降糖搽剂药效学研究与毒性作用测定

目的：通过降糖搽剂对皮肤用药的药效学研究以了解它是否优于口服用药以及了解它对局部用药的毒性强弱。方法：按内分泌系统药物药效学指导原则中的胰岛类及降糖药试验方法和局部用药的毒性试验方法进行。结果：降糖搽剂对大鼠和家兔皮肤给药降血糖试验表明：以3.2mg/kg,4.8mg/kg,8mg/kg(临床用量7、10、16倍）给药，对正常大鼠和家兔降血糖用量分别为20%、30%、50%及10%、20%、30%。另外，对大鼠和家兔糖耐量试验表明：以3.2mg/kg的对大鼠和家兔糖耐量都没有降低的作用。毒性作用测定结果表明：本品对家兔皮肤急性毒性不引起动物死亡，对豚鼠不致敏，对家兔皮肤无刺激作用。结论：降糖搽剂对大鼠和家兔皮肤用药的药效学作用比口服用药的药效学作用强。     

Safety of long-term treatment with cyclosporin A in resistant chronic plaque psoriasis: a retrospective case series

BACKGROUND: An intermittent short course of cyclosporin A (CyA) therapy is a good choice in the treatment of severe psoriasis. Nevertheless, some severe or resistant patients might benefit from long-term treatment. Adverse effects of long-term use of CyA are investigated and the results are compared with the literature. PATIENTS AND METHODS: A retrospective study of adverse effects of CyA treatment in a group of 53 patients suffering from psoriasis. The mean treatment time was 31.4 +/- 23.2 months with a minimum of 4 months to a maximum of 95 months, with very few short interruptions of treatment (from 2 to 5 months in five patients). RESULTS: The group consisted of 29 women and 24 men, ranging in age from 18 to 65 years, with an average age of 44.49 years. Arterial hypertension appeared in 45.3% of patients during treatment. Pharmacological treatment was required in 32% of these patients to control the condition. Serum creatinine levels were transiently elevated in 11.3% of the cases, but withdrawal of treatment was required in none of them. DISCUSSION: Long-term CyA treatment might be necessary in some patients and this study shows that it could be sustained with a close follow-up. This involves regular visits depending on each patient, as well as common test protocol and clinical evaluation. In conclusion, this retrospective study seems to confirm the relative safety of long-term CyA treatment when patients are adequately monitored.     

Cytokines and cell signalling in the periodontium

A large number of potential regulatory mechanisms have been described which may be involved in the control of cell function in the periodontium. In this review, soluble effector molecules which may regulate normal cell turnover and which may control the maintenance of the per-iodontal space are considered. There is evidence for the involvement of growth factors including EGF, PDGF, FGFs, IGF I & II and TGFβ in these processes. The role of bone morphogenetic proteins (BMPs) in periodontal turnover is of considerable interest as they appear to be able to regulate all stages of this process from specifying cell commitment to regulating differentiated cell function.
Empirical evidence suggests the importance of mechanical stimulation in controlling the maintenance of the periodontal ligament space. The wide range of effects of mechanical stimulation are briefly reviewed and the central role of prostaglandins is considered. Recent evidence suggests the involvement of nitric oxide (NO) in the regulation of mineralised tissue function, and the potential role of NO in maintenance of the ligament space is considered. Further studies are required which address the interactions between all of these mechanisms in order to determine the key factors which may control periodontal cell function. For the future an understanding of these interactions has the potential to lead to important clinical developments in periodontal and orthodontic therapy.     

Presence of anti-Sm reactivity in autoimmune mouse strains

The investigation of the fine specificities of antinuclear antibodies (ANAs) has been fruitful in terms of the nosology and immunopathogenesis of human autoimmune syndromes. Particular reactivities serve as “markers,” in that patients with certain syndromes have a much higher incidence of such ANAs than do patients with other diseases. In this category is the almost exclusive against the nuclear acidic protein Sm. Reactivity to Sm can be detected by precipitation in agar, complement fixation, or passive hemagglutination (1,2). Autoimmune mouse strains have also provided a fertile field for the investigation of the basic phenomena of self-activity. In particular, the NZB strain and its hybrid NZB x NZW have been considered excellent models for human SLE and have therefore been studied in great detail (3,4). In addition, Murphy et al at The Jackson Laboratory, Bar Harbor, Maine, have developed several new inbred mouse strains that spontaneously develop SLE-like syndromes (5,6). These are the BXSB strain, which has a male dominant disease characterized by little antiative DNA antibody; the MRL/1, which develops massive, nonmalignant lymphadenopathy, associated with enormous increases in serum immunoglobulin levels and fulminant renal disease; and the MRL/n, which does not develop SLE-like disease until well into the 2nd yr of life, but like the MRL/1 develops high titers of ANA and fatal glomerulonephritis. The MRL/1 differs from MRL/n in only about 10 percent of its genome, including the gene responsible for the MRL/1’s lymphoproliferation. In the current study, we have used the technique of double immunodiffusion (ID) in agarose with standard human reference sera (of known ANA specificity) to survey a large number of mice from the NZB x NZW, MRL/1, MRL/n, BXSB, and other strains. We report here the finding of the anti-Sm marker” antibody almost uniquely in MRL/1 and MRL/n animals. These two related strains may serve as experimental models to explore the mechanism stimulating the production of this unique autoantibody in SLE.     

Escherichia coli bacteriuria in female adults is associated with the development of hypertension

ObjectiveTo investigate whether Escherichia coli bacteriuria is associated with the development of hypertension during a long-term follow-up.MethodsA prospective cohort study was performed among the participants of two population-based studies. Between 1974 and 1986 all women aged 39 to 68 years old, who lived in Utrecht, the Netherlands, were invited to participate in a breast cancer screening program. The participants completed a questionnaire, underwent a medical examination, and collected a morning urine sample that remained stored. From 1993 to 1997 another population-based study was performed. We performed a full cohort analysis for 444 women who participated in both studies. E. coli bacteriuria was diagnosed by a real-time PCR. Hypertension was defined as the use of antihypertensive medication and/or a measured systolic blood pressure of at least 160 mmHg or a diastolic blood pressure of 95 mmHg or higher. The mean follow-up was 11.5 ± 1.7 years.ResultsForty women (9%) had E. coli bacteriuria at baseline. Women who had bacteriuria at baseline had a mean blood pressure at study endpoint of 133 ± 20 mmHg systolic and 78 ± 11 mmHg diastolic, and women without bacteriuria had values of 129 ± 20 and 78 ± 11 mmHg, respectively (p-values for difference 0.33 and 0.88). Although E. coli bacteriuria was not associated with the blood pressure as a continuous variable, it was associated with the development of hypertension during follow-up (OR 2.8, 95% CI 1.4–5.5).ConclusionE. coli bacteriuria may increase the risk of future hypertension.