Effect of hepatic cirrhosis on the pharmacokinetics of theophylline in rats

The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethylnitrosamine (DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr) of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life (t_1/2) in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL (8.67±4.85%) decreased about four-folds, but in DMNA (73.00±9.85%) similar result, was observed as compared with the control. Increased free fraction of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline.     

Prevention of liver-tumor colonization by combined immunomodulation and liver lectin blocking

The protective effect of combined treatment (immunomodulation with Propionibacterium avidum KP-40; liver lectin blocking by D-galactose administration) on the liver colonization of RAW 117-H10 lymphosarcoma was investigated in BALB/c-mice. Both, immunomodulation with P. avidum KP-40 as well as liver lectin blocking by D-galactose treatment significantly decreased the number of liver tumor colonies in this experimental model. However, the combination of P. avidum KP-40 and D-galactose obviously proved to be superior to each monotherapy since the liver colonization by RAW 117-H 10 lymphosarcoma could be completely inhibited.     

Background on the system of integral evaluation of human exposure to toxic substances in the work and municipal environments

Exposure to toxic chemicals in the work, natural and home environments is recognised as combined exposure. The system of integral evaluation of human exposure should take account of all toxic substances occurring in all environmental media (air, water, soil and food), and all routes through which they enter the human body. To provide the integral evaluation it is necessary to develop different exposure scenarios based on dose intake or derived values. Following the toxicological criteria, calculated exposure indicators, after their standardisation and aggregation, should be converted into combined exposure indices. The index value will reflect the level of combined exposure.     

Production and characterization of monoclonal antibodies against human airway mucins

The objective of this study was to generate and characterize monoclonal antibodies (MAbs) against human airway mucins, and therefore, should serve as a useful tool in studying the regulation of airway mucins in various physiological or pathological situations of human airway. As an antigen, we used a high molecular mass mucin preparation purified from the sputum of normal human subjects. Two monoclonal hybridomas, namely MAbs HM02 and HM03 were obtained and they showed strong immunoreactivity against purified or crude mucin in sputum or bronchial washing of normal human subject. With the high immunoreactivity of these MAbs, mucin contents could be analyzed with more than 100-fold dilution of human airway secretion. The antibodies recognized carbohydrate epitopes because their immunoreactivity was completely abolished by treatment of the mucin with 5 mM periodate. Further characterization of MAbs HM02 and HM03 showed that: (1) they belong to the IgM type; (2) they bind to high molecular mass mucins based on Western blot; (3) they could indirectly immunoprecipitate human airway mucin and as we know, this is the first to demonstrate immunoprecipitation of human airway mucin with anti-human mucin antibodies; and (4) they bind to the goblet cell in airway epithelium as well as some submucosal glands based on immunohistochemistry. Therefore, MAbs HM02 and HM03 should be able to serve as an invaluable tool in studying the regulation of airway mucins in various physiological and pathological situations of human airway.     

丝光绿蝇饲养初步研究

目的通过对丝光绿蝇的室内饲养,观察其驯化以及饲养的生物学。方法采用煮熟的鲢鱼引诱丝光绿蝇产卵,收集其卵块,置于室内采用人工配制饲料进行驯化饲养。结果丝光绿蝇第１代从卵发育至成蝇需１４天,其中三龄期约５天,蛹期约６天。成蝇产卵前期约７天,卵散产。第２代从卵发育至成蝇约需１３天,其中三龄期约４天,蛹期约６天。结论丝光绿蝇室内驯养在温度２６℃～３１℃,相对湿度７５％条件下,从卵到蝇历期为１３～１４天,驯养初期,其生物学与自然条件下相比有所改变。     

The clinical usefulness of the renal allograft biopsy in the cyclosporine era: a prospective study

BACKGROUND: The renal allograft biopsy is generally accepted as the gold standard for clarifying the cause of renal dysfunction. However, the clinical usefulness of this procedure has rarely been studied prospectively, nor have most studies included follow-up of patients to delineate the influence of the biopsy on clinical outcome. In this study, we evaluated prospectively the clinical usefulness of the allograft biopsy in renal transplant recipients receiving cyclosporine (CyA). METHODS: During a 21-month period, 82 biopsies were performed. In 54 instances (47 patients), we outlined a presumed diagnosis and tentative treatment plan before the procedure. After the biopsy, a definitive diagnosis was made and an appropriate patient management approach was instituted. We analyzed the incidence of change in patient management that resulted from histological findings. All patients were followed to monitor their response to treatment and allograft survival. In cases of biopsy-proven acute cellular rejection (ACR) or cyclosporine (CyA) toxicity, clinical and laboratory data from the day of the biopsy were reviewed to determine their diagnostic value. RESULTS: One biopsy specimen was inadequate for definitive interpretation. The biopsy findings resulted in a change in patient management in 22 (41.5%) of the remaining 53 cases (change group). The incidence of altered patient management was 38.7% in biopsy specimens taken in the first month, 55.6% between 1 and 12 months, and 38.5% after 1 year posttransplantation. A change in management was required in 2 of 2 patients with chronic allograft dysfunction, in 44.4% of the 45 patients with acute allograft dysfunction, and in none of the patients with delayed graft function (n=6). Within the first week of treatment 19 of 22 (86.4%) in the change group and 25 of 31 (80.6%) in the no change group had a positive response to therapy. The 1-year allograft survival rate was also similar between the two groups. None of the clinical and laboratory data was useful in distinguishing ACR from CyA toxicity. CONCLUSIONS: Renal allograft biopsy findings alter patient management recommendations in approximately 40% of patients in whom a presumptive diagnosis had been made on the basis of clinical and laboratory findings. Patients who had a change in patient management because of biopsy findings demonstrated a response to therapy and allograft survival similar to those of patients who had no alteration in management plan after the biopsy.     

Dorsal adipofascial turn-over flap for fingertip amputations

We designed a dorsal adipofascial pedicled flap to cover amputations of the tip of the same digit. This flap includes all the adipofascial tissues from the dermis to the paratenon of the extensor tendons. After elevation of the skin, the adipofascial tissues are raised as a flap and turned over to resurface the exposed bone or joint and then covered with a split thickness skin graft. Ten digital amputations between the distal phalanx proximal to the nail matrix and the mid portion of the middle phalanx were successfully resurfaced with dorsal adipofascial turn-over flaps. All flaps survived completely and the mean follow-up was 11 months. This one-step procedure would seem to be a relatively simple way of achieving early recovery because it does not require the use of distant flaps immobilization of adjacent digits, or homodigital flaps that might jeopardize an already injured finger.     

Distribution of proteoglycans in the human trabecular meshwork: histochemical electron microscopic findings with cuprolinic blue

The distribution of sulfated proteoglycans (PGs) in the normal human trabecular meshwork was studied by histochemical electron microscopy using the cationic dye, cuprolinic blue (CB).. The trabecular meshwork was obtained from human enucleated eyes and incubated for three days. After incubation, they were stained with 0.2% CB at a critical electrolyte concentration and prepared for histochemical electron microscopy. Ultrastructurally, PG-CB complexes were found as small punctate or filamentous structures, and were associated with collagen fibrils in the cores of the trabecular beams and the basal laminae of trabecular endothelial cells. In addition, large filamentous PG-CB complexes were mainly associated with areas of amorphous extracellular matrix between the collagen fiber bundles and in the fine fibrillar material near the basal laminae of endothelial cells of Schlemm's canal. This investigation resulted in an illustration of the ultrastructural distribution of PGs in the human trabecular meshwork. Further studies will be needed to specify the nature of PGs and their role in the aqueous outflow system.     

Aggregation inhibitory activity of minor acetophenones from Paeonia species

Two minor acetophenones, 2,5-dihydroxy-4-methoxy-acetophenone (2) and 2,5-dihydroxy-4-methylacetophenone (7) from Paeonia species were found to selectively inhibit the aggregation of rabbit platelets induced by arachidonic acid. They were more potent than the major compound, paeonol (1), and 7 also inhibited the formation of TXA2 and PGD2 from arachidonic acid.