Российский экспертный совет по применению инновационного препарата анаболического действия Форстео®(терипаратид) в лечении тяжелого остеопороза

The meeting of the Russian Council of Experts for the use of the novel anabolic agent Forsteo®(teriparatide) to treat osteoporosis (OP) was held in Moscow on June 29, 2013. The meeting was attended by leading Russian OP specialists, including the members of the Russian Osteoporosis Association and its Presidium.  The participants of the Council of Experts noted the great social importance of severe OP, which was associated primarily with its consequences, such as fractures causing an increase in disability and mortality rates in elderly people, and discussed the possibilities and benefits of the new approach to treating OP with teriparatide, the first drug permitting the formation of new bone tissue. The experts have recommended teriparatide for use within the registered indications in the following groups of patients: those who have severe OP (≥1 vertebral fractures, hip fracture of vertebral bodies or a fracture of the proximal femur, multiple recurrent fractures of skeletal bones) as first-line therapy; those who had ineffective previous antiosteoporotic therapy (new fractures occurring during the treatment and/or a continuing decline in bone mineral density), those who are intolerant to other medications for OP, or who have contraindications to their use.29 июня 2013 г. в Москве состоялось заседание экспертного совета, посвященного применению нового препарата анаболического действия Форстео®(терипаратид) в лечении остеопороза (ОП). В заседании приняли участие ведущие российские специалисты в области ОП, в том числе члены Российской ассоциации по остеопорозу (РАОП) и ее президиума. Участники экспертного совета отметили огромное социальное значение проблемы тяжелого ОП, что связано в первую очередь с его последствиями – переломами, обусловливающими рост инвалидности и смертности лиц пожилого возраста, обсудили возможности и преимущества нового подхода в лечении ОП с применением терипаратида – первого препарата, способствующего формированию новой костной ткани. Эксперты рекомендовали применение терипаратида в рамках зарегистрированных показаний у пациентов следующих групп: у пациентов с тяжелым ОП (≥1 переломов тел позвонков или перелом проксимального отдела бедра, многочисленные повторные переломы костей скелета) в качестве терапии первой линии; у пациентов с неэффективностью предшествующей антиостеопоротической терапии (новые переломы, возникшие на фоне лечения, и/или продолжающееся снижение МПК); у пациентов с непереносимостью других препаратов для лечения ОП или при наличии противопоказанийдля их назначения

A case of atypical femur fracture during long-term treatment with bisphosphonates in patient with postmenopausal osteoporosis

Bisphosphonates is a first-line therapy for treatment of osteoporosis. In the last decade, the number of atypical femur fracture (AFF) cases during long-term treatment with bisphosphonates has increased. The aim of this article was to analyze the literature data on this problem, to define the diagnostic criteria of AFF and to present the case of AFF in the patient who received treatment with alendronate for 3.5 years. A 78-year-old woman, receiving oral bisphosphonate for severe postmenopausal osteoporosis for 3.5 years, suddenly started feeling pain in her right thigh while walking. Three months later, she had got a fracture in middle third of the right femur after falling from her standing height. According to instrumental diagnostics, this fracture had all criteria of AFF. Blocking intramedullary osteosynthesis with shafts was performed. A retrospective analysis of soft tissue magnetic resonance imaging in the area of right thigh, done before the fracture, showed the presence of undiagnosed incomplete right femur fracture in the middle third, which subsequently led to a complete fracture. Presented clinical case demonstrates the complexity of AFF diagnostics. The purpose of the publication is to draw attention of medical specialists to the issue of this rare side effect of bisphosphonate treatment

Function of the ribosomal E-site: a mutagenesis study

Ribosomes synthesize proteins according to the information encoded in mRNA. During this process, both the incoming amino acid and the nascent peptide are bound to tRNA molecules. Three binding sites for tRNA in the ribosome are known: the A-site for aminoacyl-tRNA, the P-site for peptidyl-tRNA and the E-site for the deacylated tRNA leaving the ribosome. Here, we present a study of Escherichia coli ribosomes with the E-site binding destabilized by mutation C2394G of the 23S rRNA. Expression of the mutant 23S rRNA in vivo caused increased frameshifting and stop codon readthrough. The progression of these ribosomes through the ribosomal elongation cycle in vitro reveals ejection of deacylated tRNA during the translocation step or shortly after. E-site compromised ribosomes can undergo translocation, although in some cases it is less efficient and results in a frameshift. The mutation affects formation of the P/E hybrid site and leads to a loss of stimulation of the multiple turnover GTPase activity of EF-G by deacylated tRNA bound to the ribosome

Long-term treatment options for postmenopausal osteoporosis: results of recent clinical studies of Denosumab

Modern medications for osteoporosis (bisphosphonates, denosumab, teriparatide) are well-tolerated drugs, which can significantly lower vertebral and non-vertebral fracture risk according to prospective and observational studies in up to 10-year period. Certain drugs (denosumab, teriparatide) are active only during the treatment period and do not prevent bone loss and fracture risk after discontinuation, while such protective effect is observed in bisphosphonates. Despite impressive success of continuous 10-year denosumab treatament of severe osteoporosis, some of the recently published data suggest that vertebral fracture incidence is increased after treatment discontinuation, along with multiple vertebral fracture incidence, especially in patients with previous fractures. Issues of osteoporosis treatment duration, sequential use of osteoporosis drugs and criteria for treatment discontinuation are now in focus of attention. European Medicines Agency (EMA) and European Calcified Tissue Society (ECTS) considered these issues in 2017. ЕМА considered fractures after denosumab discontinuation as a natural disease course and did not recommend any changes in product instruction. The main conclusion of ECTS is that the possibility of multiple fractures development after denosumab discontinuation exists, however, there is still not enough firm evidence, as well as effective countermeasures. Clinicians and patients should be aware of potential risk. Both EMA and ECTS suggest considering denosumab treatment or discontinuation after 5-year treatment period or possibly replacing with bisphosphonates. Recent data suggest that prolonged osteoporosis treatment can be done in accordance with the concept of treatment until target goal (for example, achievement of femoral T-score -2.0SD and higher). In our review, we focus on recent data concerning the issues stated above. This topic was also discussed on Russian Osteoporosis Association (ROA) expert meeting in Saint Petersburg on 24 may 2018, chaired by ROA president, professor Olga Lesnyak and Columbia University professor, J.P. Bilezikian. As a result, an Expert Council resolution was written and introduced in the article

Long-term results of microvascular decompression with video endoscopy in the treatment of patients with atypical trigeminal neuralgia

Background: The incidence of atypical trigeminal neuralgia (aNTN) varies from 1 to 7 per 100,000 population per year. The main cause of its development is compression of the trigeminal nerve (TN) root by a vein and/or artery in the cerebellar cistern. To date, the final tactics of treatment for patients with aNTN has not been specified. The effectiveness of conservative methods of therapy does not exceed 50%. The aim of this study was to evaluate the results of microvascular decompression using video endoscopy in the treatment of patients with atypical trigeminal neuralgia. Methods: In the period from 2014 to 2021, 34 patients with aNTN were operated on, of which 18 (53%) patients had neuropathic pain (more than 4 points on the DN4 scale), and 15 (44%) patients had transformation of classical trigeminal neuralgia into atypical neuralgia. The conservative therapy (carbamazepine, gabapentin, pregabalin), administered to all the patients in the preoperative period, was not accompanied by a significant relief of pain syndrome. The maximum intensity of pain upon admission to the hospital was, according to the visual analog scale (VAS), 10 points, according to the BNI (Barrow Neurological Institute) Pain Intensity Scale V (severe, persistent pain). All the patients underwent microvascular decompression of the trigeminal nerve root with the use of Teflon; in 12 (35%) patients, in addition to microscopy, video endoscopy was used. The average follow-up period after the surgery was 3.41.7 years (from 1 to 5 years). Results: In all (100%) patients, the pain was completely eliminated (BNI I) after the surgery. A total five-year excellent and good outcome of the disease on the J. Miller and BNI scale (I -II) was noted in 80% (n=27) of patients with aNTN. The risk of pain recurrence after microvascular decompression was 14% (n=3) in the first three years, and 34% (n=4) after 5 years. The use of video endoscopy made it possible to identify the blood vessels compressing the root of the trigeminal nerve with a minimal displacement of the cerebellum and cranial nerves when visualizing the neurovascular conflict. Conclusion: The microvascular decompression method with video endoscopy is effective in the treatment of patients with aNTN

The Russian Council of Experts for Use of the Innovative Anabolic Agent Forsteo®(Teriparatide) in the Treatment of Severe Osteoporosis

The meeting of the Russian Council of Experts for the use of the novel anabolic agent Forsteo®(teriparatide) to treat osteoporosis (OP) was held in Moscow on June 29, 2013. The meeting was attended by leading Russian OP specialists, including the members of the Russian Osteoporosis Association and its Presidium.  The participants of the Council of Experts noted the great social importance of severe OP, which was associated primarily with its consequences, such as fractures causing an increase in disability and mortality rates in elderly people, and discussed the possibilities and benefits of the new approach to treating OP with teriparatide, the first drug permitting the formation of new bone tissue. The experts have recommended teriparatide for use within the registered indications in the following groups of patients: those who have severe OP (≥1 vertebral fractures, hip fracture of vertebral bodies or a fracture of the proximal femur, multiple recurrent fractures of skeletal bones) as first-line therapy; those who had ineffective previous antiosteoporotic therapy (new fractures occurring during the treatment and/or a continuing decline in bone mineral density), those who are intolerant to other medications for OP, or who have contraindications to their use

ANALYSIS OF SWATH CONFIGURATION IN PICKING-UP ZONE DEPENDING ON PICKER KINEMATIC PERFORMANCE

The swath model in the form of the catenary curve is described . The dependence of the swath configuration on the technological process of t he belt conveyer picker is analyzed

STUDY ON INTERACTION NATURE OF CANVAS CONVEYER PICK-UP FINGERS WITH ROLL IN PICKUP ZONE

For the purpose of revealing the causes of grain loss after the canvas conveyer pick-up with roll, the interaction nature of its fingers in the pickup zone is determined. It is observed that the basic losses after the picker in the pickup zone of the roll are caused by its deformed fingers. The dependence of the grain loss on the deformation of picker’s fingers has been established