1. Following thiopental injection to rabbits in doses of 5 mg kg-1 intravenously (i.v.) the sleeping time lasted longer after injection by bolus than after administration made more slowly over 30 or 60s, respectively. 2. Peak concentration in the blood of the animals after bolus injection was about four time higher than after slow injection. 3. The determination of protein binding showed that the unbound fraction of thiopental at the high concentration following bolus injection is almost doubled compared with the unbound concentration following the slow injections. Therefore it is concluded that this contributes to an increased concentration of thiopental in the brain during the initial phase of distribution thus extending the sleeping time. 4. The results from experiments using a distribution model give additional evidence supporting this conception.

Anesthesia, Intravenous↗

PubMedDate not supplied

Prediction of drug distribution in vivo on the basis of in vitro binding data.

For 11 drugs it was investigated whether tissue distribution in vivo can be predicted by use of binding data obtained in vitro. The selection of drugs represented a broad spectrum of physicochemical and pharmacokinetic properties thought to be important for distribution of drugs in vivo. The extent of binding to plasma and to tissue-homogenates of rabbits was determined in vitro. The drug concentrations in plasma, liver, lungs, kidneys, and skeletal muscle of rabbits were determined in vivo after i.v. administration of the drug. The tissue-plasma partition ratios measured in vivo were compared with the theoretical tissue-plasma partition ratios calculated from the in vitro binding data. For all drugs investigated the muscle-plasma partition ratio could be reasonably well predicted by the in vitro binding data. In liver, lungs, and kidneys good agreement was found between measured and predicted tissue-plasma ratio for anionic drugs; marked differences, however, were observed between measured and predicted tissue-plasma ratios of lipophilic cationic drugs. A significant correlation was found between binding of drugs to muscle tissue in vitro and the volume of distribution of the unbound drug (Vf), opening the possibility to approximate Vf from in vitro binding studies with rabbit muscle tissue.

Animals↗

PubMedDate not supplied

Binding of non-steroid anti-inflammatory drugs and warfarin to liver tissue of rabbits in vitro.

Liver slices (10mm 0.1mm thickness) were incubated at 37 degrees C in drug solutions up to 360 min. The drugs were dissolved in Ringer solution of pH 7.0. After 60, 180, 240 and 360 min each drug concentration was determined in the incubation fluid. For all drugs tested equilibrium was obtained after 240 min. The amount of drug taken up by the slices was calculated from the difference to initial concentration. In parallel, samples of the slices were homogenized together with their incubation fluids after the same incubation intervals. The free concentration was determined by ultrafiltration. For warfarin and several non-steroid anti-inflammatory drugs (NSAID), i.e. acetylsalicylic acid, ibuprofen, ketoprofen and oxyphenbutazone, there was no difference between the free drug concentrations in the homogenized and in non-homogenized samples. This suggests that the binding of these drugs to liver tissue was not altered by homogenization. Further was studied whether NSAIDS interfere with binding of warfarin to liver tissue. Acetylsalicylic acid, flurbiprofen, ibuprofen, ketoprofen, oxyphenbutazone and proquazon markedly increased the free concentration of warfarin both in liver slices and homogenates (p less than 0.01). The extent of displacement did not differ between slices and homogenates.

Animals↗

PubMedDate not supplied

Physiology of angiogenesis.

Angiogenesis is a key prerequisite for growth in all vertebrate embryos and in many tumors. Rapid growth requires efficient transport of oxygen and metabolites. Hence, for a better understanding of tissue growth, biophysical properties of vascular systems, in addition to their molecular mechanisms, need to be investigated. The purpose of this article is twofold: (1) to discuss the biophysics of growing and perfused vascular systems in general, emphasizing non-sprouting angiogenesis and remodeling of vascular plexuses; and (2) to report on cellular details of sprouting angiogenesis in the initially non-perfused embryonic brain and spinal cord. It is concluded that (1) evolutionary optimization of the circulatory system corresponds to highly conserved vascular patterns and angiogenetic mechanisms; (2) deterministic and random processes contribute to both extraembryonic and central nervous system vascularization; (3) endothelial cells interact with a variety of periendothelial cells during angiogenesis and remodeling; and that (4) mathematical models integrating molecular, morphological and biophysical expertise improve our understanding of normal and pathological angiogenesis and account for allometric relations.

Allantois↗

PubMedDate not supplied

[Obstructive apnea in premature and young infants].

The occurrence of obstructive apneas in premature and young infants is associated with a higher risk for SIDS. In order to assess the incidence of obstructive apnoeas in infants with different risk for SIDS pneumography was performed including the registration of the nasal air flow in 312 children: 69 preterm infants, 42 children after intensive care, one infant that later died of SIDS, 14 children after ALTE, 84 children after apnoeas observed by their parents, 25 siblings of SIDS-victims and 77 controls. Obstructive apnoeas were found in 24.6% of the preterm infants, in 28.5% of the children after intensive care, in 50% of the children after ALTE and in the one infant that later died of SIDS. Obstructive apnoeas however were registered only in 16.7% in the "apnoea-group", in 12% of the SIDS-siblings and in 11.7% of the controls. We therefore conclude that obstructive apnoeas which were observed more frequently in children with a higher risk for SIDS are of predictive value for the SIDS risk. Pneumography should therefore include the measurement of the nasal air flow. Home monitoring should be performed with devices that are able to assess bradycardias as indirect signs of obstructive apnoeas.

Airway Obstruction↗

PubMedDate not supplied

[Prescription of diphosphonates in ambulatory oncology. A study of the health insurance medical services].

OBJECTIVES: As requested by the Health Ministry, the Agricultural (Mutualité Sociale Agricole) and Independant Professions (Assurance Maladie des Professions Indépendantes) Health Insurances carried out a survey to analyse the use of second generation oral biphosphonates. METHODS: The data, from 3,414 prescriptions, gathered over the twelve months from May '93, showed that clodronate is prescribed mainly for breast cancer (35%), prostate cancer (23%), multiple myeloma (19%) and carcinoma of the lung (7%). The other prescriptions (16%) were either related to various malignant diseases (18 types encountered) or non-malignant diseases (mainly osteoporosis, but also Paget's disease of bone and hyperparathyroidism). The initial prescriber was most often a cancerologist (49%) but also quite frequently (17%) a general practitioner. The treatment was prescribed for an average of 41 days. 1600 mg daily was the most frequent dose (79%). However, in non-authorised indications, especially osteoporosis, the dose was lower, generally 800 mg a day. Altogether 14% non-authorised indications were linked either to non-metastatic malignant diseases (for the prevention of metastases) or with osteo-condensing type metastases (prostate cancer: 43%) or non-malignant diseases (osteoporosis, Paget's disease of bone, hyperparathyroidism, chronic renal insufficiency, sympathetic algodystrophy, bedbound decalcification, etc.). The prescription for these cases was motivated by the expected beneficial effect on bone mineralisation. Such treatment authorised was more often initiated by a general practitioner (23%) than a specialist (12%). CONCLUSION: These data raise the problem of limiting the possibility of prescribing second generation biphosphonates as initial treatment to a specialist. They also reaffirm the need to have precise guidelines in the field of medical prescription controls.

Aged↗