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991.
Butyric acid induces fetal hemoglobin (HbF), a property of potential therapeutic advantage in patients with disorders of globin chain synthesis. We performed dose escalation studies of this compound in baboons to assess whether clinically significant increases in HbF are achievable, and to define the associated toxicities. Additionally, the effect of butyrate in combination with erythropoietin on HbF induction was assessed. HbF induction in response to butyrate was dependent on the dose and duration of treatment. Doses of butyrate less than 4 g/kg/d were associated with minimal toxicity (hypokalemia) and significant HbF induction in these nonanemic animals, with 1 g/kg/d producing an increase in HbF-containing reticulocytes (F reticulocytes) from 0.9% to 8.7% and an increase in HbF from 0.8% to 1.4%. A dose of 2 g/kg/d resulted in an increase in F reticulocytes from 2.1% to 27.8% and an increase in HbF from 0.7% to 2.2%. Doses of 4 g/kg/d in another animal produced an increase in F reticulocytes from 1% to 21.6% and in HbF from 1.9% to 5.3%. Infusions in excess of 4 g/kg/d were complicated (after a variable amount of time) by a decreased level of alertness (caused by hyperosmolality or butyrate itself) and hematologic toxicity (with declines in reticulocyte, white blood cell, and platelet counts). Prolonged infusions of high doses of butyrate (8 to 10 g/kg/d) were associated with peak F reticulocyte percentages reaching 38% to 64.5% and HbF reaching levels in excess of 20%. These high doses (8 to 10 g/kg/d) were complicated in two animals with a striking and unique neuropathologic picture and, in one animal, multiorgan system failure. Erythropoietin in combination with butyrate, induced F reticulocytosis in an additive manner. We conclude that butyric acid is a strong inducer of HbF, particularly when administered in combination with erythropoietin. As chronic toxicities remain undefined, patients in future clinical trials of this and similar compounds should be monitored closely for evidence of neurologic toxicity. 相似文献
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M Borlu† F Tanriverdi‡ CA Koc† K Unluhizarci‡ S Utas† F Kelestimur‡ 《Journal of the European Academy of Dermatology and Venereology》2007,21(2):199-204
BACKGROUND: Growth hormone (GH) may play an important role in the content and appearance of the skin. Dry, thin and pale skin has been described in hypopituitarism. Sheehan's syndrome is characterized by anterior pituitary dysfunction due to postpartum pituitary necrosis and GH is one of the hormones lost first. OBJECTIVE: The aim of this study was to examine the hydration of the skin of patients with Sheehan's syndrome using measurements of capacitance, sebum content, transepidermal water loss, pH and temperature. The data were compared with those of control subjects. METHODS: A total of 21 patients with Sheehan's syndrome and 20 women as control subjects were included in this blinded prospective study. Hormone deficiencies other than GH had been adequately replaced. The diagnosis of GH deficiency (GHD) was established by the insulin tolerance test (ITT). Skin properties were measured by non-invasive and well-established methods. RESULTS: The skin capacitance had decreased on the forehead and forearm and sebum content had decreased on the forehead of patients with Sheehan's syndrome when compared with control subjects. The pH, temperature and average transepidermal water loss (TEWL) of the skin of the patients were not statistically different from the controls. CONCLUSION: GHD results in a decrease in skin capacitance and sebum content indicating that GH and/or insulin-like growth factor-I (IGF-I) have an important role in skin function. 相似文献
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还原型谷胱甘肽抗白血病免疫佐剂作用实验研究 总被引:2,自引:0,他引:2
本研究探讨还原型谷胱甘肽(GSH)逆转反应性氧代谢物(ROM)对NK细胞抗白血病效应的抑制作用。在K562细胞、NK细胞的混合培养体系中分别加入富含单核细胞的单个核细胞(Mo)和白细胞介素-2(IL-2),观察ROM产量和K562细胞抑制率,然后分别加入GSH或二氢氯化物组胺(组胺),观察ROM产量及K562细胞抑制率的变化。结果表明:加入IL-2后,ROM的产量从33.17±25.02U/L增至223.59±59.41U/L(P<0.01),K562细胞抑制率从65.56%升至85.89%(P<0.01);在加入E/Mo=10/1、10/5、10/103种浓度的Mo后,ROM产量分别为389.79±43.83U/L,456.74±42.77U/L,601.42±21.92U/L,K562细胞抑制率分别为82.36%,81.36%,48.09%,加入组胺或GSH后,E/Mo=10/2时,ROM产量从389.79±43.83U/L,分别减至50.21±22.4U/L和-3.58±9.49U/L(P<0.05),随着GSH或组胺浓度的增加ROM产量逐减少,K562细胞抑制率从82.53%分别升至94.64%和96·39(P<0·05),ROM产量与K562细胞抑制呈负相关(P<0.05);E/Mo=10/5或10/10时,高浓度的GSH或组胺可使ROM产量减少,但K562细胞抑制率提高不明显(P>0.05)。结论:当E/Mo=10/2时,GSH逆转ROM强于组胺,提高NK细胞对K562的抑制率与组胺相似,但毒副作用轻微,GSH可能成为更理想的抗白血病的免疫佐剂。 相似文献
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Despite the many journal articles and reviews that have been published regarding the treatment of trauma to teeth, the endodontic management of these injuries is often still not fully understood. The purpose of this review is to establish clear and up-to-date guidelines for practitioners who are faced with treating dental injuries on a day-to-day basis, based on an assessment of current available scientific information relating to the endodontic management of these injuries.
Treatment is discussed under the headings: infractions, uncomplicated crown fractures, complicated crown fractures, crown-root fractures, root fractures, luxation injuries, avulsion, root resorption, pulp canal obliteration and open-apex teeth. Emphasis is placed on the treatment of traumatized immature teeth where maintenance of pulp blood supply is important to encourage continued development of the root system. Only the treatment of traumatized permanent anterior teeth is reviewed.
Information contained in this article is based on a review of the literature on dental trauma which involved a MEDLINE search using the key words "dental trauma" and the individual topics listed above. The guidelines produced by the International Association of Dental Traumatology, the American Academy of Pediatric Dentistry and the American Association of Endodontists were also reviewed and the recommendations contained in this paper are in concert with the major recommendations of these bodies. 相似文献
Treatment is discussed under the headings: infractions, uncomplicated crown fractures, complicated crown fractures, crown-root fractures, root fractures, luxation injuries, avulsion, root resorption, pulp canal obliteration and open-apex teeth. Emphasis is placed on the treatment of traumatized immature teeth where maintenance of pulp blood supply is important to encourage continued development of the root system. Only the treatment of traumatized permanent anterior teeth is reviewed.
Information contained in this article is based on a review of the literature on dental trauma which involved a MEDLINE search using the key words "dental trauma" and the individual topics listed above. The guidelines produced by the International Association of Dental Traumatology, the American Academy of Pediatric Dentistry and the American Association of Endodontists were also reviewed and the recommendations contained in this paper are in concert with the major recommendations of these bodies. 相似文献