Leptin, lipid and lipid metabolism-related hormones in chronic renal failure in Arabia

SUMMARY: In patients with chronic renal failure (CRF), hyperleptinaemia has been widely reported, but the exact mechanisms leading to elevated leptin levels are unclear. Impaired renal clearance of leptin and the influence of other hormones may be important. In this study, we measured serum leptin levels in 150 patients on haemodialysis, peritoneal dialysis or in the predialysis phase of CRF. Furthermore, we measured plasma levels of insulin, growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as well as plasma levels of triacylglycerols and total low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol. We observed significantly elevated levels of leptin, particularly in female patients, and leptin was shown to correlate significantly with insulin, total and LDL-cholesterol and log triacylglycerols. Leptin was inversely correlated with GH concentrations, but was not correlated with IGF-1 levels. Despite the multiple correlations established between leptin levels and other variables, only hyperinsulinaemia in CRF seems to be important as a determinator of leptin levels.     

Thyroid Hormone in the Treatment of Post-transplant Acute Tubular Necrosis (ATN)

Delayed graft function (DGF) in cadaver kidney transplants is a common problem and is often due to acute tubular necrosis (ATN). DGF in transplants may have a deleterious effect on long-term graft survival. Since thyroid hormone has been shown to hasten recovery from ATN in experimental models, we designed a trial to determine if a defined course of triiodothyronine (T3) would improve the short- or long-term outcome of patients with DGF in cadaveric transplants. A prospective, randomized, placebo controlled, double blind trial of T3 was carried out in patients with DGF in cadaveric renal transplants. End-points were percentage requiring dialysis, percentage recovering function, time to recovery and length of hospital stay. Long-term outcomes were percentage grafts functioning at 1 year and mean serum creatinine at 1 year. Forty-four patients were randomized to receive either T3 or placebo. Three patients were dropped from each group when early biopsies disclosed that DGF was due to rejection. The groups were well matched by age, cold ischemia time of the graft, and percentage reactivity to a random panel of antigens. Baseline thyroid function studies, including T3, reverse T3 (rT3), and thyroid stimulating hormone (TSH) levels, were similar between the two groups and typical of 'euthyroid-sick syndrome'. T3 had no effect on percentage requiring dialysis, time to recovery, percentage recovering function, or length of stay. At 1 year follow-up, graft function was similar in both groups and significantly lower than that seen in patients with good initial function. Thyroid hormone, given early in the course of DGF in cadaver kidney recipients, had no effect on the course of DGF. Long-term graft function is impaired in patients who experience post-transplant DGF compared to those who have good initial function.     

Differential Regulation of RGS-2 by Constant and Oscillating PTH Concentrations

PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system. PTH was administered intermittently (4 min/h, 10⁻⁷ M) or continuously at an equivalent cumulative dose (6.6 × 10⁻⁹ M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor. In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13 and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling.     

Stimulation of Alpha-Adrenoceptors Facilitates the Release of Growth Hormone-Releasing Hormone from Rat Hypothalamus in vitro

While extensive evidence suggests that adrenoceptors play an important role in the control of growth hormone in the rat, there are few studies involving the direct measurement of growth hormone-releasing hormone (GHRH). We have therefore developed a radioimmunoassay for rat GHRH, and used it to investigate the modulation of GHRH release by noradrenaline from incubated rat hypothalamus in vitro. The GHRH radioimmunoassay had no significant cross-reactivity with other hypothalamic or GHRH-related peptides, and was sensitive to 4 pg/tube; intra- and interassay coefficients of variation were 6% and 12% respectively. Single incubated rat hypothalami produced a stable and readily measurable output of GHRH in successive 20 min incubations after an initial 60 min preincubation; the release of GHRH was increased in the presence of 56 mM KCI, but did not respond to KCI-depolarization when calcium was excluded from the medium. Stimulated GHRH release was identical to synthetic rat GHRH(1–43) on high-performance liquid chromatography and Sephadex G-75 chromatography.
Noradrenaline stimulated GHRH secretion in a dose-dependent manner in the concentration range 10⁻¹⁰— 10⁻⁶M, with a plateau in response at 10⁻⁷M. Stimulation with noradrenaline 10⁻⁷M was blocked by idazoxan 10⁻⁵M and attenuated by thymoxamine 10⁻⁵M, but was unaffected by timolol 10⁻⁵M. Both the α₂-adrenoceptor agonist guanfacine, and the α₁-adrenoceptor agonist methoxamine, specifically stimulated GHRH secretion.
It is concluded that noradrenaline stimulates the release of GHRH at both α₁ and α₂-adrenoceptors.     

人参皂苷对人肝细胞HL-7702内性激素受体水平的影响

目的 观察人参皂苷（ginsenoside,GSS）对人肝细胞HL-7702内性激素受体水平的调节作用。方法 以四唑盐比色法（MTT）观察细胞生长以确定药物浓度，应用免疫组化法，免疫蛋白印迹法（Western blot）和RT PCR法分析人参皂苷对HL-7702细胞性激素受体蛋白和其mRNA水平的影响。结果 随GSS药物浓度增大，细胞内雌激素受体（estrogen receptor，ER）、孕激素受体（progesterone receptor，PR）、雄激素受体（androgen receptor，AR）蛋白及mRNA表达水平均逐渐增高，与溶剂对照组比较，差异有统计学意义（P<0.05），且细胞内性激素受体蛋白及mRNA表达呈剂量依赖性增加。结论 GSS可上调HL-7702细胞内性激素受体蛋白及mRNA的表达。     

107例胃肠间质瘤的病理学分析及临床诊治

目的总结胃肠间质瘤(GIST)的临床病理和免疫组织化学(免疫组化)特征,并评价预后。方法对1996年4月至2005年10月收治的107例GIST患者的临床资料进行回顾性分析。结果107例GIST病例中,73例(68.2%)为胃间质瘤,其他为小肠、结肠和系膜、网膜及后腹膜间质瘤;肿瘤直径0.7～20cm。CD117和vimentin阳性率100%,CD34阳性率83.2%。107例患者均接受手术治疗,联合脏器切除14例次。总随访率83.2%,平均随访24.5个月。14例(13.1%)发现复发或转移,其中4例为GIST中度恶性风险者。10例为高度恶性风险者;死亡4例。结论GIST的确诊主要依靠病理及免疫组化,CD117是诊断GIST的重要标记物,手术完整切除肿瘤效果满意,恶性GIST宜行较大范围的切除术。必要时须行联合脏器切除。     

全器械吻合法在全胃切除术后胃肠道重建中的应用(附56例报告)

目的评价机械吻合在全胃切除后消化道重建中的应用价值。方法回顾性分析56例胃恶性肿瘤患者全胃切除后应用管状吻合器吻合进行消化道重建的临床资料。结果本组每例手术时间为70～180min，平均手术时间90．5min。无手术死亡。术后无一例发生吻合口瘘（食管空肠吻合处）；4例发生吻合口溃疡，2例发生吻合口狭窄，吻合口狭窄率为3．57％，吻合口溃疡发生率为7．10％。结论全机械吻合在全胃切除术中具有操作简便、安全可靠、疗效确切，可缩短手术时间，减少术后吻合口瘘及吻合口狭窄率等优点，值得推广应用。     

前列腺增生症证型与体内性激素水平的临床研究

目的:研究前列腺增生症中医证型与体内性激素水平的相关性.方法:选择500例患者,中医辨证分为血瘀下焦、膀胱湿热、肾阴亏虚、肾阳不足、肺热气闭,均在就诊次日上午抽空腹血4 mL,进行血清性激素测定.结果:T值以血瘀下焦、肾阴亏虚证较高,肾阳不足证明显偏低,两者比较差别有显著性(P＜0.01);膀胱湿热证和肺热气闭证居中,与血瘀下焦、肾阴亏虚证比较差别也具有显著性(P＜0.05).E2值以肾阳不足证明显偏高,血瘀下焦和膀胱湿热证次之,肾阴亏虚和肺热气闭证较低.各组间比较差别具有显著性(P＜0.01).结论:前列腺增生症各证型与血清性激素水平变化有一定规律可循,同时也为证型客观化、微观化提供了相应证据.     

十二指肠间质瘤的临床特征及外科治疗

目的探讨十二指肠间质瘤的临床特征及外科治疗效果. 方法回顾性分析我科1990～2004年14例十二指肠间质瘤的临床资料. 结果病理类型:良性2例,潜在恶性4例,恶性8例.50.0%(7/14)发生在降部,其中恶性占57.1%(4/7).临床表现为右上腹肿物(6/14),右上腹隐痛不适(5/14)和乏力、体重下降(3/14),诊断手段为十二指肠低张造影(13/14)、B超(13/14)和CT(9/14).肿瘤距离十二指肠大乳头＜3 cm或位于降部、直径≥5 cm者宜行胰十二指肠切除术,肿瘤距离十二指肠大乳头＞3 cm及较小者宜行十二指肠节段性切除术. 结论十二指肠间质瘤恶性多见,临床表现无特异性,主要依靠十二指肠低张造影、B超、CT、EUS确诊,对无远处转移的肿瘤应积极争取根治性切除.