients each. Permixon was taken in a standard dose of 320 mg/day for 3, 6 and 12 months, respectively. Mean duration of BPH was 3.7 years (0-8 years). Mean value of PCA was 6.0 ng/ml. The control group of 13 patients were not given permixon. Multifocal prostatic biopsy was performed in all the patients before and after the treatment or follow-up. Stromal-parenchymatous correlation in the study group significantly increased (by 59%)--from 3.28 (0.25-9.61) to 5.22 (1.20-10.67) (p = 0.0002). For the control group this correlation was insignificant. Permixon-treated patients demonstrated inhibition of prostatic epithelium proliferative activity by 32% (p = 0.0001) and a rise in the stage of proliferative centers development from stage II-III to IV-V. Intensity of inflammation in prostatic tissue decreased by 53% in the study group and insignificantly in the control group. Thus, permixon treatment of BPH leads to a significant rise in stromal-parenchymatous correlation due to inhibition of proliferative activity of prostatic epithelium and attenuation of inflammation.

[The results of long-term permixon treatment in patients with symptoms of lower urinary tracts dysfunction due to benign prostatic hyperplasia]. / Rezul'taty dolgosrochnogo primeneniia permiksona u bol'nykh s simptomami narusheniia funktsii nizhnikh mochevykh putei, obuslovlennymi dobrokachestvennoi giperplaziei predstatel'noi zhelezy.

The trial enrolled 155 patients (mean age 65 years) with documented benign prostatic hyperplasia and lower urinary tracts symptoms (LUTS) (IPSS > 6). All the patients received permixon in a dose 160 mg twice a day for 2 years. The data on 130 patients eligible for assessment were processed statistically by dynamics of IPSS, quality of life (QOL), index of sexual function (MSF-4), size of the prostate, urodynamic and biological parameters which were estimated in 6 (V6), 12 (V12), 18 (V18) and 24 months (V24). Clinical examination with registration of all side effects was made each 3 months. Permixon was found to noticeably reduce IPSS and QOL and increase maximal urine flow speed. The size of the prostate diminished insignificantly. Sexual function remained unchanged for 1 year and improved markedly within the second year (p = 0.001). Permixon had no effect on the level of prostate-specific antigen. Plasma hormones (testosterone, DHT, estradiol, LH, androstendion) did not change. Nine patients developed 10 side effects but they were unrelated to the treatment.

[Role of cytokines in the diagnosis of chronic prostatitis]. / Rol' tsitokinov v diagnostike khronicheskogo prostatita.

Chronic prostatitis affects 30-60% males and significantly deteriorates quality of their life. Clinical and experimental investigations have revealed changes in immune status in the onset and development of prostatic inflammation. As some other urologists, we made an attempt to determine the role of cellular immunity and immunoglobulins in the diagnosis of chronic prostatitis. The study was made in 30 patients with chronic abacterial prostatitis (mean age 42.5 years, duration of the disease 1.8 years). In addition to standard examination, all the patients have undergone analysis of the immune status and measurement of proinflammatory cytokines (TNF alpha and IL-12b) in biological media: blood serum, urine, ejaculate, prostatic secretion. The patients had moderate symptoms: IPSS--10.4 scores, life quality index--4.3 scores, on the average. Prostamol-uno was given to all the patients in a standard dose 1 capsule (320 mg) a day for 3 to 6 months. The results were processed statistically. A good effect of prostamoluno was registered in 26 patients, a satisfactory one--in 2. Two patients refused to take prostamol-uno because of lack of a prominent effect. The scores of IPSS lowered from 10.4 to 6.3 (by 39%), life quality improved by 42%. Ultrasound monitoring of the size of the prostate showed no significant changes in the size. Tolerance was good in all 30 patients. Side effects were absent. After 3 months of the treatment serum, urine, ejaculate and prostatic secretion cytokines changed. TNF alpha elevated while IL-1 beta level lowered almost to normal value. In 6 months both IL-1 beta and TNF alpha returned to normal values confirming stabilization of cytokine system and the end of inflammation. Cellular immunity did not change much. Thus, as inflammation in prostatic tissue is characterized by elevation of proinflammatory cytokines, in diagnosis of chronic prostatitis it will be valid to use markers TNF alpha and IL-1 beta as criteria of immune prognosis of prostatic exacerbation. Prostamol-uno does not induce changes in lymphocyte populations and impairment of immune status.

[Prostaplant treatment of benign prostatic hyperplasia]. / Lechenie dobrokachestvennoi giperplazii predstatel'noi zhelezy preparatom prostaplantom.

80 patients aged 48 to 91 years with verified benign prostatic hyperplasia (BPH) stage I and II, having contraindications to surgery, received prostaplant, extract of Sabal serrulata palm fluit, in a dose 320 mg once a day. The treatment resulted in improvement of subjective and objective parameters (the total IPSS score improved by 32.3%, quality of life by 36.4%; maximal urine flow rate by 27.4%, respectively). Residual urine volume reduced in patients of group I by 26.8%, in patients of group II by 25.5%. The drug tolerance was good. 3 patients failed treatment. Good and satisfactory effects were achieved in 69 and 8 patients, respectively. Therefore, prostaplant is effective in BPH.

Effect of extract of Rhazya stricta, a traditional medicinal plant, on rat brain tribulin.

Rhazya stricta leaves, which have both antidepressant and sedative properties in animal models, are widely used in folk medicine in the Arabian peninsula. In this study, the effects of oral administration of leaf extracts on rat brain tribulin levels [endogenous monoamine oxidase (MAO) A and B inhibitory activity], were determined. In an acute study, low doses brought about an increase in MAO A inhibitory activity, while intermediate doses caused a significant reduction. The highest doses had no significant effects on activity. There were no significant effects on MAO B inhibitory activity at any dose. Subchronic administration (21 days) caused a significant decrease in MAO A inhibitory activity, most prominent at low dosage, and an increase in MAO B inhibitory activity. Acute intramuscular administration also resulted in a similar pattern. Such paradoxical effects were at least partially explained when different extracts of the leaves were used; a weakly basic chloroform fraction caused an increase in MAO A inhibitory activity, whereas butanol extracts brought about a decrease. These fractions had no significant effects on MAO B inhibitory activity. The findings show that Rhazya stricta leaves contain at least two different components that affect MAO inhibitory activity in opposite directions. It may be that the antidepressant and sedative actions of the plant are explicable in terms of these different components.

cDNA cloning, genomic structure, and chromosome mapping of the human epithelial membrane protein CL-20 gene (EMP1), a member of the PMP22 family.

CL-20 is a novel gene encoding a protein that is structurally related to but distinct from the peripheral myelin protein PMP22. Like PMP22, CL-20 is likely to play important roles in the regulation of cell proliferation, differentiation, and cell death. In this study, we describe the cloning and sequencing of a cDNA encoding the human homologue of CL-20 and characterize the genomic structure of this gene. The hCL-20 gene (HGMW-approved symbol EMP1) encodes a protein of 157 amino acids that exhibits 76% identity to the rabbit CL-20 and to the rat EMP-1, which have been described recently, and 39% identity to human PMP22. CL-20 contains four hydrophobic domains, suggesting that it is an integral membrane protein. In particular the second hydrophobic domain encoded within the fourth exon is highly conserved among CL-20, EMP-1, and PMP22, suggesting a functional role for this region. CL-20 mRNA is abundant in squamous-differentiated bronchial epithelial cells; however, low levels of CL-20 mRNA can be detected in several human tissues by Northern analysis. Retinoic acid, which inhibits squamous differentiation, represses CL-20 expression in normal human bronchial epithelial cells. The genomic structure of the hCL-20 gene was analyzed using a P1 vector containing this gene. The hCL-20 gene contains five exons about 0.2, 0.12, 0.1, 0.14, and 2.2 kb and four introns about 15, 1.9, 0.1, and 0.7 kb. We have mapped the hCL-20 gene to chromosome 12p12 by fluorescence in situ hybridization.

Cloning of a cDNA encoding the murine orphan receptor RZR/ROR gamma and characterization of its response element.

In this study, we describe the cloning of the mouse homologue of the orphan receptor, RZR/ROR gamma, a member of the nuclear receptor superfamily, from a mouse muscle cDNA library. The amino acid sequence of mouse ROR gamma (mROR gamma) is highly homologous to that of human ROR gamma, with an overall identity of 88%. Northern blot analysis using RNA from different tissues showed that mROR gamma was found to be highly expressed in skeletal muscle, liver and kidney. Analysis of the ROR gamma-response element using in vitro synthesized ROR gamma revealed that it binds as a monomer to response elements composed of a single core motif GGTCA preceded by a 6 bp AT-rich sequence. The ROR gamma-binding specificity was further defined by mutational analysis of the consensus RORE. ROR gamma was able to activate RORE-dependent transcription of the CAT reporter gene in mouse fibroblast D1 cells. ROR alpha 1 and ROR gamma inhibit the transactivation induced by GAL4(DBD)-ROR gamma in fibroblast D1 cells suggesting that these receptors compete for binding to the same coactivators.

Frontal cortex leads other brain structures in generalised spike-and-wave spindles and seizure spikes induced by picrotoxin.

Generaliszed spike-and-wave (SW) spindles (5-7 Hz) associated with myoclonic jerks precede the occurrence of regular spikes (2-3 Hz) associated with convulsive seizure induced by picrotoxin. SW spindles occur spontaneously in rodent and cat under some experimental conditions and are considered to be models of human generalised epilepsy. These spindles have been proposed as being led by a thalamic pacemaker. To examine this possibility in picrotoxin-induced SW spindles and seizure spikes, we recorded EEG using chronically implant unipolar electrodes during intravenous picrotoxin infusion in freely behaving rat. The 6 EEG signals were digitally sampled at 1000 Hz. Linear correlation, spectral, coherence and phase analyses were undertaken to determine time differences (TDs) between EEG channels and the brain structure leading seizure activity. One frontal cortex led all other structures during SW spindles. TD between SW spindles in the leading frontal cortex (Fr1) and the contralateral Fr1 was 3.6 + / - 0.5 msec. All ipsilateral structures (hippocampus, thalamus, amygdala, caudate nucleus and occipital cortex) were delayed by more than 3 msec from Fr1 (intralaminar thalamic nuclei - by 6.3 + / - 0.9 msec). TDs of SW spindles between subcortical regions were less than 1.5 msec. Similar relationships with slightly smaller TDs were found with spikes during convulsive seizure except TDs between frontal cortices did not significantly differ from zero. We suggest that seizure activity induced by picrotoxin is led by one Fr1 during SW spindles and by both frontal cortices working as one system during convulsive seizure.

Opioid receptor activation resets the hypothalamic clock generating growth hormone secretory bursts in the rat.

Plasma growth hormone (GH) concentrations were measured serially every 20 min for 6 h in unrestrained chronically-catheterised male rats to define physiological GH pulsatile secretory patterns. Bursts of GH secretion lasted 69 +/- 5 min and occurred every 177 +/- 4 min. Intravenous administration of the opioid receptor agonist morphine (200 micrograms/kg) caused an immediate GH burst of normal duration (63 +/- 3 min) in all animals. This burst of secretion occurred whatever the phase of the background GH cycle and was followed by normal trough GH levels; a second GH burst occurred 177 +/- 6 min later, an inter-burst period not different from controls. Opioid receptor blockade with naloxone (5 mg/kg) administered i.v. every 20 min during spontaneous GH bursts significantly lengthened the interburst interval from 177 +/- 4 to 200 +/- 9 min (P = 0.015). Naloxone did not affect synchronisation of the GH rhythm induced by morphine but lengthened the duration of GH secretory bursts from 69 +/- 5 to 94 +/- 9 min (P = 0.017). The findings indicate that opioid receptor activation resets the hypothalamic mechanism generating pulsatile GH secretion and that both the period of the GH rhythm and duration of the GH burst is normally shortened by opioid mechanisms.

[Retinoic acid intensifies the suppression of the proliferation of K562 cells by phorbol ester]. / Retinoevaia kislota usilivaet podavlenie proliferatsii kletok K562 forbolovym éfirom.

The effect of forbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the growth of cultured human chronic promyelocytic leukemia (K562) cells has been studied using cells growing in a medium consisting of RPMI 1640 supplemented with 10% fetal serum and with or without retinoic acid. All the used concentrations of TPA (100.0, 10.0, 1.0 and 0.1 ng/ml) cause the expected inhibition of proliferation of these cells. Moreover, a block of proliferation of K562 cells became stronger after cotreatment with TPA and retinoic acid, although this acid itself did not have any effect on proliferation and differentiation of K562 cells.

[The effect of autotransfusion of photo-modified blood on the growth of Walker's carcinosarcoma]. / Vliianie autotransfuzii fotomodifitsirovannoi krovi na rost kartsinosarkomy Uokera.

The study deals with the influence of autotransfusion of blood treated with ultraviolet light on the growth of experimental Walker's carcinosarcoma in rats. Animals of the study group survived longer than controls. Autotransfusion of the photo-modified blood did not influence tumor growth rate. The anti-anemic action, the inhibitory effect on lipid peroxidation and retardation of immunodepression by photo-modified blood are the possible mechanisms accounting for an increase in resistance to tumor growth in rats.

[Spectral and coherence EEG analysis of rats differing in the level of seizure readiness]. / Spektral'nyi i kogerentnyi analiz EEG krys, razlichaiushchikhsia po urovniu sudorozhnoi gotovnosti.

The resting EEGs of several brain structures (motor and visual cortex, caudate nucleus and intralaminar thalamic nuclei) were submitted to spectral and coherence computer analyses in two rat strains. Genetically predisposed to convulsive state KM rats were shown to differ from nonpredisposed Wistar rats in EEG spectral properties. KM rats EEG pattern was characterized by increase of low frequencies (1-2 Hz) power and decrease of faster activity (5-12 Hz) power in cortical spectrograms as well as by decrease of caudate nucleus EEG absolute power. The coherence value between cortical or subcortical structures at below 4 Hz was intensified in KM rats. Reinforcement of cortical auto-oscillating properties manifested by ECoG synchronization in cortical-thalamic resonance interaction as well as weakening of striatal inhibitory system may constitute neurophysiological mechanisms of enhanced convulsive readiness. The probable role of mediator imbalance in these mechanisms is discussed.