The goal of research was to determine the frequency, intensity, time of occurrence, duration and causes of breakthrough pain (BTP) in patients whose carcinoma pain was treated by transdermal fentanyl. (TDF). A prospective study was conducted in a hospice for recumbent patients of the Centre for Palliative Care (hospice) University Clinical Centre Tuzla from October 2009 to December 2010. 33 patients in terminal stage of carcinoma, who had been treated by transdermal fentanyl due to their excruciating pain (7-10 mark on numerical scale) with initial dosage of 25 microg as a strong opiate analgesic, were monitored within the time period of 10 days. In the statistics we used the even T - test, the Wilcox test and Mann-Whitney test. The difference was seen to be significant at p < 0.05. Treatment by transdermal fentanyl significantly reduces the intensity of strong carcinoma pain (p < 0.0001), with a frequent requirement for dose increase with bone metastasis. The intensity of BTP is higher compared to the pain experienced upon reception. The frequency and intensity of BTP are significantly reduced already in the second day of treatment by transdermal fentanyl (p = 0.0024). The BTP is most intense in patients with neck and head tumours (9.26 +/- 0.66), and most frequent with abdomen and pelvic tumour. The biggest number of BTP (68.3 %) occurs within first three days of treatment. BTP most frequently occurs in the evening or at night (between 18:00 and 06:00 h in 62.2 % of the cases), with the duration of usually less than 15 minutes (65.2 % of the cases). In 61.6 % cases the occurrence of BTP is related to physical activities or psychosocial incidents, while the cause is undetermined in 38.4 % of examinees. BTP is most frequent within first three days of treatment by TDF. Using the optimal dosage a good control of carcinoma pain is enabled, regardless of the occurrence of bone metastasis, while it also helps reduce the frequency and intensity of BTP.

Quality of life in patients with cervical cancer FIGO IIb stage after concomitant chemoradiotherapy Background. The literature reports are unclear regarding the quality of life in patients after the concomitant chemoradiotherapy. Our aim was to define and compare the quality of life of patients with cervical cancer FIGO IIb stage before and after the concomitant chemoradiotherapy. Methods. Nineteen patients were irradiated to 45 Gy in 25 fractions over 5 weeks to the pelvis and additional 20-24 Gy in 4-6 fractions were given by intracavitary high dosage rate (HDR) brachytherapy. Patients received 40 mg/m2 of cisplatin once a week, starting from the first day of the intracavitary brachytherapy treatment, which is a total of 4-6 cycles of cisplatin. Patients were surveyed with two questionnaires for the assessment of the quality of life. They were developed by the European Organisation for Research and Treatment of Cancer (EORTC): one was cancer specific (EORTC QLQ-C30) and one was site specific (EORTC QLQ-Cx24). Patients answered the questions for the period immediately before diagnosed cervical cancer (thus being a control group) and for the period starting 12 months after the completion of the concomitant chemoradiotherapy (thus being an experimental group). Results. A statistically significant difference between the median scores of these two groups has been found in the quality of life, role function, emotional function, social function, pain, fatigue and vaginal problems. Conclusions. The quality of life of patients with cervical cancer FIGO IIb stage was better after concomitant chemoradiotherapy than before it.

Problem  The objective of this study was to compare serum concentrations of progesterone‐induced blocking factor (PIBF), anti‐inflammatory (IL‐10), and pro‐inflammatory (IL‐6, TNFα, and IFNγ) cytokines of women with threatened pre‐term delivery, with those of women with normal pregnancy and to evaluate the impact of PIBF on the outcome of pregnancy.

Cervical dysplasia, a premalignant lesion that can progress to cervical cancer, is caused primarily by a sexually transmitted infection with an oncogenic strain of the human papillomavirus (HPV). The HPV infections are treated through destroying the clinical lesions: laser, cryotherapy, podophyllin... The hope is that by causing local tissue inflammation that the body will be stimulated to mount an antibody response and thereby prevent recurrence. In contrast to other prevention approaches, vaccines can reduce susceptibility in uninfected partners by stimulating the immune system. Aloe vera has also been reported to retard tumour growth and stimulate the immune response to viruses. A list of possible actions of propolis includes: antibacterial, antifungal, antiviral, antioxidant, anticarcinogenic, antithrombotic and immunomodulatory. Research on the possible role of some B vitamins in preventing cancer began in the last few decades, but however this complex have an influence on immune status. The aim of our study is to try to treat the HPV infection as confirmed cause of neoplastic transformation with some herbal therapy and interferon and to try define the guidelines in the management of the HPV positive patients. Goal of this paper is to search for evidence of efficacy of any treatment for HPV infection of the cervix mostly in woman with no concomitant CIN. Fifty five woman affected by HPV genital infection were enrolled in the study from September 2005 to April 2006. Patients were classified according to the results of the HPV testing prior and after the therapy. Patients were randomized into two groups: the first group was HPV positive woman treated with other than recommended therapy (n=20), (control group); the second group was pharmacologically treated with intravaginal administration of an interferon and aloe vera-propolis in recommended scheme (n=35) with treatment of the possible fungal or bacterial genital infection prior to the specific therapy. The almost same therapy was recommended to the male partner. Patients from the second group used B complex during the therapy. Patients were retested for the HPV presence after three or six month from therapy depend of the presence bacterial or fungal genital coinfection. Three months after applied therapy HPV infection was still present in more than 90% of the patients in the first group. In the second group treated according to the recommended therapy scheme HPV infection disappeared in 71.42% of the patients after three months and in 100% of patients after six months. Samples of the cervical smear for the HPV analysis were being taken during routine gynecological examinations, by using sticks with cotton, taken from the Digene Specimen Collection Kit, from the whole surface of a portion, and by mild rotating moves from the outer cervical entrance. Our results suggest that the combination of interferon and herbal therapy with B complex is effective, atraumatic and simple non-surgical treatment of HPV infection. Since prospective efficacy trials will take several years to complete, considering alternative approaches is also worthwhile.

In about 70% of cases, ovarian carcinoma has been diagnosed at an advanced stage. Invasion and metastasis of solid tumors request protease activity resulting in basal membrane destruction and surrounding matrix. In that process, urokinase plasminogen activator (uPA) and its receptor, urokinase plasminogen activator receptor (suPAR) play a key role, that via plasmin activation lead to basal membrane and matrix degradation in surrounding of the tumor, enable to its invasion and metastasis. Determination of serum concentration of those tumor markers can be useful in preoperative as well as in postoperative period. Their serum concentrations in ovarian cancer patients may help in good monitoring of remission or progression during chemotherapy treatment. In late 1950s and ear1y 1960s, when it was found out that malignant ovarian tumors were chemosensitive, their chemotherapy treatment has begun. In the beginning it was used only mono-therapy, and by discovering new cytostatics it was replaced by poly-chemotherapy. Now days, in the therapy of advanced stages of ovarian carcinoma combination of cisplatine or carboplatine with paclitaxel is considering as standard treatment. Aim of this study was to determine serum uPA, suPAR and CEA in FIGO II and III patients with different histological type (serous, mucinous, clear cell tumor) before and after PT chemotherapy protocol during following three cycles. In this prospective study we have analyzed 17 patients with ovarian carcinoma, those have been after surgery treated by chemotherapy. Serum levels of uPA and suPAR have been determined by ELISA-test (Imubind uPA, Imubind uPAR, American Diagnostica), and CEA by OPUS Imunoassay method. Results of this study have shown that uPA, suPAR and CEA met criteria for prognostic markers for monitoring of successfulness of platina/taxol chemotherapy protocol for serous, mucinous and clear cell tumor FIGO II and III stage of ovarian carcinoma. In case of PT chemotherapy protocol suPAR was better prognostic marker for monitoring of chemotherapy successfulness (Pearson coefficient 0,9 do 1,0; p<0,00l) than uPA (Pearson coefficient between 0,86 and 0,92; p<0,02) and CEA (Pearson coefficient 0,5 do 0,89; p<0,04).

PURPOSE Detection of ovarian malignancy in early stage is one of the main problems of modern medicine. In FB&H problem is even larger due to fact that official demographic data are insufficient while National Cancer Registry and National strategy for early detection of ovarian malignancy are not established yet. Overlook of ovarian malignancy in Federation B&H considers comprehensive and precise analysis of populations' characteristics with highlights of risk factors such as: age, parity, hereditary factors, menstrual cycle characteristics, environmental factors. WORK METHOD Retrospective multi-centric study. Disease histories of 272 patients with ovarian cancer within the Federation B&H were analyzed. Usual statistic methods were performed (T- test, chi2 -Test, Fisher exact test) using statistical programme Arcus Quick Stat. WORK RESULTS 1) Disease was diagnosed most often in stage III and IV (60%); 2) Epithelial cancer was diagnosed in 88.6% cases; 3) most frequently in age of 55 to 70; 4) Out of 272 patients null-parity was seen in 16.9% while 19.8% had just one pregnancy; 5) Approximately 1.8% patients had close relatives with cancer of breast, ovary or colon; 6) Menstrual cycle duration shorter than 21day was found in 26,5% cases. DISCUSSION Ovarian cancer is severe disease which is detected mostly in advanced stages and has poor prognosis. Most often disease is detected in perimenopause. Epithelial carcinoma is most often histological type. There are some proven risk factors: age, parity, genetic predisposition. Seeking for those that belong to risk group should be main task in National strategy. Family doctors who are supposed to cover whole population with their activity should be involved in process of identification of risk groups bearing in mind their role in Health System Reform. CONCLUSION Ovarian cancer known as "Silent Killer" due to lack of symptoms and insufficiency of diagnostics methods for early detection. There are some particular problems existing in B&H caused by the lack of National strategy for ovarian cancer early detection. We recommend to medical health officials several activities that should be performed to improve prognosis for patient with such deadly disease: 1. To establish of Cancer registry; 2. To form available official and precise demographic database; 3. To involve family doctors in process of risk group identification; 4. To identify medical centres for early diagnostic, treatment and follow up; 5. To establish algorithms for: diagnostic, treatment and follow up.

INTRODUCTION The activation of PI-3 kinase/AKT/PKB signal transduction pathway has implicated in the cell growth regulation and proliferation. AIM To determine a role of PI-3 kinase/AKT/PKB signal transduction pathway in the kidney of Angiotensin II-induced hypertensive rats. METHODS NZW (New Zealand White) rats have been infused by Angiotensin II using osmotic minipump for six days (n = 8). Control group was untreated rats (n = 6). PI-3 inase and AKT/PKB activities were measured in the presence or absence of different inhibitors. RESULTS Angiotensin II elevated mean arterial blood pressure (MABP) to 182 +/- 2 mm Hg (p < 0.001) vs untreated control rats (95 +/- 3 mm Hg). Ras-GTPase and PI-3 Kinase activities were elevated in angiotensin II-treated group. Ras inhibitors FPT III and BMS/191563 attenuated MABP to 122 +/- 2 and 127 +/- 4 mm Hg (p < 0.05) and abolished Ras-GTPase and PI-3 Kinase activities. AKT/PKB activity followed the PI-3 kinase activity. CONCLUSION PI-3 kinase/AKT/PKB signal transduction pathway in the kidney is activated and mediates Angiotesin II-induced hypertension.

Precancerous and early cancerous lesions of the cervix uteri (ASCUS, AGUS, LSIL and HSIL) are precursors of invasive cancer of the cervix uteri. By Papanicolaou test they are graded as Pap III and Pap IV. Different factors may increase a risk for those lesions as well as converting low stage lesion into higher one. Oral contraceptive use is one of the most potential risk factor for those lesions. The goal of this study was to examine a relationship between oral contraceptive use and precancerous and early cancerous lesion of the cervix lesion of the cervix uteri by using Papanicolaou test. After adjustment for other potential risk factors our results have shown: 1) there is high significant positive relationship between oral contraceptives use and precancerous and early cancerous lesions of the cervix uteri; 2) the users of oral contraceptives have shown Pap III and Pap IV smear grade five to ten years earlier than non-users; 3) long-term users have shown Pap III and Pap IV five years earlier than short-term users for middle age group (35-44 years); 4) the border between Pap III and Pap IV is shifted for five years toward earlier age.

Pancreatic ribonuclease A (RNase A) is a endonuclease that catalyzes depolymerization of ribonucleic acid (RNA) releasing oligonucleotides. In the process of binding enzyme with substrate are involved several non-catalytic phosphate binding subsites, one of them is p2, additional to main catalytic site p1. RNaza A prefers binding and cleavage of longer substrate molecules, and 3',5'-phosphodiester bond should be some six-seven residues apart from the end of molecules of the chain of RNA. In this work is analysed endonuclease activity of recombinant pancreatic RNase A (K7H), that in position seven instead of a lysine there is a histidine, amino acid residue that participates in main catalytic site p1. Mutant enzyme is obtained by site-directed mutagenesis by Kunkel. Results of this investigation have shown that substitution of lysine by histidine in position seven of RNase A has produced total deletion of p2 subsite, and K7H has lost endonuclease activity, and has become exonuclease. These results confirm central role of Lys-7 in establishing p2 subsite and endonuclease activity of pancreatic RNase A.

Pancreatic ribonuclease A is an enzyme that binds up ribonucleic acid (RNA) along the multiple binding subsites that essentially recognize the negatively charged phosphates of the substrate. It is endoribonuclease that catalyse depolimerization of single-stranded RNA. This work gives additional support to the existence of the phosphate-binding site p2 and confirms the central role of Lys-7 in establishing and electrostatic interraction with a phosphate group of the substrate. In this work catalytic properties of recombinant ribonuclease K7H have been studied. This enzyme is a mutant enzyme which contains histidine instead of lysine in a position 7, amino-acid that participates in the main catalytic center of RNase A, named p1. It was obtained by site-directed mutagenesis. Kinetic parameters of K7H have determined with C > p i poli (C) as substrates at pH 5.5 i 7.5. Kinetic parameters of K7H for C > p and as a substrate at pH 5.5 have not altered, but at pH 7.5 were significantly increased. Value Km was also increased, that indicates decreasing of affinity. Increasing of catalysis was double. Results of kinetic parameters of K7H with poli (C) as a substrate in pH 5.5 have shown slight difference according to kinetic parameters of commercial RNase A with poli (C). Significant decreasing of values of all kinetic parameters for K7H were reaction at pH 7.5.