A theophylline dosage regimen which reduces round-the-clock variations in plasma concentrations resulting from diurnal pharmacokinetic variation

Summary Slower drug absorption at night can leave residual drug from an evening dose of a sustained-release product remaining to be absorbed at the time of the next morning's dose, thereby giving higher plasma concentrations of the drug during the day than the night.When a capsule product releasing theophylline over 12 h after a morning dose was given repetitively at 8 a.m. and 8 p.m. for 4 days, daytime plasma concentrations from 4 h to 8 h after the dose were about 40% greater than corresponding night-time concentrations, and the mean steady-state concentration during the night-time interval was only 81% of that during the daytime interval.Altering the regimen to one capsule at 12 noon and one at 10 p.m. eliminated all significant differences between a.m. and corresponding p.m. plasma concentrations of theophylline and between the mean steady-state concentrations for each of the interdose intervals within a day.     

Prolactin responses to haloperidol in drug-free and treated schizophrenic patients

Summary The prolactin response to 5 mg haloperidol i.m. was studied in 12 schizophrenic patients in a drug-free state and after a month treatment with haloperidol, as a possible index of dopamine receptor sensitivity and occupancy. Blood samples were taken at times 0, 60, 90 and 120 minutes. The increase in PRL observed in the drug-free state disappeared after drug treatment. The PRL plasma levels after treatment with 60 mg haloperidol per os were higher than the maximal PRL responses after 5 mg i.m. The increases in baseline PRL caused by the treatment correlated positively to the reduction in the BPRS score. The test was also performed in a group of 11 patients chronically treated with haloperidol during a daily dose of 60 mg, and 15 days after reduction of the dose to 30 mg. PRL increases after 5 mg haloperidol i.m. were observed only after reduction of the dose. It is suggested that the prolactin response to haloperidol is an index of the occupancy of receptors that are involved in the PRL releasing mechanisms, and could be used to verify their blockade by the neuroleptics, especially in patients that do not respond positively to drug treatment.     

Coronavirus induced primary demyelination: indications for the involvement of a humoral immune response

Coronavirus MHV-JHM infection of rodents can result in demyelinating encephalomyelitis. We analysed histological changes induced by coronavirus MHV-JHM infection in Lewis rats. Besides an acute disease (AE), chronic panencephalitis (CPE) and subacute demyelinating encephalomyelitis (SDE) were induced. These disease types were differentiated by the incubation period, the localization of lesions, the type of tissue damage and distribution of virus antigen. In AE and CPE, virus antigen was detected in neurons, astrocytes and oligodendrocytes, whereas in SDE neurons lacked virus antigen. Viral nucleocapsid protein (N) was present in the cytoplasm and the spike protein (S) was displayed on the surface of infected neural cells. However, expression of S protein relative to N protein was severely impaired in SDE lesions. Quantitative analysis of infiltrating inflammatory cells revealed that the number of macrophages and T cells were similar in lesions of AE, CPE and SDE. In contrast to that, SDE lesions contained a significantly higher number of IgG + B cells and plasma cells. In addition active demyelinating SDE lesions displayed an enhanced IgG content and deposits of complement C9. These results indicate that virus induced primary demyelination could be a consequence of antibody mediated cytotoxicity. Furthermore, a reduction in the number of cells producing spike protein in the chronic forms of the disease indicates down-regulation of this protein, possibly mediated by anti-S antibodies.     

Effects of the phosphodiesterase inhibitor rolipram on the acoustic startle response in rats

Systemic administration of the phosphodiesterase inhibitor rolipram (0.05–10.0 mg/kg, IP) produced a rapid and dose-related increase in the amplitude of the acoustic startle response in rats. The (−) isomer was more potent than the (+) isomer in enhancing startle amplitude. Rolipram increased startle responses that were elicited by brief electrical stimulation of the ventral cochlear nucleus or nucleus reticularis pontis caudalis, two brainstem relay nuclei of the startle neural circuit. A low (5 μg) dose of rolipram produced an excitatory effect on startle following spinal (lumbar intrathecal) infusion but not following supraspinal (lateral ventricle) infusion. Rolipram (0.5 mg/kg, IP) excitation of startle was not blocked by drugs which differentially disrupt the release of monoamines (DSP4, reserpine + alpha-methylpara-tyrosine, reserpine + para-chloro-phenylalanine) or by drugs which differentially block monoamine receptors (haloperidol, prazosin, idazoxan, cinanserin, or cyproheptadine). The marked increase in startle seen following systemic rolipram injection is attributable, at least in part, on an action in the lumbar spinal cord that directly or indirectly facilitates neural transmission along the reticulospinal component of the startle reflex neural pathway. The startle reflex should be a useful behavioral test system for studying the mechanism of action of rolipram and related compounds purported to selectively inhibit calmodulin-independent forms of phosphodiesterase.     

Opsonization of yeast by the plasma of Biomphalaria glabrata (Gastropoda): a strain-specific, time-dependent process

Phagocytosis of yeast by haemocytes of Biomphalaria glabrata, intermediate host of Schistosoma mansoni, is influenced strongly by host plasma components, although it can occur without involvement of such factors. Plasma from two strains of B. glabrata which are resistant to S. mansoni differs in its opsonic properties from the plasma of a susceptible strain. This may reflect the principles which determine compatibility or incompatibility in this host-parasite system. Opsonization is a time-dependent process: short periods of incubation in plasma from all strains reduces subsequent phagocytosis in the absence of plasma factors, whereas longer incubation in resistant strain plasma is markedly opsonic. Haemocytes from all strains examined are equally competent in their recognition of either native or opsonized yeast.     

协同刺激分子CD28在结核杆菌抗原体外激活人外周血γδT细胞中的作用

目的 :为了探讨CD2 8协同刺激分子在结核杆菌 (Mtb)低分子多肽抗原体外激活人外周血γδ T细胞中的作用。方法 :采用激发型抗CD2 8单抗模拟第二信号 ,Mtb低分子多肽抗原作为刺激原 ,对纯化的人外周血T细胞进行体外刺激和培养 ;用流式细胞仪检测γδ T细胞上CD2 8分子的表达、γδ T细胞的增殖效应及活化的γδ T细胞上CD6 9分子的表达。结果 :人外周血γδ T细胞中有 5 0 %左右表达CD2 8分子 ;抗CD2 8单抗协同Mtb抗原可刺激γδ T细胞的活化和增殖 ;但抗CD2 8单抗或Mtb抗原单独刺激则无作用。活化的γδ T细胞表面表达CD6 9分子。结论 :Mtb抗原在选择性活化人外周血γδ T细胞时需要第二信号的参与 ;CD2 8在Mtb抗原激活γδ T细胞时可提供协同刺激信号 ;CD6 9可作为γδ T细胞的早期活化标志。     

静脉注射大剂量人体丙种球蛋白对儿童重症病毒性脑炎预后的影响

①目的　探讨静脉注射大剂量人体丙种球蛋白 (IVIG)对儿童重症病毒性脑炎 (SVE)预后的影响。②方法　将 5 6例SVE病儿随机分为常规组 (n =2 2 ,给予抗病毒、降颅压、止惊、冬眠疗法、加压氧和糖皮质激素等常规治疗 )和IVIG组 (n =34,在常规治疗基础上尽量在 7d内给予IVIG ,剂量为每天 4 0 0～ 6 0 0mg/kg体质量 ,共2～ 3d) ,比较两组病儿治疗后的近期和远期预后 ,测定两组治疗前后血浆白细胞介素 6 (IL 6 )、肿瘤坏死因子 α(TNF α)水平并与对照组进行比较。③结果　与常规组比较 ,IVIG组治疗过程中呼吸衰竭、消化道出血、院内感染的发生率和病死率明显降低 (χ2 =6 .5 10～ 13.86 0 ,P <0 .0 5 ,0 .0 1) ;病后遗留脑性瘫痪者明显减少 (χ2 =4 .0 2 7,P <0 .0 5 ) ;病后 3,6 ,12个月IVIG组除瘫痪外 ,癫痫、脑影像学损害、脑电图和脑干听觉诱发电位异常者均明显减少 (χ2 =6 .4 5 1～ 4 5 .5 81,P <0 .0 5 ,0 .0 1) ;病后 6 ,12个月IVIG组的言语智商和总智商较常规组明显高 (t =2 .0 81～ 3.4 13,P <0 .0 5 ,0 .0 1)。IVIG组在病后 3,6个月时血浆IL 6 (15 .1,7.5ng/L)和TNF α(2 0 .4 ,11.8ng/L)水平较对照组 (4.2 ,8.5ng/L)明显升高 (z =- 3.337～ - 3.899,P <0 .0 1) ,但病后 12个月时血浆IL 6和TNF      

放免法检测乙型慢性活动性肝炎病人红细胞C3b受体的研究

用放免法检测乙型慢性活动性肝炎病人的红细胞ｃ３ｂ受体（ＫＢＣＣＲ１）．结果：病人ＲＢＣＣＲ１明显低于献血员（Ｐ＜０．０５）；抗－ＨＢｓ特异性免疫复合物阳性病人ＲＢＣＣＲ１明显低于阴性病人（Ｐ＜０．０１），与红细胞Ｃ３ｂ受体花环试验检测结果一致。表明乙型慢性活动性肝炎病人ＲＢＣＣＲ１数量减少，活性下降。其原因可能是特异性循环免疫复合物占据了ＲＢＣＣＲ１空位，使ＣＲ１活性下降。     

Altered islet Beta-cell function before the onset of Type 1 (insulin-dependent) diabetes mellitus

Summary To define the glucose to insulin dose-response relationship before the onset of diabetes, we studied 22 nondiabetic co-twins of patients with Type 1 (insulin-dependent) diabetes mellitus and nine control subjects. All had intravenous glucose tests at 0.02, 0.1 and 0.5 g/kg and were followedup prospectively for at least 6 years. Seven twins developed diabetes a mean of 7 months later; the remaining 15 are now unlikely to develop diabetes. The seven pre-diabetic twins had higher fasting insulin levels than control subjects (4.2±2.0 vs 1.8±1.8 nmol/l; p<0.05); but lower glucose clearance (1.0±0.5 vs 1.9±0.7 %/min; p<0.05), first phase insulin response at 0.5 g/kg (21.1±23.2 vs 143±50 nmol/l; p<0.0001), and total insulin responses at 0.1 g/kg (p<0.05) and 0.5 g/kg (p<0.00005). Using a curve-fitting programme, the normal glucose to insulin relationship was lost in prediabetic twins who had lower coefficient of determination (R²) than control subjects (p<0.01). In contrast, 15 low-risk twins and their nine control subjects had similar fasting glucose and insulin levels, glucose clearance, R² and insulin secretory responses to different glucose loads. The positive predictive values of subnormal R² and subnormal first phase insulin response were 67 % and 58 % respectively. These observations demonstrate an altered glucose to insulin dose-response relationship and loss of maximum insulin secretory response to glucose before the onset of Type 1 diabetes.     

控制性肺膨胀在食管癌术后应用的临床对比研究

目的　观察在食管癌术后应用控制性肺膨胀防止急性呼吸衰竭的疗效。方法　随机设立应用控制性肺膨胀组 4 3例和对照组 33例 ,年龄和手术时间等无显著差异。观察撤离呼吸机时间。撤机后 1 2、2 4h的呼吸频率、心率、血氧饱和度和氧分压。结果　 (1 )应用控制性肺膨胀后 ,撤机时间由 (1 0 4± 1 5 )min缩短到 (87± 1 3)min。 (2 )撤机后 1 2h ,控制性肺膨胀组血氧饱和度和氧分压异常的患者率分别由 30 .30 %下降到 6 .98% ,2 4 .2 4 %下降到 6 .98%。 (3)撤机后 2 4h ,血氧饱和度异常的患者率由1 8.1 8%下降到 2 .33%。结论　食管癌术后应用控制性肺膨胀能有效防止急性呼吸衰竭的发生。