[Clinical guidelines for male infertility: controversial issues and the need to reach interdisciplinary consensus].

A review of controversial issues about the terminology on male infertility and reproductive function, which is currently used, as well as proposals for updating clinical guidelines for the diagnosis and treatment of male infertility and men in infertile couples are presented in the article. An algorithm is described, the elements of which ensure referral of patients based on the possibility and timing of restoration of reproductive function, taking into account the reproductive health of a woman, as well as increasing the likelihood of successful treatment aimed at the birth of a healthy child.

[Endonasal balloon dacryoplasty in partial and complete obstruction of dacryocystorhinostomy ostium]. / Endonazal'naya ballonnaya dakrioplastika pri chastichnom i polnom zarashchenii dakriostomy.

Despite the success of dacryocystorhinostomy (DCR) in the treatment of lacrimal drainage system (LDS) obliteration and the use of medical and surgical methods to prevent its recurrence, the number of relapses reaches 37%. The main etiological factor leading to this pathology is partial (stenosis) or complete obstruction of the ostium. PURPOSE: To study the effectiveness of endonasal balloon dacryoplasty in partial or complete obstruction of dacryocystorhinostomy ostium. MATERIAL AND METHODS: The study involved 122 patients (127 cases) with relapse after endonasal endoscopic dacryocystorhinostomy performed 6 months to 3 years ago to treat partial or complete obstruction of lacrimal sac neck. Patients of the 1st group (41 cases) underwent endonasal balloon dacryoplasty, patients of the 2nd group (42 cases) underwent endonasal balloon dacryoplasty with bicanalicular silicone stenting, patients of the 3rd group (44 cases) underwent revision endonasal endoscopic dacryocystorhinostomy with bicanalicular silicone stenting. RESULTS: After 12 months follow-up, positive results were observed in 85.7% of cases with ostium stenosis and 80.0% of cases with complete obstruction of the ostium among group 1 patients; in 86.4% of cases with ostium stenosis and 85.0% of cases with complete obstruction of the ostium among group 2 patients; and in 81.0% of cases with ostium stenosis and 82.6% of cases with complete obstruction of the ostium among group 3 patients. CONCLUSION: The obtained results give grounds to recommend inclusion of endonasal balloon dacryoplasty in the standards of treatment for patients with partial (stenosis) and complete obliteration of dacryocystorhinostomy ostium.

[Transcanalicular balloon dacryoplasty for the treatment of post-dacryocystorhinostomy recurrent stenoses]. / Transkanalikulyarnaya ballonnaya dakrioplastika ­ metod lecheniya retsidiva posle dakriotsistorinostomii.

PURPOSE: To compare the effectiveness of minimally invasive techniques used for the treatment of common canalicular (CC) ostium stenosis (or obliteration) in post-dacryocystorhinostomy (post-DCR) patients. MATERIAL AND METHODS: The study included 121 patients (127 cases), of which 61 patients (64 cases) had stenosis of the CC ostium and 60 patients (63 cases) had CC ostium obliteration. All stenoses and obliterations were recurrent and developed 6 months to 5 years after primary endonasal endoscopic DCR. Patients were divided into 3 groups. Group 1 included 20 patients (20 cases) with stenosis and 21 patients (22 cases) with CC ostium obliteration who underwent transcanalicular balloon dacryoplasty (DCP), group 2 - 20 patients (21 cases) with stenosis and 20 patients (21 cases) with CC ostium obliteration who underwent transcanalicular DCP and bicanalicular intubation, and group 3 - 21 patients (23 cases) with stenosis and 19 patients (20 cases) with CC ostium obliteration who received bicanalicular intubation alone. Results were evaluated 12 months after the intervention. RESULTS: The treatment was effective in as many as 80% and 68.2% of cases (respectively) in group 1, 76.2% and 66.7% of cases (respectively) in group 2, and 56.5% and 50% of cases (respectively) in group 3. CONCLUSION: The study proves transcanalicular DCP effective alone and shows no need in potentially complicated lacrimal ducts intubation.

[Reproductive disorders and preservation of fertility in males with benign and malignant brain tumors]. / Narusheniia reproduktivnoi funktsii i vozmozhnosti sokhraneniia fertil'nosti muzhchin s dobrokachestvennymi i zlokachestvennymi opukholiami golovnogo mozga.

Brain tumors rank third in the incidence rate among cancer nosologies. However, improvement of neurosurgical treatment methods and the use of modern regimens of chemotherapy and radiotherapy have increased survival of patients with benign and malignant brain tumors. A significant proportion of patients with brain tumors are young people in the reproductive age who are interested in maintaining their fertility. Surgical removal of tumors, mainly in the hypothalamo-pituitary area as well as the use of chemotherapy and radiotherapy for malignant brain tumors of any localization may be complicated by hypogonadism and infertility. At present, a simple and reliable method of preserving male fertility is sperm cryopreservation. Neurosurgeons as well as oncologists and radiologists should inform patients with brain tumors about a potential risk of hypogonadism and infertility after treatment and about opportunities of sperm cryopreservation, which increases the chances of having future genetic progeny.

[Docosahexaenoic acid in the treatment of idiopathic male infertility].

AIM: docosahexaenoic acid is one of the most common fatty acids in the cell membranes of sperm. This substance is a structural component of cell membranes, and is responsible for such properties as plasticity and fluidity which are necessary for the implementation of the process of capacitation and acrosome reaction. In addition, docosahexaenoic acid has antioxidant properties. Aim of our study was to assess the effect of dietary supplement docosahexaenoic acid (Brudi PLUS) on such markers of male fertility as the sperm DNA integrity, standard indicators of semen analysis and cryotolerance in infertile men. MATERIALS AND METHODS: a randomized, multicenter, double-blind, placebo-controlled study was conducted. A total of 109 infertile men were recruited to participate in the study. All patients underwent different analyzes, including semen analysis, sperm DNA fragmentation, MAR-test, test of cryotolerance and electron microscopy analysis of spermatozoa. In active treatment group patients were prescribed to drug containing 350 mg of docosahexaenoic acid 3 times a day for 90 days. In the control group, patients were administered to a placebo with a similar scheme. All analyzes were repeatedly performed after 3-months of therapy. RESULTS: An increase in the progressive mobility and sperm viability was determined after the test of cryotolerance in the active treatment group. According to electron microscopy analysis of spermatozoa, positive changes were observed in the number of heads of the normal form with the normal structure of chromatin and acrosome, as well as a decrease in the number of spermatozoa with insufficiently condensed chromatin. CONCLUSIONS: the therapy with drug Brudi PLUS in patients with male infertility allows to increase in cryotolerance of sperms as well as decrease in number of sperm ultrastructure defects.

[Intraoperative prevention of dacryocystitis relapse]. / Intraoperatsionnye sposoby profilaktiki retsidivov dakriotsistita.

The article reviews the literature devoted to modern intraoperative methods of preventing cicatricial process at the site of dacryostoma after endonasal endoscopic dacryocystorhinostomy. Despite the constant improvement of the surgery technique, complications in the postoperative period still occur. They include the formation of granulation tissue at the sites of dacryostoma, synechiae in the nasal cavity, or narrowing of the dacryostoma, which ultimately leads to a relapse of the disease. The main prevention methods are construction of flaps from the medial wall of the lacrimal sac, from mucosa of the nasal cavity, and intubation of the dacryostoma with the lacrimal implant. They are used separately and in various combinations.

[N-stearoylethanolamine effect on the level of 11-hydroxycorticosteroids, cytokines IL-1, IL-6 and TNFalpha in rats with nonspecific inflammation caused by thermal burn of skin].

The mechanisms of anti-inflammatory action of saturated N-acylethanolamine--N-stearoylethanolamine (NSE) were investigated on the rat model of nonspecific inflammation (thermal burns of the skin). The results showed that the NSE application in a form of aqueous suspension (10 mg/ml) on the damaged skin area during 12 days significantly accelerated the healing process of burned wounds. NSE also prevented the increase of 11-hydroxycorticosteroids content in the blood of rats with burns. There was also found a significant decrease of cytokines (IL-1beta, IL-6 and TNFalpha) levels under the NSE action. This way may be one of the mechanisms of NSE anti-inflammatory action.

False-positive results in ELISA-based anti FVIII antibody assay may occur with lupus anticoagulant and phospholipid antibodies.

The evaluation of a prolonged aPTT often includes Lupus Anticoagulant, Antiphospholipid Antibodies, and Factor VIII (FVIII) inhibitors. We have noticed that patient samples positive for lupus antibody (LA) are frequently also positive for FVIII IgG antibodies in an enzyme-linked immunosorbent assay (ELISA), indicating the need for follow-up testing with a more labour-intensive functional assay for FVIII inhibition. This study evaluates the potential for a FVIII IgG ELISA to yield false-positive results in patient samples positive for LA or other antiphospholipid antibodies. A total of 289 residual de-identified patient samples positive for LA (n = 143), anti-cardiolipin IgG (n = 84), or beta2-glycoprotein antibody (n = 62) were tested for FVIII IgG using a commercial ELISA. Samples with positive FVIII IgG ELISA results were further tested for FVIII activity using a clot-based FVIII inhibitor assay. The FVIII IgG ELISA yielded positive results in 39 (13%) of the samples tested, including 13/143 (13%) LA-positive, 15/85 (18%) aCL IgG-positive and 6/62 (10%) ß2-glycoprotein IgG-positive samples. The clot-based FVIII inhibitor assay yielded negative results in all 39 FVIII IgG-positive specimens tested, indicating discrepancy with the FVIII IgG ELISA results. Patient specimens positive for LA, aCL IgG, or ß2-glycoprotein IgG may yield false-positive results for FVIII antibodies. Caution is warranted in interpreting FVIII antibody results in these cases.

Efficacy of transcranial magnetotherapy in the complex treatment of alcohol withdrawal syndrome.

A total of 54 patients with alcoholism were studied during abstinence. Of these, 29 patients in the experimental group received basal therapy supplemented with physical treatment consisting of transcranial dynamic magnetotherapy (TcDMT), while the control group of 25 patients received only basal therapy. Comparison of the status of patients in the experimental and control groups during treatment demonstrated advantages of TcDMT in relation to improving the functional state of the CNS, memory, and attention, the autonomic nervous system, and the psychoemotional status of the patients (with decreases in the severity of anxiety and depression).

[Anti-inflammatory effect of N-stearoylethanolamine in experimental burn injury in rats].

The biochemical mechanisms of anti-inflammatory effect of endocannabinoid congener N-stearoylethanolamine (NSE) was studied on the model of experimental burn in rats. The animals after the thermal burn of the skin received per os during 7 days the water suspension of NSE in a doze 10 mg/kg of body weight. In the other groups of rats the suspension was applied to the wound (the concentration of NSE was 10 mg/ml). It was shown for the first time that NSE accelerated the process of burn wound healing by the inhibition of proinflammatory cytokines (TNFalpha, IL-6) production. NSE caused the normalization of the iNOS and cNOS activity and of nitrite content in plasma, erythrocytes, liver and spleen of rats. NSE also modified the antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) activity and diminished the level of lipid peroxidation. The discovered anti-inflammatory NSE properties suggest the possibility of its usage for burn treatment.

Measurement of von Willebrand factor-FVIII binding activity in patients with suspected von Willebrand disease type 2N: application of an ELISA-based assay in a reference laboratory.

Laboratory diagnosis of von Willebrand disease type 2N (VWD2N) is based on costly mutation analysis or in vitro measurement of the ability of plasma von Willebrand factor (VWF) to bind exogenous factor VIII (FVIII); however, the VWF-FVIII binding activity assay is complex and not widely used. Our aim was to assess the utility of the in-house VWF-FVIII binding assay in the investigation of patients with suspected VWD2N. A previously described ELISA-based FVIII binding method was simplified and adapted for the clinical laboratory use by optimizing incubation time, reagent concentrations and assay standardization. The assay was validated using samples from eight individuals with known homozygous or heterozygous VWD2N mutations, and 100 healthy adults. An additional 392 patient samples were tested, including 314 with FVIII activity <50% of normal and 78 received for routine VWF-FVIII binding activity testing. Intra- and inter-assay variations were less than 10% and 17%, respectively, and the limit of quantification was estimated as 0.12. The reference range for healthy adults was 0.73-1.42. VWF:FVIII binding activity was consistent with the genotype in subjects with available genetic data, being low in three individuals with homozygous mutation (<0.12) and intermediate in five heterozygous individuals (0.44-0.61). Screening of the 392 clinical samples identified reduced VWF:FVIII binding in 19 subjects. This assay provides accurate measurement of VWF:FVIII binding activity and successfully identifies homozygous VWD2N patients and heterozygous carriers. Use of this ELISA-based assay may help avoid the need for mutation analysis in patients with unexplained low FVIII activity.

[Phospholipids composition of the myocardium in patients with ischemic heart disease and its connection to arrhythmias].

The purpose of this study was to establish phospholipid composition of the myocardium in patients with ischemic heart disease, and to estimate possible correlation of biochemical parameters with myocardium extrasystolic activity. The patients (n = 28) including 15 patients with ischemic heart disease and 13 patients with secondary atrium septum defect (control group) were studied. During surgical intervention the right atrium myocardium bioptates were taken. Phospholipid metabolism was studied in the myocardium samples. At the eve of surgical intervention a holter monitoring was performed. Deep changes in the myocardium lipid metabolism were found, including accumulation of free and estherified cholesterol, lysophospholipids, and sphingomyeline. An increase of free cholesterol content was accompanied by accumulation of sphingomyeline. This can be an evidence of changes in the constitution of lipid rafts. Extrasystoles, particularly ventricular ones, in patients with ischemic heart disease might depend on accumulation of lysophospholipids as they took place simultaneously with it.

[Effectiveness of transcranial magnetic therapy in the complex treatment of alcohol abstinent syndrome].

Fifty-four abstinent alcohol-dependent patients have been studied. Twenty-nine patients (a main group) received, along with basic therapy, a physiotherapeutic treatment (transcranial dynamic magnetic therapy) and 25 patients (a control group) received only basic therapy. The comparison of the efficacy of treatment in patients of the main and control groups revealed the benefits of transcranial dynamic magnetic therapy in CNS function, performance on memory and attention tests, state of autonomic nervous system and psychoemotional state of patients (the reduction of anxiety and depression).

ELISA system for detection of immune responses to FVIII: a study of 246 samples and correlation with the Bethesda assay.

Inhibitors of FVIII are usually IgG polyclonal antibodies that develop as alloimmune responses in patients with congenital haemophilia A or as autoimmune responses resulting in acquired haemophilia. Their recognition can be difficult, especially when the titre is low. Furthermore, results from a Bethesda assay often require several days as samples are referred to a specialty laboratory. The aim of this study is to assess the utility of an ELISA system for detecting immune responses to FVIII. A total of 246 plasma samples submitted from 176 individuals with immune responses to FVIII, as verified with the Bethesda assay, and samples from 50 control subjects were tested for the presence of FVIII-specific IgG using an ELISA-based assay. Paired sera from 18 of the patients were also tested by the ELISA. Of the 246 samples that were positive for a FVIII inhibitor by the Bethesda assay, 235 (95.5%) were also positive by ELISA. The regression coefficient, using Log BU was r = 0.82. The correlation data were strengthened when 27 inhibitor samples were diluted further. There was a strong correlation between ELISA results for the 18-paired serum and plasma samples (r = 0.99). There is a strong correlation between the ELISA and Bethesda methods in detecting immune responses to FVIII. The ELISA provides rapid screening that could be available well in advance of confirmation by the Bethesda assay.

[Neuroprotective effect of N-acylethanolamines in chronic morphine dependence. II. Effect on the rat brain fatty acid composition].

The effect of N-acylethanolamines mixture (NAE) with saturated and unsaturated acyl chains on the fatty acid composition of the rat brain under chronic morphine dependence was investigated. Long-term administration of NAE reduced morphine-induced decrease of mono- and polyunsaturated fatty acids in the rat brain crude lipid extract. Furthermore, NAE restored the acyl chain spectrum, especially the content of docosahexaenoic acid in essential phospholipids--phosphatidylcholine and phosphatidylethanolamine. Pharmacological activity of NAE depended on a dose.

Treatment of factor XI inhibitor using recombinant activated factor VIIa.

A 30-year-old female with severe factor XI deficiency of 0-2% acquired factor XI inhibitor following many infusions for fresh frozen plasma (FFP) for surgical procedures starting at 4 years of age. Seven months before this inhibitor was diagnosed, surgery was complicated by prolonged bleeding resistant to FFP, requiring epsilon aminocaproic acid (EACA) and surgical packing. The inhibitor was measured at 2.2 Bethesda units, 7 months since the last FFP. The inhibitor was confirmed as specific anti-XI and anti-XIa binding by patient's IgG to immobilized factor XI and factor XIa from whole plasma and purified IgG. For repair of a painful anterior cruciate ligament (ACL) defect she was given recombinant factor VIIa (rVIIa) at 90 mug kg(-1), starting one-half hour preoperatively and continued every 2 h for 8 h when haemostasis was complete. Thereafter the rVIIa was given every 3 h for two doses, and then every 4 h for four doses at which time she was discharged on EACA which was continued for 6 days. There was excellent haemostasis during and following the surgery. There was no evidence of consumptive coagulopathy, with no change in the fibrinogen, platelet count, or D-D dimer; and no increase of platelet factor 4, beta-thromboglobulin, or prothrombin fragment F 1.2. The thrombin-antithrombin complex increased over baseline after 24 h. There was no postoperative deep vein thrombosis or pulmonary embolus. In this patient with a factor XI inhibitor, the recombinant factor VIIa was effective and safe, ensuring adequate haemostasis with no thrombotic complications. This product which was designed for patients with inhibitors to factor VIII or factor IX, and factor VII deficiency, has now been given successfully to four patients with factor XI inhibitors.

Incorporation of labelled N-acylethanolamine (NAE) into rat brain regions in vivo and adaptive properties of saturated NAE under x-ray irradiation.

Regional distribution of exogenous N-palmitoylethanolamine in the rat brain was investigated in the study. Possible protective and adaptive effect of N-stearoylethanolamine under 2 Gy whole-body X-irradiation and changes of brain lipid composition were also studied. It was found that after per os administration to rats N-([9,10-3H]-palmitoyl)-ethanolamine was primarily accumulated in hypothalamus, pituitary and adrenal glands and the label amount in brain was 0.95% of the oral dose. Quantities of palmitic acid in total brain phospholipids and plasmalogen form of phosphatidylcholine were increased; free cholesterol and diacyl form of phosphatidylcholine were decreased in 2 weeks after irradiation. 11-OH-corticosteroid level in the blood of exposed rats was decreased in comparison with control animals. N-stearoylethanolamine pre-treatment prevented from increasing the plasmalogen form of phosphatidylcholine and decreasing its diacyl form and restored 11-OH-corticosteroid level in the blood of irradiated rats. Recovering of brain free cholesterol level was observed when N-stearoylethanolamine was post-treated. So, the accumulation of N-([9,10-3H]-palmitoyl)ethanolamine in brain indicates its penetration through blood-brain barrier and suggests the possible role of saturated N-acylethanolamines in brain functioning, particularly, in stress response regulation of the organism by hypothalamus-pituitary-adrenal system. N-stearoylethanolamine treatment of irradiated rats causes protective effect concerning the of irradiation induced changes in the brain lipid composition and in 11-OH-corticosteroid level and modifies phospholipid fatty acid composition.

[Neuroprotective effect of N-acylethanolamines in chronic morphine dependence. I. Rat brain phospholipids as a target of their action]. / Neiroprotektornyi efekt N-atsyletanolaminiv za khronichnoï morfinnoï zalezhnosti. I. Fosfolipidy holovnoho mozku shchuriv iak mishen' dlia ïkhn'oï diï.

The influence of saturated and unsaturated N-acylethanolamines (NAEs) mixture on the rat brain lipid composition under the chronic morphine dependence was studied. It was shown that the long-term administration of NAE to rats with experimental morphine dependence restored the morphine-induced alterations of the brain phospholipid composition. This effect can probably be explained by a fatty acyl transfer from NAE to sn-1 position of some brain glycerophospholipids. Another reason of NAE beneficial effect could be due to its antioxidative property, thus providing the remodelling of phospholipid composition. The restoration of the brain essential phospholipids is associated with the decline in morphine consumption in rats with experimental morphine dependence. The mechanism of this phenomenon requires further investigations.

[Revascularization of the lower limbs for ischemic diabetic foot with pyonecrotic tissue lesions]. / Revaskuliarizatsii nizhnikh konechnostei pri ishemicheskoi forme diabeticheskoi stopy s gnoino-nekroticheskimi porazheniiami tkanei.

This paper analyzes the results of the treatment of 213 patients with ischemic diabetic foot marked by pyonecrotic tissue lesions. On examination of the patients the authors were governed by the clinical findings as well as by the data supplied by the research methods such as ultrasound Doppler, percutaneous oxymetry, contrast angiography and laser flowmetry. Altogether 89 patients underwent revascularisation of the lower limbs by means of restoring arterial circulation; 72 patients were provided lumbar sympathectomy. The indications were elaborated for use of one or another revascularization technique. It has been established that of the 161 patients provided limb revascularization, the satisfactory results with limb salvage were obtained in 132 (81.9%) patients; high amputations were performed in 22 (13.6%) cases; 7 (4.3%) patients did not improve; after operation no lethal outcomes were recorded. Of the 52 patients who did not undergo lower limb revascularization, the beneficial results were obtained in 37 (71.1%), high amputations were performed in 15 (28.9%) patients. The conclusion is drawn that limb revascularization allows to minimize the number of high amputations more than two fold.

[Effect of N-stearoylethanolamine and ionizing radiation on lipid components of the liver and heart microsomes in rats]. / Vplyv N-stearoïletanolaminu na lipidni komponenty mikrosom pechinky ta sertsia za diï na shchuriv ionizuiuchoho vyprominiuvannia.

The influence of irradiation and NSE on the microsomal lipid composition of the rat liver and heart was studied. It was shown, that radiation treatment in a dose of 2 Gy had not a significant affect on the heart phospholipid composition, whereas in the liver the amounts of the phosphatidylethnolamine and phosphatidylinositol were increased and the amounts of the phosphatidylcholine and sphyngomieline were decreased. NSE did not impact on these characteristics. The alterations of the plasmalogen/diacyl forms ratio of the PC and PE also took place only in the liver microsome. The analysis of the fatty acids esterified to phospholipids showed similar situation: the fatty acids of the heart microsome less were changed than those of the liver microsome undergo irradiation. The amount of arachidonic acid rise after the adding of NSE to rats. Investigation of the important component of biological membranes--cholesterol and its esters also showed that the liver tissue is more vulnerable to irradiation than the heart. NSE led to insignificant increase of the not esterified cholesterol in the liver. As a result of the present work we may conclude that the liver microsome is more vulnerable than the heart under X-ray radiation and NSE has protective effect in these conditions.