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.     

Recent trends of age-specific pneumoconiosis mortality rates in the United States, 1985-1996: coal workers' pneumoconiosis, asbestosis, and silicosis

The authors examined the temporal trends of age-specific pneumoconiosis mortality from coal worker's pneumoconiosis (CWP), asbestosis, and silicosis in the United States in 1985-1996. Mortality data were derived from the National Center for Health Statistics multiple causes of death files for the period. Age-specific mortality rates were computed for three age groups (15-44, 45-64, and > or = 65 years) among decedents with mention of CWP, asbestosis, or silicosis. Linear regression analysis was performed to examine the annual changes in age-specific mortality rates, by age group, with each specific condition. The CWP mortality rates declined significantly (p = 0.0001) in the groups 45 years old and older, but not in the age group 15-44. Asbestosis mortality rates declined significantly (p = 0.005) for the age group 45-64, while increasing (p = 0.0001) for those aged 65 years and older. However, in the younger age group 15-44, the rates showed no significant trend. Silicosis mortality rates declined significantly (p = 0.0001) for all groups. The continued occurrence of deaths from CWP, asbestosis, and silicosis among young adults may be the result of high levels of exposure to occupational risks. These results suggest that pneumoconiosis surveillance may help to evaluate the temporal pneumoconiosis mortality patterns in the United States.     

Pseudomonas aeruginosa septicaemia in burns

Out of 1415 patients treated as inpatients at Al-Babtain Center for Burns and Plastic Surgery, Ibn Sina Hospital, Kuwait spanning over a period of 6 years from June 1992 to June 1998, 102 developed clinically and microbiologically proven septicaemia. Only 15 out of them had either single or multiple episodes of septicaemia due to Pseudomonas aeruginosa and were studied during their stay in the hospital. Five of them were males and 10 females, with a mean age of 26 years (range 3-51 years) and mean total body surface area of burns (TBSA) of 66% (range 25-90%). All of them had flame burns and resuscitation was found to be difficult in eight patients either due to delayed hospitalization or accompanied inhalation injury. Seven patients were intubated, four due to inhalation injury and three for septicaemic complications. Among the 15 patients under study, a total of 36 septicaemic episodes were detected of which 21 were due to P. aeruginosa. This organism was found in the first episodes in nine patients, in second episodes in six, in third episodes in three and fourth, fifth and sixth episodes in one patient, each at a variable postburn day. Ten patients had 38 sessions of excision and skin grafting, six of them survived. Nine of the 15 patients under study died due to septicaemia, but only six of them had P. aeruginosa as the last isolate. Except for one, all patients had > 40% TBSA burn, two had difficult resuscitation and four were intubated. The day of death varied between 3 to 52 days postburn (mean 19 days). This study showed that females with flame burns are susceptible to P. aeruginosa septicaemia. Difficult resuscitation and intubation also proved to be important risk factors. Septicaemia could occur quite early in the postburn days and the mortality due to this organism was quite high. Early excision and grafting with other effective management may result in a better outcome.     

Development of receptoral responses in pigmented and albino guinea-pigs (Cavia porcellus)

We describe the postnatal development of the electroretinogram (ERG) receptoral response in the guinea pig. In addition, the time course and nature of maturation was compared between albino and pigmented strains to consider the role that melanogenesis might have in this process. Electroretinograms were collected on groups of albino and pigmented animals from postnatal day (PD) PD1 to PD60. A-wave amplitudes and implicit times were extracted from filtered data (0–75 Hz). Receptoral components were modelled using the delayed gaussian model of Hood and Birch [1] fitted as an ensemble to the raw data. Guinea pigs show saturated amplitudes (Rm_P3) that are 50% of adult values at birth, these mature by PD12. Receptoral delay (t_d) also undergoes some postnatal maturation, while phototransduction gain (log S) is adult-like at birth. Albino animals had significantly (p<0.05) larger Rm_P3 and log S across all ages. Guinea pigs have significant postnatal development in their receptoral response. Maturation of Rm_P3 implies a postnatal increase in rod outer segment length. Whereas the adult values of log S implies a mature phototransduction process at birth. We argue that the likely cause for the larger log S of albino eyes is compatible with theories of increased levels of internal light. Whereas the larger Rm_P3, even after allowing for increased light effectiveness, may reflect a lower ocular resistance in albino eyes due to their lower levels of melanin. Furthermore, decreased Rm_P3 and log S with age is observed in the pigmented group only and is consistent with increased ocular resistance due to melanin development in this strain. This revised version was published online in July 2006 with corrections to the Cover Date.     

Synthesis and analgesic and anti-inflammatory activities of 1,2-benzothiazine derivatives

Three 1,2-benzothiazine derivatives were synthesized, and their analgesic/anti-inflammatory efficacy and their effects on gastric irritation were evaluated. Among the three compounds, 39 exhibited the most potent analgesic action, but the effect was weaker than that of piroxicam. Nonetheless, the compound showed 4 times more potent analgesic action with less gastric damage than did ibuprofen. These compounds did not show anti-inflammatory effect at an oral dose of 5 mg/kg.     

Physical properties and heavy metal uptake of encapsulated Escherichia coli expressing a metal binding gene (NCP).

A recombinant Escherichia coli expressing the Neurospora crassa metallothionein gene (NCP) has previously been shown to remove low levels of Cd and other metals from solution. For further development as a biosorbent, the encapsulation of the NCP is investigated by various matrices. The NCP was encapsulated in alginate, chitosan-alginate or kappa-carrageenan, and its physical properties characterized. Results indicated that encapsulation in alginate resulted in fragile beads, whereas encapsulation in kappa-carrageenan or chitosan-alginate provided more physical and chemical integrity to the beads. Maximal heavy metal removal by cells encapsulated in carrageenan occurred within 3 h, while a gradual increase in removal was observed up to 24 h for cells encapsulated in chitosan-alginate. Metal removal by cells encapsulated in alginate beads was lower than those encapsulated in carrageenan or chitosan-alginate.     

Spiramycin is comparable to oxytetracycline in eradicating H. pylori when given with ranitidine bismuth citrate and metronidazole

BACKGROUND: We have consistently achieved about 90% eradication of H. pylori with liquid bismuth, metronidazole and oxytetracycline. AIM: To test eradication and adverse events of ranitidine bismuth citrate (RBC) when given with metronidazole and either oxytetracycline or spiramycin. METHODS: One hundred and eighty-three patients were randomized to one of four 10-day regimens: RBC400OM: RBC 400 mg b.d., oxytetracycline 500 mg q.d.s.; RBC400SM: RBC 400 mg b.d., spiramycin 1 g q.d.s.; RBC200OM: RBC 200 mg q.d.s., oxytetracycline 500 mg q.d.s.; RBC200SM: RBC 200 mg q.d.s., spiramycin 1 g q.d.s. Additionally, all patients received metronidazole 400 mg q.d.s. A 14C-urea breath test was performed at 8 weeks. RESULTS: Intention-to-treat eradication rates were 94%, 91%, 94% and 89% with RBC400OM, RBC400SM, RBC200OM and RBC200SM, respectively (P = 0.81). Eradication was significantly higher in ulcer patients (97%) than in those with diagnoses other than ulcer (86%) (P = 0.009). There was a strong tendency to better eradication among those who had never smoked (100%) compared with ex-smokers (93%) and smokers (89%) (P = 0.06). Fifty-three per cent experienced at least one moderate or severe adverse event, and women had more adverse events than men (P = 0.0002). CONCLUSIONS: All four regimens had comparable efficacy and adverse events. Eradication was significantly better in ulcer patients but there was a trend to better eradication in those who smoked less, used less alcohol and exercised more. Adverse events were frequent, perhaps because of the large dose of metronidazole used, but few patients stopped treatment.     

The “Scandinavian Star” ferry disaster 1990 -a challenge to forensic odontology

Summary With 158 victims, the fire on board the Scandinavian Star was one of the world's worst ferry disasters. A team of identification experts, including dentists, were employed to secure evidence for identification and to remove the victims from the ferry. Four parallel teams, each with 2 dentists, examined and autopsied the victims at the Institute of Forensic Medicine, University of Oslo. Using the INTERPOL Disaster Victim Identification forms and aided by computers, all victims were identified within 17 days. Dental identity could be established in 107 cases (68%).     

Biological evaluation of Korean medicinal plants(III)

The extracts of sixty Korean plants were evaluated for their biological activities such as antitumor activities against Sarcoma 180, Leukemia SN-36 and Ehrlich ascites carcinoma, antimicrobial activities and behavioral observation in mice. The results are tabulated.