Present status and future prospects of oral iron chelation therapy in thalassaemia and other diseases

In the last few years we have witnessed the emergence of oral chelation which is a new form of therapy for transfusional iron-loaded patients in thalassaemia and other refractory anaemias. The need for a cheap, non-toxic, orally effective iron chelator is paramount because it could potentially save the lives of many thousands of patients. At present, less than 10% of the patients requiring iron chelation therapy worldwide receive the widely used chelating drug desferrioxamine (DF) because of its high cost, oral inactivity and toxicity. The most promising oral iron chelator is 1, 2-dimethyl-3-hydroxypyrid-4-one (L1 or INN: Deferiprone), which has so far been taken by over 450 patients in 15 countries, and in some cases daily for over 4 years with very promising results. L1 was shown at 50–100 mg/kg/day to be effective in bringing patients to negative iron balance. It increases urinary iron excretion, decreases serum ferritin levels and reduces liver iron in multi-transfused iron-loaded patients. Toxic side effects were mainly encountered at high doses (80–100 mg/kg/day) and include transient agranulocytosis (5 cases), transient musculoskeletal and joint pains (10–20%), gastric intolerance (2–6%) and zinc deficiency (1%). The incidence of these toxic side effects was reduced by using lower doses of 50–75 mg/kg/day. The overall efficacy and toxicity of L1 is comparable to that of DF in animals and humans. Further work is required for identifying susceptible individuals to L1 toxicity, and also optimum dose protocols of L1 which can maximise iron excretion and minimise the incidence of toxic side effects.     

孕产妇及胎儿血浆儿茶酚胺水平的研究

采用高效液相色谱层析技术，检测了７８例孕产妇、９例非孕妇女、６０例脐血的血浆儿茶酚胺（ＣＡ）水平。结果表明，在孕期除去甲肾上腺素明显降低外，各组间ＣＡ水平无明显变化；脐动脉ＣＡ明显高于脐静脉（Ｐ＜０．０１）；剖宫产组脐血浆ＣＡ水平明显低于阴道产组（Ｐ＜０．０１）；胎儿窘迫的脐血浆ＣＡ水平明显增高，其幅度与新生儿窒息的发病率有关。作者认为胎儿血浆ＣＡ水平产生于自身，并非母体所传递；胎儿窘迫ＣＡ升高，可做为早期诊断胎儿窘迫及其严重程度的一项辅助指标。     

活血止痛液制备工艺的研究

目的：探索活血止痛液制备的最佳工艺。方法：采用了正交设计法考察乙醇的提取浓度,用量、提取次数及时间４个因素,以甲醇浸出物与阿魏酸的含量为考察指标,同时采用高效液相法测定成品中阿魏酸的含量。结果：最佳制备工艺为４倍量６０％乙醇回流提取３次,每次２ｈ。测定活血止痛液１ｍｌ中阿魏酸含量≥０．０５ｍｇ。结论;制剂稳定;测定方法简便,灵敏,准确,重复性好。     

An atomic force microscopy investigation of bioadhesive polymer adsorption onto human buccal cells

Atomic force microscopy (AFM) was used to examine the buccal cell surface in order to image the presence of adsorbed bioadhesive polymers identified from previous work. Isotonic saline solution (5 ml) containing either polycarbophil (pH 7.6), chitosan (pH 4.5) or hydroxypropyl methylcellulose (pH 7.6) (0.5% w/v) was exposed to freshly collected buccal cells (ca. 48×10⁴ cells/test) for 15 min at 30°C. The cells were then rinsed with a small volume of double distilled water, allowed to air-dry on a freshy cleaved mica surface and imaged using contact mode AFM. Untreated cells showed relatively smooth surface characteristics, with many small ‘crater-like’ pits and indentations spread over cell surfaces. Cells that had been treated with all the investigated polymers appeared to have lost the crater and indentation characteristic and gained a higher surface roughness. These results suggest that polymer chains had adsorbed onto the cell surfaces. Quantitative image analysis of cell topography showed significant increases (P<0.05) in arithmetic roughness average (R_a) for all the investigated polymer treated cells surfaces with respect to untreated control specimens. The changes in surface topography indicate the presence of adsorbed polymer, confirming previous work. This study demonstrates the suitability of AFM as a powerful and sensitive technique for detecting and imaging bioadhesive polymers present on mucosal cell surfaces.     

燃煤砷污染对人体血细胞DNA合成、DNA损伤及修复的影响

目的与方法：采用液体闪烁计数法及＾１２５Ｉ后标记法检测燃煤型砷中毒人群血细胞ＤＮＡ自发合成、ＤＮＡ－蛋白质交联物（ＤＰＣ）水平及非程序外ＤＮＡ合成（ＵＤＳ）反应,以探讨燃煤砷污染以人体ＤＮＡ合成、ＤＮＡ损伤及修复的影响。结果：病区非病人及中毒病人的ＤＮＡ合成明显降低,ＤＰＣ水平随病情加重而升高;而ＵＤＳ反应则只在中毒病人体内增强,差异均有显著性。结论：燃煤砷可在早期致人体内ＤＰＣ形成,引起严重的Ｄ     

Thrombospondin-1 expression in oral squamous cell carcinomas: correlations with tumor vascularity, clinicopathological features and survival

Thrombospondin-1 (TSP-1) is a 450 kd glycoprotein synthesized and incorporated into the extracellular matrix by numerous cell types and reported to suppress tumor growth and progression by its inhibition of angiogenesis. In order to clarify the biological role of TSP-1 and determine its clinicopathological significance in oral squamous cell carcinomas (SCCs), we identified TSP-1 protein expression in 54 oral SCCs by immunohistochemistry and correlated it with microvessel density (MVD), clinicopathological features and patient's survival. Thirty-two out of 54 carcinomas (59%) were identified as having a low level of TSP-1 expression (TSP-1-L), and 22/54 (41%) carcinomas identified as having a high level of TSP-1 expression (TSP-1-H). The MVD counts (mean±S.D.=9.0±4.9) in TSP-1-H tumors was significantly lower than that (mean±S.D.=12.7±4.4) in TSP-1-H tumors (P=0.0065). The level of TSP-1 expression was not correlated with T category and histologic grade, but inversely correlated with the pattern of tumor invasion (P=0.0136) and with lymph nodal status (P=0.0119). Furthermore, Kaplan–Meier analysis showed that the 5-year survival rate of TSP-1-H group was significantly higher than that of TSP-l-L group. Our results suggested that TSP-1 expression exerts an inhibitory effect on tumor vascularity, and that it has value in assessment of aggressiveness and prognosis of oral SCCs.     

Behavior of squamous cell carcinoma of the floor of the mouth. Is supraomohyoid neck dissection sufficiently safe to manage clinically N0 patients?

Aim

The main aim of the present report is to study the behavior of SCC of the floor of the mouth.

The contribution of gustatory nerve input to oral motor behavior and intake-based preference. I. Effects of chorda tympani or glossopharyngeal nerve section in the rat

Two-bottle intake tests and taste reactivity (TR) tests were used to reveal whether changes in ingestive behavior would follow bilateral section of either the chorda tympani (CT) or the glossopharyngeal (GP) nerve. Rats received two-bottle intake tests to compare 24-h ingestion of water to that of NaCl, MgCl2, quinine, or sucrose. Prior to each long-term intake test, rats received a 1 min, 1 ml intraoral infusion of the same chemical stimulus. Ingestive and aversive oral motor responses elicited by these 1 ml infusions were videotaped and subsequently analyzed. GP-section did not alter quinine or sucrose preference; overall, preference of MgCl2 and NaCl was also similar to controls. In contrast, TR tests in GP-sectioned rats revealed that most quinine, MgCl2 and NaCl stimuli elicited significantly fewer aversive oral motor responses. In addition, the latency of aversive responses to these 3 chemical stimuli was increased for these rats. Intake-based preference tests failed to show any difference between rats with CT nerve section and controls. In TR tests, however, CT-sectioned rats displayed significantly fewer ingestive oral motor responses to NaCl, MgCl2, and quinine than controls. Neither sucrose intake nor sucrose-elicited TR were altered by CT or GP nerve section. This report confirms the failure of long-term intake tests to uncover behavioral deficits following the section of gustatory nerves. In contrast, the use of a different behavioral test makes clear for the first time that gustatory nerve section has dramatic consequences on ingestive behavior. The examination of taste elicited oral motor behaviors reveals a coherent and nerve specific pattern of neurological deficit following peripheral nerve section.     

Metabolic control after kidney and pancreas transplantation: whole series results and effects of segmental duct obstruction versus whole pancreas with bladder diversion technique

From October 1976 to December 1990 181 pancreatic transplants were performed in our centre on 171 Type 1 (insulin-dependent) diabetic patients. Oral glucose tolerance test evaluated 1 year after surgery in 31 subjects showed an impaired glucose tolerance at 120 min (blood glucose 9.5±0.6 mmol/l). Similar results were obtained in seven patients 3 years after transplantation (blood glucose at 120 min 8.3±1.08 mmol/l). 24h metabolic profiles performed at the same intervals showed near normal blood glucose levels and good insulin release. Preliminary data concerning a randomized, comparative study between whole pancreas with bladder diversion and segmental pancreas transplantation, showed better metabolic control in the patients who received the whole pancreas, probably due to the greater islet mass grafted.     

Acquisition of oral phencyclidine (PCP) self-administration in rhesus monkeys: effects of dose and an alternative non-drug reinforcer

 The effects of drug dose and a non-drug alternative reinforcer on acquisition of oral PCP self-administration in rhesus monkeys were examined. Acquisition was studied using three groups of monkeys (seven subjects per group). One group received a low PCP dose (0.0375 mg/delivery) and the other two received a high PCP dose (0.15 mg/delivery). One of the high dose groups had concurrent access to a saccharin solution (0.03% w/v) and water during the intersession (17.5-h) period. Food non-restricted monkeys were initially given access to water under a fixed-ratio (FR) 1 schedule during daily 3-h sessions. Water was then replaced with PCP during the session. The monkeys were then reduced to 85% of their free-feeding body weights and fed before the session, and the FR value was increased from 1 to 2, 4 and 8. Subsequently, food was given post-session and water and PCP were available under concurrent FR 8 schedules. At this final step of the procedure, acquisition of PCP self-administration was considered to occur if PCP intake consistently exceeded water intake. When all three groups were given concurrent access to PCP and water, PCP intake was greater than water intake only in the group of monkeys receiving the high PCP dose. PCP intake increased when water replaced saccharin during intersession in the high PCP dose group. Within-group data revealed that 85.7% of monkeys acquired PCP reinforcement in the group given access to the high PCP dose while only 42.8% acquired in the other two groups. These data suggest that drug dose and presence of alternative non-drug reinforcers affect acquisition of drug self administration in non-human primates. Received: 14 May 1997 / Final version: 15 December 1997