Use of cryoprotectors and antioxidants in sturgeon semen cryopreservation.

In recent years, the possibility of increasing the low cryoresistance of sturgeon sperm by using antioxidants in basic cryoprotective media has been studied. The goal of this work was to review the current literature on impact of the cryoprotectors, well-known antioxidants and new multifunctional compounds on the activity indicators and fertilizing capability of sperm, as well as on biomarkers of cryostress. A special attention is given to the radical scavenging activity of studied compounds in relation to the highly reactive oxygen species, to prevent and negate oxidative stress damage of sturgeon sperm. Also, new trends for future research through the application of novel polyfunctional antioxidants to sturgeon sperm cryopreservation were indicated.

Cryoprotective activity of phosphorus-containing phenol.

The antioxidant and cryoprotective efficiencies of a 3,5-di-tert-butyl-4-hydroxyphenyl)methylenediphosphonic acid (MDPA) differ significantly for sperm cells of various species of sturgeon fish (Russian sturgeon, beluga and Stellate sturgeon). The ability of phosphorus-containing phenol MDPA to decrease the level of lipid peroxidation of sperm, beneficial effect on the activity indicators of the sperm of native sturgeon and of the defrosted one after deep freezing as well as on the fertility of sperm cells was shown.

[Migraine burden and clinical inertia: what can we do?] / Migren' i klinicheskaia inertsiia: chto my mozhem sdelat'?

AIM: To study the compliance of neurologists and headache specialists to chronic headache and chronic migraine (CM) diagnosis and treatment guidelines. MATERIAL AND METHODS: The survey included 634 neurologists from all regions of the Russian Federation. Mean age of respondents was 40.7±8.5 years, mean years of experience 14.2±7.8 years. RESULTS: Most doctors work in outpatient or hospital settings (49% and 24%, respectively), 7% were headache specialists. Tension-type headache (TTH) was diagnosed in 30% and CM in 17% of patients while 44% of patients were presumed to have a mixed headache disorder (TTH+CM). Only 10% of physicians do not use instrumental diagnostic methods in chronic headache. This study has shown sufficient attention to comorbid conditions and frequent prescription of headache preventative treatment. Botox prescription data is equivocal: 35% of physicians recommend such treatment, 27% do not, while other doctors prescribe it for off-label indications. CONCLUSION: To overcome clinical inertia, further education in chronic headaches and their optimal treatment is warranted.

[Migraine in women: clinical and therapeutical aspects]. / Migren' u zhenshchin: klinicheskie i terapevticheskie aspekty.

Migraine is one of the most common neurological disorders, affecting women. Physiological changes in the hormonal status can modulate the functional status of pain and analgesic systems of the brain and, by involving different pathophysiological mechanisms, change the course of migraine. In addition to an analysis of epidemiological data, the review provides current views on the clinical features of the disease in women population at different periods of life, particular attention was focused on menstrual migraine. It has certain features, such as acute and long attacks and treatment difficulties. One of main issues is the use of oral contraceptives in women with migraine according to the ratio of potential benefit to cardiovascular risk. The problems of treatment headaches in pregnant and breastfeeding women are also considered. An influence of migraine on the course and outcome of pregnancy was shown. The authors analysed the results of the studies on the course of migraine during perimenopause and postmenopause and recommendations for women with migraine attacks and climacteric syndrome. The data presented in the review are useful for clinicians, because this information represents new views on pathogenetic mechanisms, clinical features and treatment of migraine in women.

Aids to management of headache disorders in primary care (2nd edition) : on behalf of the European Headache Federation and Lifting The Burden: the Global Campaign against Headache.

The Aids to Management are a product of the Global Campaign against Headache, a worldwide programme of action conducted in official relations with the World Health Organization. Developed in partnership with the European Headache Federation, they update the first edition published 11 years ago.The common headache disorders (migraine, tension-type headache and medication-overuse headache) are major causes of ill health. They should be managed in primary care, firstly because their management is generally not difficult, and secondly because they are so common. These Aids to Management, with the European principles of management of headache disorders in primary care as the core of their content, combine educational materials with practical management aids. They are supplemented by translation protocols, to ensure that translations are unchanged in meaning from the English-language originals.The Aids to Management may be individually downloaded and, as is the case for all products of the Global Campaign against Headache, are available without restriction for non-commercial use.

[Real-world migraine burden: clinical and economic aspects]. / Bremia migreni v real'noi klinicheskoi praktike: klinicheskie i ékonomicheskie aspekty.

AIM: To evaluate the rationale for different approaches to preventive chronic migraine (CM) treatment by comparing clinical outcomes and financial burden of the disease in the real-world practice. MATERIAL AND METHODS: Sixty-six patients with CM were enrolled at the Alexander Vein Headache Clinic (60 women and 6 men, aged 28-51). All patients were divided into 3 groups: group 1 (n=22) received oral preventative treatment with topiramate, up to 100 mg daily, for three months; group 2 (n=20) received 12 acupuncture sessions (3 sessions a week); group 3 (n=24) received 155-195 units of botulinum toxin type A (botox, BTA). The follow-up period in all groups was 3 months. Efficacy was evaluated by clinical examination, the Headache Impact Test (HIT-6) and questionnaires to assess subjective patient satisfaction and treatment tolerability. RESULTS: BTA demonstrated the highest efficacy in this study. Compared to the oral preventative treatment and acupuncture, BTA reduced the frequency of headache faster and more significantly facilitating CM transformation into episodic migraine (headache frequency was 16.1±0.1; 18.0±0.02; and 13.9±0.3 in groups 1, 2 and 3, respectively, after one month of treatment). BTA also improved the quality of life faster and more significantly and was better tolerated (good - 51%, 75% and 85% in groups 1, 2 and 3, respectively; satisfactory - 35%, 25% and 15% in groups 1, 2 and 3, respectively; bad 14% in the oral prevention group). In the BTA group, the majority of patients demonstrated earlier treatment satisfaction. Despite higher (compared to topiramate) direct costs in the BTA group (RUB 29 931.51 and RUB 32 085.87, respectively), the predicted cost of a headache-free day was the smallest and totaled RUB 652.15 (compared to RUB 692.86 and RUB 1017.60 in the topiramate and acupuncture groups, respectively). CONCLUSION: The data on the efficacy and costs of different CM prevention strategies would facilitate optimal treatment choice for neurologists and patients.

[Ways of optimizing the management of patients with migraine in Russia (resolution of the council of experts)]. / Puti optimizatsii vedeniia patsientov s migren'iu v Rossii (rezoliutsiia soveta ékspertov).

Migraine is the third most common disease in the world. The overall prevalence of migraine in the Russian Federation is estimated at 20% with an estimated global prevalence of 14.7%. Migraine affects mostly people of working age and has a significant negative impact on the quality of life, the level of adaptation, ability to work, social functioning. Migraine represents a significant social and economic burden for patients and society as a whole. A team of national experts on migraine offers a program to prioritize quality of management of patients with headache.

The antioxidant 2,6-di-tert-butylphenol moiety attenuates the pro-oxidant properties of the auranofin analogue.

Metal-based drugs are gaining momentum as a rapidly developing area of medicinal inorganic chemistry. Among gold pharmaceuticals, auranofin is a well known antirheumatic drug. The efficacy of gold-organic complexes largely depends on their pro-oxidant properties since auranofin targets the redox enzyme thioredoxin reductase (TrxR). However, an uncontrollable oxygen burst may be harmful for healthy cells; therefore, the search for chemical modifications to attenuate oxidation-related general toxicity of gold containing anti-inflammatory drugs is justified. In this study, we demonstrate that the incorporation of a specific antioxidant phenol fragment can counterbalance the pro-oxidative potential of the Au containing complex molecule. The electrochemical studies of AuPPh3SR (1, R= 3,5-di-tert-butyl-4-hydroxyphenyl) and its precursors AuPPh3Cl (2) and RSH (3) showed that complex 1 and phenol 3 efficiently scavenged the radicals (as detected by cyclic voltammetry) whereas 2 had no effect. Compound 1 inhibited TrxR in vitro with IC50 0.57 ± 0.15 µM, a value one order of magnitude bigger than the potency reported for auranofin. Compound 1 (5 mg kg-1 daily gavage for 14 days) caused a decrease in ex vivo spontaneous and ascorbate-induced lipid peroxidation in the homogenates of rat lung, heart muscle, spleen, liver, kidneys, testicles and brain as assessed by the thiobarbituric acid reactive substances. Importantly, in animals fed with 1, no discernible general toxicity was registered suggesting that this compound is well tolerated. Our results provide evidence for an efficient synthetic route to obtain gold containing anti-inflammatory drug candidates with balanced pro/anti-oxidative properties.

[Temporomandibular disorder as the most prevalent cause of facial pain: current evidence]. / Disfunktsiia visochno-nizhnecheliustnogo sustava kak naibolee chastaia prichina boli v litse: sovremennoe sostoianie problemy.

Orofacial pain is a comprehensive and multi-faceted syndrome. After dental causes have been excluded, neurologists are challenged to diagnose the cause of pain. The paper gives a detailed review of one of the most common causes of facial pain - temporomandibular disorder (TMD). Current DC/TMD diagnostic criteria, patient examination protocols and a new perspective on TMD pathophysiology based on the recent neurological studies are presented. The article also discusses modern approaches to TMD management.

[Diagnosis and treatment of migraine: Recommendations of the Russian experts]. / Diagnostika i lechenie migreni: rekomendatsii rossiiskikh ékspertov.

These recommendations on the diagnosis and treatment of migraine were elaborated by Russian headache experts in accordance with the evidence-based practice. Together with the latest classification, diagnostic principles and criteria of different clinical sub-forms the consensus contains basic data on migraine epidemiology, pathophysiological mechanisms, differential diagnosis and most effective and evidence based approaches to pharmacological and non-pharmacological management of migraine patients.

[Diagnosis of refractory forms of chronic primary headache]. / Diagnostika refrakternykh form khronicheskoi pervichnoi golovnoi boli.

A number of patients with primary headaches remain insensitive or refractory to treatment despite correctly selected drugs, adequate therapeutic dose and duration of therapy. The importance of refractory problem is determined by the fact that patients are completely maladjusted, disabled, and keeping these patients is very difficult even for seasoned professionals. Determination of the correct tactics and success of the treatment depends, in the first place, on the correct diagnosis. This article discusses the diagnostic criteria for the most important forms such as refractory chronic migraine or refractory chronic cluster headache presented by experts of the European Headache Federation in two separate Consensus.

[The optimization of management of chronic daily headache patients]. / Optimizatsiya vedeniya patsientov s khronicheskoi ezhednevnoi golovnoi bol'yu.

AIM: To optimize the management of chronic daily headache (CDH) using cognitive-behavioral therapy (CBT). MATERIAL AND METHODS: The study included 90 patients (76 women and 14 men), aged from 23 to 78 years (mean age 46.71±11.99) with primary forms of CDH. The patients were followed-up by the neurologist during 12 months, psychological characteristics were studied together with the psychiatrist. Patients received combined treatment, including optimized pharmacotherapy, educational program, relaxation training, CBT and exercise therapy. RESULTS: The diagnosis of CDH has not been previously established in 86.7% of the patients. All patients received unnecessary additional diagnostic examinations, ineffective treatment (86.7%) that resulted in the formation of wrong conceptions about their state (90%). Three months after combined treatment, a significant positive effect has been achieved in 62.2% of the patients and after 12 months in 72.2%. CONCLUSION: The combined treatment program that included CBT can relatively rapidly help patients with CDH and exerts a stable positive effect during 12 months of the follow-up.

Application of new phenolic antioxidants for cryopreservation of sturgeon sperm.

Heterocyclic derivatives of butylated hydroxytoluene (BHT) were studied as cryoprotectants of the basic media for cryopreservation of the Russian sturgeon sperm. Rates of lipid peroxidation of sturgeon sperm before and after cryopreservation were reduced in the presence of the studied compounds, exceeding the effects of BHT and water-soluble analogue of vitamin E, trolox. The most efficient antioxidant has the effective concentration of 0.1 mM. Novel antioxidant agents as cryomedium supplements not only reduced the level of lipid peroxidation, but also enhanced the translational motility of the sperm of the Russian sturgeon after defrosting.

European Headache Federation consensus on technical investigation for primary headache disorders.

The diagnosis of primary headache disorders is clinical and based on the diagnostic criteria of the International Headache Society (ICHD-3-beta). However several brain conditions may mimic primary headache disorders and laboratory investigation may be needed. This necessity occurs when the treating physician doubts for the primary origin of headache. Features that represent a warning for a possible underlying disorder causing the headache are new onset headache, change in previously stable headache pattern, headache that abruptly reaches the peak level, headache that changes with posture, headache awakening the patient, or precipitated by physical activity or Valsalva manoeuvre, first onset of headache ≥50 years of age, neurological symptoms or signs, trauma, fever, seizures, history of malignancy, history of HIV or active infections, and prior history of stroke or intracranial bleeding. All national headache societies and the European Headache Alliance invited to review and comment the consensus before the final draft. The consensus recommends brain MRI for the case of migraine with aura that persists on one side or in brainstem aura. Persistent aura without infarction and migrainous infarction require brain MRI, MRA and MRV. Brain MRI with detailed study of the pituitary area and cavernous sinus, is recommended for all TACs. For primary cough headache, exercise headache, headache associated with sexual activity, thunderclap headache and hypnic headache apart from brain MRI additional tests may be required. Because there is little and no good evidence the committee constructed a consensus based on the opinion of experts, and should be treated as imperfect.

Cryoprotective effect of phosphorous-containing phenolic anti-oxidant for the cryopreservation of beluga sperm.

A cryoprotective effect of an addition of a new synthetic antioxidant - a representative of phosphorus-containing sterically hindered phenols is presented. The efficiency of the compound was shown to exceed the effect of lipid-soluble antioxidants butylated hydroxytoluene (BHT) and trolox in the conditions of cryopreservation of beluga sperm in the presence of the modified Stein's medium. It was shown that the level of carbonyl oxidation by-products, which can react with thiobarbituric acid (TBARS), in beluga sperm was inversely proportional to the motility time of sperm cells. The fertility of beluga sperm increased 2 times upon the addition of phosphorus-containing phenol to a modified Stein's medium. The prospects of the new antioxidant application to improve cryoresistance of beluga sperm in the conditions of cryopreservation for its efficient protection from the peroxidation processes are discussed.

Synthesis, antiradical activity and in vitro cytotoxicity of novel organotin complexes based on 2,6-di-tert-butyl-4-mercaptophenol.

A series of organotin complexes with Sn-S bonds of formulae Me2Sn(SR)2 (1); Et2Sn(SR)2 (2); (n-Bu)2Sn(SR)2 (3); Ph2Sn(SR)2 (4); R2Sn(SR)2 (5); Me3SnSR (6); Ph3SnSR (7) (R = 3,5-di-tert-butyl-4-hydroxyphenyl) were synthesized and characterized by elemental analysis, (1)H, (13)C NMR, and IR. The crystal structures of compounds 1, 4, 5, and 7 were determined by X-ray diffraction analysis. The tetrahedral geometry around the Sn center in the monocrystals of 1, 4, 5, and 7 was confirmed by X-ray crystallography. The high radical scavenging activity of the complexes was confirmed spectrophotometrically in a DPPH-test. The binding affinity of 1-7 and the starting R2SnCl2 (8) towards tubulin through their interaction with SH groups of proteins was studied. It was found that the hindered organotin complexes could interact with the colchicine site of tubulin, which makes them promising antimitotic drugs. Compounds 1-8 were tested for their in vitro cytotoxicity against human breast (MCF-7) and human cervix (HeLa) adenocarcinoma cells. Complexes 1-8 were also tested against normal human fetal lung fibroblast cells (MRC-5). Complexes 2-4 and 8 exhibit significantly lower cytostatic activity against the normal MRC-5 cell line compared to the tumor cell lines MCF-7 and HeLa used. A high activity against both cell lines 250 nM (MCF-7) and 160 nM (HeLa) was determined for the triphenyltin complex 7 while the introduction of hindered phenol groups decreases the cytotoxicity of the complexes against normal cells.

Headache-attributed burden and its impact on productivity and quality of life in Russia: structured healthcare for headache is urgently needed.

BACKGROUND AND PURPOSE: The study evaluated headache-attributed burden and its impact on productivity and quality of life (QoL) in Russia. Its purpose was to support recommendations for change. METHODS: A countrywide population-based random sample of 2725 biologically unrelated adults (aged 18-65 years) in 35 cities and nine rural areas of Russia were interviewed in a door-to-door survey. The structured questionnaire enquired into symptom burden, functional disability, lost productive time and QoL (applying the WHOQoL-8 question set), as well as willingness to pay (WTP) for adequate headache treatment, if it were available. RESULTS: Mean lost paid-work days due to headache in the previous 3 months were 1.9 ± 4.2, and mean lost household work days were 3.4 ± 5.7. The estimated annual indirect cost of primary headache disorders was USD 22.8 billion, accounting for 1.75% of gross domestic product. QoL was reduced by all types of primary headaches. According to WHOQoL-8, it was significantly lower in those with headache on ≥15 days/month than in those with episodic headache (24.7 ± 4.6 vs. 28.1 ± 5.0; P < 0.05) and lower in those with migraine than in those with tension-type headache (TTH) (27.1 ± 4.9 vs. 28.8 ± 5.0; P < 0.05). Average WTP for adequate headache treatment was RUB 455 ± 494 per month (median RUB 300), a sum sufficient in most cases, and correlated with illness severity (higher for headache on ≥15 days/month than for migraine, and for migraine than for TTH). CONCLUSIONS: Headache is common, burdensome and costly in Russia and, manifestly, poorly mitigated by existing healthcare. Structured healthcare services for headache need to be urgently put in place.

[The use of endoscopic techniques in acute strangulated adhesive small bowel obstruction, proceeded under the guise of acute pancreatitis].

We report an unusual case of AASBO presenting like postcholecystectomy syndrome and acute pancreatitis. Diagnostic and therapeutic scope of laparoscopic interventions and endoscopic nasointestinal decompression in AASBO management is demonstrated.

[Evaluation of the interferon system and major cytokines in patients with bronchial asthma].

AIM: Study of the interferon system (IFN) and the production of major cytokines in patients with bronchial asthma of various course severity. MATERIALS AND METHODS: 204 patients with atopic bronchial asthma (BA); 32 patients with allergic rhinitis (AR) and 93 mostly healthy volunteers were examined. Blood cells of patients with BA of various course severity were studied by biological method in HEP cell culture for the ability to produce IFN. Levels of cytokines in the blood sera were determined by EIA method with the corresponding commercial test systems: IL-4, IL-10, IL-13 and IFN-gamma according to user manual. RESULTS: Disorders in the ability ofleukocytes to produce IFN-alpha and IFN-gamma were detected in patients with bronchial asthma and allergic rhinitis. Misbalance in the production of pro- and anti-inflammatory cytokines depending on the level of disease severity was noted. The highest serum IFN-gamma was noticed in patients with mild persistence BA course, that is most probably determined by higher frequency of ARVI in this group of patients. Maximum level of IL-10 was detected in mild BA form and was nearly undetected in the severe course of the infection, which is characterized by higher content of IL-4 in blood sera. CONCLUSION: Increase of course severity of chronic (allergic) inflammation in bronchial tissue and higher frequency of ARVI among patients with persistent BA of medium and severe course is characterized by a lack of interferon link of the immune system and disorders of regulatory mechanisms, that is expressed by a change in the ratio of IFN-gamma/IL-4 parameters and decrease of IL-10 content in blood sera.

The prevalence of primary headache disorders in Russia: a countrywide survey.

OBJECTIVE: To estimate the 1-year prevalences of primary headache disorders and identify their principal risk factors in the general population of Russia. METHODS: A countrywide population-based random sample of 2725 biologically unrelated adults in 35 cities and nine rural areas were interviewed in a door-to-door survey using a previously validated diagnostic questionnaire. RESULTS: Of the 2725 eligible adults contacted, 2025 (74.3%) responded (females 52.6%, mean age 39.5 ± 13.4 years). Of these, 1273 (62.9%) reported headache 'not related to flu, hangover, cold, head injury' occurring at least once in the previous year. The gender- and age-standardized 1-year prevalence of migraine was 20.8%. Female gender (odds ratio (OR) = 3.8; 95% confidence interval (CI) 2.8-5.1) and obesity (OR = 1.5; 1.1-2.1) were positively associated with this type of headache. The gender- and age-standardized 1-year prevalence of tension-type headache (TTH) was 30.8%. TTH was more prevalent in urban than in rural areas (OR = 1.6; 1.3-2.0). Headache on ≥15 days/month was reported by 213 (10.5%) respondents (gender- and age-standardized prevalence 10.4%), and associated with low socioeconomic status (OR = 3.4; 2.4-4.9), obesity (OR = 3.0; 2.1-4.3), female gender (OR = 2.9; 2.1-4.1) and age over 40 years (OR = 2.6; 1.9-3.6). The majority of these respondents (68.1%) overused acute headache medications. CONCLUSION: The study demonstrated a high prevalence of migraine and a very high prevalence of headache on ≥15 days/month, and revealed unmet health-care needs of people with headache in Russia.