Acute undifferentiated leukemia: induction of partial differentiation by phorbol ester

Expression of lineage-associated surface antigens, was studied in 7 patients with acute undifferentiated leukemia (AUL), 3 patients with acute myeloid leukemia (AML), 4 patients with acute lymphoid leukemia (ALL) and bone marrow from 2 healthy donors, before and after exposure to the differentiating agent 12-O-tetradecanoylphorbol-13-acetate (TPA). The surface antigens were identified by monoclonal antibodies (My4, My8, My9, MO1, B1, CALLA, T11) and formation of EA and EAC rosettes. Adherence to plastic was also assessed. Cells from the AML patients responded to TPA with an increase in myeloid antigen positive cells and other markers of differentiation. Four of the AUL patients showed, also, a large increase in the fraction of cells expressing one or more myeloid markers, in correlation with formation of EAC rosettes. In contrast, the percentage of cells expressing myeloid antigens, did not increase in the 4 ALL patients, or in the normal donors. These findings confirm the heterogeneity of undifferentiated leukemias, and suggest the hypothesis that some AUL's can be induced to express markers of early myeloid cells.     

Pattern of renal osteodystrophy in haemodialysis patients in Saudi Arabia

In order to know the pattern of renal osteodystrophy in haemodialysispatients in Saudi Arabia we conducted a multicentre study involving209 patients. The mean age of the patients was 39.4±14(18–70) years, 128 were males and 81 females. All patientswere on acetate dialysate and their mean duration on dialysiswas 3.5 ± 1.5 years. The major symptom was bone and joint pain (25.8%). The meanserum calcium was 2.1 ±0.26 mmol/l, phosphorus 2.0 ±0.36mmol/l, alkaline phosphatase 19.7± 14.6 u/l and parathyroidhormone level was 8.9 ± 3.9mg/ml. The mean serum aluminium(AL) level was 25.4±17.7 µg/l, while that of 1,25vitamin D3 was 8.1±4.2ng/l and of fluoride was 92.2 ±31.4 µg/l. The major radiological finding was osteosclerosis(70%). Dual-photon absorptiometry (DPA) showed low bone mineraldensity (LBM) in 65% of the patients. Forty-one patients had bone biopsies with AL staining of thebiopsies. Of this group, 92% had changes of hyperparathyroidismand 66% of them were pure hyperparathyroidism. Sixty percentof them had variable degrees of AL intoxication. The radiologicalskeletal survey of those patients could detect abnormalitiesin only 46% while 70% of them had abnormal bone mineral density(BMD). In conclusion, osteosclerosis is the commonest radiologicalfinding in our dialysis patients while secondary hyperparathyroidismis the main histopathological diagnosis in bone biopsy, evenin patients with normal skeletal survey. AL intoxication isa significant problem in our population. DPA is more sensitivein detecting bone abnormalities than X-radiography.     

炔诺酮醋酸酯合成的工艺改进

以炔诺酮为原料，醋酐为酰化剂，使１７β－羟基酯化成炔诺酮醋酸酯。实验中发现在水汽蒸馏时加入酯酸钠可抑制炔诺酮醋酸酯的水解。经熔点、经外光谱以及氢核磁共振光谱增证明此化合物为炔诺酮醋酸酯。     

实验性重症肌无力小鼠脾淋巴细胞糖皮质激素受体测定

为探讨糖皮质激素受体（ＧｌｕｃｏｃｏｒｔｉｃｏｉｄＲｅｃｅｐｔｏｒ．ＧＲ）与实验性自身免疫性重症肌无力（Ｅｘｐｅｒｉ ｍｅｎｔａｌａｕｔｏｉｍｍｕｎｅｍｙａｅｔｈｅｎｉａｇｒａｖｉｓ．ＥＡＭＧ）的关系及其意义，应用放射配体法测定ＥＡＭＧ及用强的松治疗的ＥＡＭＧ小鼠脾淋巴细胞ＧＲ水平。模型组小鼠脾淋巴细胞ＧＲ的数量（４０７８±１３３６位点／细胞）以比照组（５３９１±１６０７位点／细胞）明显降低（Ｐ＜０．０１），强的松治疗组小鼠免疫细胞ＧＲ水平较模型组明显不调（Ｐ＜０．０１）。提示免疫细胞ＧＲ水平下降与重症肌无力（Ｍｙａｓｔｈｅｎｉａｇｒａｖｉｓ．ＭＧ）发病机理可能有关，应用糖皮质激素治疗ＭＧ时，也应注意药物对ＧＲ水平的影响     

皮质激素类药物的多晶型及其片剂的溶出度研究

测定了不同晶型的溶解度、熔化热和表面自由能以及相应片剂的溶出度。实验表明同质多晶型物的表面自由能、溶解度和摩尔熔化热及其相应片剂的溶出度均存在显著差异。     

The role of Ca2+ in the time-dependent pepsinogen secretion of frog oesophageal peptic glands stimulated by bombesin

Time- and dose-related stimulation of pepsinogen secretion by bombesin was studied in perifused dispersed peptic glands from the oesophagus of the American bullfrog Rana catesbeiana. The dose response to bombesin was monophasic between 10^-10 and 10^-7 M, with an EC₅₀ of 10^-9 M. Time-dependent secretion was closely monitored at 1–2 min intervals. Though there was overlap, we could discriminate an early response at ? 2 min (phase I) and a delayed or sustained response at ± 2 min (phase II) on the basis of responses in the presence and absence of external Ca²⁺. Phase I was relatively independent of external [Ca²⁺] and coincided with ⁴⁵Ca efflux following a dose-dependent increase in cytosolic [Ca²⁺], measured by Fura-2AM. Phase II was sustained at ? 80% of control at an external [Ca²⁺] of 1–5 ,μM, but was eliminated by adding 0.5–1 Mm EGTA. Bombesin caused a sustained Ca²⁺ influx and, when this was prevented by EGTA, the response to successive stimulations by bombesin and by acetylcholine was greatly attenuated. The phorbol ester, 12–O-tetradecanoyl phorbol 13–acetate, which stimulates secretion at high concentrations, was used as background at a thresehold concentration of 10^-7 M, which did not by itself stimulate secretion. At this concentration, 12–O-tetradecanoyl phorbol 13–acetate potentiated the responses to bombesin and to acetylcholine. These results define the different Ca²⁺ dependencies of the immediate and sustained secretory responses to bombesin, but indicate a complex relationship of stimulation responses to Ca²⁺ homeostasis in various agonist-sensitive Ca²⁺ pools.     

Time- and concentration-dependent increases in cell proliferation in rats and mice administered vinyl acetate in drinking water.

Chronic administration of vinyl acetate (VA) in drinking water to rats and mice has produced upper digestive tract neoplasms. These tumors were believed to arise from the intracellular metabolism of VA by carboxylesterases to cytotoxic and genotoxic compounds. We hypothesized that prolonged VA exposure at high concentrations would induce cytotoxicity and a restorative cell proliferation (CP). These endpoints were measured in F-344 rats and BDF1 mice administered drinking water containing 0, 1000, 5000, 10,000, or 24,000 ppm VA for 92 days. On test days, Days 1, 8, 29, and 92, upper digestive tract histopathology and oral cavity CP (pulsed 5-bromodeoxyuridine [BrdU] to measure S-phase DNA synthesis) were evaluated. Analysis of test solutions showed that VA spontaneously hydrolyzed, slowly releasing acetic acid and thereby lowering pH. Statistically significant, concentration-related increases in CP occurred in basal cells of the mandibular oral cavity mucosa of mice at 10,000 and 24,000 ppm but only after 92 days. CP increases were approximately 2.4- and 3.4-fold above controls and were considered to be toxicologically significant. Some statistically significant increases in CP were also measured in the oral cavity mucosa of rats; however, these changes were considered to be of equivocal biological relevance. No histopathological evidence of mucosal injury was seen in either species. The absence of cytotoxicity in the upper digestive tract mucosa suggests that the increased CP at high administered VA concentrations may be due to a mitogenic response, ostensibly from the loss of cell growth controls in oral cavity mucosa.     

Conductimetric titrimetry for assay of selected antibiotics in non-aqueous media

In this study, a conductimetric titration method is proposed for the determination of some commonly used antibiotics. The conductimetric titration of three antibiotics, namely ampicillin, amoxycillin trihydrate and rifampin, was carried out in acetic acid using perchloric acid as titrant. Ciproflaxacin hydrochloride, however, was titrated after being dissolved in acetic acid containing an excess of mercury(II) acetate. For the titration of netilmicin sulphate, barium acetate prepared in acetic acid was used as titrant. The method was found to be highly accurate and precise, having a relative standard deviation of less than 1.0% for all antibiotics studied. It was also shown that the conductimetric titrimetry could be successfully applied to the assay of commercial preparations containing the above-mentioned antibiotics. The validity of the method was tested by the recovery studies of standard addition to pharmaceuticals and the results were found to be satisfactory.     

Combined treatment with cyclosporin A and cortisone acetate minimizes the adverse bone effects of either agent alone

Although cyclosporin A (CsA) and cortisone acetate (CRT) adversely affect bone, their combined effect on bone is unknown. Sprague Dawley rats were therefore administered either vehicle or CsA (7.5 mg/kg/day) by gavage and saline or CRT (2 mg/100 mg/day) by s.c. injection for 28 days. Group A received vehicle plus saline, group B CsA plus saline, group C vehicle plus CRT, and group D CsA/CRT. Serial bloods were sampled over a 28-day period for ionized calcium (Ca), PTH, 1,25 dihydroxyvitamin D (1,25(OH)2D), and bone gla protein (BGP osteocalcin) and tibia were examined on day 28 for histomorphometry. Results were compared with group A. Ca and PTH levels in groups B, C, and D were similar to those in group A during the study period. Group B had lower body weights, elevated levels of BGP, and an increase in 1,25(OH)2D. Group C developed weight loss and a decrease in BGP and 1,25(OH)2D. Group D had weight loss, BGP levels between those of group A and group C, and 1,25(OH)2D values similar to group A. Bone histomorphometry revealed high turnover osteopenia in group B and hyperostosis in group C with a decrease in bone formation and osteoclastlike cells. Combination therapy returned these to control values. In conclusion, the adverse effects of either CsA or CRT on bone in rats are minimized by combined therapy.     

Antiinflammatory activity of the platelet-activating factor receptor antagonist A-85783

Abstract Accumulating evidence suggests an important role for the lipid mediator, platelet-activating factor (PAF), in cutaneous inflammation. In these studies the antiinflammatory effects of the potent and selective lipophilic PAF receptor antagonist A-85783 topically applied to the ventral ears of male Wistar rats were assessed. Intradermal injections of PAF into rat ears resulted in cutaneous inflammation as assessed by both ear thickness measurements and histological evaluation. Pretreatment of the ears with A-85783 resulted in an inhibition of subsequent PAF-induced inflammation. A-85783 treatment also inhibited phorbol myristic acetate-induced cutaneous inflammation, suggesting that the PAF receptor is involved in the etiology of this experimental dermatitis. These findings demonstrate that epicutaneous A-85783 is an appropriate tool to study the role of the PAF receptor in cutaneous inflammation, and suggest the possible clinical utility of this new class of antiinflammatory agents. Received: 20 March 1998