Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers.After the sublingual spray C_max was higher (39.0 ng·ml^-1) and t_max was shorter (3.9 min) than after the sublingual (22.8 ng·ml^-1 and 13.8 min) and peroral (16.9 ng·ml^-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng·ml^-1·min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively.The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions. For the a/b ratio of the finger pulse, the maximal effect was higher (e_max=130%) and the time to e_max (t_emax) shorter (16.6 min) after the spray than the sublingual tablet (84.4% and 25.5 min) or peroral tablet (90.2 and 31.3 min). The onset of effect was within 3, 5 and 7.5 min after the spray, sublingual and peroral tablets, respectively. A larger change in the orthostatically-induced decrease in systolic blood pressure and increase in heart rate was obtained following peroral than sublingual administration despite the similar plasma concentrations of ISDN. This probably reflects the larger amount of pharmacodynamically active mononitrate metabolites formed after oral dosing. The integrated effect following administration of 2.5 mg ISDN as spray was similar to that of a sublingual tablet of 5 mg.     

P53基因突变、人乳头瘤病毒16，18型感染与肺鳞癌发病的关系

应用单链构象多态性分析多聚酶链反应ＥＢ染色法（ＰＣＲ－ＳＳＣＰ－ＥＢ）对４０例肺癌组织标本的Ｐ５３基因序列５～８外显子突变进行分析，同时应用ＰＣＲ方法检测上述标本及１８例肺良性疾病组织标本中ＨＰＶ１６、１８型ＤＮＡ相关序列，旨在分析二者在肺鳞癌发病中的作用及相互关系，并就肺鳞癌与Ｐ５３基因结构和功能异常的关系进行初步探讨。     

Granulocyte elastase levels do not correlate with anaerobic and aerobic bacterial growth in seminal plasma from infertile men

Seminal culture and leucocyte elastase measurements were undertaken on samples from 30 men attending an infertility clinic. Elastase levels over 1000 ng ml-1 were obtained in 14 men and positive bacterial culture in 11 men, but there was no correlation between these two sets of measurements. While granulocyte elastase measurement in semen may reflect inflammation, our study suggests that it cannot be used as a simple marker of infection particularly in a population such as ours where the prevalence of prostatitis and genital infection is low.     

Immunoglobulin Gene Rearrangement in Plasma Cell Dyscrasias: Detection of Small Clonal Cell Populations in Peripheral Blood and Bone Marrow

The bone marrow (BM) and peripheral blood (PB) samples of 71 patients with plasma cell dyscrasias were analysed by the Southern blot technique for the presence of clonal immunoglobulin (Ig) gene rearrangements. 53% of BM samples examined were archival material such as air dried BM slides or frozen trephine biopsies. The results were related to bone marrow plasmacytosis as determined by cytology and flow cytometry, and other clinical parameters. Clonal Ig gene rearrangements were found in BM samples of 45 (83%) of 54 MM patients and in 3 of 6 patients with monoclonal gammopathy of unknown significance (MGUS). Clonal cell populations in the PB were detected in 11 (30%) of 37 examined MM patients, but in none of the patients with MGUS or solitary plasmacytoma of bone. PB involvement was associated with progressive disease. Circulating monoclonal cells were significantly associated with higher M-protein levels (p 0.05). Thus, circulating clonal precursor cells are encountered more frequently in active MM.     

LOWER POSTPRANDIAL PLASMA GLUCOSE AND INSULIN AFTER ADDITION OF ACACIA CORIACEA FLOUR TO WHEAT BREAD

Many Australian Aboriginal bushfoods contain slowly digested carbohydrate which elicit low postprandial blood glucose and insulin responses compared to Western foods, such as wheat bread. This study has shown that incorporation of flour made from a slowly digested seed, Acacia coriacea , into wheat bread (18 g/82 g wheat flour) significantly reduces the initial rise in plasma glucose levels ( p < 0.05) and the area under the plasma glucose curve ( p < 0.005) in six healthy subjects. Insulin values were also lowered at 60 minutes ( p < 0.025) and 90 minutes ( p < 0.05). Our findings suggest that Acacia flour, when used to dilute wheat flour in the manufacture of breads, produces a very palatable food which could be useful in the diets of diabetic individuals.     

Haemodynamics as a determinant of the pharmacokinetics of and the plasma catecholamine responses to isoprenaline

Summary The total body clearance and fractional extraction of isoprenaline (ISO) have been determined, and the relation between these parameters and cardiac output established. Whether desipramine, an inhibitor of neuronal uptake, altered the plasma catecholamine response to ISO was also investigated.Seven healthy subjects were given i.v., infusions of ISO in two, consecutive 25-min periods, at constant dose rates of 31–43 and 80–124 pmol·kg^–1·min^–1, respectively. The total-body (ER), pulmonary (ER_p) and forearm (ER_f) fractional extractions and the total body clearance (CL) of ISO were obtained from measurements of cardiac output and the steady-state ISO concentration in mixed central venous, arterial and forearm venous plasma.ISO-induced increases in cardiac output resulted in increases in CL, decreases in ER and no consistent change in ER_f. ER_p did not differ from zero. ISO also produced a dose-dependent increase in the mixed venous plasma concentrations of noradrenaline and 3,4-dihydroxyphenylglycol (DOPEG), and a decrease in that of adrenaline. Pretreatment with desipramine did not alter any of the pharmacokinetic parameters of ISO. Desipramine, however, reduced the mixed venous baseline plasma levels of noradrenaline (47%) and DOPEG (40%), and tended to reduce that of adrenaline (34%). It enhanced the plasma noradrenaline response 2.4-fold, abolished the plasma DOPEG response and did not alter the plasma adrenaline response to ISO.Hence, owing to its haemodynamic effects, ISO modifies its own pharmacokinetics which involve non-neuronal removal processes only. The increased DOPEG in plasma resulting from the ISO-induced increase in noradrenaline release was presynaptic in origin. Desipramine appears to reduce sympathetic activity. The enhancement by desipramine of the ISO-induced increase in plasma noradrenaline points towards recapture by neuronal uptake of at least 58% of the noradrenaline released in response to ISO.     

富血小板血浆治疗下肢慢性难愈合伤口47例随访研究

目的 探讨富血小板血浆(platelet-rich plasma,PRP)对下肢慢性难愈合伤口的修复作用. 方法 2007年5月-2007年11月,采用PRP注射治疗下肢慢性难愈合伤口47例.男41例,女6例;年龄15～68岁,平均43.2岁.原发疾病:胫腓骨骨折20例,跟骨骨折4例,跖骨骨折1例,下肢多发开放性骨折3例,胫骨骨髓炎10例,股骨骨髓炎1例,足踝部软组织损伤4例,截肢术后感染2例,足部矫形术后感染及跟腱修补术后感染各1例.外院治疗后2～4个月创口未愈合转入合并骨折未愈合23例,细菌培养结果 阳性38例.患者予2次清创加自体PRP伤口内注射,每次间隔2个月. 结果 患者均于首次注射PRP后获随访,随访时间4个月.首次注射PRP2个月后,34例伤口明显缩小,坏死组织及脓苔清除,组织色泽健康,血供良好,外露骨或肌肉组织被新牛肉芽组织覆盖.4个月随访时,无肌肉和骨组织外露患者,创面覆盖率79.3%4±18.O%,总治愈率29.8%.治疗前创口体积(11.8±5.6)mL,治疗后为(2.5±2.7)mL,创口体积缩小(9.3±4.9)mL,治疗前后创口体积比较差异有统计学意义(P＜0.05).术前23例合并骨折未愈合者,随访4个月时骨折完全愈合9例,骨痂生长明显增多12例,无明显改变2例,均无骨髓炎征象加重.细菌培养阳性结果 15例. 结论 PRP能有效促进软组织缺损修复,加速下肢慢性难愈合伤口愈合.     

ENDOSCOPIC MANAGEMENT OF A DIEULAFOY‐LIKE LESION IN A DUODENAL DIVERTICULUM

We present a 70‐year‐old man who had two episodes of melena during the preceding 8‐year period. He had a Dieulafoy‐like lesion in a diverticulum in the third portion of the duodenum. While emergency endoscopy revealed neither apparent blood nor clots around the diverticular orifice, there was a non‐bleeding vessel in the fundus of the diverticulum. The vessel ceased bleeding after argon plasma coagulation and, since then, the patient has not experienced bleeding. In cases of gastrointestinal bleeding of obscure origin, duodenal diverticulum should be considered as a possible source of bleeding, even when endoscopy discloses no apparent bleeding.     

头发、血浆、红细胞中铅对评价职业性接触水平的作用

[目的]探讨发铅、血浆和红细胞中铅对评价职业性铅接触水平的作用。[方法]用原子吸收分光光度计测定接触铅组与不接触铅对照组工人的血浆、红细胞及发中铅、铁、铜、镁、钙含量，测量数据用SAS软件处理。[结果]用0．25mol／L的HCl处理发样，能有效去除发表面的铅污染。接触组与对照组血浆铅无显著差异，而红细胞铅、发铅差异显著，血中其他元素含量无显著差异。[结论]去除表面污染的发铅和红细胞铅可作为铅接触指标。血浆铅则无意义。     

Systemic effects of two nasally administered glucocorticosteroids

Two topical corticosteroids, budesonide (BUD) and beclomethasone dipropionate (BDP), both administered as suspensions in water, were investigated in healthy volunteers regarding influence on cortisol in plasma and urine (U-cortisol) after nasal application. In the first study, single doses of 200, 400, and 800 μg of BDP and BUD were given at 10:00 pm. In the second study, 100, 200, and 400 μg were given mornings and evenings for 4 days. In the single-dose study, none of the drugs or doses showed any significant influence on cortisol in plasma. However, U-cortisol decreased significantly after BUD 400 and 800 μg. In the multidose study, U-cortisol values were significantly reduced after all doses of BUD and the highest dose of BDP. The compounds tested showed different ability to cause measurable systemic effects after nasal application. The clinical implication is that the prescriber, when choosing a compound, should take the application site into consideration and should also be encouraged to find the lowest effective dose.