Anticonvulsant effects of isopimpinellin and its interactions with classic antiseizure medications and borneol in the mouse tonic-clonic seizure model: an isobolographic transformation.

BACKGROUND: Overwhelming evidence indicates that some naturally occurring coumarins and terpenes are widely used in folk medicine due to their various therapeutic effects affecting the brain. Antiseizure medications (ASMs) are the principal treatment option for epilepsy patients, although some novel strategies based on naturally occurring substances are intensively investigated. This study was aimed at determining the influence of isopimpinellin (ISOP-a coumarin) when administered either separately or in combination with borneol (BOR-a monoterpenoid), on the antiseizure potencies of four classic ASMs (carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), and valproate (VPA)) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures. MATERIALS: Tonic-clonic seizures were evoked experimentally in mice after systemic (ip) administration of the respective doses of ISOP, BOR, and classic ASMs. Interactions for two-drug (ISOP + a classic ASM) and three-drug (ISOP + BOR + a classic ASM) mixtures were assessed isobolographically in the mouse MES model. RESULTS: ISOP (administered alone) had no impact on the anticonvulsant potencies of four classic ASMs. Due to the isobolographic transformation of data, the combination of ISOP + VPA exerted an antagonistic interaction, whereas the two-drug mixtures of ISOP + CBZ, ISOP + PHT, and ISOP + PB produced additive interactions in the mouse MES model. The three-drug combinations of ISOP + BOR with CBZ and PHT produced additive interactions, while the three-drug combinations of ISOP + BOR with PB and VPA exerted synergistic interactions in the mouse MES model. CONCLUSIONS: The most intriguing interaction was that for ISOP + VPA, for which the addition of BOR evoked a transition from antagonism to synergy in the mouse MES model.

Outcome of transobturator sling for treatment of female stress urinary incontinence applied as a single procedure or concomitantly with pelvic organ prolapse surgery.

INTRODUCTION AND OBJECTIVE: The aim of the study was to check the safety and efficacy of transobturator tape (TOT) combined with various prolapse procedures. The results were compared with outcomes of sling performed as an alone surgery. Risk factors for TOT failure were also identified. MATERIAL AND METHODS: The study comprised 219 patients with sling alone (Group SUI) and 221 after TOT combined with concomitant prolapse surgery (Group POP/SUI). Medical records were carefully reviewed to obtain demographic and clinical data, details of surgery, including intra-and postoperative complications. RESULTS: Subjective cure rate was slightly, but statistically significantly, higher in POP/SUI group (89.6% vs 82.6%; ch2 = 4.44; p = 0.035). There was no significant difference in sling efficacy dependant of type of POP surgery. Post-operative urine retention was more frequent in POP/SUI group compared to SUI group (18.6% vs 3.2%; ch2 = 34.36; p < 0.001). Logistic regression showed that age, BMI and prolonged pos-operative urine retention are independent factors affecting TOT outcome. Age ≥65years and BMI ≥30kg,m2 more than doubled the risk of failure: OR 2.348, CI 95% (1.330-4.147); p = 0.003 and 2.030, (95% CI 1.148-3.587); p = 0.015; respectively. Interestingly, post-operative urine retention appeared to be a positive prognostic factor OR 0.145, (95% CI 0.019-1.097); p < 0.05. CONCLUSIONS: Subjective efficacy of TOT used concomitantly with POP procedures is slightly higher than TOT alone. Better sling outcomes can be expected both for POP procedures involving both the anterior and posterior compartments. Age and obesity are independent factors of TOT failure, whereas prolonged post-operative urine retention is a positive predictive factor of TOT success.

Urine Nerve Growth Factor May Not Be Useful as a Biomarker of Overactive Bladder in Patients with Pelvic Organ Prolapse.

(1) Background: Overactive bladder (OAB) symptoms are frequently present in women with pelvic organ prolapse (POP). Although urinary nerve growth factor (NGF) is a promising biomarker of OAB, little is known about its role in patients with OAB secondary to POP. The aim of the study was to evaluate urinary NGF levels in patients with POP involving the anterior vaginal wall and check if it may serve as a predicting factor for postoperative resolution of OAB symptoms. (2) Methods: Eighty-three Caucasian women included in the study were divided into three groups: pure OAB, one associated with POP (POP&OAB) and a control group composed of healthy volunteers. The urine NGF and creatinine were assessed with ELISA tests to calculate the NGF/creatinine ratio. (3) Results: The NGF/creatinine ratio was significantly higher in patients with pure OAB in comparison with other groups; however, it did not differ between the control group and the POP&OAB group. There was no correlation between NGF/creatinine ratio and age, menopausal status, BMI, parity or urodynamic findings. The NGF/creatinine ratio was not a prognostic factor for OAB symptoms' resolution after surgical treatment of POP. (4) Conclusions: Urinary NGF excretion is not increased in women with OAB secondary to POP; thus, it may not serve as an OAB biomarker in these patients.

[The influence of mesh pelvic floor reconstructive surgery on OAB symptoms]. / Wplyw operacji naprawczych zaburzen statyki narzadu rodnego na redukcje objawów zespolu pecherza nadreaktywnego.

OBJECTIVES: The working hypothesis was that pelvic organs prolapse can induce overactive bladder symptoms. Therefore, restoration of pelvic anatomy with accompanying proper urodynamic parameters (cystometric volume, micturition volume, uroflow) should resolve OAB (Overactive Bladder) symptoms. MATERIALS AND METHODS: Forty eight women, aged 51-77 years (mean 62.4±7.32), with stage II, III or IV prolapse (POP-Q scale) were included into the study. Patients with LUTS (Lower Urinary Tract Symtoms--inflammation, infection, pain) were excluded. Each patient underwent clinical evaluation and full urodynamic examination (cystometry and uroflowmetry MMS Libra +). Depending on the type of the anatomical defect on the POP-Q scale--anterior defect, posterior defect or both anterior and posterior--a repair using polypropylene monofilament mesh was performed (TVM anterior, TVM posterior or TVM Total). Patients were asked to complete King's Health questionnaire before and after the reconstructive surgery. Statistical analysis was performed using Kolmogorov-Smirnov and U Mann-Whitney tests. RESULTS: Overactive bladder symptoms were diagnosed in 27 patients. Detrusor overactivity was found in 10 patients. In 17 patients, out of 27 with OAB before surgery overactivity symptoms completely resolved after the surgery (63%). On the other hand, post-op de novo OAB symptoms appeared in 2 patients (4.1%). Half of the patients with OAB symptoms after surgery had detrusor overactivity before mesh repair while only 30% of patients without OAB symptoms after surgery had DO (Detrusor Overactivity) before the surgical procedure. Micturition volume in group of patients with OAB significantly increased after the surgery (293.78 ml vs. 364.15 ml; p=0.006). Maximal cystometric capacity in patients with overactive bladder also significantly increased after the surgery (318.78 ml vs. 407 ml; p=0.0001). Quality of life measured by King's questionnaire improved in the group of patients with resolution of OAB symptoms in such domains as: Incontinence Impact, Role Limitations and Sleep/emotions, p<0.05. CONCLUSIONS: Correction of pelvic organ prolapse stage II, III and IV in patients with OAB symptoms leads to an improvement in bladder conditions in half of the patients. Such treatment also resulted in symptom resolution of detrusor overactivity ascertained in urodynamic studies. Overactive bladder syndrome with DO was more resistant to surgical treatment as compared to OAB without DO. Quality of life improved in patients who did not present with OAB bladder symptoms after the mesh surgery. Restoration of proper anatomy might also cure or improve bladder symptoms in patients with OAB symptoms, coexisting with advanced pelvic organ prolapse.

The polymorphisms of the MMP-1 and the MMP-3 genes and the risk of pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: To investigate the associations between single nucleotide polymorphism (SNP) type 1G/2G at position -1607/-1608 of the matrix metalloproteinase (MMP)-1 gene and SNP type 5A/6A at position -1612/-1617 of the MMP-3 gene and the development of pelvic organ prolapse (POP) in women. METHODS: 133 patients with symptomatic POP were included in the study group. The control group consisted of 132 women with a normal pelvic floor. 1G/2G MMP-1 and 5A/6A MMP-3 SNPs were determined by polymerase chain reaction (PCR) and restriction fragments length polymorphism analysis. RESULTS: When estimated individually none of the investigated SNPs were associated with POP. The combined MMP-1/MMP-3 SNP analysis showed that the following polymorphic pairs were overrepresented in women with POP: 1G/2G -5A/6A, 2G/2G -5A/6A, 2G/2G -5A/5A, 1G/1G -6A/6A, p=0.005. CONCLUSIONS: The combined effect of -1607/-1608 MMP-1 and -1612/-1617 MMP-3 SNPs may contribute to the development of POP in some women.

[Nerve growth factor as a biomarker in the diagnosis and treatment of overactive bladder (OAB)]. / Czynnik wzrostu nerwów (NGF) jako biomarker w diagnostyce i terapii peccherza nadreaktywnego (OAB).

Nerve growth factor is a complex regulator of neural plasticity along the micturition pathways. The aim of this review is to summarize the current evidence for a role of NGF in urinary bladder function both in experimental and clinical settings. There is bulk of strong evidence that experimental administration of NGF elicits the symptoms of increased sensation, urgency and bladder hyperreflexia which strongly resemble overactive bladder syndrome (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS). Therefore in human studies there are attempts to employ urinary NGF levels as a diagnostic marker in various forms of OAB and IC/PBS. It has been shown that urinary NGF levels are correlated with severity of OAB symptoms and in patients successfully treated with antimuscarinics agents or detrusor botulinum toxin injection, urinary NGF levels decrease significantly in association with reduction of urgency severity

Tape fixation: an important surgical step to improve success rate of anti-incontinence surgery.

PURPOSE: Mid urethral slings are effective surgical treatment for stress urinary incontinence. However, 5% to 20% of patients still experience surgical failure with clinically significant recurrent or persistent stress urinary incontinence. Since a subset of these failures may be caused by improper tape position, we elucidated whether additional paraurethral fixation of a tape to prevent displacement during tensioning could improve the transobturator sling outcome. MATERIALS AND METHODS: The study was done in 463 patients with stress urinary incontinence who were randomly allocated to treatment with a standard transobturator intravaginal monofilament sling procedure (232) or to an intravaginal transobturator monofilament sling with additional 2-point tape fixation (231). Another 2 absorbable sutures parallel to the urethra were added to fix the tape and prevent displacement during tape tensioning. Outcome was assessed by a cough test and a 1-hour pad test at 12 months. RESULTS: Clinical efficacy of the procedure with fixation was significantly higher with 195 women (95.12%) cured or improved compared to the 199 (88.73%) cured or improved with the standard sling (chi-square 5.71, p = 0.0169). There was no increase in intraoperative or postoperative complications. Also, among patients with intrinsic sphincter deficiency we noted a significantly better outcome in the fixation group than in the control group, that is 39 of 41 patients (95.1%) cured or improved vs 31 of 42 (73.8%) (chi-square 10.65, p = 0.0011). CONCLUSIONS: Tape fixation significantly increases the clinical efficacy of the transobturator sling, especially in patients with intrinsic sphincter deficiency.

[MMP-1 and MMP-3 gene encoding polymorphism and the risk of the development of pelvic organ prolapse and stress urinary incontinence]. / Polimorfizm genów kodujacych MMP-1 oraz MMP-3 a ryzyko wystapienia wysilkowego nietrzymania moczu i zaburzen statyki dna miednicy mniejszej.

OBJECTIVES: The estimation of the association between the polymorphism at position -1607/1608 of the gene promoter encoding matrix metalloproteinase type 1 (MMP- 1) and the polymorphism at position -1612/1617 of the gene promoter encoding stromelysin type 1 (MMP-3) and the risk of the occurrence of pelvic organ prolapse (POP) and stress urinary incontinence (SUI). MATERIAL AND METHODS: 347 women were included into the analysis. POP study: the study group consisted of patients with clinically significant POP (POP-Q scale: 2, 3, 4). Women with normal pelvic floor statics (POP-Q scale: 0, 1) and not reporting symptoms of urinary incontinence were included into the control group. SUI study: the study group--patients with symptoms of stress urinary incontinence, the control group--continent women with normal pelvic floor statics (POP-Q scale: 0, 1). Samples of DNA were isolated from whole blood. The type of polymorphism was detected by RFLP method. RESULTS: Both, in the POP and the SUI study we have observed no statistically significant differences in the occurrences of MMP-1 and MMP-3 promoter polymorphisms between the study and the control groups. Also, the presence of the alleles G/GG (MMP-1) or 5A/6A (MMP-3) did not modify the risk of the POP and SUI development. CONCLUSIONS: Polymorphism type G/GG of gene promoter encoding MMP-1 and polymorphism type 5A/6A of the gene promoter encoding MMP-3 are not associated with the risk of the development of POP and SUI.

Body mass index does not influence the outcome of anti-incontinence surgery among women whereas menopausal status and ageing do: a randomised trial.

INTRODUCTION AND HYPOTHESIS: A few series comparing the clinical efficacy of midurethral slings in obese and postmenopausal patients are available. The aim of the study was to assess clinical efficacy of suburethral tape operations for the surgical treatment of female stress urinary incontinence (SUI) stratified by obesity, menopause and ageing. METHODS: Five hundred thirty-seven patients underwent either retropubic or transobturator sling procedure. Patients were randomly allocated into two study groups in a ratio of 1:1. After 18 months, 398 women were available for a follow-up efficacy evaluation. RESULTS: The clinical effectiveness of surgical SUI treatment did not depend on patients' body mass index (BMI) and type of midurethral sling, but menopausal status and ageing significantly influenced the outcome of the surgery. CONCLUSIONS: We found that BMI does not influence the clinical effectiveness of SUI treatment, whereas both menopause and ageing had a detrimental influence on the final outcome of the surgery.

The clinical effectiveness of retropubic (IVS-02) and transobturator (IVS-04) midurethral slings: randomized trial.

BACKGROUND: Few series comparing the clinical efficacy of retropubic slings versus transobturator slings for the treatment of female stress urinary incontinence (SUI) are available. OBJECTIVE: To compare clinical efficacy of retropubic tape operations and transobturator suburethral tape operations for the surgical treatment of female SUI. DESIGN, SETTING, AND PARTICIPANTS: From January 2003 to December 2005, 611 patients underwent clinical and urodynamic evaluation before surgical treatment for SUI. Patients with advanced urogenital prolapse (pelvic organ prolapse-quantification scale [POP-Q] scale grade >1) were excluded, and 537 patients were included in this study. After 18 mo, 398 women were available for follow-up efficacy evaluation at a tertiary academic center. INTERVENTION: All patients underwent either a retropubic sling procedure or a transobturator sling procedure. Patients were randomly allocated into two study groups at a ratio of 1:1. MEASUREMENTS: After 18 mo all enrolled patients were clinically checked for clinical efficacy of both procedures. RESULTS AND LIMITATIONS: Demographic and urodynamic parameters of patients were similar in both groups. No bladder injury occurred in the transobturator sling group (IVS-04), whereas 13 intraoperational bladder perforations (6.5%) occurred in the retropubic sling group (IVS-02) (p<0.001). The tape erosion rate was <2.5% in both groups (p=0.7). After 18 mo, 398 patients (201 in the IVS-02 group and 197 in the IVS-04 group) were evaluated in terms of clinical efficacy of the procedures. We found out that there was no statistically significant difference in clinical efficacy between these two procedures (chi(2)=1.88, p=0.39). In the IVS-02 group, 75.1% of patients (n=151) remained dry (cured), 16.9% of patients (n=34) reported significant improvement, and 8.0% of patients (n=16) were considered as failures. In the IVS-04 group, 74.1% of patients (n=146) remained dry, 14.2% of patients (n=28) reported significant improvement, and 11.7% (n=23) were considered as failures. CONCLUSIONS: Based on an 18-mo follow-up, the efficacies of both techniques are comparable; however, the retropubic route appears to be more efficient in the intrinsic sphincter deficiency (ISD) group.

Do preoperative cytokine levels offer a prognostic factor for polypropylene mesh erosion after suburethral sling surgery for stress urinary incontinence?

When polypropylene meshes are used in reconstructive urogynecological surgery, the erosion rates vary from 3.3% to 14% and causative factors for such erosions are still unknown in many cases. Therefore, the aim of our study was to establish the role of immunologic factors in the process of polypropylene tapes erosions after suburethral sling procedures. Serum concentrations of tumor necrosis factor alpha, interleukin (IL)-2, IL-4, IL-5, IL-10, and interferon (IFN)-gamma were estimated in 123 patients suffering from stress urinary incontinence preoperatively and during 12 months follow-up using Human Th1/Th2 Cytokine Cytometric Bead Array I kit. The same immunological assessment was performed in each case of detected tape erosion. Statistical calculation was performed using UNIVARIATE, CORR, and NPAR1WAY procedures from Statistical Analysis System. The unpaired Student's t test, nonparametric Mann-Whitney U test, and Wilcoxon tests were used. Preoperative IFN-gamma concentration was significantly higher in women with subsequent polypropylene mesh erosion when compared to women with successful outcome (p < 0.05). Th1 cytokine profile may be related to the risk of the vaginal erosions following placement of polypropylene meshes. The way to lower erosion rate may involve exclusion of the patients immunologically prone to synthetic material erosion. The factor which can help to select such patients could be preoperative level of IFN-gamma.

[Occupational exposure to prions due to contact with meat and bone meal (MBM)]. / Narazenie zawodowe na priony zwiazane z praca w kontakcie z maczka miesno-kostna.

Meat and bone meal (MBM) is free from conventional biological factors if it is not subjected to a secondary pollution, but it may be a potential source of prions. Prions are widely accepted as being the casual agents of a range of serious infectious diseases characterized by degenerative processes in the nervous system. These diseases occur in both humans and animals. The recommended method of producing MBM is now regarded by experts as optimal as it sufficiently eliminates prions, which may be present in the animal material used in MBM production. However, it has been stressed that neither this nor any other method used can guarantee that all prions are completely neutralized. Workers employed in utilizing plants, which produce MBM, plants producing fertilizers and animal fodder, power stations using MBM as an alternative fuel, MBM store-houses, as well as those dealing with MBM distribution and transport form occupational groups at a higher risk. In the opinion of experts, the risk of infection with prions among workers having contact with MBM is very low and it should be regarded as acceptable for this kind of exposure. It is worth noting that guidelines on how to prevent and reduce contacts with MBM has already been elaborated.

Microbiological contamination with moulds in work environment in libraries and archive storage facilities.

Microbiological contamination with fungi, including moulds, can pose a significant health hazard to those working in archives or museums. The species involved include Aspergillus, Penicillium, Geotrichum, Alternaria, Cladosporium, Mucor, Rhizopus, Trichoderma, Fusarium which are associated mostly with allergic response of different types. The aim of the study was to analyse, both in quantitative and qualitative terms, workplace air samples collected in a library and archive storage facilities. Occupational exposure and the related health hazard from microbiological contamination with moulds were assessed in three archive storage buildings and one library. Air samples (total 60) were collected via impact method before work and at hourly intervals during work performance. Surface samples from the artifacts were collected by pressing a counting (RODAC) plate filled with malt extract agar against the surface of the artifacts. The air sample and surface sample analyses yielded 36 different mould species, classified into 19 genera, of which Cladosporium and Penicillium were the most prevalent. Twelve species were regarded as potentially pathogenic for humans: 8 had allergic and 11 toxic properties, the latter including Aspergillus fumigatus. Quantitative analysis revealed air microbiological contamination with moulds at the level ranging from 1.8 x 10(2)-2.3 x 10(3) cfu/m(3). In surface samples from library and archive artifacts, 11 fungal species were distinguished; the number of species per artifact varying from 1-6 and colony count ranging from 4 x 10(1) to 8-10(1) cfu/100 cm(2). Higher contamination levels were found only for Cladosporium cladosporioides (1.48 x 10(3) cfu/100 cm(2)) and Paecillomyces varioti (1.2 x 10(2) cfu/100 cm(2)). At the workposts examined, although no clearly visible signs of mould contamination could be found, the study revealed abundant micromycetes, with the predominant species of Cladosporium and Penicillium. The detected species included also potentially pathogenic microorganisms which can cause allergic and toxic effects, such as Aspergillus fumigatus, that could be hazardous to workers' health. For some species, the concentration levels exceeded the values considered the proposed hygienic standards for total microscopical fungi in occupational settings. The findings of the study point to unsatisfactory hygienic conditions at the worksites examined, resulting in microbiological contamination with moulds, as well as the necessity for prompt remedial activities on the part of the employers.

[The prospective comparison of the clinical effectiveness and the complication rate of retropubic (IVS-02) and transobturator (IVS-04) midurethral slings in the treatment of female stress urinary incontinence]. / Prospektywne badanie porównujace efektywnosc kliniczna i czestosc wystepowania powiklan sród- i poopera- cyjnych slingu zalonowego (IVS-02) i slingu przezzaslonowego (IVS-04) zastosowanych w leczeniu wysilkowego nietrzymania moczu u kobiet.

UNLABELLED: The prospective comparison of the clinical effectiveness and the complication rate of retropubic (IVS-02) and transobturator (IVS-04) midurethral slings in the treatment of female stress urinary incontinence. OBJECTIVES: The purpose of this study was the prospective comparison of clinical efficacy and safety of retropubic (IVS-02) and transobturator suburethral tape techniques (IVS-04) in the treatment of female stress urinary incontinence. MATERIAL AND METHODS: From January 2003 to June 2004, 145 patients with uro-dynamically proven stress urinary incontinence underwent surgical treatment (IVS-02 or IVS-04). During pretreatment work-up, all patients had under-gone full clinical and urodynamic evaluation. Patients with mixed, urge incontinence and the advanced urogenital prolapse (POPQ scale > 2) were excluded from the study. RESULTS: Patients clinical characteristics and urodynamic parameters were comparable between the analyzed groups. At one year follow-up, 122 patients (61 in each group) were evaluated in terms of clinical efficacy of the procedure. The total cure (78.7% in IVS-02 vs 70.5% in IVS-04), the improvement (14.7% vs 21.3%) and the failure rates (6.6% vs 8.2%) were similar in both analyzed groups, chi2 = 0.58; (p = 0.75). CONCLUSIONS: The transobturator route for the treatment of stress urinary incontinence appears to be as effective as the retropubic one at one year follow-up. Moreover, the shorter operation time and no need to perform cystoscopy during the surgery make the transoburator route a very attractive alternative to retropubic approach.

[Tape erosion--local process or general reaction of the organism. The erosion rate and localization of implanted polypropylene tape in female pelvis]. / Czy erozja tasmy polipropylenowej jest reakcja miejscowa, czy ogólnoustrojowa organizmu kobiety oraz czy wystapienie tego zjawiska zalezy od miejsca implantacji tasmy w miednicy mniejszej?

OBJECTIVES: Our study was aimed to reveal whether the tape rejection is associated with increase in serum C-reactive protein level and to assess if localization of implanted polypropylene tape predisposes to its rejection. MATERIAL AND METHODS: Between January 2002 and June 2005, 780 women with SUI or pelvic organ prolapse underwent retropubic sling procedure--IVS 02 (n = 379) or transobturator suburethral tape--IVS 04 (n = 283) or posterior IVS operation (n = 118). IVS multifilament tape (Tyco Healthcare) was used in all surgeries. The same antibiotic prophylaxis and disinfected procedure were applied in all cases. Follow-up visits were performed 4-6 weeks after the operation and next were scheduled every 3 months during first year after surgery and every 6 months in the years to follow. Blood to CRP level analysis (ELISA method) was collected form all patients with mesh erosion without any concomitant inflammatory or immunologic diseases. RESULTS: Until January 2006 we have observed 28 cases of tape rejection: 5 after posterior IVS operation, 14 after IVS 02 and 9 after IVS 04. The chi-square test revealed no statistically significant differences between these groups. Ten women with mesh rejection were completely asymptomatic, two had fever and abscessi. Also, four women had pyogenic discharge from the skin or the vagina. Ten women complained of dyspareunia, vaginal bleeding and irritating voiding. We have found CRP values normal in all cases beside woman with fever and abscesi two. CONCLUSIONS: The process of mesh erosion in most cases is limited to local cellular response. The tape rejection rate is not associated with the localization of the implant in female pelvis.

Pharmacokinetic and pharmacodynamic interactions of aminophylline and topiramate in the mouse maximal electroshock-induced seizure model.

The aim of this study was to determine the influence of acute (single) and chronic (twice daily for 14 consecutive days) treatments with aminophylline (theophylline(2).ethylenediamine) on the anticonvulsant potential of topiramate (a broad-spectrum antiepileptic drug) in the mouse maximal electroshock-induced seizure model. Additionally, the effects of acute and chronic administration of aminophylline on the adverse effect potential of topiramate were assessed in the chimney test (motor performance). To evaluate pharmacokinetic characteristics of interaction between topiramate and aminophylline, total brain concentrations of topiramate and theophylline were estimated with fluorescence polarization immunoassay technique. Results indicate that aminophylline in non-convulsive doses of 50 and 100 mg/kg (i.p.), both in acute and chronic experiments, markedly attenuated the anticonvulsant potential of topiramate by raising its ED(50) value against maximal electroconvulsions. Aminophylline at a lower dose of 25 mg/kg did not affect significantly the ED(50) value of topiramate in the acute experiment, but the drug markedly increased the ED(50) value of topiramate during the chronic treatment in mice. Only, aminophylline at 12.5 mg/kg, in both acute and chronic experiments, did not affect the antielectroshock action of topiramate in mice. Moreover, aminophylline at a dose of 100 mg/kg had no impact on the adverse effect potential of topiramate in the chimney test. Pharmacokinetic evaluation of total brain concentrations of topiramate and theophylline revealed that topiramate significantly increased total brain theophylline concentrations following both acute and chronic applications of aminophylline. Conversely, aminophylline did not alter total brain concentrations of topiramate in mice. Based on this preclinical study, one can conclude that aminophylline attenuated the antiseizure action of topiramate in the mouse maximal electroshock-induced seizure model and the observed interaction between drugs was both pharmacokinetic and pharmacodynamic in nature.

Polymorphism of the gene encoding alpha-1 chain of collagen type I and a risk of pelvic organ prolapse--a preliminary study.

INTRODUCTION: Polymorphism of the gene encoding alpha-1 chain of type I collagen (COL1A1) may influence the mechanical properties of the pelvic floor connective tissue. AIM OF STUDY: We examined possible role of G-->T substitution in transcription factor Sp1 binding site in the gene encoding alpha-1 chain of type I collagen (COL1A1) in the development of pelvic organ prolapse. MATERIALS AND METHODS: The study group consisted of 37 women with pelvic floor defects graded according POPQ scale as stage II, III and IV. All study group patients underwent reconstructive surgery of the pelvic floor. We enrolled forty control subjects. All of them were treated for benign gynecological conditions other then stress urinary incontinence or pelvic organ prolapse. DNA was obtained from peripheral blood leukocytes. The fragment of the first intron of COL1A1 gene containing Sp1 binding site was amplified by PCR and analysis of restriction fragment length polymorphism was done. RESULTS: The GG polymorphism in COL1A1 gene was identified in 26 (70.3%), GT sequence in 10 (27%) and TT in 1 (2.7%) patient. The distribution of the investigated polymorphisms in the control group were: 27 (67.5%), 9 (22.5%) and 4 (10%), respectively. We do not found association between investigated polymorphic variants and pelvic organ prolapse (chi2 test, p=ns). CONCLUSION: G-->T substitution in transcription factor Sp1 binding site in the COLIA1 gene does not increase the risk of development of pelvic floor defect (POPQ stages II, III, IV).

[Caffeine and antiepileptic drugs: experimental and clinical data]. / Kofeina a leki przeciwpadaczkowe: dane doswiadczalne i kliniczne.

BACKGROUND: Caffeine, a methylxanthine derivative, is contained in coffee or tea, chocolate as well as in some beverages. In addition, it may be added to some analgesics. At high doses, similarly to other methylxanthine derivatives (theophylline, pentoxifylline) caffeine induces seizure activity in rodents. THE AIM OF STUDY: If caffeine intake from coffee drinking resulting in pharmacologically active plasma caffeine concentrations--can lead to diverse interactions with other medications. RESULTS: Since 90s of the XX century, there are experimental data available pointing to the caffeine-induced impairment of the protective activity of a number of antiepileptic drugs in basic models of epilepsy in rodents. Acute caffeine, in doses far below its convulsive potential (almost 10-20 fold lower than the ED50 of the methylxanthine of 2.03 mmol/kg for the induction of seizures), produced a significant reduction in the anticonvulsant effects of carbamazepine, phenobarbital, phenytoin, and valproate against maximal electroshock-induced seizures in mice. This interaction was pharmacodynamic in nature since caffeine did not affect the plasma concentrations of these anti-epileptics. Interestingly, there was no tolerance to this hazardous effect of caffeine since its administration at the same dosages (0.12-0.24 mmollkg) also resulted in the impairment of the protection provided by antiepileptic drugs, this effect being even more pronounced in the case of phenobarbital and carbamazepine. In case of newer antiepileptics, both acute and chronic caffeine decreased the protective potential of gabapentin and topiramate but not that of lamotrigine and tiagabine. CONCLUSIONS: The existing clinical data confirm the experimental results in that caffeine intake in epileptic patients results in increased seizure frequency. It may be concluded that epileptic patients should limit their daily intake of caffeine.

[Harmful impact of biological agents released at metalworking]. / Szkodliwe dzialanie czynników biologicznych uwalnianych podczas procesów obróbki metali z uzyciem chlodziw.

In metalworking, the temperature of the cutting edge can reach 700 degrees C, which can adversely affect either the surface of the metal processed or the cutting edge itself. To reduce the heat and friction, the metalworking fluids and coolants are used. The most common are the oil-in-water emulsions, which are a mixture of concentrated mineral oils, different additives, and water. The presence of water and organic substrates generates conditions for microbial growth. Bacterial endotoxins can also be frequently detected in metalworking fluids. Rapid rotation of the metalworking tools makes various biological agents to be released as droplet bioaerosols that can be inhaled by the workers, thus producing adverse health effects, mainly on the respiratory system. More than 130 species of bacteria (including pathogens), moulds and yeasts have so far been found in the metalworking fluids and coolants. This paper summarizes the outcomes of projects on the impact of biological agents present in metalworking fluids. Exposure to oil mist, bacteria and endotoxins as well as the variety of health effects resulting from that exposure have been discussed. The findings indicate that the most frequent symptoms reported by the workers include cough with phlegm, wheezing breath, chest tightness and throat irritation. The most common among the diagnosed diseases are chronic allergic bronchitis, asthma, hypersensitivity pneumonitis and acute respiratory dysfunction indicated by decreased FEV1 values. The main skin diseases include oil acne, bacterial infections, dermatomycosis and allergic reactions. The review made the authors conclude that the problem of occupational exposure to biological agents released with coolants during metalworking has not been well recognized in Poland.