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Kan högt blodtryck bero på selenbrist?

Kan högt blodtryck bero på selenbrist?Ja, detta framgår av en ny studie publicerad i Free Radical Biology & Medicine. Det tyder alltså på att selenbrist via olika mekanismer minskar utsöndringen av natrium i njurarna, vilket leder till högt blodtryck. Studiens resultat är mycket relevant, eftersom högt blodtryck och resulterande tidig död är ett växande problem över hela världen. Samtidigt är selenbrist också ett växande problem, eftersom man tror att upp till en miljard människor lider brist på detta livsviktiga spårämne, främst på grund av selenfattiga markförhållanden som finns i stora delar av Kina, Europa och många andra platser i världen.

Epidemiologiska studier har tidigare visat ett samband mellan ett lågt seleninnehåll i kroppen och en ökad risk för att utveckla högt blodtryck. Men man har inte vetat varför. I den nya studien har ett forskarteam nu funnit att råttor som fick en diet utan selen i 16 veckor utvecklade högt blodtryck, samtidigt som de utsöndrade mindre natrium (salt).
Det är allmänt känt att natrium ”binder” vätska, och om natrium ansamlas i kroppen kan högt blodtryck uppstå. Det är också känt att kalium reglerar hur mycket natrium njurarna utsöndrar och att förhållandet mellan de två mineralerna är viktigt. Och det visar sig nu att selen också har betydelse för utsöndringen av natrium i njurarna.
I den nya studien fann forskarna att högt blodtryck hos råttor med selenbrist hänger samman med ett ökat uttryck av receptorn för angiotensin 2 typ 1 i njurarna, och effekten på blodtrycket beror på att angiotensin 2 har en sammandragande effekt på blodkärlen.
Dessutom fann forskarna att selenbrist ökar bildandet av väteperoxid (H2O2), som är en typ av fria radikaler. Väteperoxid är en naturlig biprodukt av cellernas energiomsättning, som är ganska stor i njurarna. Det är samtidigt viktigt att dessa fria radikaler neutraliseras av antioxidanter, så att det inte uppstår oxidativ stress som kan skada celler och vävnader. I detta sammanhang ingår selen i de kraftfulla antioxidanterna GPx1, som normalt sett måste neutralisera väteperoxid och andra fria radikaler.
Forskarna fann också att brist på GPx1 ökade aktiviteten av NF-kB. Det är ett proteinkomplex i de flesta celltyper som är involverat i cellernas respons på stress, fria radikaler och infektioner.
Enligt den nya studien tyder det på att selen påverkar njurarnas funktion och deras utsöndring av natrium via flera mekanismer.

  • Njurarna innehåller relativt stora mängder selen.
  • Detta beror på att selen har betydelse för energiomsättningen och andra metaboliska processer.
  • Samtidigt ingår selen i de kraftiga antioxidanterna GPx som skyddar celler och vävnad mot oxidativ stress.

Högt blodtryck är som en tickande bomb

Högt blodtryck är en av de största riskfaktorerna för blodproppar, hjärtsvikt, stroke och andra hjärt-kärlsjukdomar. Antalet patienter med högt blodtryck har fördubblats från 1990–2019, och det är en av de största dödsorsakerna. Många är också helt omedvetna om att de lider av högt blodtryck, vilket obehandlat kan jämföras med en tickande bomb.
Utvecklingen av högt blodtryck är komplex då den involverar gener, kost, miljömässiga faktorer och sjukdomar som metaboliskt syndrom och diabetes. Det är allmänt känt att för mycket salt och för många raffinerade kolhydrater hänger samman med ett högt blodtryck. Detsamma gäller brist på kalium, som vi främst får från grönsaker och frukt.
Under senare år har forskarna också lagt ökat fokus på spårämnenas betydelse, däribland selen.

Selenbrist är ett världsomspännande problem

Selen finns i inälvsmat, fisk, ägg, korn och grödor. Men jordens innehåll av selen, som återspeglas i hela näringskedjan, är avgörande för det dagliga intaget. Eftersom marken är fattig på selen i Europa, Kina och många andra platser i världen har detta bidragit till att mellan 500 miljoner och en miljard människor lider av selenbrist. Detta får enorma konsekvenser för folkhälsan.
Selen är ett spårmineral som ingår i 25 selenberoende proteiner med betydelse för en lång rad ämnesomsättningsprocesser och kroppens antioxidantförsvar. Det är sedan tidigare känt att selenbrist är kopplat till ett antal hjärt-kärlsjukdomar, som omfattar åderförkalkning, ischemisk hjärtsjukdom och hjärtsvikt. Den nya studien har nu visat att selenbrist också kan bidra till utvecklingen av högt blodtryck.

Referenser:

Lifu Lei et al. Selenium deficiency causes hypertension by increasing renal AT1 receptor expression via GPx1/H2O2/NF-κB pathway. Free Radical Biology and Medicine 2 March 2023

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  • SELECT `a`.`id`,`a`.`asset_id`,`a`.`title`,`a`.`alias`,`a`.`introtext`,`a`.`fulltext`,`a`.`state`,`a`.`catid`,`a`.`created`,`a`.`created_by`,`a`.`created_by_alias`,`a`.`modified`,`a`.`modified_by`,`a`.`checked_out`,`a`.`checked_out_time`,`a`.`publish_up`,`a`.`publish_down`,`a`.`images`,`a`.`urls`,`a`.`attribs`,`a`.`version`,`a`.`ordering`,`a`.`metakey`,`a`.`metadesc`,`a`.`access`,`a`.`hits`,`a`.`metadata`,`a`.`featured`,`a`.`language`,`fp`.`featured_up`,`fp`.`featured_down`,`c`.`title` AS `category_title`,`c`.`alias` AS `category_alias`,`c`.`access` AS `category_access`,`c`.`language` AS `category_language`,`fp`.`ordering`,`u`.`name` AS `author`,`parent`.`title` AS `parent_title`,`parent`.`id` AS `parent_id`,`parent`.`path` AS `parent_route`,`parent`.`alias` AS `parent_alias`,`parent`.`language` AS `parent_language`,ROUND(`v`.`rating_sum` / `v`.`rating_count`, 1) AS `rating`,`v`.`rating_count` AS `rating_count` FROM `has_content` AS `a` INNER JOIN `has_categories` AS `c` ON `c`.`id` = `a`.`catid` LEFT JOIN `has_content_frontpage` AS `fp` ON `fp`.`content_id` = `a`.`id` LEFT JOIN `has_users` AS `u` ON `u`.`id` = `a`.`created_by` LEFT JOIN `has_categories` AS `parent` ON `parent`.`id` = `c`.`parent_id` LEFT JOIN `has_content_rating` AS `v` ON `a`.`id` = `v`.`content_id` WHERE ( (`a`.`id` = :pk AND `c`.`published` > 0 AND `a`.`language` IN (:preparedArray1,:preparedArray2)) AND (`a`.`publish_up` IS NULL OR `a`.`publish_up` <= :publishUp)) AND (`a`.`publish_down` IS NULL OR `a`.`publish_down` >= :publishDown) AND `a`.`state` IN (:preparedArray3,:preparedArray4)455μs22.19KBParams/components/com_content/src/Model/ArticleModel.php:215Copy
  • SELECT `c`.`id`,`c`.`asset_id`,`c`.`access`,`c`.`alias`,`c`.`checked_out`,`c`.`checked_out_time`,`c`.`created_time`,`c`.`created_user_id`,`c`.`description`,`c`.`extension`,`c`.`hits`,`c`.`language`,`c`.`level`,`c`.`lft`,`c`.`metadata`,`c`.`metadesc`,`c`.`metakey`,`c`.`modified_time`,`c`.`note`,`c`.`params`,`c`.`parent_id`,`c`.`path`,`c`.`published`,`c`.`rgt`,`c`.`title`,`c`.`modified_user_id`,`c`.`version`, CASE WHEN CHAR_LENGTH(`c`.`alias`) != 0 THEN CONCAT_WS(':', `c`.`id`, `c`.`alias`) ELSE `c`.`id` END as `slug` FROM `has_categories` AS `s` INNER JOIN `has_categories` AS `c` ON (`s`.`lft` < `c`.`lft` AND `c`.`lft` < `s`.`rgt` AND `c`.`language` IN (:preparedArray3,:preparedArray4)) OR (`c`.`lft` <= `s`.`lft` AND `s`.`rgt` <= `c`.`rgt`) WHERE (`c`.`extension` = :extension OR `c`.`extension` = 'system') AND `c`.`access` IN (:preparedArray1,:preparedArray2) AND `c`.`published` = 1 AND `s`.`id` = :id ORDER BY `c`.`lft`469μs3.98KBParams/libraries/src/Categories/Categories.php:375Copy
  • SELECT `m`.`tag_id`,`t`.* FROM `has_contentitem_tag_map` AS `m` INNER JOIN `has_tags` AS `t` ON `m`.`tag_id` = `t`.`id` WHERE `m`.`type_alias` = :contentType AND `m`.`content_item_id` = :id AND `t`.`published` = 1 AND `t`.`access` IN (:preparedArray1,:preparedArray2) AND `language` IN (:preparedArray3,:preparedArray4)4.21ms4.11KBParams/libraries/src/Helper/TagsHelper.php:388Copy
  • SELECT `c`.`id`,`c`.`asset_id`,`c`.`access`,`c`.`alias`,`c`.`checked_out`,`c`.`checked_out_time`,`c`.`created_time`,`c`.`created_user_id`,`c`.`description`,`c`.`extension`,`c`.`hits`,`c`.`language`,`c`.`level`,`c`.`lft`,`c`.`metadata`,`c`.`metadesc`,`c`.`metakey`,`c`.`modified_time`,`c`.`note`,`c`.`params`,`c`.`parent_id`,`c`.`path`,`c`.`published`,`c`.`rgt`,`c`.`title`,`c`.`modified_user_id`,`c`.`version`, CASE WHEN CHAR_LENGTH(`c`.`alias`) != 0 THEN CONCAT_WS(':', `c`.`id`, `c`.`alias`) ELSE `c`.`id` END as `slug` FROM `has_categories` AS `s` INNER JOIN `has_categories` AS `c` ON (`s`.`lft` < `c`.`lft` AND `c`.`lft` < `s`.`rgt` AND `c`.`language` IN (:preparedArray3,:preparedArray4)) OR (`c`.`lft` <= `s`.`lft` AND `s`.`rgt` <= `c`.`rgt`) WHERE (`c`.`extension` = :extension OR `c`.`extension` = 'system') AND `c`.`access` IN (:preparedArray1,:preparedArray2) AND `c`.`published` = 1 AND `s`.`id` = :id ORDER BY `c`.`lft`488μs3.98KBParams/libraries/src/Categories/Categories.php:375Copy
  • SELECT DISTINCT a.id, a.title, a.name, a.checked_out, a.checked_out_time, a.note, a.state, a.access, a.created_time, a.created_user_id, a.ordering, a.language, a.fieldparams, a.params, a.type, a.default_value, a.context, a.group_id, a.label, a.description, a.required, a.only_use_in_subform,l.title AS language_title, l.image AS language_image,uc.name AS editor,ag.title AS access_level,ua.name AS author_name,g.title AS group_title, g.access as group_access, g.state AS group_state, g.note as group_note FROM has_fields AS a LEFT JOIN `has_languages` AS l ON l.lang_code = a.language LEFT JOIN has_users AS uc ON uc.id=a.checked_out LEFT JOIN has_viewlevels AS ag ON ag.id = a.access LEFT JOIN has_users AS ua ON ua.id = a.created_user_id LEFT JOIN has_fields_groups AS g ON g.id = a.group_id LEFT JOIN `has_fields_categories` AS fc ON fc.field_id = a.id WHERE ( (`a`.`context` = :context AND (`fc`.`category_id` IS NULL OR `fc`.`category_id` IN (:preparedArray1,:preparedArray2,:preparedArray3)) AND `a`.`access` IN (:preparedArray4,:preparedArray5)) AND (`a`.`group_id` = 0 OR `g`.`access` IN (:preparedArray6,:preparedArray7)) AND `a`.`state` = :state) AND (`a`.`group_id` = 0 OR `g`.`state` = :gstate) AND `a`.`only_use_in_subform` = :only_use_in_subform AND `a`.`language` IN (:preparedArray8,:preparedArray9) ORDER BY a.ordering ASC1.41ms4.81KBParams/libraries/src/MVC/Model/BaseDatabaseModel.php:166Copy
  • SELECT `alias` FROM `has_content` WHERE `id` = :id241μs1.31KBParams/components/com_content/src/Service/Router.php:168Copy
  • SELECT `alias` FROM `has_content` WHERE `id` = :id1.16ms1.31KBParams/components/com_content/src/Service/Router.php:168Copy
  • SELECT `m`.`id`,`m`.`title`,`m`.`module`,`m`.`position`,`m`.`content`,`m`.`showtitle`,`m`.`params`,`mm`.`menuid` FROM `has_modules` AS `m` LEFT JOIN `has_modules_menu` AS `mm` ON `mm`.`moduleid` = `m`.`id` LEFT JOIN `has_extensions` AS `e` ON `e`.`element` = `m`.`module` AND `e`.`client_id` = `m`.`client_id` WHERE ( ( (`m`.`published` = 1 AND `e`.`enabled` = 1 AND `m`.`client_id` = :clientId AND `m`.`access` IN (:preparedArray1,:preparedArray2)) AND (`m`.`publish_up` IS NULL OR `m`.`publish_up` <= :publishUp)) AND (`m`.`publish_down` IS NULL OR `m`.`publish_down` >= :publishDown)) AND (`mm`.`menuid` = :itemId OR `mm`.`menuid` <= 0) AND `m`.`language` IN (:preparedArray3,:preparedArray4) ORDER BY `m`.`position`,`m`.`ordering`5.75ms212.84KBParams/libraries/src/Cache/Controller/CallbackController.php:51Copy
  • SELECT `a`.`id`,`a`.`title`,`a`.`catid`,`a`.`language`, CASE WHEN CHAR_LENGTH(`a`.`alias`) != 0 THEN CONCAT_WS(':', `a`.`id`, `a`.`alias`) ELSE a.id END AS `slug`, CASE WHEN CHAR_LENGTH(`cc`.`alias`) != 0 THEN CONCAT_WS(':', `cc`.`id`, `cc`.`alias`) ELSE cc.id END AS `catslug` FROM `has_content` AS `a` LEFT JOIN `has_categories` AS `cc` ON `cc`.`id` = `a`.`catid` WHERE `a`.`catid` = :catid AND `a`.`state` = :state AND `a`.`access` IN (:preparedArray1,:preparedArray2) AND (`publish_up` IS NULL OR `publish_up` <= :nowDate1) AND (`publish_down` IS NULL OR `publish_down` >= :nowDate2) AND `a`.`language` IN (:preparedArray3,:preparedArray4) ORDER BY CASE WHEN `a`.`publish_up` IS NULL THEN `a`.`created` ELSE `a`.`publish_up` END DESC10.5ms109.75KBParams/plugins/content/pagenavigation/src/Extension/PageNavigation.php:188Copy
  • SELECT `c`.`id`,`c`.`asset_id`,`c`.`access`,`c`.`alias`,`c`.`checked_out`,`c`.`checked_out_time`,`c`.`created_time`,`c`.`created_user_id`,`c`.`description`,`c`.`extension`,`c`.`hits`,`c`.`language`,`c`.`level`,`c`.`lft`,`c`.`metadata`,`c`.`metadesc`,`c`.`metakey`,`c`.`modified_time`,`c`.`note`,`c`.`params`,`c`.`parent_id`,`c`.`path`,`c`.`published`,`c`.`rgt`,`c`.`title`,`c`.`modified_user_id`,`c`.`version`, CASE WHEN CHAR_LENGTH(`c`.`alias`) != 0 THEN CONCAT_WS(':', `c`.`id`, `c`.`alias`) ELSE `c`.`id` END as `slug` FROM `has_categories` AS `s` INNER JOIN `has_categories` AS `c` ON (`s`.`lft` < `c`.`lft` AND `c`.`lft` < `s`.`rgt` AND `c`.`language` IN (:preparedArray3,:preparedArray4)) OR (`c`.`lft` <= `s`.`lft` AND `s`.`rgt` <= `c`.`rgt`) WHERE (`c`.`extension` = :extension OR `c`.`extension` = 'system') AND `c`.`access` IN (:preparedArray1,:preparedArray2) AND `c`.`published` = 1 AND `s`.`id` = :id ORDER BY `c`.`lft`3.04ms3.98KBParams/libraries/src/Categories/Categories.php:375Copy
  • SELECT custom_data FROM has_extensions WHERE element = 'yootheme' AND folder = 'system' LIMIT 1941μs536B/templates/yootheme/packages/platform-joomla/src/Storage.php:30Copy
  • SELECT `language`,`id` FROM `has_menu` WHERE `home` = '1' AND `published` = 1 AND `client_id` = 0382μs704B/libraries/src/Language/Multilanguage.php:123Copy
  • SELECT `alias` FROM `has_content` WHERE `id` = :id184μs1.31KBParams/components/com_content/src/Service/Router.php:168Copy
  • SELECT `alias` FROM `has_content` WHERE `id` = :id85μs1.31KBParams/components/com_content/src/Service/Router.php:168Copy
  • SELECT `c2`.`language`,CONCAT_WS(':', `c2`.`id`, `c2`.`alias`) AS `id`,CONCAT_WS(':', `ca`.`id`, `ca`.`alias`) AS `catid` FROM `has_content` AS `c` INNER JOIN `has_associations` AS `a` ON `a`.`id` = `c`.`id` AND `a`.`context` = :context INNER JOIN `has_associations` AS `a2` ON `a`.`key` = `a2`.`key` INNER JOIN `has_content` AS `c2` ON `a2`.`id` = `c2`.`id` INNER JOIN `has_categories` AS `ca` ON `c2`.`catid` = `ca`.`id` AND `ca`.`extension` = :extension2 WHERE `c`.`id` = :id AND c2.access IN (1,5) AND c2.language != 'sv-SE' AND (c2.publish_up IS NULL OR c2.publish_up <= '2025-04-10 19:15:24') AND (c2.publish_down IS NULL OR c2.publish_down >= '2025-04-10 19:15:24') AND c2.state = 12.03ms3.97KBParams/libraries/src/Language/Associations.php:145Copy
  • SELECT `a`.`id`,`a`.`title`,`a`.`alias`,`a`.`introtext`,`a`.`fulltext`,`a`.`checked_out`,`a`.`checked_out_time`,`a`.`catid`,`a`.`created`,`a`.`created_by`,`a`.`created_by_alias`,`a`.`modified`,`a`.`modified_by`,CASE WHEN `a`.`publish_up` IS NULL THEN `a`.`created` ELSE `a`.`publish_up` END AS `publish_up`,`a`.`publish_down`,`a`.`images`,`a`.`urls`,`a`.`attribs`,`a`.`metadata`,`a`.`metakey`,`a`.`metadesc`,`a`.`access`,`a`.`hits`,`a`.`featured`,`a`.`language`,LENGTH(`a`.`fulltext`) AS `readmore`,`a`.`ordering`,`fp`.`featured_up`,`fp`.`featured_down`,CASE WHEN `c`.`published` = 2 AND `a`.`state` > 0 THEN 2 WHEN `c`.`published` != 1 THEN 0 ELSE `a`.`state` END AS `state`,`c`.`title` AS `category_title`,`c`.`path` AS `category_route`,`c`.`access` AS `category_access`,`c`.`alias` AS `category_alias`,`c`.`language` AS `category_language`,`c`.`published`,`c`.`published` AS `parents_published`,`c`.`lft`,CASE WHEN `a`.`created_by_alias` > ' ' THEN `a`.`created_by_alias` ELSE `ua`.`name` END AS `author`,`ua`.`email` AS `author_email`,`uam`.`name` AS `modified_by_name`,`parent`.`title` AS `parent_title`,`parent`.`id` AS `parent_id`,`parent`.`path` AS `parent_route`,`parent`.`alias` AS `parent_alias`,`parent`.`language` AS `parent_language`,COALESCE(NULLIF(ROUND(`v`.`rating_sum` / `v`.`rating_count`, 1), 0), 0) AS `rating`,COALESCE(NULLIF(`v`.`rating_count`, 0), 0) AS `rating_count` FROM `has_content` AS `a` LEFT JOIN `has_categories` AS `c` ON `c`.`id` = `a`.`catid` LEFT JOIN `has_users` AS `ua` ON `ua`.`id` = `a`.`created_by` LEFT JOIN `has_users` AS `uam` ON `uam`.`id` = `a`.`modified_by` LEFT JOIN `has_categories` AS `parent` ON `parent`.`id` = `c`.`parent_id` LEFT JOIN `has_content_frontpage` AS `fp` ON `fp`.`content_id` = `a`.`id` LEFT JOIN `has_content_rating` AS `v` ON `a`.`id` = `v`.`content_id` WHERE `a`.`access` IN (:preparedArray1,:preparedArray2) AND `c`.`access` IN (:preparedArray3,:preparedArray4) AND `c`.`published` = 1 AND `a`.`state` = :condition AND (`a`.`publish_up` IS NULL OR `a`.`publish_up` <= :publishUp) AND (`a`.`publish_down` IS NULL OR `a`.`publish_down` >= :publishDown) AND `a`.`language` IN (:preparedArray5,:preparedArray6) ORDER BY RAND() ASC LIMIT 10146ms167.16KBParams/libraries/src/MVC/Model/BaseDatabaseModel.php:166Copy
  • SELECT `c2`.`language`,`c2`.`id` FROM `has_menu` AS `c` INNER JOIN `has_associations` AS `a` ON `a`.`id` = `c`.`id` AND `a`.`context` = :context INNER JOIN `has_associations` AS `a2` ON `a`.`key` = `a2`.`key` INNER JOIN `has_menu` AS `c2` ON `a2`.`id` = `c2`.`id` WHERE `c`.`id` = :id187μs1.38KBParams/libraries/src/Language/Associations.php:145Copy
  • SELECT `name`,`element` FROM `has_extensions` WHERE `type` = 'plugin' AND `folder` = 'finder' AND `enabled` = 12.08ms640B/administrator/components/com_finder/src/Helper/LanguageHelper.php:135Copy
  • SELECT `title` FROM `has_finder_taxonomy` WHERE `parent_id` = 1 AND `state` = 1 AND `access` IN (1,5)1.7ms584B/administrator/components/com_finder/src/Indexer/Taxonomy.php:314Copy
  • SELECT DISTINCT a.id, a.title, a.name, a.checked_out, a.checked_out_time, a.note, a.state, a.access, a.created_time, a.created_user_id, a.ordering, a.language, a.fieldparams, a.params, a.type, a.default_value, a.context, a.group_id, a.label, a.description, a.required, a.only_use_in_subform,l.title AS language_title, l.image AS language_image,uc.name AS editor,ag.title AS access_level,ua.name AS author_name,g.title AS group_title, g.access as group_access, g.state AS group_state, g.note as group_note FROM has_fields AS a LEFT JOIN `has_languages` AS l ON l.lang_code = a.language LEFT JOIN has_users AS uc ON uc.id=a.checked_out LEFT JOIN has_viewlevels AS ag ON ag.id = a.access LEFT JOIN has_users AS ua ON ua.id = a.created_user_id LEFT JOIN has_fields_groups AS g ON g.id = a.group_id WHERE ( (`a`.`context` = :context AND `a`.`access` IN (:preparedArray1,:preparedArray2)) AND (`a`.`group_id` = 0 OR `g`.`access` IN (:preparedArray3,:preparedArray4)) AND `a`.`state` = :state) AND (`a`.`group_id` = 0 OR `g`.`state` = :gstate) AND `a`.`only_use_in_subform` = :only_use_in_subform AND `a`.`language` IN (:preparedArray5,:preparedArray6) ORDER BY a.ordering ASC2.01ms4.75KBParams/libraries/src/MVC/Model/BaseDatabaseModel.php:166Copy
  • SELECT `title` FROM `has_finder_taxonomy` WHERE `parent_id` = 1 AND `state` = 1 AND `access` IN (1,5)203μs584B/administrator/components/com_finder/src/Indexer/Taxonomy.php:314Copy
  • SELECT SUM(CASE WHEN `a`.`next_execution` <= :now THEN 1 ELSE 0 END) AS due_count,SUM(CASE WHEN `a`.`locked` IS NULL THEN 0 ELSE 1 END) AS locked_count FROM `has_scheduler_tasks` AS `a` WHERE `a`.`state` = 12.09ms1.37KBParams/administrator/components/com_scheduler/src/Model/TasksModel.php:466Copy
  • SELECT `session_id` FROM `has_session` WHERE `session_id` = ?159μs1KBParams/libraries/vendor/joomla/session/src/Handler/DatabaseHandler.php:291Copy
  • UPDATE `has_session` SET `data` = ? , `time` = ? WHERE `session_id` = ?2.88ms592BParams/libraries/vendor/joomla/session/src/Handler/DatabaseHandler.php:318Copy