Anti-Inflammatory and Antioxidant Pyrrolo[3,4-d]pyridazinone Derivatives Interact with DNA and Bind to Plasma Proteins-Spectroscopic and In Silico Studies.

From the point of view of the search for new pharmaceuticals, pyridazinone derivatives are a very promising group of compounds. In our previous works, we have proved that newly synthesized ligands from this group have desirable biological and pharmacokinetic properties. Therefore, we decided to continue the research evaluating the activity of pyrrolo[3,4-dpyridazinone derivatives. In this work, we focused on the interactions of five pyridazinone derivatives with the following biomolecules: DNA and two plasma proteins: orosomucoid and gamma globulin. Using several of spectroscopic methods, such as UV-Vis, CD, and fluorescence spectroscopy, we proved that the tested compounds form stable complexes with all biomacromolecules selected for analysis. These findings were also confirmed by the results obtained by molecular modeling. All tested pyridazinone derivatives bind to the ctDNA molecule via groove binding mechanisms. All these molecules can also be bound and transported by the tested plasma proteins; however, the stability of the complexes formed is lower than those formed with serum albumin.

Protopine and Allocryptopine Interactions with Plasma Proteins.

A comprehensive study of the interactions of human serum albumin (HSA) and α-1-acid glycoprotein (AAG) with two isoquinoline alkaloids, i.e., allocryptopine (ACP) and protopine (PP), was performed. The UV-Vis spectroscopy, molecular docking, competitive binding assays, and circular dichroism (CD) spectroscopy were used for the investigations. The results showed that ACP and PP form spontaneous and stable complexes with HSA and AAG, with ACP displaying a stronger affinity towards both proteins. Molecular docking studies revealed the preferential binding of ACP and PP to specific sites within HSA, with site 2 (IIIA) being identified as the favored location for both alkaloids. This was supported by competitive binding assays using markers specific to HSA's drug binding sites. Similarly, for AAG, a decrease in fluorescence intensity upon addition of the alkaloids to AAG/quinaldine red (QR) complexes indicated the replacement of the marker by the alkaloids, with ACP showing a greater extent of replacement than PP. CD spectroscopy showed that the proteins' structures remained largely unchanged, suggesting that the formation of complexes did not significantly perturb the overall spatial configuration of these macromolecules. These findings are crucial for advancing the knowledge on the natural product-protein interactions and the future design of isoquinoline alkaloid-based therapeutics.

The Role of the Unbinding Cycle on the Coordination Abilities of the Bi-Cyclopeptides toward Cu(II) Ions.

Bicyclic peptides have attracted the interest of pharmaceutical companies because of their remarkable properties, putting them on a new path in medicine. Their conformational rigidity improves proteolytic stability and leads to rapid penetration into tissues via any possible route of administration. Moreover, elimination of renal metabolism is of great importance, for example, for people with a history of liver diseases. In addition, each ring can function independently, making bicyclic peptides extremely versatile molecules for further optimization. In this paper, we compared the potentiometric and spectroscopic properties studied by UV-vis, MCD, and EPR of four synthetic analogues of the bi-cyclic peptide c(PKKHP-c(CFWKTC)-PKKH) (BCL). In particular, we correlated the structural and spectral properties of complexes with coordinating abilities toward Cu(II) ions of MCL1 (Ac-PKKHPc(CFWKTC)PKKH-NH2) that contains the unbinding cycle and N- and C-terminal linear parts with two histidine residues, one per part; two monocyclic ligands containing one histidine residue, both in the N-terminal position, i.e., MCL2 (Ac-PKKHPc(CFWKTC)PKKS-NH2) and in the C-terminal position, i.e., MCL3 (Ac-PKKSPc(CFWKTC)PKKH-NH2), respectively; and the linear structure LNL (Ac-PKKHPSFWKTSPKKH-NH2). Potentiometric results have shown that the bicyclic structure promotes the involvement of the side chain imidazole donors in Cu(II) binding. On the other hand, the results obtained for the mono-cyclic analogues lead to the conclusion that the coordination of the histidine moiety as an anchoring group is promoted by its location in the peptide sequence further from the nonbinding cycle, strongly influencing the involvement of the amide donors in Cu(II) coordination.

Interaction of Positively Charged Oligopeptides with Blood Plasma Proteins.

In this project, we combine two areas of research, experimental characterization and molecular docking studies of the interaction of positively charged oligopeptides with crucial blood plasma proteins. The investigated peptides are rich in NH2 groups of amino acid side chains from Dap, Orn, Lys, and Arg residues, which are relevant in protein interaction. The peptides are 9- and 11-mer with the following sequences: (Lys-Dab-Dab-Gly-Orn-Pro-His-Lys-Arg-Lys-Dbt), (Lys-Dab-Ala-Gly-Orn-Pro-His-Lys-Arg), and (Lys-Dab-Dab-Gly-Orn-Pro-Phe(2-F)-Lys-Arg). The net charge of the compound strongly depends on the pH environment and it is an important aspect of protein binding. The studied oligopeptides exhibit therapeutic properties: anti-inflammatory activity and the capacity to diminish reactive oxygen species (ROS). Therefore, the mechanism of potential binding with blood plasma components is the next challenge. The binding interaction has been investigated under pseudo-physiological conditions with the main blood plasma proteins: albumin (BSA), α1-acid glycoprotein (AAG), and γ-globulin fraction (GGF). The biomolecular quenching constant (kq) and binding constant (Kb) were obtained by fluorescence spectroscopy at various temperatures. Simultaneously, the changes in the secondary structure of proteins were monitored by circular dichroism (CD) and infrared spectroscopy (IR) by quantity analysis. Moreover, molecular docking studies were conducted to estimate the binding affinity, the binding domain, and the chemical nature of these interactions. The results show that the investigated oligopeptides could be mainly transported by albumin, and the binding domain I is the most favored cavity. The BSA and GGF are able to form stable complexes with the studied compounds as opposed to AAG. The binding reactions are spontaneous processes. The highest binding constants were determined for Lys-Dab-Dab-Gly-Orn-Pro-His-Lys-Arg-Lys-Dbt peptide, in which the values of the binding constants Kb to BSA and GGF were 10.1 × 104 dm3mol-1 and 3.39 × 103 dm3mol-1, respectively. The positively charged surface of peptides participated in salt bridge interaction with proteins; however, hydrogen bonds were also formed. The secondary structure of BSA and GGF after contact with peptides was changed. A reduction in the α-helix structure was observed with an increase in the ß-sheet and ß-turn and random coil structures.

Synthesis, Biological, Spectroscopic and Computational Investigations of Novel N-Acylhydrazone Derivatives of Pyrrolo[3,4-d]pyridazinone as Dual COX/LOX Inhibitors.

Secure and efficient treatment of diverse pain and inflammatory disorders is continually challenging. Although NSAIDs and other painkillers are well-known and commonly available, they are sometimes insufficient and can cause dangerous adverse effects. As yet reported, derivatives of pyrrolo[3,4-d]pyridazinone are potent COX-2 inhibitors with a COX-2/COX-1 selectivity index better than meloxicam. Considering that N-acylhydrazone (NAH) moiety is a privileged structure occurring in many promising drug candidates, we decided to introduce this pharmacophore into new series of pyrrolo[3,4-d]pyridazinone derivatives. The current paper presents the synthesis and in vitro, spectroscopic, and in silico studies evaluating the biological and physicochemical properties of NAH derivatives of pyrrolo[3,4-d]pyridazinone. Novel compounds 5a-c-7a-c were received with high purity and good yields and did not show cytotoxicity in the MTT assay. Their COX-1, COX-2, and 15-LOX inhibitory activities were estimated using enzymatic tests and molecular docking studies. The title N-acylhydrazones appeared to be promising dual COX/LOX inhibitors. Moreover, spectroscopic and computational methods revealed that new compounds form stable complexes with the most abundant plasma proteins-AAG and HSA, but do not destabilize their secondary structure. Additionally, predicted pharmacokinetic and drug-likeness properties of investigated molecules suggest their potentially good membrane permeability and satisfactory bioavailability.

The 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl Phthalimide Derivatives as Prodrugs-Spectroscopic and Theoretical Binding Studies with Plasma Proteins.

Many publications in databases deal with the interactions of new drugs with albumin. However, it is not only albumin that is responsible for binding pharmaceutical molecules to proteins in the human body. There are many more proteins in plasma that are important for the study of the ADME pathway. Therefore, in this study, we have shown the results of the interactions between the plasma proteins albumin, orosomucoid, and gamma globulins and non-toxic anti-inflammatory phthalimide analogs, which due to the promising obtained results, may be potential candidates in the group of analgesic and anti-inflammatory drugs. Using spectroscopic methods and molecular modeling, we showed that all four tested compounds form complexes with the analyzed proteins. The formation of a complex with proteins raises the pharmacological efficacy of the drug. Therefore, the obtained results could be a step in the study of the pharmacokinetics and pharmacodynamics of new potential pharmaceuticals.

Cationic Peptides and Their Cu(II) and Ni(II) Complexes: Coordination and Biological Characteristics.

Antimicrobial peptides are a promising group of compounds used for the treatment of infections. In some cases, metal ions are essential to activate these molecules. Examples of metalloantibiotics are, for instance, bleomycin and dermcidin. This study is focused on three new pseudopeptides with potential biological activity. The coordination behavior of all ligands with Cu(II) and Ni(II) ions has been examined. Various analytical methods such as potentiometric titration, UV-Vis and CD spectroscopies, and mass spectrometry were used. All compounds are convenient chelators for metal ion-binding. Two of the ligands tested have histidine residues. Surprisingly, imidazole nitrogen is not involved in the coordination of the metal ion. The N-terminal amino group, Dab side chains, and amide nitrogen atoms of the peptide bonds coordinated Cu(II) and Ni(II) in all the complexes formed. The cytotoxicity of three pseudopeptides and their complexes was evaluated. Moreover, their other model allowed for assessing the attenuation of LPS-induced cytotoxicity and anti-inflammatory activities were also evaluated, the results of which revealed to be very promising.

New N-Substituted-1,2,4-triazole Derivatives of Pyrrolo[3,4-d]pyridazinone with Significant Anti-Inflammatory Activity-Design, Synthesis and Complementary In Vitro, Computational and Spectroscopic Studies.

Regarding that the chronic use of commonly available non-steroidal and anti-inflammatory drugs (NSAIDs) is often restricted by their adverse effects, there is still a current need to search for and develop new, safe and effective anti-inflammatory agents. As a continuation of our previous work, we designed and synthesized a series of 18 novel N-substituted-1,2,4-triazole-based derivatives of pyrrolo[3,4-d]pyridazinone 4a-c-9a-c. The target compounds were afforded via a convenient way of synthesis, with good yields. The executed cell viability assay revealed that molecules 4a-7a, 9a, 4b-7b, 4c-7c do not exert a cytotoxic effect and were qualified for further investigations. According to the performed in vitro test, compounds 4a-7a, 9a, 4b, 7b, 4c show significant cyclooxygenase-2 (COX-2) inhibitory activity and a promising COX-2/COX-1 selectivity ratio. These findings are supported by a molecular docking study which demonstrates that new derivatives take position in the active site of COX-2 very similar to Meloxicam. Moreover, in the carried out in vitro evaluation within cells, the title molecules increase the viability of cells pre-incubated with the pro-inflammatory lipopolysaccharide and reduce the level of reactive oxygen and nitrogen species (RONS) in induced oxidative stress. The spectroscopic and molecular modeling study discloses that new compounds bind favorably to site II(m) of bovine serum albumin. Finally, we have also performed some in silico pharmacokinetic and drug-likeness predictions. Taking all of the results into consideration, the molecules belonging to series a (4a-7a, 9a) show the most promising biological profile.

Design, synthesis, biological evaluation and in silico studies of novel pyrrolo[3,4-d]pyridazinone derivatives withpromising anti-inflammatory and antioxidant activity.

Novel Mannich base analogues of pyrrolo[3,4-d]pyridazinone 7a,b-13a,b are designed and synthesized as potential anti-inflammatory agents. The title compounds are obtained via convenient one-pot synthesis with good yields. Their structures and properties are described by spectroscopic techniques and elemental analyses. The aim of this study is to evaluate the inhibitory activity of the new derivatives against both cyclooxygenase isoforms COX1 and COX2 as well as their cytotoxicity. The results clearly indicate that the tested compounds 7a,b-13a,b are not toxic, all show better affinity towards isoform COX-2, and some of them act as selective COX-2 inhibitors. Moreover, every examined derivative of pyrrolo[3,4-d]pyridazinone demonstrates better inhibitory activity towards COX-2 and a superior COX-2/COX-1 selectivity ratio compared to the reference drug meloxicam. Molecular docking studies confirm that compounds 7a,b-13a,b preferably bind COX-2 and all of them bind to the active site of cyclooxygenase in a way very similar to meloxicam. Subsequently, taking into account that inflammation is strongly correlated with oxidative stress and both of these processes can potentiate each other, synthesized Mannich bases are evaluated for potential antioxidant activity. Most of the investigated derivatives reduce induced oxidative and nitrosative stress. Moreover, compounds 7a,b, 8a, 10a,b, 11b, 12a,b-13a,b protect chromatin from oxidative stress and decrease the number of DNA strand breaks caused by intracellular growth of free radicals. Finally, a study of the binding mechanism between compounds 7a,b-13a,b and bovine serum albumin (BSA) was carried out. According to spectroscopic and molecular docking studies, all examined derivatives interact with BSA, which suggests their potential long half-life in vivo.

Paranasal sinus disease could be a reason for unsuccessful immunotherapy of inhalant allergy in children.

PURPOSE: The aim of this study was to evaluate the role of paranasal sinuses condition assessed in computed tomography on inhalant allergen desensitization effects. MATERIALS & METHODS: Retrospective analysis of medical records of children undergoing allergen immunotherapy in outpatient otolaryngology clinic of University Children Hospital in Lublin was performed. Control group consisted of children who underwent allergen immunotherapy and obtained satisfying effects; study group consisted of children who did not experience significant improvement after desensitization therapy. RESULTS: Computed tomography of nose cavity and paranasal sinuses exposed numerous pathologic changes affecting both, control and study group. Blockage of ostiomeatal complex was twice more common in children who did not respond adequately to desensitization therapy. In our study group, radiological findings suggesting rhinosinusitis were found in 73% of patients, while retention cysts in maxillary sinuses were discovered in 27% of patients. CONCLUSIONS: Pathological findings in paranasal sinuses in computed tomography may arise from uncontrolled allergic rhinitis. If chirurgical management is indicated, allergen immunotherapy should be postponed until total recovery from operational procedure and repeated.

The Binding Ability of a Bicyclic Somatostatin Analogue Towards Cu(II) Ions.

Somatostatin (SST) analogues have aroused the interest of scientists for years. This group of compounds is used in the diagnosis and treatment of neuroendocrine tumors. However, new molecules useful as radiopharmaceuticals in targeted therapy are still searched for. Bicyclic peptides seem to be very interesting in this context. These molecules are associated with beneficial properties. In this work, we present studies on the binding ability of the bicyclic analogue of somatostatin toward Cu(II) ions which could potentially be a chelator for copper radionuclides. The research is focused on the analysis of Cu(II) interactions with the metal binding cycle of the ligand and the influence of the receptor binding site on the coordination process. This is a novelty in comparison to the SST analogues used in medicine, where a metal ion is coordinated by a chelator and connected with a bioactive molecule by the linker. In this work, we present the first coordination study for a bicyclic ligand. The obtained results showed that the complexes with only imidazole donors are characterized by significantly higher stability in comparison to the other peptides.

Detailed Insight into the Interaction of Bicyclic Somatostatin Analogue with Cu(II) Ions.

Somatostatin analogues are useful pharmaceuticals in peptide receptor radionuclide therapy. In previous studies, we analyzed a new bicyclic somatostatin analogue (BCS) in connection with Cu(II) ions. Two characteristic sites were present in the peptide chain: the receptor- and the metal-binding site. We have already shown that this ligand can form very stable imidazole complexes with the metal ion. In this work, our aim was to characterize the intramolecular interaction that occurs in the peptide molecule. Therefore, we analyzed the coordination abilities of two cyclic ligands, i.e., P1 only with the metal binding site and P2 with both sites, but without the disulfide bond. Furthermore, we used magnetic circular dichroism (MCD) spectroscopy to better understand the coordination process. We applied this method to analyze spectra of P1, P2, and BCS, which we have described previously. Additionally, we analyzed the MCD spectra of P3 ligand, which has only the receptor binding site in its structure. We have unequivocally shown that the presence of the Phe-Trp-Lys-Thr motif and the disulfide bond significantly increases the metal binding efficiency.

Design, Synthesis and Comprehensive Investigations of Pyrrolo[3,4-d]pyridazinone-Based 1,3,4-Oxadiazole as New Class of Selective COX-2 Inhibitors.

The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in treatment of different chronic inflammatory disorders is strongly restricted by their serious gastrointestinal adverse effects. Therefore, there is still an urgent need to search for new, safe, and efficient anti-inflammatory agents. Previously, we have reported the Mannich base-type derivatives of pyrrolo[3,4-d]pyridazinone which strongly inhibit cyclooxygenase, have better affinity to COX-2 isoenzyme and exert promising anti-oxidant activity. These findings encouraged us to perform further optimization of that structure. Herein, we present the design, synthesis, molecular docking, spectroscopic, and biological studies of novel pyrrolo[3,4-d]pyridazinone derivatives bearing 4-aryl-1-(1-oxoethyl)piperazine pharmacophore 5a,b-6a,b. The new compounds were obtained via convenient, efficient, one-pot synthesis. According to in vitro evaluations, novel molecules exert no cytotoxicity and act as selective COX-2 inhibitors. These findings stay in good correlation with molecular modeling results, which additionally showed that investigated compounds take a position in the active site of COX-2 very similar to Meloxicam. Moreover, all derivatives reduce the increased level of reactive oxygen and nitrogen species and prevent DNA strand breaks caused by oxidative stress. Finally, performed spectroscopic and molecular docking studies demonstrated that new compound interactions with bovine serum albumin (BSA) are moderate, formation of complexes is in one-to-one ratio, and binding site II (subdomain IIIA) is favorable.

Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of N-substituted 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones Derivatives.

Inhibition of cyclooxygenase is the way of therapeutic activities for anti-inflammatory pharmaceuticals. Serum albumins are the major soluble protein able to bind and transport a variety of exogenous and endogenous ligands, including hydrophobic pharmaceuticals. In this study, a novel N-substituted 1H-pyrrolo[3-c]pyridine-1,3(2H)-diones derivatives were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases and interactions with BSA. In vitro, COX-1 and COX-2 inhibition assays were performed. Interaction with BSA was studied by fluorescence spectroscopy and circular dichroism measurement. The molecular docking study was conducted to understand the binding interaction of compounds in the active site of cyclooxygenases and BSA. The result of the COX-1 and COX-2 inhibitory studies revealed that all the compounds potentially inhibited COX-1 and COX-2. The IC50 value was found similar to meloxicam. The intrinsic fluorescence of BSA was quenched by tested compounds due to the formation of A/E-BSA complex. The results of the experiment and molecular docking confirmed the main interaction forces between studied compounds and BSA were hydrogen bonding and van der Waals force.

[Probiotics intake as gut-microbiota modulating therapy in an interdisciplinary aspect]. / Rola probiotyków jako modulatora regulacji zaburzen mikroflory jelitowej w podejsciu interdyscyplinarnym.

The gut microbiota was defined as one of the endocrine organs. It consists of many various microorganisms with huge metabolic potential. An imbalance of the gut microbiota was assessed as one of risk factors for various metabolic, infectious, and inflammatory disorders, but also stress-related disorders. Link between the gut microbiological environment and the development of such pathologies as: metabolic syndrome, diabetes, obesity, inflammatory bowel disease, colorectal cancer, depression, anxiety disorders, attention deficit hyperactivity disorder or PCO syndrome has been proven. Diet with probiotics intake could be effective in the prevention and treatment of many diseases and associated metabolic disorders. Increasing the amount of "beneficial" gut microbiota may favorably affect the functioning of the whole organism. Treatment options for specific diseases must be compliant with the guidelines of recommendations for these disorders. However, probiotic supplementation can positively strengthen the results of this treatment. It is recognized that probiotics, by increasing beneficial intestinal microflora, inhibit development of pathogens and change metabolic and enzymatic activity. It reduces inflammation and positively regulates immunologic activity of intestines. On the base of conducted studies beneficial effects of probiotic supplementation in patients with metabolic, endocrine and mental disorders were noted. Prebiotics and probiotics influence on modification of gastrointestinal microflora. Changes of gut microbiota, by diet with probiotics intake, cause the maintenance of gut epithelial barrier integrity and may be useful in prevention and treatment of many diseases and concomitant metabolic disorders. It may have potential implications for protection against adverse, long-term health consequences of these disorders.

Assessment of ovarian reserve as an indicator of fertility and health consequences in patients with chronic kidney disease stages 3-4.

The aim of the study was to evaluate whether ovarian reserve depends on chronic kidney disease. Twenty-four patients, 23-45 years with chronic kidney disease (CKD) stages 3-4 were included in the study. All the patients underwent transvaginal ultrasounds to assess antral follicle count (AFC) and ovarian volume. The serum samples were obtained on days 3-5 of the menstrual cycle from all participants for anti-Mullerian hormone (AMH), follicle stimulating hormone (FSH), and estradiol (E2) levels. On the base of the study, it was concluded that the most sensitive parameters of ovarian reserve are AMH and AFC. AMH levels and number of antral follicles in both ovaries were statistically significantly lower in the group of patients with CKD than in control ones. But there were no significant differences in the ovarian volumes (right and left ovary), FSH and E2 levels between study and control groups. Ovarian reserve is not dependent on the duration of CKD and hormonal parameters of ovarian reserve like FSH and estradiol (E2) are not dependent on the presence or absence of proteinuria in patients with CKD, but the most sensitive parameter - AMH is significantly lower in patients with CKD and proteinuria.

[Polycystic ovary syndrome - current state of knowledge]. / Zespól policystycznych jajników ­ aktualny stan wiedzy.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder, affecting 5-10% women of reproductive age. It is one of the most common causes of functional infertility and a clinical problem that can be faced by doctors of many specialities. PCOS is characterized by hyperandrogenism, oligoovulations and metabolic disorders. ESHRE/ASRM (2003) or AES (2006) criteria are used to diagnose a patient with polycystic ovary syndrome. Although a lot of studies are carried out, ethiology and pathogenesis of PCOS is still not clear. The treatment must be long-term, causal and depending on the patient's expectations. The fundamental part of the therapy are lifestyle modifications and weight loss. Losing as little as 5% of body mass increases frequency of ovulations, chances of pregnancy and improves hormonal profile. First-line therapy is clomiphene citrate and for hyperandrogenism reduction combined oral contraceptive pill is frequently used. Metformin, not only improves carbohydrate metabolism, but also increases ovulations' frequency and chances of pregnancy. Metabolic syndrome, diabetes mellitus type 2, hypertension and higher risk of endometrial cancer are characteristic for patients with PCOS.

[New methods of uterine fibroids treatment]. / Nowe metody leczenia miesniaków macicy.

Uterine fibroids are the most common benign tumors of the uterus. Their main symptoms are prolonged menstrual bleeding, leading over time to a secondary anemia, bleeding and spotting between periods, pelvic pain and infertility. It is recognized that fibroids are the most common indication for surgery in gynecology. Currently radical surgical treatment of fibroids is abandon. Ulipristalu acetate is used in pharmacological treatment. This medicine reduces the growth of fibroids. New non-invasive technique is also MR-guided focused ultrasound surgery using thermal tissue destruction by focusing ultrasound beam. Ability to avoid the often crippling surgery makes conservative methods increasingly popular.

[Role of office hysteroscopy in the diagnosis and treatment of uterine pathology]. / Rola minihisteroskopii w diagnostyce i leczeniu patologii jamy macicy.

Nowadays endoscopic techniques are one of the basic diagnostic and operative methods in gynecology. Laparoscopy and hysteroscopy are the most popular of them. Office hysteroscopy is a modern diagnostic and therapeutic method feasible in an outpatient room because no necessity of anesthesia. It is the first-line procedure in the infertility diagnosis and treatment of uterine pathology such as polyps, submucosal fibroids and adhesions. Limitation of this method is the cervical canal atresia. Contraindications to it are: pregnancy, uterine bleeding, active inflammation of pelvic organs, cervical cancer. Due to the high sensitivity and specificity, simplicity of execution and no need for patient hospitalization, office hysteroscopy becomes important diagnostic and therapeutic procedure in uterine pathologies.

[Urinary stress incontinence - one of basic diseases of modern society]. / Wysilkowe nietrzymanie moczu - jedna z podstawowych chorób wspólczesnego spoleczenstwa.

One of the most common women's chronic diseases is urine incontinence (UI). Currently considered to be a social disease of women in all age groups. The etiology of urine incontinence is multifactorial and the most common is stress urinary incontinence (SUI). UI is a interdisciplinary problem, lying in the sphere of interests of different specialties. According to the recommendations of the Polish Gynecological Society IU diagnostics can be divided into a preliminary stage and specialized stage. Initial diagnosis should start by gathering medical history and it can be completed by quality of life questionnaire. Today, one of the non-invasive diagnostic methods is the ultrasound study. In a situation where diagnosis can not be placed or when surgical treatment is needed, the patient should have urodynamic study. Conservative methods and surgery are used in the treatment of SUI. Conservative procedure should be the first choice in patients with symptoms of IU. Over 200 types of various operations have been described in the history of the surgical treatment of SUI. Until now the most common are: Burch colposuspension, TVT and TOT and implantation of an artificial sphincter.