Common leptin receptor polymorphisms do not modify the effect of alcohol ingestion on serum leptin levels in a controlled feeding and alcohol ingestion study.

We explored whether serum leptin response to alcohol ingestion was related to common leptin receptor gene polymorphisms, K109R (Lys109Arg), Q223R (Gln223Arg), S343S [Ser(T)343Ser(C)], and K656N (Lys656Asn), of reported physiologic significance during a controlled intervention. Fifty-three participants rotated through three 8-week treatment periods and consumed 0, 15 (equivalent to one drink), or 30 g (equivalent to two drinks) of alcohol (95% ethanol in 12 ounces of orange juice) per day, in random order. During the controlled feeding periods, all food and beverages including alcoholic beverages were prepared and supplied by the staff of the Beltsville Human Nutrition Research Center's Human Study Facility (Beltsville, MD), and energy intake was adjusted to maintain a constant weight. Blood was collected after an overnight fast on 3 separate days during the last week of each controlled feeding period and pooled for hormone analysis. Circulating serum leptin concentration was measured in duplicate by RIA and genotype analysis was done on DNA extracted from WBC using real-time PCR analysis amplification (TaqMan). Linear mixed models with a single random intercept reflecting a participant effect were used to estimate changes in serum leptin levels at 15 and 30 g of alcohol per day relative to 0 g of alcohol per day. No significant effects were found between common leptin receptor polymorphisms and serum leptin levels (P > or = 0.26).     

Cyclosporin A is a broad-spectrum multidrug resistance modulator.

PURPOSE: Overexpression of the multidrug resistance proteins P-glycoprotein (Pgp), multidrug resistance protein (MRP-1), breast cancer resistance protein (BCRP), and lung resistance protein (LRP) is associated with treatment failure in acute myeloid leukemia (AML) and other malignancies. The Pgp modulator cyclosporin A has shown clinical efficacy in AML, whereas its analogue PSC-833 has not. Cyclosporin A is known to also modulate MRP-1, and we hypothesized that broad-spectrum multidrug resistance modulation might contribute to its clinical efficacy. EXPERIMENTAL DESIGN: We studied the effects of cyclosporin A and PSC-833 on in vitro drug retention and cytotoxicity in resistant cell lines overexpressing Pgp, MRP-1, and BCRP and on nuclear-cytoplasmic drug distribution and cytotoxicity in cells overexpressing LRP. Cellular drug content was assessed by flow cytometry and nuclear-cytoplasmic drug distribution by confocal microscopy. RESULTS: Cyclosporin A enhanced retention of the substrate drug mitoxantrone in cells overexpressing Pgp (HL60/VCR), MRP-1 (HL60/ADR), and BCRP (8226/MR20, HEK-293 482R) and increased cytotoxicity 6-, 4-, 4-, and 3-fold, respectively. Moreover, cyclosporin A enhanced nuclear distribution of doxorubicin in 8226/MR20 cells, which also express LRP, and increased doxorubicin cytotoxicity 12-fold without an effect on cellular doxorubicin content, consistent with expression of wild-type BCRP, which does not efflux doxorubicin. Cyclosporin A also enhanced nuclear doxorubicin distribution in a second cell line with LRP overexpression, HT1080/DR4. PSC-833 enhanced mitoxantrone retention and cytotoxicity in cells overexpressing Pgp, but had no effect in cells overexpressing MRP-1, BCRP, or LRP. CONCLUSIONS: Cyclosporin A modulates Pgp, MRP-1, BCRP, and LRP, and this broad-spectrum activity may contribute to its clinical efficacy.     

一氧化氮与白内障相关性的临床研究

目的探讨一氧化氮（NO）诱导白内障的可能机制。方法30例白内障患者晶状体分为老年性白内障组及糖尿病性白内障组，以正常晶状体作对照，制备晶状体匀浆上清，测NO、NO合成酶（NOS）。结果正常晶状体中存在NO、NOS，老年性白内障组晶状体中N0、NOS含量与正常晶状体组比较显著上升（P〈0．05），且糖尿病性白内障组NO、NOS含量上升非常显著（P〈0．01）。结论正常晶状体中存在NO、NOS，不同浓度的NO、NOS具有维持晶状体透明性的生理作用及诱导白内障的病理作用。     

经宫颈输卵管镜在输卵管疾病诊治中的进展

经宫颈输卵管镜是一种新的技术,是一种在宫腔镜辅助下探查输卵管的内部状况的器械,通过输卵管镜的检查可以清除管腔内的碎片及粘连,具有诊断与治疗兼容的功效,同时,既可以给予患者适当的治疗,又可以决定是否有进一步手术治疗的需要.输卵管镜在诊断和治疗输卵管疾病中起着重要作用.现就输卵管镜的分类、应用以及在实际操作中的困难和并发症综述.     

Effects of a PPARgamma agonist,GI262570, on renal filtration fraction and nitric oxide level in conscious rats

PPARgamma agonists ameliorate insulin resistance and lower blood pressure. Volume expansion/edema has been observed in susceptible patients treated with these agents. Alterations of renal hemodynamics affect renal tubular reabsorption, and thus may contribute to volume expansion. This study seeks to determine whether volume expansion caused by a PPARgamma agonist, GI262570, is related to changes in glomerular filtration rate, effective renal plasma flow, or renal filtration fraction. Chronically catheter-implanted conscious rats were studied to determine the effects on glomerular filtration rate, effective renal plasma flow, and renal filtration fraction after 1, 4, and 10 days of GI262570 treatment (8 mg/kg, p.o., B.I.D.). Elevated adipose mRNA of PPARgamma target genes confirmed PPARgamma activation in GI262570-treated rats. GI262570 treatment for 10 days decreased hematocrit, hemoglobin, and serum albumin (all P < 0.05), indicating volume expansion, but did not alter glomerular filtration rate, effective renal plasma flow, or renal filtration fraction. However, nitrate + nitrite was significantly higher in plasma and hind limb muscle of GI262570-treated rats (both P < 0.05). This study demonstrated that treatment with PPARgamma agonist GI262570 resulted in volume expansion and increased nitric oxide, but did not affect glomerular filtration rate, effective renal plasma flow, or renal filtration fraction, indicating PPARgamma agonist-induced volume expansion is not related to changes in renal filtration fraction, and increased nitric oxide may contribute to the PPARgamma agonist-induced blood-pressure lowering.     

Relationship between serum leptin levels and alcohol consumption in a controlled feeding and alcohol ingestion study

We examined serum leptin levels in a controlled feeding and alcohol ingestion study to elucidate potential mechanisms by which alcohol may affect cancer and immunologically related health risks. A total of 53 healthy, nonsmoking postmenopausal women completed a random-order, three-period crossover design study in which each woman received zero (0 g of alcohol), one (15 g of alcohol), or two (30 g alcohol) drinks per day. After accounting for differences in body mass index, women who consumed 15 or 30 g of alcohol per day had 7.3% (95% confidence interval [CI] = 3.0% to 15.1%) and 8.9% (95% CI = 1.6% to 16.7%) higher serum leptin levels, respectively (P(trend) =.018), than women who consumed 0 g of alcohol per day. Younger women (i.e., 49-54 years) demonstrated a statistically significantly larger association of alcohol consumption level with the increase in serum leptin levels than older women (i.e., 55-79 years) (24.4%, 95% CI = 9.3% to 42.0% versus 3.7%, 95% CI = -4.1% to 12.1% increase in serum leptin levels for 30 g of alcohol per day relative to 0 g of alcohol per day for the lowest age quartile compared with the three highest age quartiles combined; P =.022). These results indicate that moderate alcohol consumption (15-30 g of alcohol per day) increases serum leptin levels in postmenopausal women and may predispose moderate drinkers to the morbidities associated with chronic elevations of this hormone including cancer.     

Spongy hydroxyapatite in hand surgery--a five year follow-up

Twenty-two patients were treated for enchondromas or cysts of the hand by curettage and complete filling of the defect with hydroxyapatite. Postoperatively no complications occurred and marginal osseous integration was radiologically complete after 6 to 8 weeks. Patients were re-examined after a minimum of 5 years after operation and the functional and aesthetic results were excellent in all patients. Radionuclide imaging showed identical bone activity to that in the contralateral healthy hand and there were no signs of inflammation.