Мигрень представляет собой форму первичной головной боли, от которой страдает не менее 10% населения планеты. Кроме рекомендаций по модификации образа жизни пациента, менеджмент мигрени подразумевает купирование уже возникшего приступа и/или профилактику его возникновения. В абортивном лечении этой цефалгии могут использоваться фармакологические агенты как неспецифического (например, ненаркотические анальгетики), так и специфического действия. К числу последних относят, в частности, серотонинергические средства классов триптанов (селективных агонистов 5-НТ1B/1D-рецепторов), дитанов (избирательных 5-НТ1F-миметиков) и алкалоидов спорыньи (неселективных модуляторов различных подтипов 5-НТ-рецепторов). В обзоре представлены известные к настоящему времени результаты множества фундаментально-прикладных исследований препаратов указанных групп, в ходе которых были выявлены нейрональные и сосудистые составляющие их антимигренозной фармакодинамики. Значительная часть этих данных получена invivo на различных экспериментальных моделях мигрени, основанных на тригемино-васкулярной теории ее патогенеза. Другие сведения являются итогами работы ехvivo на изолированных тканях и клеточных культурах. При анализе результатов этих исследований приводятся доказательства в пользу схожих механизмов реализации антимигренозного потенциала представителей всех перечисленных фармакологических классов, у которых нейротропная активность преобладает над прямым вмешательством в сосудистый тонус. Специальное внимание уделено неоднозначным и дискуссионным вопросам в этой области, успешное решение которых является залогом дальнейшего прогресса в фармакотерапии мигрени.
Предпросмотр статьи
Идентификаторы и классификаторы
- SCI
- Биология
Из всех болевых синдромов первое место по распространенности занимает головная боль (ГБ), под которой понимается любое неприятное ощущение выше орбитомеатальной линии и/или затылочного гребня.
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Обзор посвящен применению методов нелинейной динамики к анализу динамических изменений в паттернах физиологических ритмов мозга при возникновении нарушений, связанных с хронически повышенным артериальным давлением и с нарушением сердечного ритма по типу фибрилляции предсердий при наличии и отсутствии умеренных когнитивных нарушений. Показана возможность применения этих методов для выявления маркеров этих нарушений. Эти маркеры связаны с параметрами фазовой синхронизации между ритмическими фотостимулами и ответами мозга в виде электроэнцефалографических паттернов.
Широкое распространение заболеваний центральной нервной системы (ЦНС) требует непрерывного поиска методов и средств их фармакологической коррекции. Основные подходы экспериментального моделирования данных заболеваний включают использование грызунов, недостатками которых является стоимость проводимых исследований, сложность содержания, ухода и долгий рост организма. Использование альтернативных модельных организмов, таких как рыба зебраданио (Danio rerio, zebrafish), в трансляционной нейробиологии и медицине позволяет проводить быстрые экспериментальные работы на фоне простоты содержания и манипуляций, а также ускоренного онтогенеза. Зебраданио также чувствительны к основным классам фармакологических препаратов, что делает данную модель незаменимой для доклинических исследований широкого спектра физиологически активных веществ. Сходство нейрохимических систем, высокая физиологическая и генетическая гомология с человеком, возможность проведения исследований на личинках и взрослых особях, легкость генетических манипуляций, прозрачность эмбрионов и ряд других биологических особенностей открывают широкий спектр возможностей использования зебраданио для моделирования различных патологий ЦНС.
Сократительная функция сердца осуществляется за счет согласованного взаимодействия основных свойств миокарда – растяжимости, сократимости и расслабимости. Нарушение сократимости миокарда по каким-либо причинам создает ситуацию хронической сердечной недостаточности (ХСН). Выраженность ХСН определяется способностью кровеносной системы в определенной степени компенсировать ослабление сократимости сердца, критерием которой является величина фракции выброса. Форма ХСН с сохраненной фракцией выброса определяется как диастолическая дисфункция. Это первый этап ХСН, его отличительными особенностями являются замедленное расслабление и повышенное диастолическое давление в левом желудочке. Обзор посвящен рассмотрению структуры диастолы при 4 типах ХСН – ишемической болезни сердца при инфаркте миокарда или микроинфарктах, вызванных изопротеренолом, повреждении миокарда, индуцированном доксорубицином и сахарном диабете 1 типа. Общим признаком всех видов ХСН является повышение растяжимости миокарда и замедление расслабления. Показано, что в их основе лежит изменение свойств коннектина (титина) – саркомерного белка, соединяющего концы миозиновых нитей с границами саркомера. Его свойства определяют растяжение и расслабление миокарда, и эти изменения лежат в основе первичной компенсаторной реакции сердца на ослабление его сократимости. Также мобилизуются механизмы, увеличивающие приток к сердцу и снижающие периферическое сопротивление. Степень их мобилизации зависит от степени снижения сократимости миокарда. Наряду с этим, каждая форма ХСН имеет свою специфику, которую необходимо учитывать при выборе средств терапии.
Лимфатическая система играет определяющую роль в иммунитете, выходящую далеко за рамки простого транспорта иммунных клеток и антигенов. Эндотелиальные клетки в различных отделах этой сосудистой сети высоко специализированы для выполнения различных специфических функций. Лимфатические капилляры экспрессируют хемокины и молекулы адгезии, которые в тканях способствуют привлечению и трансмиграции иммунных клеток. Сигнальные молекулы, продуцируемые эндотелиальными клетками лимфатических капилляров при воспалении, модулируют в лимфатических узлах миграцию лимфоцитов через венулы с высоким эндотелием из крови в паренхиму лимфатических узлов. Лимфатические сосуды обеспечивают активный регулируемый транспорт иммунных клеток и антигенов в лимфатические узлы. В лимфатических узлах с их сложной структурой, организованной стромальными клетками, создаются оптимальные условия для контактов антигенпрезентирующих клеток с лимфоцитами. Различные субпопуляции лимфатических эндотелиальных клеток лимфатических узлов выполняют специфические функции в соответствии с локализацией в лимфатическом узле и способствуют как врожденному, так и приобретенному иммунному ответу посредством презентации антигена, ремоделирования лимфатического узла и регуляции входа и выхода лейкоцитов.
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- ФИО
- Николай Николаевич Федосеенков (Директор)
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