Dependencia química / Ibogaina
Tratamento de drogas
O atual momento da ibogaína merece uma tomada de consciência e um grande senso de responsabilidade das pessoas... Estão aparecendo a cada dia novas pseudo-clínicas, todas alardeando uma experiência e um conhecimento que não possuem, buscando atrair os incautos pacientes e familiares que, desesperados, tentam qualquer coisa sem pensar direito no que estão fazendo.
Como sempre dizemos, o tratamento com ibogaína é um procedimento que não é isento de riscos, deve ser feito em ambiente médico-hospitalar, com o paciente internado, para ser protegido e monitorado. O paciente deve estar limpo de drogas e de remédios por um tempo variável, de acordo com cada situação individual, e deve ser submetido a uma bateria de exames antes do procedimento. E a medicação utilizada, deve ser GMP, ou seja, fabricada segundo as boas práticas farmacêuticas.
Não confie em locais que usam, como diferencial para fazer propaganda, o argumento de que não é necessária internação, nem exames e nem abstinência prévia. Pelo menos 60 dias de internação são necessárias sim, para inclusive proteger o paciente de qualquer evento adverso .
Não confie em locais e sites que dão a entender que a ibogaína é a "cura" da dependência química, isso é simplificar demais um problema sério.
Desde que se descobriram os efeitos anti-dependência da ibogaína, em 1962, ocorreram cerca de 20.000 tratamentos em todo o mundo. Nestes 20.000 tratamentos, ocorreram 19 mortes, todas relacionadas a problemas de saúde prévios ( que teriam sido detectados se o paciente tivesse feito um check-up antes do procedimento) e também a uso de drogas muito perto do uso da ibogaína ( o que teria sido evitado se o paciente estivesse sob vigilância especializada).
Então, não confie em pessoas que menosprezam o poder da substância, que não entendem do assunto e visam apenas lucro.
Não confie tambem em locais que indicam a ibogaína como uma panacéia, que cura tudo, desde a dependência até queda de cabelo. Claramente, isso é uma tentativa de angariar mais pacientes e aumentar os lucros.
Mesmo sendo derivada de uma planta, certos cuidados devem ser tomados. Não é toda medicação derivada de plantas que é "tranquila" ou "fraquinha", quem fala isso demonstra que não entende do assunto.
A ibogaína é muito eficiente, principalmente se comparada aos outros tratamentos disponíveis, mas para atingir bons resultados, é necessária uma expertise que alguns locais que fazem propaganda disseminada não possuem.
Apenas a título de informação, aqui está o link para um trabalho científico comentando essas mortes às quais me referi. Observe como no texto é dito que esses casos todos foram de pacientes com problemas de saúde prévios, usando medicação de origem desconhecida.
Evaluation of Antidepressant Activity of Aqueous Extract of Withania Somnifer...iosrjce
Anti-depressants play a major role in today’s life style. There are evidences of the ayurvedic
formulation withania somnifera (roots) being effective in various neuro- psychiatric conditions. The antidepressant
activities of aqueous extract Withania somnifera roots (AEWS) were studied using - Forced swim
test (FST). Effect of different doses of AEWS (30,40,50 mg/kg), Imipramine (15mg/kg)were studied on
behavioural despair tests induced immobility time . WS produced dose dependent decrease in immobility
time in FST, maximum effect being observed with WS 50 mg/kg. The findings support the use of WS as potential
adjuvant in depressive disorders.
International Journal of Engineering Research and Applications (IJERA) is an open access online peer reviewed international journal that publishes research and review articles in the fields of Computer Science, Neural Networks, Electrical Engineering, Software Engineering, Information Technology, Mechanical Engineering, Chemical Engineering, Plastic Engineering, Food Technology, Textile Engineering, Nano Technology & science, Power Electronics, Electronics & Communication Engineering, Computational mathematics, Image processing, Civil Engineering, Structural Engineering, Environmental Engineering, VLSI Testing & Low Power VLSI Design etc.
Pharmacological screening of Anti-psychotic agentsAbin Joy
Presentation contents are:
Introduction, Definition of psychosis, Classification of anti-psychotics, MOA of anti-psychotic agents and screening models.
Gamma Glutamyl Transferase Activity (Ggt) In Albino Rats Treated With Orphena...iosrjce
The use of orphenadol as a wide spectrum painkiller (analgesics) has been reported to elicit some
toxic effects. This research examined the hepatobiliary effect of orphenadol solution on hepatobiliary system in
albino rats. Twenty male albino rats, distributed into four groups (A, B, C and D), with five rats in each group,
were used in this research. Groups A, B and C were given oral treatment of 21, 42 and 84mg/kg respectively of
the drug solution for seven days consecutively, while the animals in group D were kept as control. Treatment of
animals with the drug sample resulted to a decrease in physical activities, body weights, and feed and water
intake during the period of treatment relative to the control. Measurement of the total protein concentration in
the serum of the rats did not reveal any significant difference (P>0.05) between the test and the control groups.
The activity of gamma glutamyl transferase recorded in the test groups were significantly higher than the
control (P<0.05). These effects of orphenadol solution on this enzyme and total protein concentration were
found to be dose-dependent. The findings of this research indicate that the toxic effects or the adverse effect of
orphenadol may include the hepatobiliary system.
The Central and Peripheral effects of the methanol extract of Fadogia cienkow...iosrjce
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Evaluation of Antidepressant Activity of Aqueous Extract of Withania Somnifer...iosrjce
Anti-depressants play a major role in today’s life style. There are evidences of the ayurvedic
formulation withania somnifera (roots) being effective in various neuro- psychiatric conditions. The antidepressant
activities of aqueous extract Withania somnifera roots (AEWS) were studied using - Forced swim
test (FST). Effect of different doses of AEWS (30,40,50 mg/kg), Imipramine (15mg/kg)were studied on
behavioural despair tests induced immobility time . WS produced dose dependent decrease in immobility
time in FST, maximum effect being observed with WS 50 mg/kg. The findings support the use of WS as potential
adjuvant in depressive disorders.
International Journal of Engineering Research and Applications (IJERA) is an open access online peer reviewed international journal that publishes research and review articles in the fields of Computer Science, Neural Networks, Electrical Engineering, Software Engineering, Information Technology, Mechanical Engineering, Chemical Engineering, Plastic Engineering, Food Technology, Textile Engineering, Nano Technology & science, Power Electronics, Electronics & Communication Engineering, Computational mathematics, Image processing, Civil Engineering, Structural Engineering, Environmental Engineering, VLSI Testing & Low Power VLSI Design etc.
Pharmacological screening of Anti-psychotic agentsAbin Joy
Presentation contents are:
Introduction, Definition of psychosis, Classification of anti-psychotics, MOA of anti-psychotic agents and screening models.
Gamma Glutamyl Transferase Activity (Ggt) In Albino Rats Treated With Orphena...iosrjce
The use of orphenadol as a wide spectrum painkiller (analgesics) has been reported to elicit some
toxic effects. This research examined the hepatobiliary effect of orphenadol solution on hepatobiliary system in
albino rats. Twenty male albino rats, distributed into four groups (A, B, C and D), with five rats in each group,
were used in this research. Groups A, B and C were given oral treatment of 21, 42 and 84mg/kg respectively of
the drug solution for seven days consecutively, while the animals in group D were kept as control. Treatment of
animals with the drug sample resulted to a decrease in physical activities, body weights, and feed and water
intake during the period of treatment relative to the control. Measurement of the total protein concentration in
the serum of the rats did not reveal any significant difference (P>0.05) between the test and the control groups.
The activity of gamma glutamyl transferase recorded in the test groups were significantly higher than the
control (P<0.05). These effects of orphenadol solution on this enzyme and total protein concentration were
found to be dose-dependent. The findings of this research indicate that the toxic effects or the adverse effect of
orphenadol may include the hepatobiliary system.
The Central and Peripheral effects of the methanol extract of Fadogia cienkow...iosrjce
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
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Preclinical Toxicity Studies-Tool of Drug Discoverydynajolly
As per WHO “Drug is any substance or product that is used or is intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient”. Hence the prime objective of using any substance as a drug is that it must be beneficial for the humans. A large number of compounds are synthesized every year but they cannot be directly used in humans as drugs because no one knows or can predict the possible harmful effects of these compounds in humans. That is why to explore the complete pharmacological profile of these compounds and to ensure complete human safety they are first tested on animals before clinical use. Preclinical Studies thus can be defined as “Testing the newly discovered compound in animals with the objective of gaining information regarding the various aspects of the compound with respect to the biological systems so that the same can be extrapolated for the use of that compound in humans”. As the evaluation progresses undesirable compounds gets rejected at each step, so that only a few out of thousands reach the stage when administration to the humans is considered.
Pharmacovigilance and Pharmacoepidemiology journal accepts articles from different disciplines as below but not constrained to only these Pharmacovigilance signal, Pharmacovigilance data management, Design and development of drug, Principles of pharmacology, Quality system and pharmacovigilance, Pharmacovigilance softwares, Drug regulatory activities, Drug reactions and diagnosis, Reporting systems, Clinical trials and pharmacovigilance, Marketing surveillance, Pharmacovigilance ethics and regulations, Biomarkers and pharmacology , Concepts and trends in pharmacovigilance, Pharmaceutical medicines, Drug delivery systems, Statistics and data management.
This is a descriptive and simple molecular biology lab manual.For students who do not have P.C in their home and can not use the virtual lab videos available online.
ANTI-INFLAMMATORY AND ANALGESIC EFFECTS OF METHANOLIC EXTRACT OF Afrofritomia...paperpublications3
Abstract: Methanolic extract of the leaf of Afrofritomia sylvestris was investigated for its anti-inflammatory and analgesic effects. The extract was evaluated using carragenaan-induced paw oedema in rats (anti-inflammatory effect) as well as acetic acid-induced writhing (analgesic effect) in mice, after intra-peritoneal injection of the extract (250mg/kg, 500mg/kg and 1000mg/kg). The negative control animals were given normal saline (10ml/kg) and the effects were compared with that of Acetylsalicylic acid (100mg/kg), as a positive control drug. Each experiment consisted of twenty five animals divided into 5 groups of 5 animals each. Tail immersion reaction time and Naloxone antagonism of the extracts and morphine were further used to investigate the mode of action of the analgesic activity of the leaf. The extract significantly inhibited carageenan-induced hind paw inflammation in rats (P<0.05-0.01)><0.01). The methanolic extract failed to raise the pain threshold of mice towards heat stimulus and Naloxone did not show any significant antagonism (blocking effect) against the extract in the tail immersion experiment, thus ruling out the involvement of opioid receptors in the mechanism of analgesic action of the extract. Phytochemical analyses of the plant show the presence of flavonoids, alkaloids, saponins, tannins, steroids, triterpenes and cyanogenic glycosides. The LD50 of the extract was determined to be 3050+223.65mg/kg using the method of Tainter and Miller.In this study, methanolic extract of Afrofritomia sylvestris leaf was found to possess significant anti-inflammatory and analgesic effects in the tested models.
Analgesic Effect of Lidocaine in Orofacial Pain Of RatsQUESTJOURNAL
ABSTRACT: In dental treatment, lidocaine is currently used as local anesthetic, but studies on the control of orofacial pain are limited. The aim of this study was to investigate whether pre-treatment with lidocaine would involved in pain modulation in inflammatory orofacial pain.Male Sprague-Dawley white rats (240-280g) were used. The experimental group were divided into 3 groups(n=5); formalin (5 %, 50 μL), Administer 0.2%, 2% lidocaine, after administration, formalin (s.c). To induced orofacial pain, 5% formalin (50 μL) was injected under the skin on the right region of the whiskers of the experimental animals (n=5), and the act of rubbing or scratching the facial area in which the drug was injected was considered pain index. The administration of lidocaine at 2% concentration was found that the formalin-induced pain behavioral reaction was effectively reduced. The level of Nrf2 protein expression increased by formalin noticeably decreased in the medulla oblongata after lidocaine administration. Nuclear factor erythroid 2–related factor 2 (Nrf2) is an oxidative stress-mediated transcription factor. Both ginsengs significantly down-regulated the increased Nrf2 level in formalin group. These results indicate that lidocaine could be a promising regulated in the treatment of inflammatory orofacial pain
Dependência Química
Buscar o prazer acima de tudo, essa é a grande questão – e o grande tormento – existente na vida dos
dependentes químicos. Nas últimas décadas uma variedade de novas drogas têm surgido e vêm se
disseminando entre crianças, jovens e até mesmo pessoas da terceira idade.
No corpo humano, o principal responsável pelo efeito transtornador que a droga proporciona ao ser
humano é o sistema de recompensa do cérebro – o mesmo que lhe dá prazer ao comer, beber, estar entre
amigos ou fazer sexo.
Ao consumir uma substância química como a maconha ou a cocaína, por exemplo, o cérebro acessa em
poucos segundos esse sistema de recompensa, gerando sensações prazerosas junto de uma dependência
cada vez maior. Com a mesma rapidez que a sensação de prazer aparece, ela vai embora, deixando a
necessidade de consumo e sintomas de depressão e ansiedade.
Quimicamente, as drogas se dividem em três categorias: Depressoras – álcool, soníferos, inalantes, entre
outros; Estimulantes – cocaína, ecstasy e anfetaminas em geral e as Perturbadoras do sistema nervoso,
comumente chamadas de psicodélicas – LSD, Maconha, etc.
Atualmente é possível ver o reflexo dos vícios nessas substâncias em nossa sociedade, sendo mais
perceptível as comunidades de dependentes de crack - substância estimulante e altamente viciante feita da
cocaína. Os usuários de crack vivem nas ruas, consumindo freneticamente a droga, reduzindo cada vez mais
o contato com a família e amigos. Muitos vivem nessas comunidades e praticam atividades ilícitas para
sustentar o vício.
Os dependentes químicos são considerados hoje indivíduos com transtornos mentais, pela maneira com a
qual as substâncias modificam as estruturas cerebrais e precisam de cuidados específicos para abandonar o
vício.
Métodos terapêuticos e medicamentos desintoxicantes são muito utilizados como tratamento, mas
combinados com ajuda psicológica e acompanhamento vitalício na manutenção da abstinência, caso do
método utilizado na nossa clínica, a chance de sucesso e de cura do dependente são enormes. Métodos
dessa linha são utilizados na Clínica Cleuza Canan.
Clinica de dependência química Curitiba
Drogas ficaram mais potentes e baratas nos últimos 20 anos, diz estudo com foco na dependência química.
Estudo também aponta que o crescimento na apreensão de drogas não teve efeito correspondente no consumo
Maconha está entre as drogas que, segundo estudo canadense, deveriam ser descriminalizadas
Uma pesquisa realizada no Canadá revelou que as drogas tornaram-se mais baratas e mais puras ao redor do mundo nos últimos 20 anos, sugerindo um "fracasso" dos esforços para conter a produção, consumo e tráfico de entorpecentes.
O estudo do International Centre for Science in Drug Policy (Centro Internacional para a Ciência em Políticas de Drogas, Clinica de dependência química Curitiba) foi publicado na revista científica British Medical Journal Open e avaliou programas de contenção e vigilância de governos de diferentes países.
De acordo com os responsáveis pela pesquisa, os governos deveriam passar a considerar o uso de drogas um aspecto de saúde pública, e não um assunto para a Justiça. "Nós deveríamos procurar implementar políticas que colocam a saúde e a segurança no topo das nossas prioridades, e considerar o uso de drogas como um aspecto de saúde pública, ao invés de um problema para a Justiça criminal", diz Evan Wood, um dos responsáveis pelo estudo.
"Com o reconhecimento do improvável sucesso dos esforços para reduzir o fornecimento de drogas, dependencia quimica, há uma necessidade clara para aumentar o tratamento do vício e de outras estratégias para diminuir de forma efetiva os danos relacionados ao uso de drogas", complementa.
Preços, pureza e disponibilidade
De forma geral, os números compilados pelo centro canadense mostram que entre 1990 e 2010 os preços das drogas caíram, enquanto a pureza e a potência aumentaram. Na região andina (Peru, Bolívia e Colômbia) a apreensão de folhas de coca aumentou em quase 200% entre 1990 e 2007, mas isso não levou a uma grande redução do consumo de cocaína em pó nos Estados Unidos, colocando em xeque as políticas públicas focadas na contenção do fornecimento de entorpecentes.
Nós deveríamos procurar implementar políticas (Clinica de dependência química Curitiba) que colocam a saúde e a segurança no topo das nossas prioridades, e considerar o uso de drogas como um aspecto de saúde pública, ao invés de um problema para a Justiça criminal
Evan Wood
Na Europa, o preço médio das drogas à base de ópio e da cocaína, reajustados de acordo com a inflação e o grau de pureza, diminuíram em 74% e 51% respectivamente entre 1990 e 2010. Além disso, as drogas estão mais puras e mais disponíveis ao redor do mundo.
Os números do relatório mostram que houve um aumento significativo em diversos países com relação à apreensão de cocaína, heroína e maconha, conforme os registros governamentais desde 1990.
Tratamento para dependência química em Curitiba
Localizada em Curitiba, a Clínica Cleuza Canan atua há 30 anos com a recuperação de dependentes das mais
diversas substâncias químicas. Na capital do Paraná, o número estimado de dependentes químicos chega a
170 mil – aproximadamente 10% da população - de acordo com pesquisa feita no início de 2013 baseada
em atendimentos e abordagens feitas pelo Departamento de Políticas Públicas sobre Drogas.
Com metodologia especial, criada através de anos de observação das recaídas de dependentes em métodos
tradicionais, o tratamento consiste em focar na saúde mental, física, espiritual e psicológica do paciente.
Durante o tratamento, além da desintoxicação, o dependente aprende a lidar com o vício de maneira
independente, utilizando um método terapêutico que auxilia na firmeza ao deparar-se com a abstinência. O
objetivo é fazer com que o paciente adquira habilidades (que posteriormente se tornam um hábito e parte
da personalidade do mesmo) para enfrentar a constante manutenção da doença.
Além do tratamento feito com o paciente, a Clínica Cleuza Canan atua com os familiares do usuário
mostrando que a dependência é uma doença metabólica, que exige cuidados mas que é estacionável. Esse
auxílio contribui com a inserção do ex- dependente no convívio familiar e social.
Dependencia química / Ibogaina
Tratamento de drogas
O atual momento da ibogaína merece uma tomada de consciência e um grande senso de responsabilidade das pessoas... Estão aparecendo a cada dia novas pseudo-clínicas, todas alardeando uma experiência e um conhecimento que não possuem, buscando atrair os incautos pacientes e familiares que, desesperados, tentam qualquer coisa sem pensar direito no que estão fazendo.
Como sempre dizemos, o tratamento com ibogaína é um procedimento que não é isento de riscos, deve ser feito em ambiente médico-hospitalar, com o paciente internado, para ser protegido e monitorado. O paciente deve estar limpo de drogas e de remédios por um tempo variável, de acordo com cada situação individual, e deve ser submetido a uma bateria de exames antes do procedimento. E a medicação utilizada, deve ser GMP, ou seja, fabricada segundo as boas práticas farmacêuticas.
Não confie em locais que usam, como diferencial para fazer propaganda, o argumento de que não é necessária internação, nem exames e nem abstinência prévia. Pelo menos 60 dias de internação são necessárias sim, para inclusive proteger o paciente de qualquer evento adverso .
Não confie em locais e sites que dão a entender que a ibogaína é a "cura" da dependência química, isso é simplificar demais um problema sério.
Desde que se descobriram os efeitos anti-dependência da ibogaína, em 1962, ocorreram cerca de 20.000 tratamentos em todo o mundo. Nestes 20.000 tratamentos, ocorreram 19 mortes, todas relacionadas a problemas de saúde prévios ( que teriam sido detectados se o paciente tivesse feito um check-up antes do procedimento) e também a uso de drogas muito perto do uso da ibogaína ( o que teria sido evitado se o paciente estivesse sob vigilância especializada).
Então, não confie em pessoas que menosprezam o poder da substância, que não entendem do assunto e visam apenas lucro.
Não confie tambem em locais que indicam a ibogaína como uma panacéia, que cura tudo, desde a dependência até queda de cabelo. Claramente, isso é uma tentativa de angariar mais pacientes e aumentar os lucros.
Mesmo sendo derivada de uma planta, certos cuidados devem ser tomados. Não é toda medicação derivada de plantas que é "tranquila" ou "fraquinha", quem fala isso demonstra que não entende do assunto.
A ibogaína é muito eficiente, principalmente se comparada aos outros tratamentos disponíveis, mas para atingir bons resultados, é necessária uma expertise que alguns locais que fazem propaganda disseminada não possuem.
Apenas a título de informação, aqui está o link para um trabalho científico comentando essas mortes às quais me referi. Observe como no texto é dito que esses casos todos foram de pacientes com problemas de saúde prévios, usando medicação de origem desconhecida. www.cleuzacanan.com
drogas, dependencia quimica, ibogaina, tratamento de drogasDra. Cleuza Canan
Dependencia química / Ibogaina
Tratamento de drogas
O atual momento da ibogaína merece uma tomada de consciência e um grande senso de responsabilidade das pessoas... Estão aparecendo a cada dia novas pseudo-clínicas, todas alardeando uma experiência e um conhecimento que não possuem, buscando atrair os incautos pacientes e familiares que, desesperados, tentam qualquer coisa sem pensar direito no que estão fazendo.
Como sempre dizemos, o tratamento com ibogaína é um procedimento que não é isento de riscos, deve ser feito em ambiente médico-hospitalar, com o paciente internado, para ser protegido e monitorado. O paciente deve estar limpo de drogas e de remédios por um tempo variável, de acordo com cada situação individual, e deve ser submetido a uma bateria de exames antes do procedimento. E a medicação utilizada, deve ser GMP, ou seja, fabricada segundo as boas práticas farmacêuticas.
Não confie em locais que usam, como diferencial para fazer propaganda, o argumento de que não é necessária internação, nem exames e nem abstinência prévia. Pelo menos 60 dias de internação são necessárias sim, para inclusive proteger o paciente de qualquer evento adverso .
Não confie em locais e sites que dão a entender que a ibogaína é a "cura" da dependência química, isso é simplificar demais um problema sério.
Desde que se descobriram os efeitos anti-dependência da ibogaína, em 1962, ocorreram cerca de 20.000 tratamentos em todo o mundo. Nestes 20.000 tratamentos, ocorreram 19 mortes, todas relacionadas a problemas de saúde prévios ( que teriam sido detectados se o paciente tivesse feito um check-up antes do procedimento) e também a uso de drogas muito perto do uso da ibogaína ( o que teria sido evitado se o paciente estivesse sob vigilância especializada).
Então, não confie em pessoas que menosprezam o poder da substância, que não entendem do assunto e visam apenas lucro.
Não confie tambem em locais que indicam a ibogaína como uma panacéia, que cura tudo, desde a dependência até queda de cabelo. Claramente, isso é uma tentativa de angariar mais pacientes e aumentar os lucros.
Mesmo sendo derivada de uma planta, certos cuidados devem ser tomados. Não é toda medicação derivada de plantas que é "tranquila" ou "fraquinha", quem fala isso demonstra que não entende do assunto.
A ibogaína é muito eficiente, principalmente se comparada aos outros tratamentos disponíveis, mas para atingir bons resultados, é necessária uma expertise que alguns locais que fazem propaganda disseminada não possuem.
Apenas a título de informação, aqui está o link para um trabalho científico comentando essas mortes às quais me referi. Observe como no texto é dito que esses casos todos foram de pacientes com problemas de saúde prévios, usando medicação de origem desconhecida.
Dependencia química / Ibogaina
Tratamento de drogas
O atual momento da ibogaína merece uma tomada de consciência e um grande senso de responsabilidade das pessoas... Estão aparecendo a cada dia novas pseudo-clínicas, todas alardeando uma experiência e um conhecimento que não possuem, buscando atrair os incautos pacientes e familiares que, desesperados, tentam qualquer coisa sem pensar direito no que estão fazendo.
Como sempre dizemos, o tratamento com ibogaína é um procedimento que não é isento de riscos, deve ser feito em ambiente médico-hospitalar, com o paciente internado, para ser protegido e monitorado. O paciente deve estar limpo de drogas e de remédios por um tempo variável, de acordo com cada situação individual, e deve ser submetido a uma bateria de exames antes do procedimento. E a medicação utilizada, deve ser GMP, ou seja, fabricada segundo as boas práticas farmacêuticas.
Não confie em locais que usam, como diferencial para fazer propaganda, o argumento de que não é necessária internação, nem exames e nem abstinência prévia. Pelo menos 60 dias de internação são necessárias sim, para inclusive proteger o paciente de qualquer evento adverso .
Não confie em locais e sites que dão a entender que a ibogaína é a "cura" da dependência química, isso é simplificar demais um problema sério.
Desde que se descobriram os efeitos anti-dependência da ibogaína, em 1962, ocorreram cerca de 20.000 tratamentos em todo o mundo. Nestes 20.000 tratamentos, ocorreram 19 mortes, todas relacionadas a problemas de saúde prévios ( que teriam sido detectados se o paciente tivesse feito um check-up antes do procedimento) e também a uso de drogas muito perto do uso da ibogaína ( o que teria sido evitado se o paciente estivesse sob vigilância especializada).
Então, não confie em pessoas que menosprezam o poder da substância, que não entendem do assunto e visam apenas lucro.
Não confie tambem em locais que indicam a ibogaína como uma panacéia, que cura tudo, desde a dependência até queda de cabelo. Claramente, isso é uma tentativa de angariar mais pacientes e aumentar os lucros.
Mesmo sendo derivada de uma planta, certos cuidados devem ser tomados. Não é toda medicação derivada de plantas que é "tranquila" ou "fraquinha", quem fala isso demonstra que não entende do assunto.
A ibogaína é muito eficiente, principalmente se comparada aos outros tratamentos disponíveis, mas para atingir bons resultados, é necessária uma expertise que alguns locais que fazem propaganda disseminada não possuem.
Apenas a título de informação, aqui está o link para um trabalho científico comentando essas mortes às quais me referi. Observe como no texto é dito que esses casos todos foram de pacientes com problemas de saúde prévios, usando medicação de origem desconhecida.
Dependencia química / Ibogaina
Tratamento de drogas
O atual momento da ibogaína merece uma tomada de consciência e um grande senso de responsabilidade das pessoas... Estão aparecendo a cada dia novas pseudo-clínicas, todas alardeando uma experiência e um conhecimento que não possuem, buscando atrair os incautos pacientes e familiares que, desesperados, tentam qualquer coisa sem pensar direito no que estão fazendo.
Como sempre dizemos, o tratamento com ibogaína é um procedimento que não é isento de riscos, deve ser feito em ambiente médico-hospitalar, com o paciente internado, para ser protegido e monitorado. O paciente deve estar limpo de drogas e de remédios por um tempo variável, de acordo com cada situação individual, e deve ser submetido a uma bateria de exames antes do procedimento. E a medicação utilizada, deve ser GMP, ou seja, fabricada segundo as boas práticas farmacêuticas.
Não confie em locais que usam, como diferencial para fazer propaganda, o argumento de que não é necessária internação, nem exames e nem abstinência prévia. Pelo menos 60 dias de internação são necessárias sim, para inclusive proteger o paciente de qualquer evento adverso .
Não confie em locais e sites que dão a entender que a ibogaína é a "cura" da dependência química, isso é simplificar demais um problema sério.
Desde que se descobriram os efeitos anti-dependência da ibogaína, em 1962, ocorreram cerca de 20.000 tratamentos em todo o mundo. Nestes 20.000 tratamentos, ocorreram 19 mortes, todas relacionadas a problemas de saúde prévios ( que teriam sido detectados se o paciente tivesse feito um check-up antes do procedimento) e também a uso de drogas muito perto do uso da ibogaína ( o que teria sido evitado se o paciente estivesse sob vigilância especializada).
Então, não confie em pessoas que menosprezam o poder da substância, que não entendem do assunto e visam apenas lucro.
Não confie tambem em locais que indicam a ibogaína como uma panacéia, que cura tudo, desde a dependência até queda de cabelo. Claramente, isso é uma tentativa de angariar mais pacientes e aumentar os lucros.
Mesmo sendo derivada de uma planta, certos cuidados devem ser tomados. Não é toda medicação derivada de plantas que é "tranquila" ou "fraquinha", quem fala isso demonstra que não entende do assunto.
A ibogaína é muito eficiente, principalmente se comparada aos outros tratamentos disponíveis, mas para atingir bons resultados, é necessária uma expertise que alguns locais que fazem propaganda disseminada não possuem.
Apenas a título de informação, aqui está o link para um trabalho científico comentando essas mortes às quais me referi. Observe como no texto é dito que esses casos todos foram de pacientes com problemas de saúde prévios, usando medicação de origem desconhecida.
Dependencia química / Ibogaina
Tratamento de drogas
O atual momento da ibogaína merece uma tomada de consciência e um grande senso de responsabilidade das pessoas... Estão aparecendo a cada dia novas pseudo-clínicas, todas alardeando uma experiência e um conhecimento que não possuem, buscando atrair os incautos pacientes e familiares que, desesperados, tentam qualquer coisa sem pensar direito no que estão fazendo.
Como sempre dizemos, o tratamento com ibogaína é um procedimento que não é isento de riscos, deve ser feito em ambiente médico-hospitalar, com o paciente internado, para ser protegido e monitorado. O paciente deve estar limpo de drogas e de remédios por um tempo variável, de acordo com cada situação individual, e deve ser submetido a uma bateria de exames antes do procedimento. E a medicação utilizada, deve ser GMP, ou seja, fabricada segundo as boas práticas farmacêuticas.
Não confie em locais que usam, como diferencial para fazer propaganda, o argumento de que não é necessária internação, nem exames e nem abstinência prévia. Pelo menos 60 dias de internação são necessárias sim, para inclusive proteger o paciente de qualquer evento adverso .
Não confie em locais e sites que dão a entender que a ibogaína é a "cura" da dependência química, isso é simplificar demais um problema sério.
Desde que se descobriram os efeitos anti-dependência da ibogaína, em 1962, ocorreram cerca de 20.000 tratamentos em todo o mundo. Nestes 20.000 tratamentos, ocorreram 19 mortes, todas relacionadas a problemas de saúde prévios ( que teriam sido detectados se o paciente tivesse feito um check-up antes do procedimento) e também a uso de drogas muito perto do uso da ibogaína ( o que teria sido evitado se o paciente estivesse sob vigilância especializada).
Então, não confie em pessoas que menosprezam o poder da substância, que não entendem do assunto e visam apenas lucro.
Não confie tambem em locais que indicam a ibogaína como uma panacéia, que cura tudo, desde a dependência até queda de cabelo. Claramente, isso é uma tentativa de angariar mais pacientes e aumentar os lucros.
Mesmo sendo derivada de uma planta, certos cuidados devem ser tomados. Não é toda medicação derivada de plantas que é "tranquila" ou "fraquinha", quem fala isso demonstra que não entende do assunto.
A ibogaína é muito eficiente, principalmente se comparada aos outros tratamentos disponíveis, mas para atingir bons resultados, é necessária uma expertise que alguns locais que fazem propaganda disseminada não possuem.
Apenas a título de informação, aqui está o link para um trabalho científico comentando essas mortes às quais me referi. Observe como no texto é dito que esses casos todos foram de pacientes com problemas de saúde prévios, usando medicação de origem desconhecida.
Dependencia química / Ibogaina
Tratamento de drogas
O atual momento da ibogaína merece uma tomada de consciência e um grande senso de responsabilidade das pessoas... Estão aparecendo a cada dia novas pseudo-clínicas, todas alardeando uma experiência e um conhecimento que não possuem, buscando atrair os incautos pacientes e familiares que, desesperados, tentam qualquer coisa sem pensar direito no que estão fazendo.
Como sempre dizemos, o tratamento com ibogaína é um procedimento que não é isento de riscos, deve ser feito em ambiente médico-hospitalar, com o paciente internado, para ser protegido e monitorado. O paciente deve estar limpo de drogas e de remédios por um tempo variável, de acordo com cada situação individual, e deve ser submetido a uma bateria de exames antes do procedimento. E a medicação utilizada, deve ser GMP, ou seja, fabricada segundo as boas práticas farmacêuticas.
Não confie em locais que usam, como diferencial para fazer propaganda, o argumento de que não é necessária internação, nem exames e nem abstinência prévia. Pelo menos 60 dias de internação são necessárias sim, para inclusive proteger o paciente de qualquer evento adverso .
Não confie em locais e sites que dão a entender que a ibogaína é a "cura" da dependência química, isso é simplificar demais um problema sério.
Desde que se descobriram os efeitos anti-dependência da ibogaína, em 1962, ocorreram cerca de 20.000 tratamentos em todo o mundo. Nestes 20.000 tratamentos, ocorreram 19 mortes, todas relacionadas a problemas de saúde prévios ( que teriam sido detectados se o paciente tivesse feito um check-up antes do procedimento) e também a uso de drogas muito perto do uso da ibogaína ( o que teria sido evitado se o paciente estivesse sob vigilância especializada).
Então, não confie em pessoas que menosprezam o poder da substância, que não entendem do assunto e visam apenas lucro.
Não confie tambem em locais que indicam a ibogaína como uma panacéia, que cura tudo, desde a dependência até queda de cabelo. Claramente, isso é uma tentativa de angariar mais pacientes e aumentar os lucros.
Mesmo sendo derivada de uma planta, certos cuidados devem ser tomados. Não é toda medicação derivada de plantas que é "tranquila" ou "fraquinha", quem fala isso demonstra que não entende do assunto.
A ibogaína é muito eficiente, principalmente se comparada aos outros tratamentos disponíveis, mas para atingir bons resultados, é necessária uma expertise que alguns locais que fazem propaganda disseminada não possuem.
Apenas a título de informação, aqui está o link para um trabalho científico comentando essas mortes às quais me referi. Observe como no texto é dito que esses casos todos foram de pacientes com problemas de saúde prévios, usando medicação de origem desconhecida.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
2. (12-14), have profound implications for both understanding the mechanism of
action of ibogaine and the molecular mechanism of drug addiction and
dependence. Ibogaine affects a substantial number of neurotransmitter pathways,
including N-methyl-D-aspartate (NMDA) and κ-opioid receptors, as well as
dopamine and serotonin uptake sites and σ sites [for a review, see (14)]. However,
the “antiaddictive” effects of ibogaine are still poorly understood, particularly at
the psychological level.
In the current paradigm of drug development, findings gained in behavioral
research ultimately direct our understanding of the drug’s mechanism of action,
provide evidence of its effectiveness in an animal model, and ultimately decide
whether a substance becomes a therapeutic agent (15). Findings gathered in
behavioral studies often raise questions concerning whether the given substance
may or may not be effectively used in a given clinical application, and also about
its “side effects.” In addition, the effects found in behavioral studies that are not
directly related to the purported mechanism of action often raise new questions
such as the relevance of a “side effect” to a therapeutic action. This appears to be
the case for ibogaine that, besides diminishing self-administration of drugs of
abuse and alleviating the severity of opioid withdrawal, produces
psychotomimetic effects, affects learning and memory processes (16-18), and has
anxiogenic actions (14).
It is beyond the scope of this overview to provide direct evidence linking these
“miscellaneous” or “side-effect”-like actions of ibogaine to its purported
“antiaddictive” effects. Nonetheless, these “miscellaneous” or “side-effect”-like
actions of ibogaine cannot be neglected, since they may indeed have some
therapeutic implications, and their understanding may facilitate the discovery of
its molecular mechanism(s) of action.
Operant and classical conditioning, habituation, and sensitization play
important roles in determining the level of drug tolerance, addiction, dependence,
and craving (19). Thus, inhibitory effects of ibogaine on drug addiction could be
linked to a general interference with learning and memory processes. Often, drug-
addicted individuals do not realize the roots of their habits—why they are,
indeed, drug addicted. There are numerous possibilities, including traumatic
experiences, such as events that took place in childhood. It can be hypothesized
that a therapy, able to uncover these experiences, would be helpful in localizing
and eliminating the cause of the disorder. This is the role of the psychotherapist,
but perhaps with the help of ibogaine, this role could be made easier.
It is known that ibogaine produces a variety of psychotomimetic effects. It is
debatable whether these are important from the clinical perspective. It would be
hard to argue that the “antiaddictive” effects in laboratory animals are due to the
hallucinogenic actions. It is also worth noting that there are many
psychotomimetic compounds that are not “antiaddictive.” Nonetheless, Naranjo,
who explored the possibility of using ibogaine to facilitate psychotherapy,
228 popik and wróbel
3. concluded that ibogaine could act as a psychological catalyst, which could
compress a long psychotherapeutic process into a shorter time (20).
II. Ibogaine and Anxiety
A. Experimental Rationale
In humans, ibogaine has been reported to produce anxiety, fear, and
apprehension (21). These effects are important, as they may influence the process
of psychotherapy and/or in some cases, can be regarded as a confounding factor.
Recently, Benwell and colleagues (22), while studying the possible effects of
ibogaine on the neurochemical actions of nicotine in rats, found that ibogaine
administered at the dose of 40 mg/kg, 22 hours before the test, produced an
anxiogenic effect. It must be considered that such an anxiogenic effect of
ibogaine may confound several measures of drug-seeking and taking behavior in
animal models of drug addiction. The present work was designed to determine if
the same effects on anxiety could be identified in mice following the
administration of lower doses of ibogaine given after a shorter time interval.
B. Experimental Methodology
1. Animals
Male Albino Swiss mice (26-32 g) obtained from the Institute of Pharmacology
breeding facility, were housed under standard laboratory conditions (lights on at
0600 hours, lights off at 1800 hours; room temperature 23 ± 1°) with pelleted
food and tap water available ad libitum. They were kept in 43 x 27 x 15 cm plastic
cages (eight mice per cage). All animals were used only once.
2. Drugs
Hydrochloride salt of ibogaine (Sigma) and the reference compound picrotoxin
were dissolved in the physiological saline that served as a placebo. Injections
were done i.p. in the volume of 10 ml/kg. The selection of doses was based on
previous studies with ibogaine (22) and picrotoxin (23,24).
3. Apparatus and Procedure
An elevated plus maze (23) was used to study the anxiety in mice. It was made
of plywood and consisted of two open arms (30 x 5 cm) and two enclosed arms
(30 x 5 x 15 cm). The arms extended from a central 5 x 5 cm platform. The maze
was painted black and mounted on a wooden base, raising it 50 cm above the
22912. anxiogenic action of ibogaine
4. floor. The apparatus was lit with two 15-watt lightbulbs placed 60 cm above the
open arms.
The experiments were carried out between 0900 and 1700 hours. Drugs were
administered 30 minutes before the test that lasted for 5 minutes. Mice were
tested in an order counterbalanced for the treatment condition. There were 8 to 10
mice in each group. Mice were placed on the central platform, and the time spent
on each of the four arms as well as the number of entries into arms was manually
recorded using PLUS MAZE 2.0 program on a PC-compatible computer. After
each mouse, the apparatus was cleaned and dried. The experimenter was blind to
the treatment condition. The percentage of open/total time ([open arm time/open
arm + closed arm time] x 100) as well as the percentage of open/total arm entries
([open arm entries/open arm + closed arm entries] x 100) served as the measures
of anxiety. The number of closed arm entries was used as the measure of
locomotor activity.
The experiments were carried out according to the National Institutes of Health
Guide for Care and Use of Laboratory Animals (publication No. 85-23, revised
1985) and were approved by the internal Bioethics Commission.
230 popik and wróbel
TABLE 1.
Anxiogenic Effects of Ibogaine in Mice
Treatment % Open/ % Open/total Closed arm
(mg/kg) total time arm entries entries [n]
Placebo [10] 6.21 ± 1.33 18.6 ± 1.36 13.1 ± 0.81
Ibogaine 10 [10] 3.07 ± 1.33 10.3 ± 3.12 12.3 ± 1.34
Ibogaine 20 [10] 2.03 ± 0.90* 10.7 ± 2.96 11.2 ± 0.73
Ibogaine 40 [9] 1.56 ± 0.73* 5.77 ± 2.50** 10.4 ± 1.27
ANOVA F(3,35) = 3.49, F(3,35) = 4.21, F(3,35) = 1.19,
P<0.05 P<0.05 NS
Placebo [10] 7.53 ± 0.86 20.8 ± 1.66 12.6 ± 0.68
PIC 0.25 [8] 5.03 ± 1.10 16.0 ± 1.85 12.0 ± 1.39
PIC 0.5 [8] 3.64 ± 1.19* 13.2 ± 2.66 11.4 ± 1.29
PIC 1 [10] 0.56 ± 0.35*** 9.15 ± 3.83* 6.20 ± 0.83***
ANOVA F(3,32) = 11.9, F(3,32) = 3.53, F(3,32) = 8.81,
P<0.001 P<0.05 P<0.0001
Presented are means ± S.E.M. of: (1) percentage of open/total arm time, (2) percentage of open/total arm entries,
and (3) the number of closed arm entries in the elevated plus maze. Results of (1) and (2) reflect the measures related
to the anxiety. The number of closed arm entries is regarded as the measure of general locomotor activity. Mice were
treated with placebo (physiological saline), ibogaine, and picrotoxin [PIC] 30 minutes before the test.
NS not significant
* (P < 0.05)
** (P < 0.01)
*** (P < 0.001)
Statistically significant difference compared to placebo treatment (Newman-Keul’s Multiple Comparison Test).
The number of mice used for each dose is indicated in the brackets.
5. 4. Statistical Analysis
For the statistics, one way between subjects ANOVA was performed for each
treatment condition, followed by Newman-Keul’s multiple comparison post-hoc
test.
C. Results
Ibogaine reduced the percentage of open/total arm time (20 and 40 mg/kg) and
the percentage of open/total arm entries (40 mg/kg). The decrease of the
percentage of open/total time and the percentage of open/total arm entries
produced by ibogaine was comparable to that observed in mice treated with
picrotoxin (0.5 and 1 mg/kg) (Table I). Mean locomotor activity (closed arm
entries) was not affected by the drugs tested, with the exception of picrotoxin (1.0
mg/kg) (Table I).
III. Discussion
The elevated plus maze (25) offers a reliable means of investigating anxiety in
rodents. Ibogaine and picrotoxin reduced the percentage of open/total time as
well as percentage of open/total arm entries, indicating that these compounds
increased the anxiety. The anxiogenic effect of picrotoxin is well known (23,25)
and therefore supports the use of this compound as reference. As in our study,
Dalvi and Rodgers (24) reported that the anxiogenic effect of picrotoxin in mice
at doses higher than or equal to 1 mg/kg was confounded by the behavioral
suppression.
Perhaps the first documented notion that ibogaine produces a subjective state
of anxiety was made by Sigg, who, after ingestion of 200 mg of ibogaine,
reported: “Subjectively, the most unpleasant symptoms were the anxiety, the
extreme apprehension, and the unheimliche Grundstimmung (~unfamiliar mood)
associated with visual and bodily hallucinations” (26), p. 94. More recent studies
indicate that ibogaine reduced the number of open arm entries in the elevated
plus-maze test in rats tested 22 hours after pretreatment with ibogaine (40 mg/kg,
i.p.). Such a long time between the drug administration and the test may suggest
the involvement of a long-lasting ibogaine metabolite, since ibogaine’s plasma
half-time in rodents is about 1 hour (27).
Ibogaine affects a substantial number of neurotransmitter pathways, including
NMDA and κ-opioid receptors, as well as dopamine and serotonin uptake sites
and σ sites [for a review, see (14)]. Ibogaine antagonistic activity at NMDA
receptors cannot explain its anxiogenic effects, because NMDA receptor
23112. anxiogenic action of ibogaine
6. antagonists reduce, rather than increase, anxiety in rodents (28). The high affinity
of ibogaine at the k-opioid receptors is supported by its ability to block the effects
of a κ-opioid agonist to inhibit dopamine and serotonin release (29), suggesting
that ibogaine may act as a κ-opioid antagonist. This is, in turn, supported by
findings indicating that κ-opioid agonists produce anxiolytic effects in the
elevated plus maze in rats (30). However, in light of other reports suggesting
agonist activity of ibogaine at κ-opioid receptors (31), it remains to be assessed
whether ibogaine’s activity at κ-opioid receptors plays a role in its anxiogenic
effect.
In conclusion, it remains to be established whether the acute (present study)
and delayed (22) anxiogenic effects of ibogaine are related to its inhibitory effects
on drug-seeking and taking behavior or if it may be regarded only as the
confounding factor. Alternatively, it is possible that the anxiogenic actions of
ibogaine revealed in mice may have nothing to do with their putative
antiaddictive actions in humans.
Acknowledgments
This work was supported by the statutory activity of the Institute of Pharmacology Polish Academy
of Sciences.
References
1. J. Dybowsky and E. Landrin, C. R. Acad. Sci. (Paris) 133, 748 (1901).
2. A. Haller and E. Heckel, Compt. Rend. Soc. Biol. 133, 850 (1901).
3. H.S. Lotsof, U.S. Patent 4,499,096 (1985).
4. S.G. Sheppard, J. Subst. Abuse Treat. 11, 379 (1994).
5. K.R. Alper, H.S. Lotsof, G.M.N. Frenken, D. Luciano, and J. Bastiaans, Am. J. Addict. 8, 234
(1999).
6. S.L.T. Cappendijk and M.R. Dzoljic, Eur. J. Pharmacol. 241, 261 (1993).
7. S.D. Glick, M.E. Kuehne, J. Raucci, T.E. Wilson, D. Larson, R.W. Keller, and J.N. Carlson,
Brain Res. 657, 14 (1994).
8. P. Popik, R.T. Layer, L. Fossom, M. Benveniste, B. Getter-Douglas, J.M. Witkin, and P.
Skolnick, J. Pharmacol. Exp. Ther. 275, 753 (1995).
9. R.T. Layer, P. Skolnick, C.M. Bertha, M.E. Kuehne, and P. Popik, Eur. J. Pharmacol. 309, 159
(1996).
10. I. Moroz, L.A. Parker, and S. Siegel, Exp. Clin. Psychopharm. 5, 119 (1997).
11. L.A. Parker, S. Siegel, and T. Luxton, Exp. Clin. Psychopharm. 3, 344 (1995).
12. W.I. Taylor, in “The Alkaloids: Chemistry and Physiology” (R.H.F. Manske, ed.), Volume 8,
p. 203. Academic Press, New York, NY, 1965.
232 popik and wróbel
7. 13. W.I. Taylor, in “The Alkaloids: Chemistry and Physiology” (R.H.F. Manske, ed.), Volume 11,
p. 79. Academic Press, New York, NY, 1968.
14. P. Popik and P. Skolnick, in “The Alkaloids: Chemistry and Biology” (G.A. Cordell, ed.),
Volume 52, p. 197. Academic Press, San Diego, CA, 1999.
15. P. Willner in “Behavioural Models in Psychopharmacology: Theoretical, Industrial and
Clinical Perspectives” (P. Willner, ed.), p. 3. Cambridge University Press, Cambridge, 1991.
16. R.P. Kesner, P. Jackson-Smith, C. Henry, and K. Amann, Pharmacol. Biochem. Behav. 51, 103
(1995).
17. P. Popik, Life Sci. 59, 379 (1996).
18. S. Helsley, D. Fiorella, R.A.Rabin, and J.C.Winter, Pharmacol. Biochem. Behav. 58, 37
(1997).
19. S. Siegel, in “Psychopathology in Animals, Research and Clinical Implications” (J.D. Keehn,
ed.), p. 143. Academic Press, New York, NY, 1979.
20. C. Naranjo, Clin. Toxicol. 2, 209 (1969).
21. J.A. Schneider and E.B. Sigg, Ann. N.Y. Acad. Sci. 66, 765 (1957).
22. M.E.M. Benwell, P.E. Holtom, R.J. Moran, and D.J.K. Balfour, Br. J. Pharmacol. 117, 743
(1996).
23. R.G. Lister, Psychopharmacology 92, 180 (1987).
24. A. Dalvi and R.J.Rodgers, Psychopharmacology 128, 380 (1996).
25. S. Pellow, P. Chopin, S.E. File, and M. Briley, J. Neurosci. Meth. 14, 149 (1985).
26. J.A. Schneider and E.B. Sigg, in “Progress in Neurobiology. Psychopharmacology;
Pharmacologic Effects on Behavior” (H.H. Pennes, ed.), p. 75. New York, NY, 1958.
27. H.I. Dhahir, Diss. Abstr. Int. 32/04-B, 2311 (1971).
28. J.L. Wiley, A.F. Cristello, and R.L. Balster, Eur. J. Pharmacol. 294, 101 (1995).
29. H. Sershen, A. Hashim, and A. Lajtha, Brain Res. Bull. 36, 587 (1995).
30. T.H. Privette and D.M. Terrian, Psychopharmacology 118, 444 (1995).
31. S.D. Glick, I.M. Maisonneuve, and S.M. Pearl, Brain Res. 749, 340 (1997).
23312. anxiogenic action of ibogaine