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At least 1,207 records · Page 67Linked to original sources
PubMed2003

Gene expression, neurogenesis, and healing: psychosocial genomics of therapeutic hypnosis.

The historical lineage of therapeutic hypnosis in James Braid's "psychophysiology", Pierre Janet's "physiological modification", and Milton Erickson's "neuro-psycho-physiology" is extended to include current neuroscience research on activity-dependent gene expression, neurogenesis, and stem cells in memory, learning, behavior change, and healing. Three conditions that optimize gene expression and neurogenesis--novelty, environmental enrichment, and exercise--could integrate fundamentals of the theory, research, and practice of therapeutic hypnosis. Continuing research on immediate-early, activity-dependent, behavior state-related, and clock gene expression could enhance our understanding of how relaxation, sleep, dreaming, consciousness, arousal, stress and trauma are modulated by therapeutic hypnosis. It is speculated that therapeutic and post-hypnotic suggestion could be focused more precisely with the time parameters of gene expression and neurogenesis that range from minutes and hours for synthesizing new synapses to weeks and months for the generation and maturation of new, functioning neurons in the adult brain.

Gene Expression↗
PubMed1993

Play and therapeutic action.

Children in clinical psychoanalysis are able to resolve conflicts and move ahead developmentally. This therapeutic process is facilitated by the psychoanalyst's understanding of the child, reflected in multi-faceted and thoughtful clinical technique. We review aspects of the analyses of four developmentally deviant children who were engaged in child psychoanalysis because of ego disturbances that impaired their ability to learn. These clinical analyses are used to exemplify three intertwined processes related to the therapeutic action of child psychoanalysis: therapeutic alliance, transference, and the role of the child analyst as a real person. These processes were expressed in and were influenced by the emergence of particular types of play in which the children explored complex issues in their lives. Along with other aspects of psychoanalytic technique, including interpretation, the analyses of these four children illustrate the therapeutic meanings of play in child psychoanalysis.

Child↗
PubMed1999

Emotional activation during therapeutic interaction in traumatic brain injury: effect of apathy, self-awareness and implications for rehabilitation.

Apathy and reduced self-awareness are frequent occurring neurobehavioural sequelae following traumatic brain injury (TBI). Apathy, in terms of reduced goal directed activity and lowered motivation, and reduced self-awareness have a negative impact on the rehabilitation process. In this study, 30 patients suffering severe TBI were clinically rated for apathy and monitored for cardiovascular and electrodermal reactivity during baseline, neutral speech and therapeutic interaction. Applying a cut-off score criterion, two thirds of the TBI sample were classified as apathetic. The apathetic patients showed less psychophysiological reactivity from neutral speech to therapeutic interaction, compared to non-apathetic patients. They also reported less perceived emotional discomfort in the therapeutic situation measured with a visual analogue scale. Moreover, reduced self-awareness was associated with low autonomic reactivity. The results suggest that the reduced psychophysiological reactivity in apathetic patients may be a correlate to the lack of emotional responsivity, disengagement, lack of insight and concern about their own situation. Clinically, these results may have implications for psychotherapeutic intervention aimed at improving self-awareness. Recording psychophysiological responses during therapeutic interaction may serve as a method for monitoring emotional involvement during psychotherapy with TBI patients.

Adolescent↗
PubMed2004

Treatment motivation and therapeutic engagement in prison-based substance use treatment.

Studies of community-based substance use treatment show that motivation for treatment is critical for clients becoming therapeutically engaged. Little research, however, has been conducted on therapeutic engagement in corrections-based substance use treatment. The current study examines the association between internal treatment motivation and therapeutic engagement for a sample of 220 male substance-using offenders enrolled in a corrections-based treatment program. Findings showed that problem recognition and desire for help were associated with cognitive indicators of therapeutic engagement, specifically confidence in and commitment to treatment. Increased focus on internal motivation for treatment may lead to more effective treatment for substance-using offenders. Pretreatment motivational interventions therefore are recommended for substance-using offenders with low internal motivation for treatment.

Adult↗
PubMed2006

Recommendation of the use of myeloblast percentage among non-erythroid cells instead of percentage among total nucleated cells for therapeutic response assessment in acute erythroid leukemia.

The diagnostic criteria of acute erythroid leukemias (AEL) has been revised by WHO in 2001. The National Cancer Institute (NCI) published a set of standardized diagnostic and response criteria for acute myeloid leukemia in 1990, which was revised in 2003. The aim of the present study was to establish the best criteria for therapeutic response assessment in the newly classified AEL and evaluate patient outcomes. Fifty-two patients with AEL as defined by the new WHO criteria were evaluated in this study. The following seven indices for therapeutic response assessment were evaluated: (i) NCI criteria (myeloblast percentage among total nucleated cells (TNC) and cellularity); (ii) myeloblast percentage among non-erythroid cells (NEC) and cellularity; (iii) erythroid series percentage among TNC; (iv) pronormoblast percentage among erythroid cells; (v) ratio of pronormoblasts and blasts; (vi) maturation arrest index; and (vii) disappearance of erythroid dysplasia. Complete remission (CR) patients with <5% of myeloblast/NEC (NEC-CR) showed significantly longer overall survival periods (mean 55.8 months) compared to CR patients with >5% myeloblast/NEC (mean 11.7 months, P = 0.006). NEC-CR patients also had longer event-free survival (median 16.4 months) compared to patients with >5% and <20% of myeloblast/NEC (median 6.2 months) (P = 0.044). The other indices for therapeutic response assessment are not significant for predictability of relapse and outcomes. Therefore, we recommend that the myeloblast percentage among NEC be used instead of myeloblast percentage among TNC for therapeutic response assessment in AEL.

Adolescent↗
PubMed2006

Failure of therapeutic coma and ketamine for therapy of human rabies.

The recent success in treating a human rabies patient in Milwaukee prompted the use of a similar therapeutic approach in a 33-year-old male Thai patient who was admitted in the early stages of furious rabies. He received therapeutic coma with intravenous diazepam and sodium thiopental to maintain an electroencephalographic burst suppression pattern, which was maintained for a period of 46 h, as well as intravenous ketamine (48 mg/kg/day) as a continuous infusion and ribavirin (48 to 128 mg/kg/day) via a nasogastric tube. He never developed rabies virus antibodies and he died on his 8th hospital day. At least three other patients have been treated unsuccessfully with a similar therapeutic approach. Because of the lack of a clear scientific rationale, high associated costs, and potential complications of therapeutic coma, the authors recommend caution in taking this approach for the therapy of rabies outside the setting of a clinical trial. More experimental work is also needed in cell culture systems and in animal models of rabies in order to develop effective therapy for human rabies.

Adult↗
PubMed2026

Proteomic insights into Helicobacter pylori infection in stomach cells, revealing host response and host-targeted therapeutics repurposing.

BACKGROUND: Helicobacter pylori (H. pylori) is a globally prevalent gastric pathogen strongly associated with chronic gastritis, peptic ulcers, and gastric cancer. While bacterial factors have been extensively studied, host proteomic responses and their therapeutic potential remain largely underexplored. RESEARCH DESIGN AND METHODS: Current analyses employed a systematic proteomics-based data integration and harmonization approach (retrospective qualitative cohort study) to identify important differentially regulated host proteins. Proteomic datasets were curated from in vitro studies and analyzed for functional enrichment, protein-protein interaction networks, and hub protein identification. To explore therapeutic repurposing, drug repositioning was performed using the DrugBank database. RESULTS: Data summation describing protein differential regulation in human gastric cells as a result of the infection revealed 1672 perturbed host proteins. Bioinformatics analysis revealed 11 proteins including CSK, MET, RELA, MARK2, GRB2, FTO, PLCG1, CRKL, RPS5, RPS9, and RPS27A to be ideal host targets for therapeutic repurposing. Clinically approved drugs such as Dasatinib (targeting CSK) and Crizotinib (targeting MET) emerged as promising candidates due to favorable pharmacokinetics and known bioactivity. CONCLUSIONS: Host-directed therapeutics could offer alternative strategies to conventional antibiotic therapy, addressing challenges such as resistance and infection recurrence, providing a foundation for future experimental validation and development of host-targeted interventions for infection control.

Humans↗
PubMed1989

Toxicity and therapeutic efficacy of high-dose interleukin 2. In vivo infusion of antibody to NK-1.1 attenuates toxicity without compromising efficacy against murine leukemia.

In the current study we used the therapy of established murine leukemia to identify the lymphocyte subsets responsible for toxicity and for therapeutic efficacy of high-dose IL-2. Initial results confirmed that high-dose IL-2 induces marked proliferation of a variety of host cells, including NK cells, Lyt-2+ T cells, L3T4+ T cells, and B cells. Infusion of antibody to NK-1.1 depleted NK-1.1+ cells in vivo and greatly reduced the toxicity of IL-2, but did not decrease therapeutic efficacy. By marked contrast, depletion of host T cells, either Lyt-2+ or L3T4+, had no effect on toxicity but greatly reduced therapeutic efficacy. The requirement for host T cells for the curative effect of IL-2 gives credence to the possibility that substantial efficacy of high-dose IL-2 against established malignancy may require existent host antitumor immunity. Since the human tumors that have been shown to have the most substantial responses to IL-2 (i.e., malignant melanoma and renal cell carcinoma) are those long considered to be immunogenic in the autochthonous host, the current study predicts that for these, as well as other immunogenic human tumors, it should be possible to decrease the toxicity and thus increase the therapeutic index of IL-2 by selectively depleting NK cells in vivo.

Animals↗
PubMed2000

Visions of a cure. Visualization, clinical trials, and controversies in cardiac therapeutics, 1968-1998.

In the early 1970s physicians engaged in fierce debates over the most appropriate method of evaluating the efficacy of coronary artery bypass grafting (CABG). With millions of patients and billions of dollars at stake, CABG sparked fierce controversy. Skeptics demanded that randomized controlled trials (RCTs) be performed, while enthusiasts argued that they already had visual proof of CABG's efficacy. When RCTs appeared, they did not settle the controversy. Participants simply reasserted their preconceptions, defending a trial's strengths or exploiting its flaws. The debate centered on standards of knowledge for the evaluation of therapeutic efficacy. Specifically, cardiologists and cardiac surgeons struggled to assess the relevance of different measures of therapeutic success: physiological or clinical, visual or statistical. Many factors contributed to participants' decisions, including disciplinary affiliation, traditions of research, personal experience with angiography, and assessments of the history of cardiac therapeutics. Physicians had to decide whether angiography provided a meaningful representation of the disease and its treatment or whether demonstrations of therapeutic success could come only from long-term statistical evaluation of mortality data.

Attitude of Health Personnel↗
PubMed2002

Cytokines as therapeutic drugs.

Cytokines are a growing group of proteins that are responsible for the communication of cells of the immune system, hematopoietic cells, and other cell types. They play a dominant role in various diseases, particularly in promoting and perpetuating inflammation. Cytokine production is a reaction of the body to a pathologic state to restore homeostasis. In such cases, the therapeutic intervention should support the reaction of the body by giving the cytokine itself (agonistic therapeutics). In other cases, manifestation of a disease results from an overproduction of cytokines, making cytokine antagonists desirable therapeutic drugs. Furthermore, cytokines may be good candidates as cancer therapeutics, especially to support the restoration of blood cell populations after chemotherapy or radiation.

Animals↗
PubMedDate not supplied

The emerging functions of UCP2 in health, disease, and therapeutics.

The uncoupling proteins (UCPs) are attracting an increased interest as potential therapeutic targets in a number of important diseases. UCP2 is expressed in several tissues, but its physiological functions as well as potential therapeutic applications are still unclear. Unlike UCP1, UCP2 does not seem to be important to thermogenesis or weight control, but appears to have an important role in the regulation of production of reactive oxygen species, inhibition of inflammation, and inhibition of cell death. These are central features in, for example, neurodegenerative and cardiovascular disease, and experimental evidence suggests that an increased expression and activity of UCP2 in models of these diseases has a beneficial effect on disease progression, implicating a potential therapeutic role for UCP2. UCP2 has an important role in the pathogenesis of type 2 diabetes by inhibiting insulin secretion in islet beta cells. At the same time, type 2 diabetes is associated with increased risk of cardiovascular disease and atherosclerosis where an increased expression of UCP2 appears to be beneficial. This illustrates that therapeutic applications involving UCP2 likely will have to regulate expression and activity in a tissue-specific manner.

Aging↗
PubMed2020

Translating CRISPR-Cas Therapeutics: Approaches and Challenges.

CRISPR-Cas clinical trials have begun, offering a first glimpse at how DNA and RNA targeting could enable therapies for many genetic and epigenetic human diseases. The speedy progress of CRISPR-Cas from discovery and adoption to clinical use is built on decades of traditional gene therapy research and belies the multiple challenges that could derail the successful translation of these new modalities. Here, we review how CRISPR-Cas therapeutics are translated from technological systems to therapeutic modalities, paying particular attention to the therapeutic cascade from cargo to delivery vector, manufacturing, administration, pipelines, safety, and therapeutic target profiles. We also explore potential solutions to some of the obstacles facing successful CRISPR-Cas translation. We hope to illuminate how CRISPR-Cas is brought from the academic bench toward use in the clinic.

CRISPR-Cas Systems↗
PubMed1997

Therapeutic efficiency and safety of a second-generation replication-conditional HSV1 vector for brain tumor gene therapy.

A second-generation replication-conditional herpes simplex virus type 1 (HSV) vector defective for both ribonucleotide reductase (RR) and the neurovirulence factor gamma34.5 was generated and tested for therapeutic safety and efficiency in two different experimental brain tumor models. In culture, cytotoxic activity of this double mutant HSV vector, MGH-1, for 9L gliosarcoma cells was similar to that of the HSV mutant, R3616, which is defective only for gamma34.5, but was significantly weaker than that of the HSV mutant hrR3, which is defective only for RR. The diminished tumoricidal effect of the gamma34.5 mutants could be accounted for by their reduced ability to replicate in 9L cells. The MGH-1 vector did not achieve significant prolongation of survival in vivo in the syngeneic 9L rat gliosarcoma model for either single brain tumor focus or multiple intracerebral and leptomeningeal tumors, when the vector was applied intratumorally or intrathecally, respectively, and with or without subsequent ganciclovir (GCV) treatment. In identical 9L brain tumor models with single and multiple foci, application of hrR3 with or without GCV was previously shown to result in marked long-term survival. Contrary to the findings with intrathecal injection of hrR3, no vector-related mortality was observed in any animals treated with MGH-1. Thus, in these rat brain tumor models, the double mutant, replication-conditional HSV vector MGH-1 showed a higher therapeutic safety than the RR-minus vector, hrR3, but had clearly decreased therapeutic efficiency compared to hrR3. The development of new HSV vectors for brain tumor gene therapy will require a balance between maximizing therapeutic efficacy and minimizing toxicity to the brain. Standardized application in brain tumor models as presented here will help to screen new HSV vectors for these requirements.

Animals↗
PubMed2005

Induction of therapeutic antitumor immunity by in vivo administration of a lentiviral vaccine.

Direct in vivo administration of a lentiviral vaccine has been shown to transduce dendritic cells (DCs) in order to induce antigen-specific CD8+ T cell responses, but the efficacy of antitumor immunity has not been reported. In this study we tested whether direct in vivo administration of a lentiviral vaccine can induce selfantigen- based therapeutic antitumor immunity in murine tumor models. Lentiviral vector (LV) transduced DCs efficiently in vitro and was able to transduce DCs in vivo. LV-transduced DCs effectively presented antigens to T cells. Compared with a naked DNA tyrosinase-related protein-2 (TRP2)-heat shock protein-70 (hsp70) vaccine, the TRP2-specific interferon-gamma-producing CD8+ T cell response was augmented by direct in vivo administration of an LV-TRP2hsp70 vaccine, which induced significant therapeutic antitumor immunity in subcutaneous B16 and subcutaneous GL-26 models. Moreover, in vivo administration of an LV-NeuEDhsp70 vaccine induced significant therapeutic antitumor immunity against spontaneous breast tumors in a BALB/c- Neu transgenic model. Our observations indicate that direct in vivo administration of a lentiviral vaccine not only enhances antigen-specific CD8+ T cell responses, but also generates significant therapeutic antitumor activities.

Animals↗
PubMed2005

Elements of style: consent form language and the therapeutic misconception in phase 1 gene transfer trials.

The therapeutic misconception arises wherever human subjects misinterpret the primary purpose of a clinical trial as therapeutic. Such misconceptions are particularly prevalent in trials involving severely ill subjects or novel and well-publicized investigational agents. In order to identify possible sources of the therapeutic misconception in gene transfer trials, 286 phase 1 human gene transfer consent documents were analyzed for their description of purpose, alternatives, and their use of the term gene transfer. We report that 20% of trials fail to explain their purpose as safety and dosage, only 41% of oncology trials identify comfort care as an alternative to participation, and that the term gene therapy is used with twice the frequency of the term gene transfer. Trends and coherence in consent form language were analyzed as well. Our results indicate that consent forms used in gene transfer phase 1 trials often contain language that promotes, or does little to deter, therapeutic misconceptions.

Clinical Trials, Phase I as Topic↗
PubMed2006

Lentivirus-mediated gene transfer to the central nervous system: therapeutic and research applications.

The management of disorders of the nervous system remains a medical challenge. The key goals are to understand disease mechanisms, to validate therapeutic targets, and to develop new therapeutic strategies. Viral vector-mediated gene transfer can meet these goals and vectors based on lentiviruses have particularly useful features. Lentiviral vectors can deliver 8 kb of sequence, they mediate gene transfer into any neuronal cell type, expression and therapy are sustained, and normal cellular functions in vitro and in vivo are not compromised. After delivery into the nervous system they induce no significant immune responses, there are no unwanted side effects of the vectors per se to date, and manufacturing and safety testing for clinical applications are well advanced. There are now numerous examples of effective long-term treatment of animal models of neurological disorders, such as Parkinson's disease, Alzheimer's disease, Huntington's disease, motor neuron diseases, lysosomal storage diseases, and spinal injury, using a range of therapeutic genes expressed in lentiviral vectors. Significant issues remain in some areas of neural gene therapy including defining the optimum therapeutic gene(s), increasing the specificity of delivery, regulating expression of potentially toxic genes, and designing clinically relevant strategies. We discuss the applications of lentiviral vectors in therapy and research and highlight the essential features that will ensure their translation to the clinic in the near future.

Alzheimer Disease↗
PubMed1999

Intravitreal toxicology and therapeutic efficacy of the carboxymethyl ester of the 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA-O-Me), a novel lipid antiviral prodrug for intraocular drug delivery.

This study was conducted to evaluate the vitreous clarity and intraocular therapeutic index of three preparations ofthe carboxymethyl ester of 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA-O-Me), a long acting lipid derivative of foscarnet with potent anti-CMV activity. Twenty-six New Zealand white rabbits were intravitreally injected with one of three preparations of ODG-PFA-O-Me or control diluent. The vitreous clarity was graded after injection using indirect ophthalmoscopy and fundus photography. Drug intraocular toxicity was evaluated by electroretinography and by post-sacrifice tissue pathology using light and electron microscopy. Intravitreal injection of micellar ODG-PFA-O-Me showed variable local retinal toxicity and vitreal compound aggregates in eyes with the middle and high doses. The intraocular therapeutic index was lower than 465:1. Intravitreal injection of liposomal ODG-PFA-O-Me, either free acid or sodium salt, revealed clear vitreous for the 0.632 and 0.84 mM final intravitreal concentrations. No retinal toxicity was confirmed for the 1.12 mM final intravitreal concentration at the eight week observation following injection. The intraocular therapeutic index was between 585-1037:1. ODG-PFA-O-Me possesses better vitreous compatibility than ODG-PFA. Liposomal ODG-PFA-O-Me can be intravitreally injected with a resulting clear vitreous and high intraocular therapeutic index. Liposomal ODG-PFA-O-Me could be a long acting nontoxic intravitreous injectable drug for CMV retinitis.

Animals↗
PubMed1990

Free and liposomal doxorubicin treatment of intraperitoneal colon 26 tumor: therapeutic and pharmacologic studies.

Intraperitoneal (i.p.) chemotherapy is being investigated as an adjunct to surgery to kill residual cancer cells, inhibit cancer cell seeding, local recurrence, and metastases for ovarian, gastric, and colon cancers. In this report, the therapeutic effects of Doxorubicin (Dox) and liposome-entrapped Dox (Dox-Lip) against i.p. mouse colon 26 (C26) tumor were compared. It was found that Dox-Lip was less toxic than Dox after i.p. administration in non-tumor bearing animals. I.P. Dox and Dox-Lip significantly inhibited the growth of C26 tumor when the treatment was initiated 1 day after tumor cell inoculation, but both administration forms were ineffective against well-established (8-day) tumors. Multiple dose schedules did not improve the therapeutic response. Dox-Lip was not therapeutically superior to Dox at equal doses or at approximately equi-toxic doses. In addition, the relative retention of Dox and Dox-Lip in the peritoneal cavity and their plasma pharmacokinetics were investigated. It was found that Dox levels in the peritoneal cavity were maintained for longer periods after i.p. Dox-Lip was administered. However, the results show that maintenance of elevated drug levels in the peritoneal cavity does not necessarily lead to increased therapeutic effects.

Animals↗