Effect of perindopril on vasoreactivity in patients with hypertensive chronic cerebrovascular disease. A comparative analysis of different brain structures

BACKGROUND AND PURPOSE: The angiotensin-converting enzyme inhibitor perindopril (CAS 107133-36-8) helps to prevent stroke recurrence by improving cerebral vasomotor reactivity (CVR). Perindopril-induced vasoreactivity changes in different brain structures of patients with chronic cerebrovascular disease were compared. METHODS: The study population consisted of 6 hypertensive patients (mean age 65.5 +/- 9.9) who had experienced a cerebrovascular event; three each had minor ischemic episodes and hemorrhage. The administration of 4 mg/day perindopril was started one month after stroke onset; the follow-up lasted more than one year. Their cerebral blood flow (CBF), assessed at the start of perindopril administration and again 3 months later, was examined both at rest and after the administration of 15 mg/kg acetazolamide and the CVR was calculated. Regions of interest were cortical and subcortical areas on the CT scans. RESULTS: In the course of this study, none of the patients suffered stroke recurrence. The 3-month administration of perindopril lowered their systemic blood pressure without decreasing CBF and significantly increased cerebral vasoreactivity in the lesioned (p = 0.04355) and contralateral (p = 0.04090) cortical areas without producing significant changes in CVR in the subcortical gray matter (striatum and thalamus). CONCLUSION: The CVR in cortical structures recovered sooner than that in subcortical gray matter. Although the number of stroke patients included in this study was small, it is concluded that this phenomenon may be attributable to the earlier vasoreactivity increase in the cortical vessels than the subcortical perforators.     

Organochlorine residues in the blubber and liver of bottlenose dolphins (Tursiops truncatus) stranded in the Canary Islands, North Atlantic Ocean

Polychlorinated biphenyls (PCBs) and chlorinated pesticides: dichlorodiphenyltrichloroethane and its metabolites (DDTs), chlordanes (CHLs), dieldrin, and hexaclorobenzene (HCB) were detected in the blubber and liver of 11 bottlenose dolphins (Tursiops truncatus) from the Canary Islands (North Atlantic Ocean). Samples were obtained from stranded dolphins over the period 1997-2005. Among the organochlorines analyzed, PCBs and DDTs were predominant in the two tissues, followed in decreasing order by chlordane, trans-nonachlor > cis-nonachlor > dieldrin and HCB. The sum 11 PCBs in the blubber ranged between 301 and 33,212 ng g(-1) ww (990 and 136,679 ng g(-1) lw). Highly chlorinated PCBs such us CB153, CB180, and CB138 were the prominent congeners, accounting for 51% of the total PCBs. The sum DDT concentration in the blubber ranged between 147 and 21,050 ng g(-1) ww. (490-105,250 ng g(-1) lw) The main DDT metabolite was p,p'-DDE, representing 83% of DDTs in the blubber. In general, the levels of PCBs and DDTs detected were similar to those found in bottlenose dolphins in the North of Europe. The 2,3,7,8-TCDD toxic equivalent (TEQ) in blubber and liver was calculated for the toxicity assessment of mono-ortho substituted PCBs congeners (CB105, CB118, CB156). It is important to mention that TEQ values and p,p'-DDE concentration in adult male specimens are approaching the levels associated with adverse effects found in marine mammals. The information provided represents the first tissue loads of organochlorine compounds in small cetaceans from this area.     

Theophylline-terbutaline, a steady state study on possible pharmacokinetic interactions with special reference to chronopharmacokinetic aspects.

1. The pharmacokinetic interaction of terbutaline and theophylline and chronopharmacokinetics of both drugs were studied in a three-way crossover study with repeated administration of terbutaline (Bricanyl Depot) 7.5 mg twice daily, theophylline (Theo-Dur) 300 mg twice daily alone or the combination of both for 7 days to 12 healthy volunteers (six male and six female). 2. After the morning dose on day 7, blood and urine were sampled for 12 h, and after the evening dose on day 7, blood and urine were sampled for 48 h. Theophylline concentrations in plasma and concentrations of unchanged drug and metabolites in urine were determined by two selective high performance liquid chromatography methods. Terbutaline concentrations in plasma and urine were measured with a gas chromatography-mass spectrometry method. Area under the plasma concentration-time curve, fluctuations in plasma concentration, mean residence time, elimination half-life, renal clearance as well as maximal, minimal and average plasma concentration at steady state were evaluated. 3. The addition of terbutaline to the repeated administration of theophylline lowered the relative bioavailability of theophylline by approximately 11% during the night interval. The rate of elimination of theophylline and mean residence time were influenced accordingly. No significant changes in excretion of the theophylline metabolites were observed, but the excretion of 3-methylxanthine was slightly reduced by the concomitant terbutaline administration. None of the observed changes should be of any clinical importance. 4. The addition of theophylline did not influence any of the calculated pharmacokinetic parameters of terbutaline. 5. It can be concluded that no dosage adjustment is necessary when terbutaline and theophylline are given together.(ABSTRACT TRUNCATED AT 250 WORDS)     

Integrative assessment of the developmental pharmacology and developmental toxicology, with special reference to the brain]

Increasing numbers of neurotoxins or therapeutic agents that have specific target cells or receptors can be used to assess the developmental correlation between the structure and function of various organs including the brain. Patients with chronic diseases are now able to maintain their social activities but still must be medicated for a long period of their life. This might increase the potential hazard of prenatal drug exposure in the progeny. Functional teratology is quite a new concept in neuroscience. Recent observations of our laboratory and those of others suggest that the sensitive period for functional teratology might encompass the whole stage of fetal life in animals and humans. The shortage of precise information on the developmental integration of the structure and function of the neurons with different properties is a problem to be solved for the further progress of developmental pharmacology and toxicology. Single exposures to drugs at a different stage during the gestational period of rats or mice might provide more useful information on the relationship between the lesioned area and related functional disorders manifested postnatally. This paper reviews recent advances in developmental neuropharmacology and functional neuroteratology including beneficial points of the short-term exposures to drugs.     

Evaluation of retard drug forms with special reference to their therapeutic aspects

The useful development and application of controlled-release dosage forms is an important possibility to improve the pharmacotherapy of many diseases. However, according to the present social conditions of reproduction the introduction of a new drug has to be directed not only to a high therapeutic benefit but also to an increased social efficiency i.e., to an improvement of cost-benefit-relation. In the present study, therefore, the effect of using controlled-release dosage forms on the development of social efficiency is discussed. Basing on a comprehensive estimation of the therapeutic efficiency (therapeutic advantages and disadvantages) of controlled-release dosage forms the criteria of cost and benefit being of importance for a complex evaluation of efficiency are described.