刺五加对肺纤维化BALF中IL－6抑制作用的研究

在用石棉灌肺制成大鼠支气管肺纤维化模型基础上，应用刺五加注射液进行体内实验治疗。测定了治疗及非治疗组大鼠支气管肺泡灌洗液中单个核细胞自分泌白细胞介素６（ＩＬ－６）水平，经统计学处理两组差异显著（Ｐ＜０．０１）。说明了刺五加对ＩＬ－６的分泌有抑制作用。可能对细胞因子网络紊乱有调节作用，为临床应用刺五加治疗肺纤维化提供了实验依据。     

Involvement of leukocytes and cytokines in the ovulatory process and corpus luteum function

The role of leukocytes and cytokines in ovarian physiology isnow established, although the function of each cell type andcytokine remains to be determined in detail. Current knowledgeof these effects on follicle development, ovulation, luteinizationand luteotrophic process and luteolysis is reviewed. It is possiblethat further research will help to unravel some of the clinicalmysteries in ovarian function, including polycystic ovary syndrome,premature menopause, ovulatory disorders, and luteal phase defect.Furthermore, the increasing use of cytokines and their antagonistsin clinical practice may have significant effects upon reproductivefunction.     

Immune Adherence of Platelets to Sensitized Leukocytes: a Model of Hyperacute Rejection

Specifically hypersensitized recipients of canine renal allotransplants demonstrate an accumulation of host platelets in the transplanted kidney within minutes following implantation. Transplant function is ra,idly lost. The present work describes an in vitro model of this hyperacute rejection mechanism. Renal donor leukocytes sensitized with host serum are incubated with donor platelets. Within a few minutes the platelets adhere to the sensitized leukocytes to form rosettes. Serum complement is required for platelet rosette formation. Platelets act as indicators in this reaction and they may be obtained from any dog. Donor platelets were used to avoid the transfer of specific antibody to the test mixture. The in vitro model supports the view that hyperacute rejection in the dog is a specific example of the immune adherence reaction in which platelets bind to antigen-antibody-complement complexes.     

Alpha1-adrenoceptor-mediated inhibition of cellular cAMP accumulation in neonatal rat ventricular myocytes

Summary We studied adrenergic regulation of cellular cAMP in neonatal rat ventricular myocytes. Since CAMP content depends on synthesis, breakdown and egress, the contribution of each of these mechanisms was assessed. In the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, cAMP accumulation stimulated by the -adrenoceptor agonist (–)-isoprenaline was diminished when the mixed + adrenoceptor agonist (–)-noradrenaline was coincubated with (–)-isoprenaline. Moreover, adenylyl cyclase activation stimulated by (–)-isoprenaline was decreased by (–)-noradrenaline and by the selective a₁-adrenoceptor agonists (–)-phenylephrine and methoxamine, suggesting that -adrenoceptor agonism regulates CAMP metabolism through its effect on the synthetic pathway. Evidence for ₁-adrenoceptor mediation of this response was enhancement of (–)-noradrenaline-induced cAMP generation by the selective ₁-adrenoceptor antagonist terazosin (10 nmol/l). The selective ₂-adrenoceptor antagonist yohimbine (10 nmol/l) had no effect. The ₁-adrenoceptor mediated depression of (–)-isoprenaline-stimulated CAMP generation and adenylyl cyclase activation was prevented by terazosin and in separate experiments markedly enhanced by pertussis toxin pretreatment, suggesting involvement of a guanine-nucleotide regulatory protein in this process.Occupation of the ₁-adrenoceptor by (–)-noradrenaline did not accelerate the rate of CAMP breakdown in the absence of phosphodiesterase inhibition. Furthermore, there was no enhancement of total phosphodiesterase activity by (–)-noradrenaline in the presence of (–)-propranolol. By contrast, pertussis toxin pretreatment augmented phosphodiesterase activity. Neither pertussis toxin nor (–)-noradrenaline increased CAMP egress.We conclude that in rat neonatal cardiac myocytes agonist occupation of the ₁-adrenoceptor inhibits -adrenoceptor stimulated CAMP accumulation most likely by coupling to a guanine nucleotide inhibitory protein.Supported by a grant from the Department of the Veterans Affairs Research Service and Program Project Grant HL 25847 from the National Heart, Lung and Blood Institute     

Antibiotic therapy: what to consider when treating geriatric patients

The epidemiology, etiology, clinical manifestations, diagnostic approach, and therapeutic choices may be quite different for infections that occur in elderly patients compared with those that occur in younger adults. Given these variables, it is essential for clinicians who care for older patients to understand how to prescribe antibiotics appropriately for this population. This article examines the unique characteristics of infections in the elderly as well as provides recommendations on the use of specific antibiotic agents commonly used to treat infections in geriatric patients.     

Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties

1. 15-Lipoxygenase (15-LO) has been implicated in the pathogenesis of atherosclerosis because of its localization in lesions and the many biological activities exhibited by its products. To provide further evidence for a role of 15-LO, the effects of PD 146176 on the development of atherosclerosis in cholesterol-fed rabbits were assessed. This novel drug is a specific inhibitor of the enzyme in vitro and lacks significant non specific antioxidant properties.
2. PD 146176 inhibited rabbit reticulocyte 15-LO through a mixed noncompetitive mode with a K_i of 197 nM. The drug had minimal effects on either copper or 2,2′-azobis(2-amidinopropane)hydrochloride (ABAP) induced oxidation of LDL except at concentrations 2 orders higher than the K_i.
3. Control New Zealand rabbits were fed a high-fat diet containing 0.25% wt./wt. cholesterol; treated animals received inhibitor in this diet (175 mg kg⁻¹, b.i.d.). Plasma concentrations of inhibitor were similar to the estimated K_i (197 nM). During the 12 week study, there were no significant differences in weight gain, haematocrit, plasma total cholesterol concentrations, or distribution of lipoprotein cholesterol.
4. The drug plasma concentrations achieved in vivo did not inhibit low-density lipoprotein (LDL) oxidation in vitro. Furthermore, LDL isolated from PD 146176-treated animals was as susceptible as that from controls to oxidation ex vivo by either copper or ABAP.
5. PD 146176 was very effective in suppressing atherogenesis, especially in the aortic arch where lesion coverage diminished from 15±4 to 0% (P<0.02); esterified cholesterol content was reduced from 2.1±0.7 to 0 μg mg⁻¹ (P<0.02) in this region. Immunostainable lipid-laden macrophages present in aortic intima of control animals were totally absent in the drug-treated group.
6. Results of these studies are consistent with a role for 15-LO in atherogenesis.

     

An in-vitro evaluation of coralline porous hydroxyapatite as a scaffold for osteoblast growth

The purpose of this study was to determine the potential of coralline calcium phosphate ceramics to support osteoblast growth for a proposed bone-ceramic composite for skeletal tissue repair. The goal was the development of a matrix with both osteogenic and osteoconductive properties, as compared to ceramic alone, which is solely osteoconductive. MC3T3-E1 osteoblast-like cells were seeded onto sintered and non-sintered porous coralline hydroxyapatite (HA), and onto non-porous hydroxyapatite discs. These in-vitro studies demonstrated that coralline HA supported the growth of osteoblast-like cells. Porous discs supported higher numbers of cells than non-porous discs. Sintering encouraged cell growth, with higher numbers of cells adhered to sintered porous HA discs by day seven. The results suggest that HA can provide a support for osteoblast cells as part of a matrix which may prove to be osteogenic in vivo and may, accordingly, enhance the bone repair process.     

Ethical issues and dilemmas in the mental health organization

Agency directors, middle managers in large organizations, and managers in general must be concerned with managing ethics as part of personnel management. The authors discuss the ethical dilemmas that face administrators and how such issues can be resolved.