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PubMed2005

Integral therapeutic potential of bone marrow mesenchymal stem cells.

Bone marrow derived mesenchymal stem cells (MSC) are adult stem cells that reside within the bone marrow compartment. In the traditional developmental model, adult stem cells are able to differentiate only to the tissue in which they reside. Recent data have challenged the committed fate of the adult stem cells, presenting evidence for their multi-lineage differentiation potential. In addition, potential therapeutic benefits of MSC administration have been the main concern of much research, including clinical trials. These studies promote adult stem cell therapy by shedding some light on the therapeutic potential of MSC and their mechanism of action. Many doubts have found their way into MSC research. They question MSC potency and beneficial contribution. However, these obstacles should not arrest but set a challenge to MSC researchers to examine their achievements under a magnifying glass. Therapeutic benefits of MSC exogenous delivery do not run counter to its possible participation in endogenous repair. Several reports imply MSC involvement in physiological repair but no explicit data support this hypothesis. This review tries to put MSC research into perspective. Possible therapeutic applications of MSC therapy for damaged tissue replacement, tissue engineering and the underlying repair mechanisms will be discussed. In addition, reported data about MSC possible involvement in physiological multiple tissue repair, their homing to injury and site-specific differentiation will be presented.

Animals↗
PubMed2006

TGF-beta: its role in asthma and therapeutic potential.

Asthma is a chronic disease of the airways affecting around 10% of the population. The majority of cases are well controlled with current therapies, however in approximately 20% of severe asthmatics the available therapeutic strategies are inadequate. Structural changes in the asthmatic airway, including an increase in smooth muscle mass and an increased deposition of extracellular matrix proteins, which correlate with airway hyperresponsivenes, reduced lung function and an increase in fibroblast/myofibroblast numbers, are not specifically targetted by current therapeutic agents and therefore represent an area of unmet need. The mechanisms involved in the development of airway remodelling are incompletely understood but are thought to involve one or more isoforms of transforming growth factor-beta (TGF-beta). The TGF-betas are pleiotropic mediators which have important roles in the regulation of inflammation, cell growth, differentiation and wound healing. All three mammalian isoforms of TGF-beta are present in the airways and at least TGF-beta1 and TGF-beta2 have been shown to be increased in asthmatic airways and cells, together with evidence of increased TGF-beta signalling. In addition, evidence from animal models suggests that airway remodelling may be prevented or reversed using agents which target TGF-beta. Therefore modulation of TGF-betas or their activity represent a potential therapeutic target for asthma. This review focuses on the current knowledge of TGF-beta1-3, their their role in normal and asthmatic airways, as well as the potential for modulating the TGF-betas and their effects as a therapeutic approach to asthma.

Animals↗
PubMed2006

Glycogen synthase kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions.

Glycogen synthase kinase-3 (GSK3) has recently been linked to mood disorders and schizophrenia, and the neurotransmitter systems and therapeutic treatments associated with these diseases. GSK3 is a widely influential enzyme that is capable of phosphorylating, and thereby regulating, over forty known substrates. Four mechanisms regulating GSK3 (phosphorylation, protein complexes, localization, and substrate phosphorylation) combine to provide substrate-specific regulation of the actions of GSK3. Several intracellular signaling cascades converge on GSK3 to modulate its activity, and several neurotransmitter systems also regulate GSK3, including serotonergic, dopaminergic, cholinergic, and glutamatergic systems. Because of changes in these neurotransmitter systems and the actions of therapeutic drugs, GSK3 has been linked to the mood disorders, bipolar disorder and depression, and to schizophrenia. Inhibition of GSK3 may be an important therapeutic target of mood stabilizers, and regulation of GSK3 may be involved in the therapeutic effects of other drugs used in psychiatry. Dysregulated GSK3 in bipolar disorder, depression, and schizophrenia could have multiple effects that could impair neural plasticity, such as modulation of neuronal architecture, neurogenesis, gene expression, and the ability of neurons to respond to stressful, potentially lethal, conditions. In part because of these key actions of GSK3 and its associations with mood disorders and schizophrenia, much research is currently being devoted to identifying new selective inhibitors of GSK3.

Animals↗
PubMed2006

Novel methods for the non-invasive administration of DNA therapeutics and vaccines.

To develop a successful protein therapeutic, effective DNA delivery technologies are required that induce high and sustained levels of protein production in appropriate targets sites, whereas robust and long-lasting immune responses need to be induced by a DNA-based vaccine. Vectors for gene therapy and DNA vaccines must be resistant to degradation and attack by the immune system, have a satisfactory safety profile, and be able to express the therapeutic protein for the desired period of time. Effective non-viral vectors, which can express the proteins of interest at high levels, are available. However, since most of the DNA delivered in vivo is degraded before it can enter the nucleus, proper formulation and delivery are critical to the development of effective gene-based therapeutics and vaccines. These systems must be safe for human and veterinary clinical applications and yet ensure that the DNA survives the extra- and intracellular environment and is capable of entering the appropriate cellular compartments. In this review various potential and proven non-invasive chemical, mechanical, physical and biological DNA delivery systems for therapeutic and vaccine applications are discussed. A few of these approaches have been evaluated and proven to be promising in target species. Others, which promise to be less invasive, have only just started to be explored.

Animals↗
PubMed2005

Therapeutic perspectives of inhibitors of endocannabinoid degradation.

The study of the cannabinoids can be established in the middle sixties with the elucidation of the structure of the active principle of Cannabis sativa plant, the delta9-tetrahydrocannabinol. However, the existence of an endogenous cannabinoid system (ECS) has not been unequivocally accepted until recently. The last two decades have witnessed an impressive advance in the knowledge about cannabinoids, their chemistry, the enzymes involved in their metabolism, and their physiological and pathological roles. In particular, we have made progress in modifying the activity of the ECS with selective compounds, validating the ECS as a new therapeutic target. Endocannabinoids play a role in physiological and pathological processes, and their levels are affected in several disorders. Therefore, it should be possible to ameliorate these pathologies by correcting their altered levels. This review focuses on the current therapeutic opportunities of endocannabinoid-directed drugs, and pays special attention to the therapeutic possibilities underlying the inhibition of the endocannabinoid inactivation. The strategy of manipulating the ECS might open new avenues in the development of therapeutic approaches for a number of disorders, both central and peripheral, that lack as yet effective treatments.

Animals↗
PubMed2005

Matrix metalloproteinases as therapeutic targets in cancer.

Degradation of extracellular matrix is crucial for malignant tumor growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected in tumor tissue or serum of patients with advanced cancer, and their role as prognostic indicators in cancer has been widely examined. In addition, therapeutic intervention in tumor growth and invasion based on inhibition of MMP activity is under intensive investigation and several MMP inhibitors (MMPIs) are in clinical cancer trials. Even though results of the first clinical trials in advanced cancer have been mostly disappointing, there are also positive results. Recent observations show, that certain MMPs limit tumor growth. Therefore, identification of proper MMPs for therapeutic intervention with array-based molecular classifications of tumors and targeting these with more specific MMPIs in combination with conventional chemotherapy is expected to provide a feasible approach for cancer therapy. MMPIs represent a totally different therapeutic modality from proven anti-cancer drugs and thus traditional approaches to evaluate drug efficiency cannot be used without modification. In this review, we discuss the current view on the feasibility of MMPs as targets for therapeutic intervention in cancer.

Animals↗
PubMedDate not supplied

[Therapeutic of septic children with purpuric presentation with two antibiotic schedules]

OBJECTIVE: The authors evaluate the therapeutic efficacy of two antibiotic schedules, ceftriaxone alone and the combined use of ampicillin and chloramphenicol, in the treatment of septic children with purpuric presentation.METHODS: A randomized open clinical trial was conducted including septic children with purpuric presentation treated at a pediatric intensive care unit from April 1988 to June 1992. All cases with systemic purpura standing for less than a week were included in one of two groups, except for those recently hospitalized or with previous hemorrhagic disturbs. Patients in group A received ampicillin and chloramphenicol and those in group B were given ceftriaxone. Quantitative parameters were adopted to compare the efficacy of the two antibiotic schedules: sensitivity of bacteria isolated at blood and liquor cultures, complications, therapeutic procedures, period of hospitalization, and sequelae.RESULTS: 19 cases were included in the group A and 16 in group B, both homogenous on clinical-laboratorial aspects. The parameters evaluated did not show different efficacy between the two antimicrobial schedules tested, except for the number of complications observed during hospitalization, which was higher among the children that received ampicillin and chloramphenicol. The overall mortality for the patients treated was 13.8%, excluded the undernourished. CONCLUSIONS: The authors verify similar clinical therapeutic efficacy with the combined use of ampicillin and chloramphenicol or ceftriaxone, as observed previously. It must be pointed that the number of complications detected during hospitalization were higher in the group that received the combined antibiotic schedule. Low mortality in the present study may be attributed to the early diagnosis and therapeutic measures adopted at the pediatric intensive care unit.

Journal Article↗
PubMed1994

Evaluation of the costs to Medicare of covering therapeutic shoes for diabetic patients.

OBJECTIVE: A three-year demonstration was fielded in three states to evaluate the cost to Medicare of a therapeutic shoes benefit for Medicare Part B beneficiaries with severe diabetic foot disease. RESEARCH DESIGN AND METHODS: Eligible Medicare beneficiaries who applied were randomly assigned to either a treatment group that received the extra therapeutic shoe coverage or a control group that received only standard Medicare coverage. This study analyzes the Medicare payments and service use of 3,428 demonstration participants in California, Florida, and New York for whom data on a 12-month follow-up period were available. These results are comparable to those for the entire sample over a variable length follow-up period that averaged 20 months but ranged from 3 months to 3 years. RESULTS: Differences between groups are not statistically significant. However, Medicare payments for all services among the treatment group were $451 (3.8%) higher than those for all services among the control group. Similarly, Medicare payments for foot-care services were $318 (14.6%) higher among beneficiaries in the treatment group, which considerably exceeded the cost of the shoe benefit ($118). CONCLUSIONS: The demonstration produced no definitive evidence that expanding Medicare Part B to cover therapeutic shoes for beneficiaries with severe diabetic foot disease would increase total Medicare costs. However, our findings indicate that the demonstration was successful at increasing therapeutic shoe ownership and was instrumental in increasing beneficiaries' use of the shoes when walking outdoors.

Aged↗
PubMed1990

Psychiatric nurses' and patients' perceptions of discussion topics in therapeutic groups.

Discussion topics for outpatient group therapy sessions were rated for importance by 84 psychiatric outpatients from 6 therapeutic groups and 26 psychiatric nurses. Topics were measured by scales of personal problems and feelings, lifestyle, response to health care, and nonhealth self-disclosure. No significant differences in importance ratings among therapeutic groups or between nurses and patients were found. Scale rankings were the same among patient groups and between nurses and patients, with personal problems and feelings receiving the highest score. Results support the existence of a common goal implicit among therapeutic groups that is known by nurses and augurs well for group cohesion, behavior in accordance with norms, and the efficacy of nurses as leaders of therapeutic groups.

Goals↗
PubMedDate not supplied

Anxiety and therapeutic touch.

This four-group, repeated-measures experimental design divided 40 healthy professional caregivers/students into high- and low-anxiety groups and further into "therapeutic touch" and comparison groups. The effectiveness of the use of therapeutic touch in reducing anxiety was evaluated, as were the methodologies used. Three self-report measures of anxiety (Profile of Mood States, Spielberger's State/Trait Anxiety Inventory, and visual analogue scales) were evaluated for equivalence and concurrent validity to determine their potential for use in future studies. The correlations among these instruments were highly significant. The small sample size prevented differences between groups from reaching statistical significance, but the reduction of anxiety in the high-anxiety group was greater for those who had received therapeutic touch than for those who did not. Using variability data, the sample size necessary to find statistically significant differences between those who had therapeutic touch and those who did not was determined.

Anxiety↗
PubMed1994

Improvement of therapeutic effect of human recombinant superoxide dismutase on ischemic acute renal failure in the rat via cationization and conjugation with polyethylene glycol.

Therapeutic effect of superoxide dismutase (SOD) and three derivatives: a conjugate with polyethylene glycol (SOD-PEG2), a cationized derivative (cSOD), and a mannosylated derivative (Man-SOD), on acute renal failure induced by ischemia/reperfusion was studied in rats. SOD and derivatives were administered intravenously to the rat after nephrectomy of the right kidney and before and after 60 min occlusion of the left renal artery. At 48 hr after reperfusion, the renal function was evaluated by determining the urinary excretion rate of 14C-inulin injected intravenously. No therapeutic effect on the impaired renal function was shown in the case of low dose SOD (2600 unit/kg) treatment. In contrast, administration of cSOD which was shown to be taken up by the isolated perfused kidney from its capillary side and SOD-PEG2 which maintained high plasma concentration exhibited significant therapeutic effect, as did SOD at ten-fold higher dose (26,000 unit/kg). On the other hand, renal damage was promoted by Man-SOD. Thus, the present study demonstrated that chemical modification may improve the therapeutic effect of SOD on the ischemic acute renal failure and increased SOD concentration in the renal vascular space is an important factor for the improved effect.

Acute Kidney Injury↗
PubMed1996

Pleuroscopy: therapeutic applications.

Pleuroscopy is mostly regarded as a diagnostic procedure. Although therapeutic uses of pleuroscopy were popular when pulmonary tuberculosis was common, they are less well known today. This review of modern therapeutic pleuroscopy is based on both personal experience and previous reports. We have grouped the purposes of therapeutic pleuroscopy as 1) to provoke formation of pleural adhesions in the management of pleural effusion, recurrent pneumothorax, chylothorax or (in selected cases) empyema, 2) to divide adhesions in persistent pneumothorax, 3) to perform pleural toilet in the fibrinopurulent stage of empyema, 4) to retrieve foreign bodies, and 5) to achieve haemostasis and removal of clotted blood following operation or trauma. These applications of pleuroscopy should be studied and popularized so that the method can attain recognition as a revived therapeutic procedure.

Chylothorax↗
PubMed2001

Systematic reviews of wound care management: (5) beds; (6) compression; (7) laser therapy, therapeutic ultrasound, electrotherapy and electromagnetic therapy.

BACKGROUND: Chronic wounds such as leg ulcers, diabetic foot ulcers and pressure sores are common in both acute and community healthcare settings. The prevention and treatment of these wounds involves many strategies: pressure-relieving beds, mattresses and cushions are universally used as measures for the prevention and treatment of pressure sores; compression therapy in a variety of forms is widely used for venous leg ulcer prevention and treatment; and a whole range of therapies involving laser, ultrasound and electricity is also applied to chronic wounds. This report covers the final three reviews from a series of seven. AIMS: To assess the clinical effectiveness and cost- effectiveness of: (1) pressure-relieving beds, mattresses and cushions for pressure sore prevention and treatment; (2) compression therapy for the prevention and treatment of leg ulcers; (3) low-level laser therapy, therapeutic ultrasound, electrotherapy and electromagnetic therapy for the treatment of chronic wounds. METHODS - DATA SOURCES: Nineteen electronic databases, including MEDLINE, CINAHL, EMBASE and the Cochrane Controlled Trials Register (CENTRAL), were searched. Relevant journals, conference proceedings and bibliographies of retrieved papers were handsearched. An expert panel was also consulted. METHODS - STUDY SELECTION: Randomised controlled trials (RCTs) which evaluated these interventions were eligible for inclusion in this review if they used objective measures of outcome such as wound incidence or healing rates. RESULTS - BEDS, MATTRESSES AND CUSHIONS FOR PRESSURE SORE PREVENTION AND TREATMENT: A total of 45 RCTs were identified, of which 40 compared different mattresses, mattress overlays and beds. Only two trials evaluated cushions, one evaluated the use of sheepskins, and two looked at turning beds/kinetic therapy. RESULTS - COMPRESSION FOR LEG ULCERS: A total of 24 trials reporting 26 comparisons were included (two of prevention and 24 of treatment strategies). RESULTS - LOW-LEVEL LASER THERAPY, THERAPEUTIC ULTRASOUND, ELECTROTHERAPY AND ELECTROMAGNETIC THERAPY: Four RCTs of laser (for venous leg ulcers), 10 of therapeutic ultrasound (for pressure sores and venous leg ulcers), 12 of electrotherapy (for ischaemic and diabetic ulcers, and chronic wounds generally) and five of electromagnetic therapy (for venous leg ulcers and pressure sores) were included. Studies were generally small, and of poor methodological quality. CONCLUSIONS (1) Foam alternatives to the standard hospital foam mattress can reduce the incidence of pressure sores in people at risk, as can pressure-relieving overlays on the operating table. One study suggests that air-fluidised therapy may increase pressure sore healing rates. (2) Compression is more effective in healing venous leg ulcers than is no compression, and multi-layered high compression is more effective than single-layer compression. High-compression hosiery was more effective than moderate compression in preventing ulcer recurrence. (3) There is generally insufficient reliable evidence to draw conclusions about the contribution of laser therapy, therapeutic ultrasound, electrotherapy and electromagnetic therapy to chronic wound healing.

Bandages↗
PubMed2026

Multi-omics approaches in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic targets and precision medicine.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options and marked molecular heterogeneity. Despite available antifibrotic therapies, disease progression remains poorly predictable, highlighting the need for improved mechanistic understanding and therapeutic targeting. This review summarizes recent advances in multi-omics research to elucidate the molecular mechanisms underlying IPF and to identify potential biomarkers and pharmacological targets. Multi-omics studies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiome profiling, and single-cell sequencing, have revealed key pathogenic mechanisms in IPF. Genetic susceptibility factors such as MUC5B promoter variants and telomere-related genes contribute to disease risk. Epigenetic regulation, including DNA methylation, histone modifications, and non-coding RNAs, plays a central role in fibrotic remodeling. Transcriptomic and proteomic analyses have identified dysregulated signaling pathways, including TGF-β, mTOR, cellular senescence, and extracellular matrix remodeling. Metabolomic alterations indicate disrupted lipid and amino acid metabolism. Importantly, integration of multi-omics datasets enables the identification of molecular endotypes, candidate biomarkers, and potential therapeutic targets. However, challenges including data integration, tissue heterogeneity, limited cohort size, and the need for functional validation remain important barriers to clinical translation. Continued development of multi-omics approaches may facilitate more accurate disease classification and support the development of personalized therapeutic strategies for IPF.

biomarkers↗
PubMed2007

[Construction of a therapeutic effect evaluation system for patients with primary liver cancer based on syndrome differentiation in traditional Chinese medicine].

OBJECTIVE: To construct a system of therapeutic effect evaluation for patients with primary liver cancer according to the theory of syndrome differentiation in traditional Chinese medicine (TCM), and to examine its reliability. METHODS: Analytic hierarchy process and 100 mm surveyor's rod method were applied to obtain bottom layer and top level syndromes, which were used to construct the method of therapeutic effect evaluation, and its reliability was verified in clinical practice by comparing with some evaluation criteria in Western medicine, such as cancer severity scale; Karnofsky performance scale; Child-Pugh classification, cancer staging classification, and quality of life scale, etc. RESULTS: A system of therapeutic effect evaluation was constructed, and it could reflect the progress of tumor, changes of hepatic function and constitution. The evaluation scores acquired from the system were highly associated with the quality of life of the patients. CONCLUSION: The system of therapeutic effect evaluation can reflect the severity of disease and the characteristics of TCM treatment.

Carcinoma, Hepatocellular↗
PubMed2005

Therapeutic effect of DA-9601 on chronic reflux gastritis induced by sodium taurocholate in rats.

AIM: To investigate the therapeutic effects of DA-9601 on sodium taurocholate (TCA)-induced chronic reflux gastritis in SD rats. METHODS: In this study, we have investigated the therapeutic effects of DA-9601 on chronic erosive and atrophic gastritis induced by 6 mo of TCA administration (5 mmol/L in drinking water) in SD rats. RESULTS: Four weeks of DA-9601 administration (0.065%, 0.216% in rat chow), following the withdrawal of TCA treatment, resulted in a significant decrease in total length of erosions in rats in a dose-dependent manner. Furthermore, the indicators of atrophic gastritis, such as reduced mucosal thickness and reduction in the number of parietal cells, were improved by the administration of DA-9601 in a dose-related manner. DA-9601 also attenuated inflammatory cell infiltration and the proliferation of collagenous fiber in the gastric mucosa. The improvement in the reduction of the gastric mucus was observed in the rats receiving a high dose of DA-9601 (0.216%). The therapeutic effect of DA-9601 on experimental chronic erosive gastritis was superior to that of rebamipide (1.08% in rat chow). Biochemical analyses showed increased mucosal prostaglandin E2 and reduced glutathione levels by DA-9601 treatment. CONCLUSION: We suggest that DA-9601 is a promising agent for the treatment of chronic erosive and atrophic gastritis with an etiological factor of bile reflux. Increased mucosal prostaglandin E2 and reduced glutathione by DA-9601 treatment may be therapeutic mechanisms for chronic erosive and atrophic gastritis.

Animals↗
PubMed1998

Therapeutic effect of Zijin capsule in liver fibrosis in rats.

AIM:To confirm the therapeutic effect of Zijin capsule on liver fibrosis in rat model.METHODS:Model group: Bovine serum albumin (BSA) Freund's incomplete adjuvant 0.5ml was injected subdermally at d(1) d(15) d(22) d(29) and d(36) for primary sensitization. Seven days after the fifth injection, BSA antibody in the serum was detected by double agar diffusion method. Normal saline of 0.4ml was injected through cauda vein to BSA antibody-positive rat twice a week for fifteen times. Traditional Chinese medicine (TCM) decoction group and Zijin capsule group: In the attack injection period, Chinese medicinal decoction or Zijin capsule was given ig, the others were the same as in the model group. NS was used in the control group. The collagen content of rat liver was determined by Bergman's method and expressed as x-±s.The liver pathological changes were divided into four grades and expressed as the avarage of the total rank sum.RESULTS:The collagen content (mg/g) of the liver in the control group (7.2± 1.9) was significantly lower than that in the other groups; it was higher in the model group (31.7± 16.6) than that in the two therapeutic groups; and lower in Zijin capsule group (9.7 ± 2.8) than that in the TCM decoction group (11.5± 5.3). The pathological changes were more aggravated in the model group (37.4) than those in the two therapeutic groups; and more severe in the TCM decoction group (30.2) than in the Zijin capsule group (22.9).CONCLUSION: The therapeutic effect of Zijin capsule on the model was confirmed.

Journal Article↗
PubMed2003

Clinical and experimental study on therapeutic effect of umbilical cord blood transplantation on severe viral hepatitis.

AIM: To investigate the therapeutic effect of umbilical cord blood transplantation (UCBT) on patients with severe viral hepatitis and on liver lesions in rats. METHODS: One hundred and fifty three patients with severe viral hepatitis were included in the study between April 1990 and July 2002. The patients were treated with adult plasma transfusion (control), UCBT, plasma exchange (PE) and UCBT combined with PE (UCBT+PE) respectively. The therapeutic effectiveness was evaluated by serial determinations of liver function, lipids and immune function in all patients before and after the treatment. The model of experimental hepatic failure was constructed in SD rats by injecting carbon tetrachloride. Then, the rats were given normal saline, adult plasma or neonate cord blood intraperitoneally. After detection of liver function, the rats were killed and morphological changes of the liver were microscopically observed. RESULTS: UCBT group and UCBT+PE group had much better improvement in liver and immune functions than control group and PE group. The patients in UCBT+PE group had the best clinical efficacy. UCBT was safe and had no side effects. The animal experiment showed significant improvements in liver function and survival rate in neonate cord blood group as compared with adult plasma group. The histopathology of rat's liver indicated that neonate cord blood application could decrease the liver injury and increase hepatocellular regeneration. CONCLUSION: UCBT demonstrated a good therapeutic effect on severe viral hepatitis and no obvious side effects. Umbilical cord blood can attenuate the liver lesions and reproduce hepatocyte. The treatment of UCBT combined with PE was much better than that of single plasma exchange, thus UCBT can enhance the therapeutic effect of plasma exchange on severe viral hepatitis.

Adolescent↗