Peroxisome proliferatorr-activated receptor-gamma $(PPAR{\gamma})$ must form a heterodimer with the retinoid-X receptor (RXR) to bind DNA, and its transcriptional activity is thought to be maximized by ligands specific for either receptor. Activated $(PPAR{\gamma})$ and $(PPAR{\gamma})$ ligands may influence tumor growth through regulation of the tumor suppressor PTEN. Our aim in this study was to determine whether co-stimulation with the $(PPAR{\gamma})$ ligand, ciglitazone, and RXR ligand can synergistically upregulate PTEN in human acute promyelocytic leukemia (APL) cells and consequently potentate the inhibition of cell growth and cell cycle progression of these cells. Human leukemia cell line, HL-60 cells were exposed to all-trans-retinol and ciglutazone. The PTEN expression was measured as the level of PTEN mRNA expression by RT-PCR and as the level of PTEN expression by western blot analysis. Cell cycle analysis was carried out by a propidium iodide (PI) staining method and analyzed with a FACScan. The $(PPAR{\gamma})$ ligand, ciglitazone, and the RXR ligand, retinoic acid, upregulated PTEN expression by HL-60 cells in time- and dose-dependent manners, respectively. This was significantly enhanced by a combination of both ciglitazone and retinoic acid. Moreover, these compounds synergistically induced arrests of both cell growth and the $G_l$ phase of the cell cycle. Thus, the activation of the $(PPAR{\gamma})$:RXR heterodimer may represent a regulatory pathway for human leukemia cells and there may be important roles for $(PPAR{\gamma})$ and RXR ligands in prophylactic and therapeutic approaches fur controlling leukemia through the upregulation of PTEN.
Cheon, Hyo Cheol;Kim, Jae Hyoo;Lee, Jung Kil;Kim, Tae Sun;Jung, Shin;Kim, Soo Han;Kang, Sam Suk;Lee, Je Hyuk
Journal of Korean Neurosurgical Society
/
v.30
no.8
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pp.992-997
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2001
Objectives : Essential hyperhidrosis is a common condition characterized by excessive body sweating. Excessive sweating beyond what is necessary to maintain normal body temperature need not be considered pathological unless it interferes with one's occupation and/or life-style. The existing non-operative therapeutic options seldom give sufficient relief or show a transient effect. In this regard, the thoracic sympathectomy may provide a definitive cure. In the past, surgical procedures were highly invasive and caused significant morbidity, but the minimally invasive thoracoscopic procedure provided detailed visualization of sympathetic ganglia and is associated with minimally postoperative morbidity. Nowadays, thoracoscopic transthoracic sympathectomy is accepted as the treatment of choice for essential hyperhidrosis. In palmar hyperhidrosis, however, the level of sympathetic chain to be blocked has been somewhat obscure. It is assumed that the incidence of compensatory hyperhidrosis may closely related to the extent of thoracic sympathectomy. Material & Methods : To compare the results of posterior midline approach with endoscopic sympathectomy, and the results of T2 with T2, 3 sympathectomy or sympathicotomy, we retrospectively studied 62 patients treated for palmar hyperhidrosis between September 1993 and May 2000. We reviewed medical records and recently interviewed the patients by telephone calls. Results : The treatment effect of T2 sympathectomy is no different from T2, 3 sympathectomy. But, the incidence of compensatory hyperhidrosis is less in the T2 sympathectomy group than the T2, 3 sympathectomy group. Conclusion : Thoracoscopic sympathectomy is considered a simple, safe, and effective method for treating palmar hyperhidrosis, with a shorter operation time, fewer hospital days, and a better cosmetic result, as compared with the open approaches. However, sympathicotomy seems to provide the advantages of a limited extent of denervation and the resultant decrease of compensatory hyperhidrosis compared to sympathectomy.
Background: The most common type of ocular lymphoma is non-Hodgkin lymphoma (NHL), categorized into two groups: indolent (slow growing) and aggressive (rapid growing). Differentiating benign reactive lymphoid hyperplasia (RLH) from malignant ocular adnexal lymphoma (OAL) is challenging. Histopathology, immunohistochemistry (IHC) and flow cytometry have been used as diagnostic tools in such cases. Materials and Methods: In this retrospective case series, from 2002 to 2013 at Farabi Eye Center, 110 patients with ocular lymphoproliferative disease were enrolled. Prevalence, anatomical locations, mean age at diagnosis and the final diagnosis of the disease with IHC were assessed. Comparison between previous pathologic diagnoses and results of IHC was made. Immunoglobulin light chains and B-cell and T-cell markers and other immuno-phenotyping markers including CD20, CD3, CD5, CD23, CD10, CYCLIND1 and BCL2 were evaluated to determine the most accurate diagnosis. The lymphomas were categorized based on revised European-American lymphoma (REAL) classification. Results: Mean age ${\pm}$ SD (years) of the patients was $55.6{\pm}19.3$ and 61% were male. Patients with follicular lymphoma, large B-cell lymphoma or chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL) tended to be older. Nine patients with previous diagnoses of low grade B-cell lymphoma were re-evaluated by IHC and the new diagnoses were as follows: extranodal marginal zone lymphoma(EMZL) (n=1), SLL(n=1), mantle cell lymphoma (MCL) (n=3), reactive lymphoid hyperplasia RLH (n=2). Two cases were excluded due to poor blocks. Flow cytometry reports in these seven patients revealed SLL with positive CD5 and CD23, MCLwith positive CD5 and CyclinD1 and negative CD23, EMZL with negative CD5,CD23 and CD10. One RLH patient was negative for Kappa/Lambda and positive for CD3 and CD20 and the other was positive for all of the light chains, CD3 and CD20. Orbit (49.1%), conjunctiva (16.1%) and lacrimal glands (16.1%) were the most common sites of involvement. Conclusions: Accurate pathological classification of lesions is crucial to determine proper therapeutic approaches. This can be achieved through precise histologic and IHC analyses by expert pathologists.
Psoriasis is a well known disorder of keratinization. In this disease, several reports revealed that dermal micro vessels are increased and angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are over-expressed. Angiogenesis may play an important role in the progression of psoriasis. Acitretin is widely used as an anti-psoriatic drug because of its potent action on keratinocyte growth and differentiation, but its effects on angiogenesis are uncertain. The goal of this immunohistochemical study was to investigate the effects of acitretin on the expression of VEGF in psoriatic lesions of the skin. We compared the expression levels of VEGF between pre- and post-acitretin treated skin - 10 psoriatic skin lesions and 3 normal (control) skins. The expressions of VEGF in psoriatic skin lesions were significantly higher than in normal control skin. The expressions of VEGF in psoriatic skin lesions post-treatment were lower than those pre-treatment. Acitretin revealed inhibitory effects on angiogenesis by reducing the expression of angiogenic factors such as VEGF in psoriatic skin lesions. We suggest that acitretin may be useful in therapeutic approaches to psoriasis management, possibly related to angiogenesis.
We investigated the role of central P2X receptors in inflammatory pain transmission in the orofacial area in rats. Experiments were carried out using male Sprague-Dawley rats weighing 230-280g. Complete Freund's adjuvant (CFA, $40{\mu}L$) was applied subcutaneously to the vibrissa pad to produce inflammatory pain. The intracisternal administration of iso-PPADS tetrasodium salt, a non-selective P2X receptor antagonist, A317491 sodium salt hydrate, a $P2X_{2/3}$ receptor antagonist, 5-BDBD, a $P2X_4$ receptor antagonist, or A438079 hydrochloride, a $P2X_7$ receptor antagonist, was performed 5 days after CFA injection. Subcutaneous injections of CFA produced increases in thermal hypersensitivity. Intracisternal injections of iso-PPADS ($25{\mu}g$) or A438079 (25 or $50{\mu}g$) produced significant anti-hyperalgesic effects against thermal stimuli compared to the vehicle group. A317491 or 5-BDBD did not affect the head withdrawal latency times in rats showing an inflammatory response. Subcutaneous injections of CFA resulted in the up-regulation of OX-42, a microglia marker, and GFAP, an astrocyte marker, in the medullary dorsal horn. The intracisternal administration of A438079 reduced the numbers of activated microglia and astrocytes in the medullary dorsal horn. These results suggest that a blockade of the central $P2X_7$ receptor produces antinociceptive effects, mediated by inhibition of glial cell function in the medullary dorsal horn. These data also indicate that central $P2X_7$ receptors are potential targets for future therapeutic approaches to inflammatory pain in the orofacial area.
Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.
The aim of our study was to investigate the protective effects of intraperitoneally-administrated vitamin E, dl-alpha lipoic acid, and linalool on the level of total lipid and fatty acid in guinea pig brains with oxidative stress that was induced by $H_2O_2$. The total brain lipid content in the $H_2O_2$ group decreased when compared to the $H_2O_2$ + vitamin E (p<0.05), $H_2O_2$ + linalool (p<0.05), ALA (p<0.05), control (p<0.01), linalool (p<0.01), and vitamin E (p<0.01) groups. While the proportion of total saturated fatty acid (${\Sigma}SFA$) in the $H_2O_2$ group significantly increased (p<0.005) when compared to the vitamin E group, it only slightly increased (p<0.01) when compared to the control and $H_2O_2$ + vitamin E groups. The ratio of the total unsaturated fatty acid (${\Sigma}USFA$) in the $H_2O_2$ groups was lower (p<0.05) than the control, vitamin E, and $H_2O_2$ + vitamin E groups. The level of the total polyunsaturated fatty acid (${\Sigma}PUEA$) in the $H_2O_2$ group decreased in when compared to the control, vitamin E, and $H_2O_2$ + vitamin E groups. While the proportion of the total w3 (omega 3), w6 (omega 6), and PUFA were found to be lowest in the $H_2O_2$ group, they were slightly increased (p<0.05) in the lipoic acid group when compared to the control and $H_2O_2$ + lipoic acid groups. However, the level of ${\Sigma}SFA$ in the $H_2O_2$ group was highest; the level of ${\Sigma}USFA$ in same group was lowest. As the proportion of ${\Sigma}USFA$ and ${\Sigma}PUFA$ were found to be highest in the linalool group, they were decreased in the $H_2O_2$ group when compared to the control group. Our results show that linalool has antioxidant properties, much the same as vitamin E and lipoic acid, to prevent lipid peroxidation. Additionally, vitamin E, lipoic acid, and linalool could lead to therapeutic approaches for limiting damage from oxidation reaction in unsaturated fatty acids, as well as for complementing existing therapy for the treatment of complications of oxidative damage.
Objectives: This study aimed to report a case that showed improvements in the symptoms of patients with alcoholic hepatitis without any indication of deterioration of the disease. Methods: Western medicine with Urusa tablets and Godex capsules and Korean medicine therapeutic approaches, including Shihogayonggolmoryo-tang, acupuncture, and moxibustion, were administered to a patient during the period of treatment. Blood tests were used to determine levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, alkaline phosphatase (ALP), gamma glutamyltransferase (GGT), total bilirubin, direct bilirubin, and total cholesterol. Fatigue was measured using the numeric rating scale (NRS), and the patient's total sleeping time was checked, daily. Results: After the combined treatment, the AST/ALT ratio and the AST, ALT, ALP, GGT, total cholesterol, and direct bilirubin levels were decreased. Through Oriental medicine for the purpose of improving symptoms, NRS of fatigue decreased from 10 to 5, and the amount of sleeping time increased from 2 to 5 hours. Conclusions: The herbal medicine had no effect on the hepatoprotective drugs such as Urusa tablets and Godex capsules used to treat alcoholic hepatitis, and no adverse reaction from the combined administration was observed. To reduce fatigue and insomnia in patients with alcoholic hepatitis, it might be helpful to combine Western medications with Korean medicine treatments, including acupuncture, moxibustion, and Shihogayonggolmoryo-tang.
Proceedings of the Korean Society of Applied Pharmacology
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2001.11a
/
pp.3-6
/
2001
Inflammation is an outcome or an end effect of disruption of complex immunological balance. A variety of approaches to control immunological unbalance have been tried, and some of them are in practice in the clinic. Since inflammatory disorders are reflection of very complex immunological responses, it should be difficult to have such disorders under complete control. Thus, most of the drugs, being marketed and under development, possess some degrees of undesired side offsets originating from disruption of immunological balance. Steroids are excellent drugs suppressing inflammation in short term, however, long-term use of steroids would incur a serious side effect of "rebound". Another example is TNF-${\alpha}$-neutralizing agents, such as enbrel and infliximab. TNF-${\alpha}$ has been known to play a key role in the exacerbation of inflammation, and knock-out of TNF-${\alpha}$ is regarded essential to control of chronic inflammation. The TNF-${\alpha}$-neutralizing drugs in the market are regarded very efficient in the management of rheumatoid arthritis. Upon long term use, however, those drugs cause sepsis to a certain proportion of patients. It is ironical that a high plasma level of TNF-${\alpha}$ is known to be responsible for sepsis, and that the drugs scavenging TNF-${\alpha}$ cause sepsis. The above two examples illustrate well the difficulty of discovering an anti-inflammatory drug without unwanted immunological side effects. An anti-inflammatory drug would make a case in the market, as long as the drug has huge therapeutic benefits compared to its expected but unwanted immunological side effects, where cyclooxygenase-2 inhibitors are positioning. In this presentation, will be discussed general aspects of cyclooxygenase-2 inhibition in conjunction with 3(2Η)furanone derivatives, a novel class of COX-2 inhibitors.
In this study, we sought to develop an effective cloning system by which human cytochrome $b_5$ (cyt $b_5$) is introduced and expressed in zebrafish. First, the 414 bp human cyt $b_5$ gene was amplified from RNA extracts of HeLa cells using RT-PCR, and the amplicon was subsequently sequenced to confirm that it was intact. Next, cyt $b_5$ was cloned into the pEGFP-N3 vector, which also encodes a fluorescent gene. One-cell stage zebrafish embryos were microinjected with the recombinant vector containing the cyt $b_5$ gene. Fluorescence microscopy confirmed high expression of the fluorescent gene in the injected fry compared to the non-fluorescent control fry. Finally, we extracted RNA from the injected fry and performed RT-PCR to determine whether the human cyt $b_5$ gene is expressed in the transgenic zebrafish. Sequencing analysis further confirmed that the cloned human cyt $b_5$ gene was intact. The transgenic zebrafish model produced in this study will be a useful tool to study therapeutic approaches to cure various diseases related to the deficiency of functional human cyt $b_5$ as well as tools for cloning useful genes in fish.
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