Possible therapeutics for Pseudomyxoma peritonei: a rare, lethal, and the least investigated disease

Pseudomyxoma peritonei (PMP) refers to a growth disorder characterized by glycoprotein neoplasm in the peritoneum, where mucin oversecretion occurs. The tumors of the appendix region are well associated with PMP; however, ovarian, colon, stomach, pancreas, and urachus tumors have also been linked to PMP. Other mucinous tumors in the pelvis, paracolic gutters, greater omentum, retrohepatic space, and Treitz ligament can be the reason for PMP. Despite being rare and having a slow growth rate, PMP can be lethal without treatment. It is treated with neoadjuvant chemotherapy with the option of cytoreductive surgery and intraperitoneal chemotherapy. In the current study, we hypothesize that there may be novel gentle ways to inhibit or eliminate the mucin. Dr. David Morris has used mucolytics - such as bromelain and N-acetyl cysteine to solubilize mucin. In the present review, we aimed to study the regulation of mucin expression by promoter methylation, and drugs that can inhibit mucin, such as boldine, amiloride, naltrexone, dexamethasone, and retinoid acid receptors antagonist. This review also explored some possible pathways, such as inhibition of Na + , Ca2+ channels and induction of DNA methyltransferase along with inhibition of ten-eleven translocation enzymes, which can be good targets to control mucin. Mucins are strong adhesive molecules that play great roles in clinging to cells or cell to cell. Besides, they have been greatly involved in metastasis and also act as disease markers for cancers. Diagnostic markers may have exclusive roles in disease initiation and progression. Therefore, the present review explores various drugs to control and target mucin in various diseases, specifically cancers. (AU)

The Current Situation of Treatment Systems for Alcoholism in Korea

Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care.

Ensaio clínico duplo-cego randomizado e placebocontrolado com naltrexona e intervenção breve no tratamento ambulatorial da dependência de álcool / A double blind, randomized and placebo-controlled clinical trial with naltrexone and brief intervention in outpatient treatment of alcohol dependence

OBJETIVO: O objetivo deste estudo é avaliar a eficácia da naltrexona com intervenção breve em pacientes com dependência de álcool. MÉTODO: Este estudo é um ensaio clínico randomizado, duplo-cego, placebo-controlado de 12 semanas. A amostra de 71 pacientes foi dividida randomicamente em dois grupos (um recebendo naltrexona e outro placebo). Sujeitos dependentes de álcool foram tratados com 50 mg de naltrexona ou placebo diariamente por 12 semanas. Ambos os grupos de tratamento receberam intervenção breve. Os desfechos clínicos primários para este estudo foram taxa de recaída e mudança no padrão de consumo de álcool. RESULTADOS: Na intenção de tratar, menor porcentagem de sujeitos tratados com naltrexona recaíram (3 por cento 21 por cento; p = 0,054). Naltrexona com intervenção breve não foi superior ao placebo para diminuir os dias de consumo (6,2 + 10,6 3,05 + 7,3; p = 0,478), os dias de consumo moderado (0 2,2 + 6,9; p = 0,345) e os dias de consumo pesado (0,03 + 0,2 0,3 + 0,9; p = 0,887). Naltrexona foi bem tolerada. Os efeitos adversos mais frequentes na presente amostra foram: cefaleia (25,4 por cento), sonolência (20,9 por cento), náuseas (16,4 por cento), hiperfagia (16,4 por cento), anorexia (14,9 por cento), ansiedade (10,4 por cento), pirose (10,4 por cento) e irritabilidade (10,4 por cento). CONCLUSÕES: Embora o grupo naltrexona tenha demonstrado tendência para reduzir taxa de recaída (> 5 doses/dia), não foi encontrada nenhuma diferença em outras variáveis de consumo de álcool entre os grupos naltrexona e placebo. Estudos futuros devem examinar a eficácia desse tipo de combinação de tratamento nos cuidados primários de saúde.

OBJECTIVE: The objective of this study is to evaluate the efficacy of naltrexone with brief intervention among patients with alcohol dependence. METHOD: This study is a 12-week randomized, double blind, placebo-controlled clinical trial. The sample of 71 patients was randomly divided in two groups (one receiving naltrexone and the other placebo). Alcohol-dependent subjects were treated with 50 mg of naltrexone or placebo daily for 12 weeks. Both treatment groups received brief intervention. The primary results for this study were relapse rate and change in drinking behaviors. RESULTS: In the intention-to-treat fewer naltrexone treated subjects relapsed (3 percent 21 percent; p = 0.054). Naltrexone with brief intervention was not effective in decreasing drinking days (6.2 + 10.6 3.05 + 7.3; p = 0.478), moderate drinking days (0 2.2 + 6.9; p = 0.345) and heavy drinking days (0.03 + 0.2 0.3 + 0.9; p = 0.887). Naltrexone was well tolerated. The most frequent adverse effects in our sample were: headache (25.4 percent), drowsiness (20.9 percent), nausea (16.4 percent), hyperphagia (16.4 percent), anorexia (14.9 percent), anxiety (10.4 percent), heartburn (10.4 percent) and irritability (10.4 percent). CONCLUSIONS: Although the naltrexone group showed a tendency to reduce relapse rate (> 5 drinks/day), no differences were found in other alcohol consumption variables between naltrexone and placebo groups. Further studies should examine the efficacy of this kind of treatment combination in the primary health care.

Actualización del tratamiento farmacológico de la dependencia alcohólica / Pharmacological review of alcoholic dependence treatment

El objetivo de la presente actualización farmacológica es abordar la problemática de la dependencia alcohólica. Partiendo de las bases biológicas y del impacto del etanol sobre los sistemas neurobiológicos y de neurotransmisión, se hará una revisión de las principales herramientas farmacológicas para el tratamiento de la dependencia alcohólica. El disulfiram, la naltrexona y el acamprosato, todas ellas con aprobación por la FDA (Food and Drug Administration) han mostrado mecanismos de acción, perfiles de eficacia, tolerabilidad y adherencia dispares. También nos referiremos al topiramato, el que está siendo estudiado actualmente con relación a esta indicación.

The aim of the present pharmacological update is to revise the problem of alcohol dependence. Starting from the biological bases and the impact of alcohol on the neurobiological and neurotransmission systems, a revision of the main pharmacological tools for alcohol dependence treatment will be done. Disulfiram, naltrexone, acamprosate, all of them approved by the FDA (Food and Drug Administration), have shown mechanisms of action, efficacy, tolerance and adherence dissimilar. We will also refer to topiramate, which is being studied for this indication.

Tratamiento del Síndrome de Retiro de Opiáceos: síndrome de retiro descrito como subjetivamente severo y objetivamente moderado / Drug therapy of opioid withdrawal

Si bien la dependencia a opiáceos es de baja frecuencia de aparición en nuestro medio, es importante conocer su manejo ya que requiere tratamiento farmacológico en la mayoría de los casos. En la actualidad, en nuestro país, se podría clasificar a las distintas poblaciones de pacientes capaces de presentar un síndrome de retiro a opiáceos en: pacientes sometidos a tratamiento crónico con opiáceos, pacientes internados en unidades de cuidados intensivos, neonato de madre adicta y pacientes adictos provenientes de la población en general o ligada al sistema de salud. Los programas de desintoxicación son caracterizados típicamente por un bajo índice de finalización del tratamiento y un alto índice de recaída. El síndrome de retiro a opiáceos es subjetivamente severo y objetivamente moderado y las metas de la terapia en el Síndrome de Retiro de Opiáceos son: evitar o reducir los síntomas objetivos y subjetivos de abstinencia; prevenir o tratar las complicaciones más serias; tratar las enfermedades psiquiátricas preexistentes o concurrentes; reducir la frecuencia o la severidad de las recaídas y rehabilitar a largo plazo.

Although the opiate dependence is of low frequency in our midst, it is important to know its management because it requires medical treatment in most cases. At present, in our country, we may classify the different patient populations able to submit an opioid withdrawal syndrome in patients undergoing chronic treatment with opioids, patients in intensive care units; neonatal mother addicted patients and addicts from the general population or linked to the health system. Detoxification programs are typically characterized by a low rate of completion of treatment and a high rate of relapse. The opioid withdrawal syndrome is objectively and subjectively severe and moderate and the goals of the therapy for the Opiates Withdrawal Syndrome are: to prevent or reduce the objective and subjective symptoms of abstinence; to prevent or treat its most serious complications; to treat preexisting or concurrent psychiatric disorders; to reduce the frequency or severity of relapses and to rehabilitate in the long term.

Experiencia interdisciplinaria en la problemática del alcoholismo / Interdisciplinary experience in the problematic one of the alcoholism

El presente estudio de investigación enuncia los resultados de la aplicación de un tratamiento integral a pacientes afectados por el alcoholismo. Realizado por un equipo interdisciplinario perteneciente a la Universidad Nacional de Santiago del Estero.

Pharmacotherapy for Alcohol Dependence: Anticraving Medications for Relapse Prevention

Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, however, in conjunction with behavioral therapy, is generating interest as another modality to prevent relapse and enhance abstinence. Naltrexone and acamprosate are at the forefront of the currently available pharmacological options. Naltrexone is an opioid receptor antagonist and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes the dysregulation of N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation that occurs in alcohol withdrawal and early abstinence.These different mechanisms of action and different target neurotransmitter systems may endow the two drugs with efficacy for different aspects of alcohol use behavior. Since not all patients seem to benefit from naltrexone and acamprosate, there are ongoing efforts to improve the treatment outcomes by examining the advantages of combined pharmacotherapy and exploring the variables that might predict the response of the medications. In addition, novel medications are being investigated to assess their efficacy in preventing relapse and increasing abstinence.

Tratamento farmacológico da dependência do álcool / The pharmacologic treatment of the alcohol dependence

As intervencões farmacológicas podem ter um papel crucial na reducão do craving, consumo de álcool e manutencão da abstinência. Este artigo revisa a farmacoterapia para a dependência de álcool com ênfase na naltrexona, dissulfiram e acamprosato. O antagonista opióide naltrexona diminui taxas de recaída, reduz dias de consumo e prolonga períodos de abstinência. Acamprosato restaura a atividade normal dos sistemas glutamato e GABA. Dissulfiram tem demonstrado ser mais efetivo para pacientes que acreditam em sua eficácia e permanecam aderentes ao tratamento. Ondansetron tem-se mostrado promissor na dependência de álcool de início precoce, mas necessita estudos mais extensivos. Topiramato (até 300 mg/dia) foi mais eficaz do que placebo no tratamento da dependência de álcool.

The use of naltrexone to treat ambulatory patients with alcohol dependence

The purpose of this study is to evaluate the efficacy of Naltrexone in decreasing craving symptoms among Puerto Rican male veterans with alcohol dependence. METHOD: This is a double blind placebo control study with a convenience sample of eleven patients divided in two groups (placebo and Naltrexone). Scales consisting of Zung Depression, Zung Anxiety, MMSE, OCD Screener, Craving, and Somatization were administered at baseline, and weekly for four weeks as follow up. RESULTS: There were no statistically significant differences between the two groups on any of the outcome variables at baseline or follow up measurements. A statistical trend was noted toward a decrease in somatization. A decrease in craving symptoms was observed in the experimental group. CONCLUSIONS: Even though our results did not show evidence of the efficacy of Naltrexone in decreasing craving symptoms, a small number of patients did benefit from the medication. The results could have been affected by the small sample size

Amenorrea hipotalámica, concepto, clasificación y alternativas terapeúticas / Hipothalamic amenorrhea, concept, clasification and therapeutical alternatives

El desarrollo de amenorrea hipotalámica refleja generalmente una respuesta individual al stress ambiental y al propio estilo de vida. En la mayoría de los casos, no hay una anormalidad anatómica detestable del eje hipotálamo-hipófisis-ovario-endometrio. Numerosas evidencias sugieren que el defecto de base es una reducción de la actividad del generador hipotalámico de pulsos de GNRH. Los factores neuroendocrinos que regulan la función de este centro son parcialmente conocidos. El sistema opioidérgico y dopaminérgico han sido implicados como posibles factores en la reducción de la secreción pulsátil de GNRH. Debido a la naturaleza por lo general funcional del trastorno, se espera una reactivación de la actividad pulsátil de GNRH una vez superado los factores que lo desencadenaron. La persistencia de la anovulación obliga a una terapia de reemplazo hormonal fundamentalmente por el riesgo de terapia de reemplazo hormonal fundamentalmente por el riesgo de osteoporosis. En las pacientes que desean fertilidad, la inducción de ovulación con GNRH pulsátil es la alternativa terapéutica más efectiva

A naturalistic analytic study of veterans using naltrexone in Puerto Rico

Los records médicos de 18 pacientes que estaban usando Naltrexona y 13 pacientes que abandonaron esta actividad terapéutica fueron estudiados al azar, para determinar aquellas carcterísticas biosiocosociales de mayor utilidad clínica en un programa de rehabilitación ambulatória. Se descubrieron sus similitudes y diferencias. Algunas hipótesis fueron presentadas ya que prometen ser de gran utilidade clínica. Um hallazgo de gran relevancia clínica (P < 0.01) fue la mayor capacidad del grupo que se mantenía usando Naltrexona para mantener uma relación marital que la del grupo que abandonó el uso del antagonista del opiaceo

Naltrexone: useful tool in the treatment of heroin users; a review of the literature

La Naltrexona, un efectivo antagonista de los opiaceos ha demostrado ser muy efectivo en la rehabilitación de adictos a opiaceos que estén motivados, cuenten con buen apoyo familiar y que tengan buenas destrezas vocacionales. El tratamiento debe ser ofrecido por equipo especializados en la rehabilitación de adictos. El uso comercial de la Naltrexona promete ser de una alta eficiencia en aumentar el impacto positivo de los programas de rehabilitación. Esperamos que junto a las otras técnicas de educación comunitaria, adecuadas presiones sociales y las múltiples técnicas terapéuticas ya conocidas pueda prevenirse muchas de las miles de pérdidas humanas que ocurren en el mundo todos los años debido a estas dependencias. Además, esta sustancia tiende a restaurar el equilibrio hormonal de cuerpo lo que parece contribuir a que los pacientes presenten menos signos de tensión y disforia en el período de abstinencia