[Structural changes in the brain according to computed tomographic data in patients undergoing combination therapy for hemispheric gliomas]. Basing on CT data, the authors analyze the qualitative changes in the brain of patients with a history of multiple-modality treatment for immature neuroectodermal tumors. Plani- and volumetric parameters of the total brain, the involved and the contralateral hemispheres are compared with the same parameters in the reference group. The pattern and degree of structural changes were found related to the site of the tumor and surgery. The brain matter in both hemispheres was lost mostly in the interstitial and end portions predominantly on the side of the tumor and surgery. Changes of the brain were individual in the patients.


[X-ray endovascular surgery of the right ovarian vein syndrome]. The author analyzes the causes of the disorders in the urodynamics and retention changes in the upper urinary routes of 43 infertile women who suffered from disordered venous reno-ovarian circulation. In chronic phlebostasis of the pelvic organs a compensatory varicose dilatation of the right ovarian vein, mediating the hemodynamic decompression of the venous bed of internal genitals, is responsible for the development of the venous compression syndrome of the right ureter. To correct the vasourethral conflict roentgenoendovascular embolization of the left ovarian vein was carried out. In the remote postembolization period 40 women presented without pain or urodynamic disorders and with normal urinalyses, in 3 women the right ureter dilatation persisted but had not progressed.


[X-ray semeiotics of cranial involvement in endocrine diseases]. The incidence and type of x-ray semeiotics of the skull involvement were studied in 703 patients with endocrine diseases (26 with acromegaly, 36 with hypercorticism, 104 with thyrotoxicosis, 23 with hypothyrosis, 98 with primary hyperparathyrosis, 302 with diabetes mellitus, 114 with hypogonadism). Craniogram analysis involved study of the thickness and structure of the vault bones, shape and size of the skull, status of the sutures, internal plate relief, changes of the base of the skull, of the sella turcica first of all, and facial bones. The characteristic x-ray symptom complexes of the involvement of the skull in some endocrine diseases were distinguished.


[Potentialities of transcutaneous and transhepatic cholangiography as a method of studying diseases of the bile excretory system]. Comprehensive examinations of 62 patients with jaundice of obscure origins involved transcutaneous transhepatic cholangiography carried out in all the patients, hepatolymphography in 60 cases, relaxation duodenography in 31, angiography in 41, ultrasonic examination of the liver in 31, endoscopic retrograde pancreatocholangiography in 28 and liver scanning in 19 patients. These studies have extended the knowledge on the biliferous system status in obturation and parenchymatous jaundices and helped define the role of transcutaneous transhepatic cholangiography among the invasive methods of radiologic examinations and pararadiologic methods.


[The role of computed tomography in the diagnosis of brain involvement in patients with posttraumatic epilepsy]. Fifteen patients with posttraumatic epilepsy (10 men and 5 women aged 15 to 47) were examined in 1990-1991. All the patients had a history of craniocerebral injury (closed in 7 and open in 8 cases), 6 of them were operated on for intracranial hematomas. Besides CAT, electroencephalography, craniography, and examination of the fundus oculi were carried out. CAT was performed with a Ct MAX (General Electric) unit. Standard positioning of the patients with sectional projections parallel to the orbital meatal line was used. Changes in the brain matter were detected in 13 of these 15 patients: foreign bodies (2 cases), meningeal cerebral cicatrices (5), dilatation of the ventricular system (4), petrificates in the brain matter (1), atrophic changes of the cerebral cortex (1). The tomograms of two patients were normal. Ten patients were operated on: 2 were subjected to anterior callosotomy, in 2 foreign bodies were removed, and in 6 patients staged plasty with removal of the meningeal cerebral cicatrix was carried out. The detected CAT changes helped diagnose the topical location of the epileptogenic focus and choose the optimal method of surgery for posttraumatic epilepsy.


[A comparative evaluation of the clinical x-ray picture of uremic osteodystrophy before and after parathyroidectomy]. The authors present the results of clinical, x-ray, and biochemical studies carried out in 51 patients with uremic osteodystrophy, treated with hemodialysis, before and after parathyroidectomy. The patients were divided into 4 groups with various patterns of x-ray symptoms. Patients with x-ray signs of fibrous osteodystrophy made up group 1, the second group consisted of patients with a combination of fibrous osteodystrophy and osteomalacia with secondary hyperparathyrosis predominance; the third group, like the second one, included patients with the mixed form of uremic osteodystrophy, but with the predominance of the osteomalacic syndrome; Group 4 patients had no x-ray signs of bone changes, and the diagnosis of uremic osteodystrophy was confirmed by clinical laboratory evidence. Analysis of the clinical and x-ray data before and after parathyroidectomy has brought the authors to a conclusion that such an intervention was effective only in cases with manifest clinical and x-ray symptoms of fibrous osteodystrophy. In Group 2 patients with the mixed form of uremic osteodystrophy and less manifest osteomalacia as against fibrous osteodystrophy, subtotal or partial parathyroidectomy is advisable only in cases when conservative therapy is of no avail and fibrous dystrophy is progressing. Surgical treatment is contraindicated to patients in whom x-ray signs of osteomalacia predominate over fibrous osteodystrophy in the total picture of uremic osteodystrophy; it may result in a rapid progress of osteomalacia.


[Echotomography and excretory urography in the diagnosis of renal parenchymal "bridges"]. Sonographically detectable parenchymal 'bridges' in the median segment of the kidney may look atypical. The most incident parenchymal 'bridges' are asymmetric irregular ovoid incomplete connections, not reaching the parenchyma at the site of renal hilus; such 'bridges' may be compared to a 'humpbacked' overturned kidney. Besides that, double and Y-shaped connections were detected, occurring in different variants of fused kidneys. Clinical significance of atypical 'bridges' of the parenchyma consists in simulation by them of echomixed processes, of renal tumors first of all. Excretory urography should be the second stage of the diagnosis after initial ultrasonic examination of the kidneys; after it repeated pointed ultrasonography should be carried out, that will help rule out the diagnosis of a renal tumor.


[A study of regional ventilation of the lungs in patients with chronic bronchitis using scanning densitometry tomograms]. A new method for examination of regional ventilation of the lungs has been developed, that permits assessment of the ventilation in patients with chronic bronchitis and detect a latent respiratory insufficiency. The results of examinations with this method conform to the results of examinations of external respiration function.


[Diagnostic capabilities of the x-ray endoscopic method of study in cholelithiasis]. The developed variants of the roentgenoendoscopic method for the examination of the pancreatobiliary system were employed in 256 patients with various diseases of the gallbladder and biliary duct. The results of application of these methods in 85 patients with cholelithiasis are presented. Different potentialities of the roentgenoendoscopic method and ultrasonic scanning for the assessment of the biliary system status in cholelithiasis were revealed. The findings recommend supplementing ultrasonic examinations with an optimal variant of the roentgenoendoscopic examination.


[The characteristics of the interaction of glycogenolytic enzymes with glycogen in endothermic and ectothermic animals]. It has been shown that the dependence of glycogenphosphorylase kinase activity on the quantity of glycogen added corresponds to the glycogenphosphorylase saturation curve by glycogen obtained during investigation of complex formation with the muscle glycogenphosphorylase of the animals: rat, frog Rana temporaria and fish Raja clavata under identical conditions. We suggest that glycogenolytic enzymes organize regular structure on glycogen particle. Glycogenphosphorylases of heat-loving animals have high affinity to glycogen that is accounted for necessity to keep the structure in natural conditions.


[The dependence of the rate of heart contractions in the long-tailed Yakutsk suslik Citellus undulatus on environmental temperature]. Decrease of ambient temperature (Ta) leads to the increase of the heart rate (HR) in active ground squirrels C. undulatus by 5.3/min/1 degree C in summer and by 3.8/min/1 degree C in winter. In a hibernation state, the dependence of the HR on Ta was in a good agreement with equation HT = 2.53.exp.(0.1.Ta). On entering into hibernation and on arousal, the HR change outruns the corresponding body temperature (Tb) change by 1.5-2 hours. A maximum HR level (up to 400/min and more) was registered on arousal when Tb reached 17-20 degrees C. A minimal HR level (4-5/min) was observed during hibernation at Ta 2-5 degrees C. The maximum Ta, at witch C. undulatus was hibernating, reached 23-24 degrees C, the HR being 23-25/min.


[The temporal organization of human fetal motor function]. Fetal motor bursts were recorded in pregnant women at 11-18, 20-24 and 30-32 weeks of pregnancy. It was stated that spontaneous motor activity in human fetus is similar to autogenic periodic motor excitation observed in other species of vertebrates, i.e. presence of the main rest-activity circles with a period near 1 minute, the existence of rhythmic components with 6-8-second intervals during active phases and decreasing of quantity of excitation bursts with age.


[The effect of vasotocin, mesotocin and adrenaline on the interrenal gland in the frog Rana temporaria under in-vitro conditions]. Morphometric studies indicate that vasotocin increases the activity of the adrenal gland in frogs, whereas mesotocin and epinephrine do not essentially affect it. Combination of epinephrine with nonapeptides in cultural medium showed that the former may abolish the effect of vasotocin on the adrenal gland.


[Study on the toxicity and antitumor activity of adriamycin-DNA and amsacrine-DNA complexes in mice]. We have compared in vitro binding of adriamycin (ADR) and amsacrine (AMSA) with DNA, the toxicity, and the antitumor activity of ADR-DNA and AMSA-DNA, after intraperitoneal (ip) injection in mice. The binding of ADR with DNA is 100-fold higher than that of AMSA with DNA. The overall toxicity of ADR-DNA is significantly lower than that of ADR. ADR-DNA is more effective than ADR against three models of S180 sarcoma (by sc, ip and i.v. inoculation into mice). The peak levels of ADR-DNA and ADR were 265 +/- 24 ng.ml-1 versus 108 +/- 16 ng.ml-1 (P < 0.01). AUC 0-12 h were 1064 +/- 84 ng.h-1 x ml-1 versus 382 +/- 27 ng.h-1 x ml-1 (P < 0.01). The levels of ADR in most of tissues and tumor after administration of ADR-DNA were higher than those after administration of ADR. Moreover, there is no difference in toxicity, therapeutic effects as well as AUC between AMSA-DNA and AMSA.


[Protective effects of cyproheptadine on calcium paradox in isolated rat hearts]. The protective effects of cyproheptadine, an antiserotonin-antihistaminic agent with calcium channel blocker activity, on calcium paradox in isolated Langendorff's heart in rats were studied. After a 5 min of calcium-free perfusion [standard Krebs-Henseleit (K-H) buffer without calcium, gassed with 95% O2 and 5% CO2] followed by a 20 min of normal K-H buffer (Ca2+ 2.5 mmol/L) perfusion, extensive and rapid myocardial injury was observed: release of massive cellular enzymes such as lactic dehydrogenase (LDH) and creatine phosphokinase (CPK), significant decrease of myocardial anti-oxygen free radical enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities but no obvious change of myocardial lipid peroxides such as malondialdehyde (MDA) content was observed. The loss of normal colour and mechanical activity, even contracture, was also observed in the injured hearts. Cyproheptadine (2.5-5 mumol/L) was shown to effectively antagonize the damage. The results suggest that the protective effects of cyproheptadine on the calcium paradox may be related to its actions of blocking calcium channel, protecting anti-oxygen free radical enzymes and scavenging oxygen free radicals in the myocardial tissues.


[The characteristics of the intragroup behavior of rhesus macaques and hamadryas baboons during the realization of food motivation in a competitive situation]. The aim of the present work is to consider the specific interrelations in "family" units of macaques (Macaca mulatta) and baboons (Papio hamadryas) during food-getting reactions in competitive conditions. Detailed analysis of dyadic interactions revealed that competing partners demonstrate more various types of behaviour tactics at the initial stage of learning. At the final one, only males of both investigated species performed instrumental reactions and received the food reward. All females demonstrated much more vocal reactions in comparison with males. Thus the variety of competing interactions between heterosexual partners, learning and possibility to realize its motivation correspond ro novelty of experimental situation and degree of intraspecies social subordination.


[Proliferation of lymphocytes T and B by prehispanolone LC-5504 of Leonurus hereterophyllus Sweet]. Leonurus hereterophyllus Sweet is a traditional Chinese herbal medicine used to treat menstrual disturbances in woman. A new labdane diterpene, prehispanolone LC-5504, namely 9 alpha, 13R,15,16-diepoxy-labdane-14-en-7-one, had been isolated. The authors studied the synergism of labdane diterpene, prehispanolone LC-5504 and Con A and LPS on T cells and B cells proliferation of BALB/c female mice in vitro. They showed that: (1) proliferation of T cells was demonstrated by administration of LC-5504 of various concentrations together with Con A. This proliferation was 5-8 times stronger than that observed when Con A was used alone. Such effect on T cells was not observed when LC-5504 was used alone. (2) Proliferation of B cells was not observed whether LC-5504 was used alone or together with LPS.


Synthesis, antiinflammatory and anticancer activity of cinnamic acids, their derivatives and analogues. Cinnamic acids were selected as lead compounds of antiinflammatory and anticancer agents through the investigation of their biological properties. Their esters and related styryl ketones were also studied. A total of nineteen compounds, fifteen of them not reported previously, were synthesized and found to be of considerable pharmacological interest. In preliminary biological tests, compounds IA, IB, IC, II2C and II5C showed significant inhibiting effect on croton oil induced mouse ear edema, IB, II5A, II5C and IIID exhibited good activity on HL-60 human cancer cells in vitro. It is well worth noticing that compounds IB and II5C exhibited excellent antiinflammatory action as well as anticancer activity.


[Chemistry and antitumor activity of hainanensine analogues]. A synthetic analogue of hainanensine 2a was further modified in order to improve its antitumor activity. Six compounds 3-8, were obtained, and among these compounds 8 showed significant activity. The diastereomer (+/-)8B was resolved by (+) tartaric acid and (-)benzoyl-tartaric acid to the corresponding enantiomers (-)8B and (+)8B, respectively and their optical purities were determined by isotope dilution method as 93% and 96%. The antitumor activity of the newly obtained compounds were tested in vitro, and (-)8B was found to have an IC50 of 1.9 mol/L, eighteen times higher than the original compound 2a.


[Structure modification of triptolide, a diterpenoid from Tripterygium wilfordii]. In this paper, the structure modification of triptolide was studied and nine triptolide derivatives were synthesized. A preliminary test for the immunosuppression activity in vitro showed that tripchlorolide (2) and tripbromolide (3) have strong activity similar to triptolide, while their toxicity are much lower. The activity of other compounds was decreased significantly. A simple method for the preparation of tripchlorolide from triptolide in 92% yield was found by reacting triptolide with HCl in acetone under mild condition.


[Study on the chemical composition of leaves and stalks of Trollius macropetalus]. A new constituent and four known compounds have been separated from the dry leaves and stalks of Trollius macropetalus Fr. Schmidt. By means of physico-chemical and spectroscopic methods, the structures of these compounds have been determined as vitexin-2''-O-beta-D-pyranxyloside (I), orientin-2''-O-beta-D-pyranxyloside (II), vitexin (III), orientin (IV) and 3-methoxy-4-hydroxyl-5-(3'-methyl-2'-)butylenzylbenzoic acid (V). I and II are found in the Trollius genus for the first time, V is a new compound named proglobeflowery acid.


[Studies on the sweet principles from the leaves of Cyclocarya paliurus (Batal.) Iljinskaya]. Four intensely sweet compounds (I-IV) were obtained from the leaves of Cyclocarya paliurus (Batal.) Iljinskaya. The structure of compound I was elucidated by chemical and spectroscopic methods as 20,24-epoxy-dammarane-(3 beta,12 beta,24R)-12-O-alpha-L-rhamnopyranosyl-25- hydroxyl-3-O-alpha-(5'-O-acetyl)-L-arabinofuranoside. It is a new natural product, named cyclocarioside A, and is the main sweet principle of this plant, possessing about 200 times the sweetness intensity of sugar.


[HPLC determination of salidroside in the roots of Rhodiola genus plants]. This paper reports a high performance liquid chromatographic (PHLC) method for the determination of salidroside in 10 samples of the plants of Rhodiola crenulata, R. alterna, R. brevipetiolata, R. yunnanensis and R. quadrifida as well as extracts of R. crenulata. Determination was carried out under the following conditions: column (mu Bondapak ODS, 10 microns, 3.9 mm x 300 mm), mobile phase (methanol-water, 2:8), flow rate (1.0 ml/min), detector (Waters 484, wavelength 276 nm). External standard method was used. The results show that HPLC is a useful tool for the quantitative analysis of salidroside in the plants of Rhodiola genus and the extracts of R. crenulata.


[The identification and determination of marker substances in xiaoyao wan by three dimensional HPLC]. A Chinese traditional patent medicine Xiaoyao Wan was analysed by three dimensional HPLC. The result shows that the Chinese traditional medicines involved in Xiaoyao Wan were identified excellently and the content of marker substances can be determined accurately. According to the results of determination, the content of saikosaponin b1, b2, glycyrrhizin, paeoniflorin and atractylenolide III in Xiaoyao Wan was 0.43, 0.53, 5.22, 3.95 and 0.16 (mg/g), respectively; The RSD was 1.2, 0.8, 0.4, 0.3 and 1.0 (%) respectively.


[Studies on transdermal delivery system of isosorbide dinitrate]. A transdermal delivery system of isosorbide dinitrate (ISDN-TDS) and an HPLC method for the measurement of ISDN were developed. The system is composed of backing, drug reservoir, control membrane, contact adhesive and protective layer. The influences of drug reservoir, solvent, control membrane, viscosity and penetration enhancer azone on the release of ISDN were investigated. The cumulative released amount of ISDN/time profile indicated that ISDN was permeated through excised skin in a zero-order kinetic in 48 h. The release of ISDN from ISDN-TDS can last 72 h at least. The mean permeation rate is 13.76 micrograms.h-1/cm2. Releasing ISDN from ISDN-TDS was more stable than that from Frandol tape-s whose release profile was found to follow a linear Q vs t1/2 relationship with a release flux of 114.39 micrograms.h-1/cm2.


[The crystal structure of triptophenolide revisited]. Triptophenolide, C20H24O3, has been assigned two isomeric structures. DF Yu et al reported the X-ray analytical structure II in 1990. In 1982, however, FX Deng et al had already reported the spectrometric assignment of structure I. Now, we report again the single crystal analysis of triptophenolide (I). The crystal belongs to space group P2(1)2(1)2(1) of orthorhombic system, with a = 7.270(6), b = 12.509(8), c = 36.20(1) A, Z = 8. The structure was solved by direct method and refined by the full-matrix least-square method to a final R factor 0.055, based on 2322 intensities with I > or = 3 sigma (I). It is highly probable that the result of DF Yu was in error with only 1292 available intensities.


[Application of derivative spectrophotometric signal multiplier method in multicomponent mixture--determination of moroxydine hydrochloride in Gan Mao Qing capsules]. This paper provides a basic principle and experimental technique of derivative signal multiplier spectrophotometry in multicomponent mixture. A microcomputer was used to process the spectral data measured on a manual spectrophotometer (UV-7520) for the determination of moroxydine hydrochloride in Gan Mao Qing capsules. Quantitative analysis of multicomponent mixture can be done without sample separation. The selection of optimal wavelength pairs is performed through the program with a computer. The method needs no special spectrophotometer and is simple, rapid and easy to operate. The mean recovery was 99.98 +/- 0.53% (n = 12).


[Solid-phase extraction and RP-HPLC screening procedure for diuretics, probenecid, caffeine and pemoline in urine]. A solid-phase extraction and reversed phase high performance liquid chromatographic method (RP-HPLC) was developed for the rapid determination of 13 diuretics (belonging to five different pharmacological groups), probenecid, caffeine and pemoline in urine. Two ml urine sample was first adsorbed on a XAD-2 column, then eluted with ether-ethyl acetate (1:1). The eluate was evaporated to dryness and reconstituted in methanol. The methanolic solution was injected into a HP LiChrosorb RP-18 column, using phosphate buffer (pH 3) and acetonitrile as the mobile phase and monitored at 216 nm, 230 nm, and 275 nm on a diode array ultraviolet detector. The extraction recoveries of 16 drugs were above 75%. The limits of detection ranged from 0.3-3.0 micrograms/ml of urine. All drugs were separately administered to healthy volunteers, positive urine samples were collected, and urinary excretion-time curves of some drugs were reported.


Tetrandrine is not a selective calcium channel blocker in vascular smooth muscle. The effects of tetrandrine (Tet) on the contractile properties of rat aortic ring preparations were studied to test the hypothesis that Tet is a Ca2+ antagonist acting on voltage-operated Ca2+ channels (VOC). The tests were performed on contractions induced by depolarizing concentrations of KCl and by alpha 1-adrenoceptor agonist, phenylephrine (Phe). These vascular effects of Tet were compared to those of nifedipine (Nif). We found that Tet behaved qualitatively similar to, but less potent than, Nif in that it inhibited KCl-induced contraction in a concentration-dependent fashion and its inhibitory effect was long-lasting. However, the effects on Phe-induced contraction of Tet was different from those of Nif in that the extracellular Ca(2+)-dependent contraction was inhibited by Tet, but not by Nif. Tet (60 mumol.L-1) completely inhibited the 45Ca2+ uptake induced by KCl and Phe in rat aortic muscle strips. When the aortic muscle contractile response was induced by addition of Ca2+ following depletion of intracellular stores by Phe in the presence of sarcoplasmic reticulum Ca(2+)-pump inhibitor, cyclopiazonic acid, Tet (60 mumol.L-1) was more effective than Nif 1 mumol.L-1 in inhibiting such a response to extracellularly added Ca2+. Furthermore, Tet, but not Nif, also significantly inhibited the contraction to Phe in Ca(2+)-free medium. Collectively, these results led us to conclude that Tet does not behave as a selective VOC blocker like Nif.


Effect of cimetidine and ranitidine on absorption of [125I]levothyroxine administered orally. Female patients with a simple goiter were pretreated on 2 occasions (at an interval of 4 wk) with po placebo or 400 mg cimetidine (Cim) (Group A, n = 10), or with placebo or 30 mg ranitidine (Ran) (Group B, n = 10), 90 and 150 min, respectively, prior to the po gelatin capsules containing [125I]levothyroxine ([125I]LT4). A double-blind randomized study protocol was kept. Venous blood samples were taken at 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, and 240 min after po [125I]LT4 and the radioactivities in serum were counted. Similar [125I]LT4 radioactivities were found after placebo pretreatment in both groups: AUC 467 +/- 82 in Group A vs 459 +/- 109 in Group B. Cimetidine decreased the serum [125I]LT4 radioactivities: AUC371 +/- 72 (Cim) vs 467 +/- 82 (placebo) (P < 0.01), but Ran did not: AUC 477 +/- 132 (Ran) vs 459 +/- 109 (placebo) (P > 0.05).


Effects of (-)-stepholidine on firing activity of dopamine neurons in ventral tegmental area of rats. Extracellular single-unit recording techniques were used to evaluate the effects of (-)-stepholidine (SPD) on the firing activity of ventral tegmental area (VTA) dopamine (DA) neurons. SPD reversed the DA agonist apomorphine (Apo)-induced inhibition of VTA DA cell firing rate (ED50 = 4.9, 4.5-5.3 micrograms.kg-1), and the reversal was more rapid than that of a classic DA antagonist haloperidol (Hal) (ED50 = 11.2, 9.1-13.8 micrograms.kg-1). Pretreatment with SPD or Hal 0.5 mg.kg-1 attenuated Apo-induced inhibition, and SPD rendered the VTA DA cells less sensitive to larger doses of Apo (1024-4096 micrograms.kg-1) than Hal did. Pharmacological analysis indicated that the effects of SPD were mainly mediated through D2 subtype receptors. In addition, SPD increased the firing rate of VTA DA cells, while higher doses (1.4, 0.6-3.3 mg.kg-1) of SPD dramatically inactivated 4/6 of the VTA DA cells sampled. This inhibition was considered to be due to depolarization inactivation. These results suggest that SPD is a DA receptor antagonist and can effectively block the D2 autoreceptors located in the VTA DA cells.


Effects of neuropeptide Y injected into A1 noradrenergic nucleus on blood pressure and catecholamines in plasma of cats. The microinjection of neuropeptide Y (NPY) 0.75 and 1.5 micrograms into A1 noradrenergic nucleus of cats produced dose-dependent falls in mean arterial blood pressure of 2.0 +/- 0.6 and 4.9 +/- 2.4 kPa, respectively. NPY microinjection (1.5 micrograms) also produced marked decreases in noradrenaline (5 +/- 4 pmol.ml-1) and adrenaline (23 +/- 8 pmol.ml-1), but no significant change in dopamine in blood plasma. The results suggest that the depressor effect of NPY in A1 noradrenergic nucleus may be realized by not only reducing the release of noradrenaline in sympathetic terminals around the peripheral vascular beds but also inhibiting the sympathetico-adrenal system.


Influences of ginsenosides Rb1, Rb2, and Rb3 on electric and contractile activities of normal and damaged cultured myocardiocytes. Free radical damage to the cultured myocardiocytes of Wistar rat was induced by adding xanthine 0.42 mmol.L-1 and xanthine oxidase 5.3 nmol.L-1 to the culture medium. 30 micrograms.ml-1 of Rb1, Rb2 or Rb3 extracted from the leaf and stem of Panax ginseng C A Meyer restored the action potentials (AP) of free radical damaged cells to normal, indicating their antioxidative action. On normal myocardial cells, Rb1, Rb2, Rb3 20 micrograms.ml-1 inhibited the AP and spontaneous contractility, (suggesting the Ca channel blockade action of panaxadiol saponins). The degrees of their inhibitory effects were found to be Rb1 > Rb2 > Rb3. Their effects against X-XO were basically the same.


Frequency-dependent depression of Vmax in K(+)-depolarized guinea pig papillary muscle by tetrandrine. The effect of tetrandrine (Tet), a calcium antagonist, on the maximal upstroke velocity (Vmax) of depolarization in K(+)-depolarized guinea pig papillary muscles was studied by standard microelectrode method with computer. The results showed that: (1) the resting block of Tet on Vmax was concentration dependent; (2) the drug (50 or 100 mumol.L-1) caused a marked frequency-dependent block of Vmax, which accounted for 65 +/- 8% of total block at a concentration of 100 mumol.L-1 and the pacing frequency of 0.3 Hz; (3) the recovery kinetics of Vmax could be characterized as a biexponential function, of which the second phase was prolonged by the drug; (4) compared with verapamil, nitrendipine, and diltiazem, the above-mentioned effects of Tet on Vmax were similar to those of diltiazem. These results suggest that Tet can block calcium channel in both frequency-dependent and frequency-independent manner, mainly the former.


Effects of berbamine on contraction and Ca2+ influx of pig basilar artery. Effects of berbamine (Ber) on KCl- and 5-HT-induced contraction of basilar artery (BA) of pigs were studied in vitro. Ber relaxed markedly KCl-induced contraction of BA (IC50 = 4.63 mumol.L-1) and its effect was antagonized by increasing the concentration of extracellular Ca2+; Ber inhibited 5-HT-induced contraction of BA, showing significant inhibition of sustained tonic contraction (STC) (IC50 = 0.64 mumol.L-1) whereas the initial fast phasic contraction (FPC) was relatively unaffected (IC50 = 19.8 mumol.L-1); the 5-HT-induced contraction of BA was dependent on the concentration of extracellular Ca2+, especially STC. The results of Ca2+ withdrawal and replacement indicated that STC was due to 5-HT-stimulated Ca2+ influx, while 5-HT-induced release of intracellular Ca2+ resulted in FPC. Ber 0.8 mumol.L-1 produced markedly inhibitory effect on Ca2+ influx induced by 5-HT (P < 0.01). The effects of Ber were similar to those of nimodipine (Nim). The present results suggested that Ber has antagonistic effect on the potential sensitive channels (PSC) and the receptor operated channels (ROC).


Reversal of doxorubicin resistance by tetrandrine in Chinese hamster ovary cell line. Tetrandrine (Tet) 0.5 microgram.ml-1 and 1 microgram.ml-1 potentiated 2.88- and 4.3-fold growth-inhibitory effects of doxorubicin (Dox) in Chinese hamster ovary cell line (CHO), respectively, while Tet 1 microgram.ml-1 and 2.5 micrograms.ml-1 potentiated 7.3- and 8.4-fold in its resistant cell line (CHO/Dox), respectively. The colony-forming efficiencies were reduced in CHO and CHO/Dox when the cells were treated with noncytotoxic doses of Tet 2.5 micrograms.ml-1 and 5 micrograms.ml-1 in combination with different concentration of Dox. Increase in accumulation of Dox in CHO/Dox cells was shown by fluorometry. The result indicated that Tet reversed the resistance to Dox in CHO/Dox cells.


Effects of tetrandrine on action potentials and afterhyperpolarization potentials in toad dorsal root ganglia. Intracellular recordings were obtained from the cytosome of type A primary afferents in the isolated toad dorsal root ganglia (DRG) preparations. Bath application of Ca2+ 8.0 mmol.L-1 led to prolong action potential duration of repolarization 100% (APD100) by 23%, afterhyperpolarization potential duration of depolarization 50% (AHPD50) by 46%, and increase afterhyperpolarization potential amplitude (AHPA) by 40%. Verapamil 3 mumol.L-1 shortened the APD100 by 7% and the AHPD50 by 13%, and reduced the AHPA by 17%. The effects of Tet 3-100 mumol.L-1 consisted of APD and AHPD50 shortening and AHPA reduction in concentration-dependent manner. Tet 100 mumol.L-1, APD100 was shortened by 16%, AHPD50 by 18%, and AHPA was reduced by 20%. The results suggested that the effects of Tet may be related to its Ca2+ channel blockade in DRG.


Effects of exogenous gamma-aminobutyric acid on experimental arrhythmias. The effects of exogenous gamma-aminobutyric acid (GABA) 10 mg.kg-1 iv in preventing arrhythmias induced by drugs and ischemia were studied in mice, rats, and guinea pigs. It was found that the threshold dose of aconitine inducing arrhythmia in mice and the recovery rate to normal sinus rhythm increased significantly, ED50 of GABA was 5.4-5.8 mg.kg-1. The duration of ventricular tachycardia (VT) induced by aconitine in rats was shortened (P < 0.01). The incidence and the mortality of ventricular fibrillation (VF) in GABA group were decreased to 0/10 vs 6/10 and 5/10 in control, respectively (P < 0.05). The doses of ouabain to induce ectopic beats (EB), VT, VF, and cardiac arrest (CA) in guinea pigs were increased (P < 0.01). The incidence of VF induced by coronary artery ligation in rats was decreased to 0/5 in GABA group vs 4/5 in control group (P < 0.01). The total amount of EB, total time of VT, and VF were 66%, 41%, and 0% of the control group, respectively. The anti-arrhythmic effects of GABA were dose-dependent and as potent as procainamide (10 or 5 mg.kg-1, iv). The results suggest GABA (10 mg.kg-1, iv) may be useful for the prevention of VT and VF.


Scavenging effects of phenylpropanoid glycosides on superoxide and its antioxidation effect. The antioxidative activities of six phenylpropaniod glycosides (PPG) extracted from Pedicularis striata and Pedicularis lasiophrys for inhibiting the lipid peroxidation induced by Fe2+/ascorbic acid in mouse liver microsome may be related to the number and steric position of phenolic hydroxyl groups (PHG) they possess (32.5 mumol.L-1 to 65.0 mumol.L-1). The scavenging effects of PPG for superoxide produced by NBT/PMS/NADH system may be related to both the number of PHG and their conjugated system (16.0 mumol.L-1 to 65.0 mumol.L-1).


Rat liver microsomal and mitochondrial metabolism of primaquine in vitro. The profiles of major metabolites of primaquine (PQ) produced from liver microsomal (MC) and mitochondrial (MT) metabolism were investigated in vitro by silica gel thin layer and reverse phase high pressure liquid chromatography (HPLC). The results indicated that 5-hydroxy primaquine (5-OH PQ) and carboxyprimaquine (CPQ) were simultaneously produced by either microsomes or pure mitochondria preparations. However, the quantitative study showed that microsomes produced approximately 19 times more 5-OH PQ but only 1/34 of the CPQ by mitochondria.


Antitumor effects of new-type recombinant interleukin-2. Two new human recombinant interleukin-2 (rIL-2), 125-Ser-rIL-2, and 125-Ala-rIL-2, were generated by protein engineering technique. Both of them maintained the proliferation of natural killer (NK) cells, CTLL-2 cells and their long-term propagations. The mutated new rIL-2 also enhanced the bioactivity of NK cells and the cytotoxicity of tumor-infiltrating lymphocytes (TIL) against the target tumor cells. The above results were all compared with that of the native rIL-2 and a similarity between them was found, which indicates that new type rIL-2 could be used for adoptive immunotherapy of malignant diseases.


Thrombolytic actions of reptilase.

Thrombolytic actions of reptilase. In thrombolytic model in vitro, reptilase (Rep, defibrase) did not show appreciable thrombolytic actions on red and white thrombi. After daily iv infusion of Rep 0.25 IU for 10 d, the time of 50% lysis of euglobulin (ELT1/2) was shortened from 9.3 +/- 0.8 to 6.7 +/- 1.0 h (P < 0.01), alteplase activity was increased from 1.9 +/- 0.7 to 3.7 +/- 0.9 IU.ml-1, and plasminogen inactivator (PI) activity reduced from 4.3 +/- 0.6 to 1.8 +/- 0.9 AU.ml-1 (all P < 0.01). The findings indicate that the thrombolytic action of Rep shown in vivo may not be from the direct action on thrombi but from the influence on alteplase and PI activity.


[Feed-back regulation of presynaptic D2 receptors blockaded by l-stepholidine and l-tetrahydropalmatine]. The activity of tyrosine hydroxylase by accumulation of L-dopa content in the striatum under decarboxylase inhibitor (benserazide, 400 mg.kg-1) was measured by HPLC-ECD to ascertain whether l-SPD possesses an agonistic or antagonistic effect on D2 receptor subtype. The accumulated L-dopa content was increased with 1,4-butyrolactone (BL, 750 mg.kg-1) to 1.8 +/- s 0.6 micrograms.g-1 in rat striatum. After the rats were ip l-SPD 5 mg.kg-1 or l-tetrahydropalmatine (l-THP) 10-20 mg.kg-1, the increment of L-dopa level was much more than that in the BL group (P < 0.01) in a dose related manner. On the contrary, apomorphine (ip 5 mg.kg-1) abolished the accumulation of L-dopa induced by BL. Furthermore, l-SPD and l-THP not only reversed the negative feed-back regulation by apomorphine on the accumulated level of L-dopa, but also increased this level over the accumulation by BL. These results showed that l-SPD and l-THP do possess the antagonistic effect on presynaptic DA receptor (D2) without agonistic effect.


[Antihypertensive effects of atenolol and nitrendipine alone or in combination on three hypertensive models of rats]. The antihypertensive effects of atenolol (Ate) or nitrendipine (Nit) alone or in combination (Ate+Nit) were studied in conscious experimental hypertensive rats. The hypotensive effects of single ig of Ate 20 + Nit 10 mg.kg-1 were rapid and persistent in spontaneously hypertensive rats (SHR). In renovascular hypertensive rats (RVHR) and DOCA-salt hypertensive rats (DHR), Ate+Nit (6 + 3, 20 + 10, 60 + 30 mg.kg-1) given ig once a day for 10 d reduced the blood pressure in a dose-dependent manner. But Ate 20 mg.kg-1 or Nit 10 mg.kg-1 alone given ig once a day for 10 d caused no obvious reduction in blood pressure in RVHR, DHR, and SHR q = 1.32. These results revealed that the synergy is present in the antihypertensive action of Ate+Nit.


[Effects of imipramine on isolated rabbit basilar artery]. Imipramine (Imi) inhibited the contractile response to BAY k 8644 (IC50 = 2.39 +/- 0.33 mumol.L-1), KCl (IC50 = 1.00 +/- 0.09 mumol.L-1), in rabbit basilar artery rings. Imi was more effective in suppressing the contractile response evoked by KCl, CaCl2, and 5-HT in basilar artery rings than in mesenteric artery rings. The effect of Imi was the same as that of diltiazem (Dil). There was no difference between the inhibitory response of Imi on contraction induced by KCl in basilar artery rings with or without endothelium. The results suggest that Imi may block the calcium channel and inhibit the rabbit basilar artery selectively, and the effect is endothelium-independent.


[Excitant effect of sodium suberogorgin on isolated rabbit ileum]. Suberogorgin was isolated from Gorgoniae suberogorgia sp from South China Sea. The isolated rabbit ileum contracted in a concentration-dependent manner by suberogorgin-Na (Sub) 2.13 mumol.L-1 or higher. Sub 213 mumol.L-1 had no effect on the relaxation induced by norepinephrine and isoprenaline 10-100 mumol.L-1 on ileum. The stimulation of Sub on ileum was antagonized by atropine 56 mumol.L-1 or indometacin 0.35 mmol.L-1 and was partly blocked by indometacin 0.17 mmol.L-1, but was not affected by diphenhydramine 10 mumol.L-1. On the contracted ileum induced by neostigmine 1.7 mumol.L-1, acetylcholine 0.1 mumol.L-1 increased the tension but Sub 213 mumolL-1 did not. Sub obviously inhibited the acetylcholinesterase (AChE) from mouse brain hemogenates in vitro. Its pI50 (negative logarithm of molar concentration causing 50% inhibition of AChE) was 4.18, while the pI50 of neostigmine was 4.75. The results indicated that the ileum-excitant action of Sub was chiefly related to the inhibition of AChE.


[Nuclear anomaly test in human lymphocytes in vitro]. To assess the usefulness and the sensitivity of the nuclear anomaly test in human lymphocytes we treated in vitro human whole blood with various concentrations of mitomycin C, thiotepa, and bimolane. After the blood samples had been stored at 37 degrees C for 17-18 h, smears of isolated lymphocytes were made. The nuclear anomalies (micronuclei, irregular, karyorrhectic, and pyknotic nuclei) were measured. The concentration-response relationship and the minimum sensitive concentration of nuclear damage indices to the test mutagens were analyzed. The results showed that all 3 drugs induced a concentration-dependent increase of other nuclear anomalies except pyknotic nucleus in lymphocytes, that the most sensitive index of nuclear damage was the micronucleus assay, that the karyorrhectic assay was as sensitive to MMC and bimolane as the micronucleus assay, and that the irregular nucleus assay and the complex nuclear anomaly assay were less sensitive, but the correlation between concentration and complex nuclear anomalies was the best among various indices of nuclear damage. Therefore, the in vitro nuclear anomaly test in lymphocytes of human whole blood could be used to evaluate genotoxic effects of chemicals.


[Pharmacokinetics of epostane in rabbits by HPLC method]. Epostane (Epo), a 3 beta-hydroxysteroid dehydrogenase inhibitor, interrupted pregnancy in rats, rhesus monkeys, and women. Epo concentrations in serum were determined by high performance liquid chromatography (HPLC) at 0.25, 0.5, 1, 2, 4, 8, 16, 32, and 48 h after intragastric Epo 96 mg.kg-1 in rabbits. The concentration-time curve exhibited a 2-compartment open model. The pharmacokinetic parameters were: T1/2ka 0.79 +/- 0.08 h, T1/2 alpha 0.96 +/- 0.08 h, T1/2 beta 6.6 +/- 1.5 h, Vc 14 +/- 3 ml.kg-1, AUC 12.0 +/- 1.9 micrograms.h.ml-1, Tmax 1.8 +/- 0.5 h, Cmax 3.3 +/- 0.5 microgram.ml-1. After rat copora luteum were incubated with hCG 10 IU.ml-1 and Epo 10 or 100 micrograms.ml-1 for 18 and 48 h, luteal cells showed various degrees of degeneration and progesterone production was significantly inhibited.


[Enhancement of antitumor activity of harringtonine in human leukemia-60 cells in vitro by verapamil]. The effect of harringtonine (Har) alone and in combination with verapamil (Ver) on the proliferation of human leukemia-60 (HL-60) cells in vitro were studied. IC50 of Har alone to the cells was about 49 ng.ml-1 which was reduced to its 1/3.3 and 1/4.5 when used with Ver 1 and 2 micrograms.ml-1, respectively. In colony forming test, the survival fraction of the HL-60 cells treated with Har 15 and 30 ng.ml-1 plus Ver 2 micrograms.ml-1 was reduced to 1/3.3 and 1/8 of the cells as when treated with Har alone, respectively. The results suggested that Ver enhanced the antitumor activity of Har in vitro and may used as an enhancer of Har in vivo.


[Effect of mebendazole on glucose uptake of Echinococcus granulosus cysts]. Mice infected with secondary cysts of Echinococcus granulosus were treated ig with mebendazole (Meb) 25 mg.kg-1.d-1 for 7-14 d. At 24 h after the last dose the endocysts in the treated mice were removed out for in vitro cultivation and exposed to [U-14C]glucose 11.1 kBq.ml-1 for 2 min, no apparent difference in radioactivity content in the cyst walls between the treated and control groups was observed. When [U-14C]glucose was given iv to the infected mice 24 h after they had been treated ig with Meb 25 mg.kg-1 or 50 mg.kg-1 daily for 14 d, the radioactivity content in the cyst wall and cyst fluid decreased significantly as compared to the corresponding control group. Nevertheless, no apparent change in the incorporation of radioactivity into the endogenous glycogen of the parasites was observed, although the glycogen in the cyst wall decreased markedly.


[Effects of dexamethasone and cyclophosphamide on development of exo-erythrocytic form of Plasmodium cynomolgi bastianellii in rhesus monkey]. The rhesus monkeys (Macaca mulatta) challenged with Plasmodium cynomolgi bastianellii sporozoites were treated with im dexamethasone (Dex) 1 mg.kg-1.d-1 x 7 d and cyclophosphamide (Cyc) 25 mg.kg-1.d-1 x 3d, respectively. On d 7 after challenge, serial sections of liver biopsy stained with HE revealed that the distributive density and size of exo-erythrocytic (EE) form of the parasites showed no difference between medicated and control monkeys. The prepatent period of the primary attack and the relapse patterns after the treatment of Dex and Cyc were also similar to each other. The radically cured monkeys challenged with the Plasmodium erythrocytic form were reinfected with sporozoites, the relapses were much less than those in control monkeys, but the density and size of EE form in liver were similar to those in control monkeys. These results suggest that Dex and Cyc exert no effect on the development of EE form (including hypnozoite) in the monkeys.


[Vascular effects of urapidil administrated during extracorporeal circulation]. Urapidil exerts a combined central sympathetic and peripheral alpha-1 adrenergic receptor inhibition. Urapidil induces arterial vasodilation but its effects on venous capacitance are more difficult to assess. During cardiopulmonary bypass with constant perfusion index (2.4 l.min-1 x m-2) total peripheral resistance varies similarly as to arterial pressure and, as the apparatus venous reservoir is filled continuously by simple gravity from the right atrium, a decrease in venous blood reservoir level reflects an increased venous capacitance. Twenty-six patients undergoing cardiac surgery were anaesthetized with fentanyl and midazolam and randomly assigned to one of two groups. During normothermic cardiopulmonary bypass, group 1 was administered i.v. urapidil 12.5 mg and group 2 a placebo. In group 1, arterial pressure decreased by 33 +/- 14% (mean +/- SD) at the second minute while total peripheral resistance decreased from 1,384 +/- 255 to 927 +/- 193 dyn.s.cm-5. Then this two parameters regained group 2 values after the eighth minute. Reservoir blood level was lower in group 1 than in group 2 from the second to the eight minute (p < 0.05) with maximum effect at 7 minutes. It is concluded that urapidil exerts arterial and venous dilation. Its arterial effects seem greater during normothermic cardiopulmonary bypass than in normal conditions and its maximum venous effects seem to occur after its maximum arterial effects. The short duration of action may be due to the small dose administered.


[Hemodynamic parameters in the severely burnt patient during the 1st 72 hours]. The haemodynamic time course of 16 patients with severe burn injury was investigated using a flow-directed balloon-tipped pulmonary artery catheter. The patients, aged 33.8 +/- 5.5 years, were burnt over 60 +/- 10% of body surface area, with a UBS score of 228 +/- 43. The measurements were obtained every six hours after insertion of the catheter. Fluid load was determined with Evans' formula, and modified according to the haemodynamic data. Catecholamines were introduced when this and a trial of fluid loading with 5 ml.kg-1 of macromolecules during a 20 min period had failed, starting with dobutamine or dopamine, followed by adrenaline as required. During the first hours after the injury, circulatory shock was partly linked to hypovolaemia: mean arterial pressure was 60.1 +/- 7.8 mmHg, right auricular pressure 4.5 +/- 2 mmHg, pulmonary wedge pressure 4.7 +/- 2 mmHg, cardiac index 3.5 +/- 0.8 l.min-1 x m-2. However, during the second and third days, cardiac output increased, with a cardiac index at 4.7 +/- 0.6 l.min-1 x m-2 and 5.2 +/- 0.2 l.min-1 x m-2 respectively, and arterial vascular resistances were decreased (536 +/- 125 dyn.s.cm-5). These data suggest a specific haemodynamic profile in severe burn patients which justifies invasive monitoring, and the use of catecholamines, in those patients that do not respond to fluid loading. The link between these data and the concomitant metabolic disturbances due to the burn injury has not yet been established. The increase in cardiac index could be related to the inflammatory response.(ABSTRACT TRUNCATED AT 250 WORDS)


[Epidural anesthesia and metabolic response to surgical stress]. Surgical stress leads to reproducible physiological metabolic and hormonal responses, characterized by on altered carbohydrate metabolism, a net loss of protein and an increased lipolysis. They are due to an increased secretion of catecholamines, ACTH, cortisol and cytokines. Epidural analgesia prevents the hyperglycaemic, cortisol and adrenocortical responses to surgery. The lipolysis and the loss of protein are also attenuated. This effect only occurs in lower abdominal surgery, with an epidural blockade extending from T4 to S5, carried out with local anesthetic agents and started before the skin incision. However, such a blockade abates, but does not suppress, the metabolic response to upper abdominal or thoracic surgery, probably because of persistent vagal afferences, the incomplete blockade of somatic afferents, and a stimulation of the diaphragm and peritoneal free nerve endings. Likewise, epidural morphine does not modify the intraoperative metabolic and hormonal responses. The main reason is most probably the failure of opioids to block the sympathetic system, as well as their insignificant effects on fast conducting fibers.


[Methods for measuring spinal cord blood flow]. This study aimed to review the techniques used most currently for measuring spinal cord blood blow flow (SCBF) in animals, i.e. the hydrogen clearance, labelled microspheres, 133Xe clearance and 14C-antipyrine autoradiographic methods. All four techniques may only be used in animals, because of their invasiveness. Flow figures varied greatly with the method, the spinal level at which measurements were carried out, and the species of animal. However, results tend to suggest that SCBF is very similar to cerebral blood flow in that it is controlled by chemical, autoregulatory and metabolic factors. Approaches to measuring SCBF in man may be made using stable xenon-enhanced computed tomographic imaging (Xes-CT) in the same way as for measuring cerebral blood flow. The calculation of SCBF is based on Fick's principle transformed by Kety and Schmidt. After a reference CT section has been obtained, twelve 8 mm thick sections are carried out whilst the patient breathes a 30% xenon-70% air/oxygen mixture. This series of views enables the SCBF to be calculated in four steps. Quantitative analysis in eight human subjects gave a mean SCBF of 58.8 +/- 5.96 ml x 100 g-1 x min-1. However, this method has a low signal to noise ratio. Moreover, the qualitative analysis of the parametric views of flow demonstrate tissue heterogeneity, partly due to the patient's movements (breathing movements). However, the method is non invasive, safe, and reproducible. As it can measure very low values of blood flow, the study of ischaemic spinal lesions is made possible, although some technical and software improvements are still required.


[Effects of continuous administration of nimodipine during the acute phase of spinal cord injury in baboons]. This study was carried out to assess the putative improvement of spinal cord blood flow obtained with a calcium channel blocker after acute spinal cord injury in ten baboons. The injury was generated by compressing the cord at L1 level for 5 seconds with a balloon catheter inflated to 2 bars with Ringer's solution. Subsequently, five monkeys received a saline infusion, and five others a nimodipine infusion (0.04 mg.kg-1 x h-1), for seven days. Spinal cord blood flow (SCBF) was measured using a scanographic technique with stable xenon. Somatosensory evoked potentials (SEP), magnetic resonance imaging (MRI) and a histological study of the spine were carried out a different times of the study. SCBF and SEP were recorded before injury. Thereafter SCBF was measured every thirty minutes during the four hours following the injury, as well as on day 7. SEP and MRI were recorded on days 1 and 7. The histological study was carried out on the eighth day. Three spinal cord and vertebral segments were collected, fixed, sliced and stained. SCBF before injury was not significantly different in either group (39.8 +/- 15.9 ml x 100 g-1 x min-1 for the treatment group 40.9 +/- 16.3 ml x 100 g-1 x min-1 for the control group). During the injury, there were major variations between animals. The results were expressed as percentages of each animal's control SCBF (before injury). Immediately after injury, SCBF increased in both groups. However, in the control group, SCBF decreased more than in the treatment group on the seventh day after injury (80 to 90% vs 25 to 50%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


[Anesthesia of patients with injury to the cervical spine]. This paper reviews the principal aspects of the immediate management of patients suffering from spinal injury. An understanding of the pathophysiology of primary and secondary spinal cord injury enables appropriate initial care to be provided, thereby avoiding exacerbation and/or progressive deterioration of the lesion. It includes protective measures, restoration of vital functions to maintain adequate tissue perfusion and oxygenation, as well as pharmacological prevention of secondary injury. Protective measures include proper immobilisation of the spine with a semi-rigid collar and tape on a long backboard, or on vacuum mattress, taking great care to avoid deleterious in-line compression forces on the spinal column. The combination of cervical spine instability, a full stomach, unopposed vagal reflexes, hypoxia and hypercarbia makes airway management of these patients difficult. Tracheal intubation under fibroscopic control, with insertion of the tube only after topical anaesthesia of the airways under titrated intravenous sedation, offers safety and comfort to the patient. However, in cases of severe deterioration of vital functions, intubation must be performed without any delay at the site of the accident or in the emergency room. Three options are available: blind naso-tracheal intubation with spontaneous breathing, modified rapid sequence induction with orotracheal intubation under double protection, and immediate surgical airway if these techniques fail. Patients with cervical spine injury may demonstrate severe hypotension requiring sympathomimetic agents and careful fluid loading to avoid pulmonary oedema. To prevent aggravation of the spinal cord injury by systemic factors, the goal of initial resuscitation is to restore an adequate perfusion pressure of at least 60 mmHg, a PaO2 > 100 mmHg, and to keep PaCO2 below 45 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)


[Pathology of cranial nerves: diagnostic orientation and aphorisms]. Despite the remarkable progress of Neuroradiology, the etiologic diagnosis of cranial nerve disorders remains, because of the numerous potential causes, one of the most difficult clinical problems in Neurology. It requires a perfect collaboration between neurologists, ophthalmologists, and ENT specialists, and also between clinicians and radiologists. First of all however, it is based on a rigorous clinical analysis in order to determine the site of the lesion and to guide complementary investigations. The purpose of this short paper is to provide a brief outline of this clinical approach and to recall some aphorisms which are essential to keep in mind when dealing with this pathology.


[3D imaging and pathology of the base of the skull in children]. Three dimensional computed tomography was performed in 150 children suffering from a bone lesion of the base of the skull and face. These lesions were either malformative, neoplastic, infectious or traumatic. 3D CT provided an essential anatomical approach to the lesions facilitating the choice of the most appropriate treatment. 3D CT is also indicated in the follow-up of these operated children, particularly of the growth of the operated bone segment and its relations with adjacent structures.


[Imaging of the facial nerve and the petrous apex]. From its origin in the pons to its extracranial exit with a long intrapetrous course, the facial nerve raises various diagnostic problems related to the site and extent of the lesions, which involves the whole field of petrous pathology. The study of the pathology of the neighbouring petrous apex completes this regional analysis. Today, in accordance with the anatomical loco-regional complexity, MRI is the predominant modality of diagnostic imaging (but must be associated with CT to allow the more accurate detection of subtle bone changes); it will be at best directed by the clinical and functional data which reflect the underlying pathophysiologic mechanisms.


[Neurosurgical treatment of essential facial neuralgia]. The authors describe the neurosurgical techniques currently available for the treatment of essential trigeminal neuralgia refractory to the usual medical treatments. They compare the advantages and disadvantages of percutaneous techniques (particularly thermocoagulation of the trigeminal ganglion) and open techniques (especially microsurgical treatment of neurovascular conflict in the cerebellopontine angle.


[Anatomy of the auditory tube: CT scan and MRI aspect]. The auditory tube is a bony and cartilaginous canal which connects the middle ear to the nasopharynx. The bony portion (protympanum), explored by computed tomography, is cone shaped, with a posterior base. The main relations are: the intrapetrous carotid, the tensor tympani muscle, the middle cerebral fossa and temporo-mandibular joint. The fibrocartilaginous portion is explored by computed tomography and mainly by magnetic resonance. The fibrocartilaginous tube is posteromedial; its upper margin is curled outward to form the roof of the cartilaginous tube. Anterioly and Laterally, the auditory tube is closed by a fibrous membrane extending along the inferior surface of the auditory tube to form its floor. The auditory tube is in contact with two main muscle: the tensor veli palatini anterolateral and the levator veli palatini posterolateral and inferior. They are bounded by fascia: the intrapharyngeal fascia is medial, the pharyngo basilar fascia (salpingopharyngeal fascia of Trölstch, is between the tensor and levator veli palatini muscles; the fascia of Weber Liel is lateral to the tensor veli palatini. The auditory tube and its muscles form the lateral wall of the rhinopharynx and prevent the extension of a pathologic process to the para pharyngeal and infratemporal spaces.


[Osteitis of the base of the skull].

[Osteitis of the base of the skull]. The base of the skull and calvarium may be the site of osteitis secondary to haematogenous or loco-regional dissemination of a nasal sinus or postoperative, external ear or middle ear infection. Although most of the complications of osteitis are eradicated by antibiotics, some persist and are still serious due to the delay in the diagnosis extensive necrosis due to the bacteria and the clinical context.


[Diagnostic orientation and radiological assessment of anosmia]. The olfactory system is made up of the olfactory epithelium, bulbs and tracts, together with olfactory areas in the brain. Anosmia may results from benign and malignant nasal sinus lesions, but also from lesions involving the CNS structures involved in olfaction. The purpose of this article is to review the different diagnose of anosmia and their CT or MR imaging characteristics.


[Retrograde perineural extension of a metastatic recurrence of a frontal skin tumor]. Perineural metastatic spread of malignant tumours has been described for a long time, but has only recently been demonstrated by medical imaging. MRI, guided by the clinical findings, with fine sections on T1-weighted sequences without and with gadolinium, allows the diagnosis of this type of spread. The tumours most frequently responsible are squamous cell carcinomas and cylindromas. The trigeminal and facial nerves are the most frequently affected. Recognition of such lesions is essential in the initial staging of a malignant tumour of the face, as it alters the therapeutic strategy.


[Epidermoid cyst of the base of the skull]. Epidermoid cysts are rare congenital tumours representing less than 1% of all intracranial tumours. They are derived from the development of abnormally situated ectodermal tissue and are often an incidental finding. We report a case confined to the base of the skull, responsible for an extradural mass.


[Unusual localization of an olfactory esthesioneuroma]. Olfactory neuroblastoma, a nerve tumour arising in the olfactory mucosa, is a relatively easy diagnosis in the case of a mass centered around the cribriform plate. It is more difficult to diagnose in its exceptional ectopic forms (maxillary sinus) in the absence of any cytological and histochemical arguments (fibrils, olfactory rosettes). Its local malignancy is variable with a 42% 5-year survival for stage C and metastases in 30% of cases (principally cervical nodes, bone and liver). The role of imaging is to define the criteria of a mass syndrome and to perform the preoperative staging in a case of apparently simple sinus obstruction.


[Magnetic resonance imaging of neurofibromatoses]. Neurofibromatosis is classified into two types. Type 1, NF1 or von Recklinghausen's disease, consists of skin and bone lesions as well as central nervous system tumours arising at the expense of glial tissue: optic tract gliomas, glioblastomas, astrocytomas and "hamartomas". Type 2 consists almost exclusively of CNS tumours arising at the expense of nerve envelopes: Schwannomas, meningiomas.


[Unusual localization of a recurrent benign parotid tumor in the infratemporal fossa]. Recurrences of parotid tumours are frequent (10 to 20% of cases) and require regular follow-up of these patients, especially when primary surgery was only partial and the initial tumour was multinodular. Malignant degeneration is reported in 1% of these tumours. The site of a parotid tumour in the infratemporal fossa is exceptional and usually indicates a malignant tumour metastasising along the internal maxillary artery and auriculotemporal nerve, as the inter-pterygoid aponeurosis is very resistant. However, this is no longer true following primary surgery in which damage to this aponeurosis is responsible for dissemination or localisation of the recurrence in the infratemporal fossa. The infiltrated appearance of the skin, muscles or fat is not suggestive of a malignant tumour and this dissemination can be explained by the multinodular and invasive potential of this tumour.


[Atypical osteomyelitis of the base of the skull and malignant otitis externa]. Osteomyelitis of the skull base is a rare, but serious disease whose incidence is tending to increase. It affects the marrow of the temporal, occipital and sphenoid bones and is generally secondary to Pseudomonas aeruginosa infection of the external auditory meatus. Based on a clinical case, the authors recall the difficulty of establishing the positive diagnosis and the possible confusion with neoplastic disease, hence the fundamental role of biopsies. They also review the literature on this subject.


New approaches for cardiac assists: "back to the future". The treatment of the modern epidemic of coronary artery disease requires the availability of various cardiac assist devices. A review and future implications of the use of retrograde coronary venous perfusion, the intraaortic balloon, a new ascending aortic pump, variable atrial septal defect, and novel energy sources are discussed.


Is a totally implantable artificial heart realistic? The incidence of local infection that occurred after the implantation of the intrathoracic Jarvik 7 total artificial heart (J-7 TAH) in patients was a major problem of this cardiac prosthesis. Infection rates increased when the J-7 TAH was implanted for longer periods of time, which was contrary to the results that were obtained by the implantation of the left ventricular assist devices (LVAD) either in the abdominal cavity or in the abdominal wall. Currently, the general belief is that the implantation of a cardiac prosthesis inside of the chest cavity is not safe, due to higher rates of infection. Thus, Part I of this paper deals with the question: "Is a total artificial heart physiologically acceptable?" We believe structural differences of the J-7 TAHs and other LVADs are an important part of the problem. The J-7 TAH is a volumetrically dynamic pump, and the other LVADs are a volumetrically fixed stationary pump. Based upon experiences of this investigator, intrathoracic implantation of a smooth surface pulsating device (or a volumetrically dynamic pump) generated persistent local inflammatory reactive tissues directly adjacent to the device. These tissue capsules were nonadherent to the device, and therefore may produce an ideal environment for allowing bacteria to grow. The findings were opposite to those for a non-pulsating surface pump inside the chest cavity. Part II of this paper discusses the question: "Is a totally implantable artificial heart technically achievable?" Many technical problems for the totally implantable TAH were already resolved during the development program of the totally implantable LVAD. However, there are three TAH specific problems that remain to be solved before achieving a clinically useful totally implantable TAH system. They are (a) anatomical compatibilities of the TAH system; (b) reliable control of the TAH system, (c) reliable and effective long-term operation of the TAH system. We have resolved the anatomical problem by the integral design of the pump-actuator system. Overall size of the hard shell Baylor TAH system is 510 cm3 with a diameter of 97 mm and a width of 82 mm. Its stoke volume was reduced to 63 cm3. The stable and reliable control of TAH performances was established by the three sets of Hall effect sensors with left master alternate mode of pumping. No physiological parameter was used as a feedback signal. Reliable long-term operation of the TAH system was established by the electromechanical actuation system. A simple drive mechanism with commercially available components and subsystems was used.(ABSTRACT TRUNCATED AT 400 WORDS)


Artificial liver support based on artificial cells with emphasis on encapsulated hepatocytes. Artificial liver support requires more than a detoxification system. We have investigated additional approaches. Microencapsulated hepatocytes increased the survival time of fulminant hepatic failure (FHF) rats. They also lowered the bilirubin in Gunn rats. Xenograft of microencapsulated rat hepatocytes into mice are immunoisolated. The viability of hepatocyte increased from 62 to 100% after 29 days. This is because of accumulation of a hepatic stimulatory factor (> 100,000 D) secreted by the hepatocytes in the artificial cells. A novel two-step method of cell encapsulation greatly improved immunoisolation and biocompatibility. Other metabolic approaches included a multienzyme system for conversion of ammonia to essential amino acid, and removal of bilirubin.


Intravascular oxygenator: a new alternative method for augmenting blood gas transfer in patients with acute respiratory failure. A unique hollow fiber membrane oxygenator (IVOX) has been developed, which is inserted into the vena caval blood stream to transfer O2/CO2 to/from circulating blood in an intact subject without involving the natural lungs. Extensive laboratory testing has demonstrated that the device can transfer significant quantities of O2 and CO2 for up to 3 weeks without significant harmful sequelae or complications. Clinical trials are in progress under FDA supervision, in which IVOX has been utilized to date in 56 patients with ARDS. Preliminary findings indicate that risks and hazards from IVOX are nil, and evidence of benefit to the patient has been demonstrated in 86% of the patients. At this time, clinical utilization of IVOX is in the experimental, data collecting mode to determine its proper role or niche as a method for temporary augmentation of blood gas transfer in patients with advanced acute respiratory failure.


Hematologic and hemostatic complications associated with long-term use of total artificial heart: clinical and experimental observations. The two most serious complications associated with long-term use of a total artificial heart (TAH) are thromboembolism and infection. In this article, we review our experience in one patient implanted with a pneumatic TAH for 396 days, and in 24 calves implanted with the same type of device for 70 to 353 (median 150) days. During his survival with the TAH, our patient suffered several thromboembolic episodes despite adequate anti-coagulation with warfarin. Autopsy showed widespread thrombotic lesions, mostly in the brain. Throughout his survival, the patient had markedly elevated plasma beta-thromboglobulin and fibrinopeptide A levels, indicating sustained activation of platelets and the coagulation system secondary to blood contact with the artificial surface. Long-term use of TAH in calves causes significant mechanical hemolytic anemia and a small reduction in the total leukocyte and neutrophil counts. The platelet count normalized to preimplantation levels by 25 to 35 weeks. At autopsy, thrombotic lesions and organ infarction were noted in 13 calves, and major septic complications were documented in 10 animals. Although impressive gains in the clinical and experimental use of TAH were achieved during the last 15 years, thromboembolism and infection remain challenging problems.


[Activities and isozymes of adenosine deaminase and lactate dehydrogenase in tuberculous pleural effusion with special reference to the presence of mycobacterium tuberculosis]. We have previously shown that tuberculous pleurisy possesses a high level of adenosine deaminase (ADA) which is predominantly composed of ADA2. In this paper, we report the cases of tuberculous pleural effusion which contained mainly ADA1. In these cases, mycobacterium tuberculosis was positive by smear examination and/or culture and granulocytes were found to be major components. Analysis of lactate dehydrogenase (LDH) revealed that its activity was high and LDH5 occupied about 50% of total activity. In the tubercle bacillus negative cases, lymphocytes were the main components and the levels of LDH containing mostly LDH3 were low. It was assumed that the difference in LDH activity and isozyme pattern is due to the differential presence of leukocytes in pleurisy i.e., granulocytes and lymphocytes in tubercle bacillus positive and negative pleurisy, respectively. In conclusion, tuberculous pleural effusions can be divided into two groups on the basis of ADA and LDH activities and isozymes which may reflect the presence of mycobacterium tuberculosis.


Antibiotic prophylaxis for prevention of bacterial endocarditis and infections of major joint prostheses [corrected]. The current trend in antibiotic prophylaxis for prevention of endocarditis is toward more simple, effective regimens to promote better patient and dentist compliance. All national medical groups are now recommending oral regimens for all at-risk patients, and most of these groups recommend single-dose oral regimens. The Swiss Working Group recommends multiple-dose amoxicillin for high-risk patients. The American Heart Association recommends two-dose oral regimens for all at-risk patients. Clindamycin appears to be the second drug of choice. The many pharmacokinetically different erythromycin preparations and the high rate of intolerance to many of these preparations has led to this change. No national or international medical groups recommended prophylaxis for patients with prosthetic joints. Most reviews conclude that there is little or no scientific evidence to support this use. It is time to stop the practice of prophylaxis for patients with prosthetic joints. The only patients with joint prostheses who should even be considered for prophylaxis are those patients considered at "high" risk.


A full numerical solution to the problem of microelastohydrodynamic lubrication of a stationary compliant wavy layered surface firmly bonded to a rigid substrate with particular reference to human synovial joints. A full numerical solution procedure has been developed for the microelastohydrodynamic lubrication analysis of a stationary compliant wavy layered surface firmly bonded to a rigid substrate. The results obtained have been compared with those using a simplified method adopted by Dowson and Jin(1) and good agreement has been obtained.


A five-station hip joint simulator for wear rate studies. The aim of the work has been the development of a hip joint simulator for comparative wear rate studies of long duration. A five-station apparatus has been designed, constructed and tested. Five total hip joints can be tested at the same time in identical conditions. The flexion-extension motion and the superior-inferior component of the joint contact force are incorporated. The motion is electromechanical and the loading pneumatic. The angle and load waveforms are fixed and simulate level walking. For accurate wear measurements each station employs a control prosthesis. The conditions of the control prosthesis in regard to loading, exposure to lubricant and environment temperature (37 +/- 1 degree C) are identical to those of the test prosthesis. The acetabular cups can be readily removed for periodic wear measurements and reassembled in exactly the original position. Extensive tests have shown that the simulator is a practical and reliable instrument in the wear rate studies of various designs of total hip joint.


A simulator study of friction in total replacement hip joints. Frictional behaviour of 22 different femoral head-acetabular cup combinations was studied on a new servo-hydraulic microcomputer-controlled hip joint simulator using various flexion-extension angle and superior-inferior load set value waveforms and using distilled water at 37 +/- 1 degrees C as lubricant. Six different head materials were included in the study, whereas all cups were ultra-high molecular weight polyethylene (UHMWPE). Most head-cup combinations studied are commercially available. No distinctly superior joint design can be pointed out, but the frictional behaviour of alumina ceramic against UHMWPE proved overall most favourable (mu min was 0.02), whereas that of non-ion-implanted titanium alloy Ti-6Al-4V against UHMWPE proved strikingly poor (mu max was 0.15). The lowest frictional torque was in 22 mm joints, but frictional torque did not always increase straightforwardly with increasing diameter of the femoral head. The measurements form an extensive comparison between a wide variety of head-cup combinations. The simulator is apparently a useful instrument in the study of frictional behaviour of new designs, materials, surface treatments and coatings that are frequently introduced.


An approach to determining the kinematic parameters of biomechanical systems with applications to the wrist. This paper presents an accurate and robust approach for determining the kinematic parameters of biomechanical systems. A computationally efficient algorithm is given for estimating the translation vector and rotation matrix of a moving body from measurements of the position of at least four spatially distributed points on the body. This algorithm provides an estimation of the spatial location and orientation of the body which is less sensitive to measurement error than other methods. It is indicated how the kinematic parameters can be used to determine the linear translation and angular rotation of the moving body in terms of an anatomically relevant coordinate system. The design, fabrication and calibration of an inexpensive, serial-link, three-dimensional mechanical digitizer for use in data acquisition is described. This device is kinematically optimized and is easy to use for accurate data collection. An implementation of this approach to quantifying certain aspects of the kinematics of the human wrist is discussed.


Non-linear finite element analysis of formation and treatment of intervertebral disc herniae. A biomechanical model of the spine motion segment L2/L3 consisting of the truncated vertebrae, endplates, intervertebral disc and pieces of anterior and posterior longitudinal ligaments has been used for a computer simulation study. A non-linear finite element analysis has shown that small loads compressing the spine, not greater than those occurring in everyday life, cause loss of stability of an intervertebral disc, resulting in lateral dislocation of its nucleus pulposus. This could be a potential cause of discopathy. The model indicates that conservative therapy of herniated disc by the traction method may result in retraction of hernia by about 40 per cent.


Finite element stress and strain analysis of the bone surrounding a dental implant: effect of variations in bone modulus. The long-term clinical performance of a dental implant is dependent upon the preservation of good quality bone surrounding the implant and a sound interface between the bone and the biomaterial. Good quality bone is itself dependent upon the appropriate level of bone remodelling necessary to maintain the bone density and the avoidance of bone microfracture and failure. Both processes are governed by the stress and strain distribution in the bone. In this study, a dental implant which had the same geometry as the Branemark system, but with a bioactive surface coating added to produce a direct bond to the bone, was analysed. A finite element stress and strain analysis has been carried out for a range of bone density distributions under axial and lateral loading. The predictions indicated that there was no evidence of strain shielding around the neck of the implant. With lateral loading, high values of von Mises stresses (18 M Pa) were predicted around the neck of the implant. A reduction in the elastic modulus of the bone around the neck of the implant by a factor of 16 only produced a twofold reduction in the peak stress. This resulted in stress levels capable of inducing fatigue failure in this much weaker bone. This analysis has demonstrated that it is extremely important to have good quality dense bone around the neck of the implant to withstand the predicted peak stresses of between 9 and 18 M Pa. Failure to achieve this after implantation and subsequent healing may result in local fatigue failure and resorption at the neck upon resumption of physiological loading.


Engineering analysis of shoulder dystocia in the human birth process by the finite element method. This paper presents an engineering analysis of shoulder dystocia (SD) in the human birth process which usually results in damaging the brachial plexus nerves and the humerus and/or clavicle bones of the baby. The goal is to study these injuries from the mechanical engineering point of view. Two separate finite element models of the neonatal neck and the clavicle bone have been simulated using eight-node three-dimensional elements and beam elements respectively. Simulated models have been analysed under suitable boundary conditions using the 'SAP80' finite element package. Finally, results obtained have been verified by comparing them with published clinical and experimental observations.


Current approaches to new drug development in cancer chemotherapy. This review summarizes and discusses current developments of new antitumor agents, with particular reference to mechanism of action, preclinical efficacy and interest for clinical evaluation. A progress is appreciable in the study of analogues of existing agents and in the identification of new series of cytotoxic compounds with a mechanism of action somewhat similar to that of conventional cytotoxic drugs. Advances in knowledge of tumor cell biology and biochemistry offer the prospect of identifying new targets for a selective drug action. The value of this new drug discovery approach remains to be established.


Cyclopentenyl ethylamines active on CNS. Two new cyclopentenylethylamines were prepared and were submitted to a pharmacological screening together with some others previously described and now reprepared. All compounds exhibited different degrees of depressive activity on CNS and good analgesic activity. Compound 5, bearing a phenyl group on the carbon atom to which the amino group is connected, appears rather interesting being the most active as analgesic and the least toxic. Compounds 2 and 3 are able to antagonize in a certain degree lethal doses of physostigmine and also, respectively, of pentylenetetrazole and strychnine.


Synthesis of N-substituted isocyanocarboxamides with antimicrobial activity. The Ugi four-component condensation between isocyanides 1, cycloketones 2, and ammonium formate affords N-substituted formylaminocarboxamides 3 which are dehydrated with POCl3/NEt3 to give the title compounds 4. The structure of the compounds 3 and 4 was confirmed by spectral data and elemental analyses. In vitro tests of antibacterial activity showed that compounds 4 are ineffective against E. coli and fairly active against K. pneumoniae, B. subtilis and S. aureus. A very good antimicotic activity was shown against C. albicans.


Synthesis and in vitro activity of alkylaminoalkyloxy chromones on protoscoleces of Echinococcus multilocularis (Cestoda). Twelve derivatives with alkylaminoalkyloxy chromone structures were synthesized and tested upon protoscoleces of Echinococcus multilocularis metacestode kept alive in vitro. Assays were performed with protoscoleces attached to the germinal layer in open and in closed vesicles. Compounds IVb and IIIe at the concentration of 0.1 mmol.L-1 killed 50% of the protoscoleces in open vesicles in 48 hours and compound IVb killed 100% of the protoscoleces in open vesicles within 96 hours at the same concentration. In closed vesicles after four days compound IVb killed all protoscoleces, compounds IIIe and IVd half of them, whereas in the controls all protoscoleces were alive. Trifluoperazine (TFP) was the reference compound; none of the new compounds showed better activity than TFP.


N-(2-hydroxy-5-carboxy-benzyliden)-4-substituted anilines and their methyl esters: synthesis and antimicrobial activity. The N-(2-hydroxy-5-carboxy-benzyliden)-4-substituted anilines (1-6) and the corresponding 5-carbomethoxy derivatives (7-12) were synthesized and characterized. Antimicrobial and antifungal activity was tested against Gram+ and Gram- bacteria and Fungi.


Formal potentials of new analogues of nifurtimox: relationship to activity. Electrochemical studies (Formal Potentials and Coulometry) were performed on several analogues of Nifurtimox, in order to gain insight on the proposed mechanism of action of these drugs. It is thought that Nifurtimox shows part of its trypanocidal activity via an electron transfer process, leading to the production of active oxygen species that kill the parasite. Formal potentials provide relevant data about the feasibility of electron transfer in vivo. All analogues tested contained the nitro group, which is the most easily reducible group in the parent drug Nifurtimox. The formal potentials values determined ranged from -1.86 to -0.46 V. Coulometric runs were carried out to study the one-electron transfer process. A good correlation between formal potentials and biological activity was found.


Post-column derivatization and fluorimetric detection for the liquid chromatographic analysis of the potential memory-enhancing agent CL 275,838 in human plasma. A chromatographic method for quantifying the potential memory-enhancing agent CL 275,838 (I) in human plasma with a limit of detection of 1.25 ng/ml is described. The procedure relies on isolation of the compounds from plasma constituents using the Sep-pack C18 cartridge, resolution by reverse-phase high pressure liquid chromatography (HPLC) and post-column oxidation of the eluate peak to from a derivative which can be measured by fluorescence detection. Peak height and compound I concentration were linearly related from 1.25 to 25 ng/ml. Intra- and inter-day validation studies indicated an acceptable precision and reproducibility of the method within the concentration range investigated, the overall coefficient of variation being less than 15%.


Bioavailability study of furosemide prodrugs in rats. According to the hydrolysis performance "in vitro" and lipophylicity, two Furosemide (F) prodrugs were chosen from a series of acyloxymethylesters of F synthesized previously: P1 (acetyloxymethyl-4-chloro-N-furfuryl-5-sulfamoylanthranilate ) and P4 (pivaloyloxymethyl-4-chloro-N-furfuryl-5-sulfamoylanthranilate+ ++). The bioavailability studies were assayed over two groups of eight male Wistar rats as a randomized two-way crossover and balanced design: group 1) a solution of P1 in propylenglycol/ethyl acetate vs an aqueous solution of F, and group 2) P1 vs. P4 solutions in oleic acid (P1#, P4#). These assays showed a better absorption performance of P1 and P4 than F, while the two prodrugs showed a similar bioavailability. The oleic acid seems to be responsible for the delay in the recovery of 50% of the total amount of F excreted in urine (T50%). When the monitoring is done in plasma after the administration of P1#, P1 was not detected as circulating prodrug. The analytical determinations of F in urine and plasma were done by high performance liquid chromatography (HPLC). From the urinary excretion data, a slope that indicates a slow elimination was found with a half-life of 12 hours approximately.


Erosion.

Erosion. With the current substantial decline in dental caries in adults, and increasing retention of teeth into old age, dental erosion is now being recognised as a major cause of tooth damage. It is easily recognised in its more advanced form, though more difficult to detect in its initial stages. Its mechanisms of action is generally not well understood. In this paper, current concepts of the chemistry of demineralisation of the mineral components of teeth are examined, with view to their providing a better understanding of some of the clinical characteristics of dental erosion of enamel. Categories and properties of potential erosive substances are reviewed. Speculation as to the potential effects of erosive substances on exposed root surfaces leads to consideration of the possible relationship between erosion and rapid caries development. The more commonly recommended mechanisms of control or prevention of erosion are described, and the rationale of their use analysed.


Sleep and sleep disorders: an overview.

Sleep and sleep disorders: an overview. Sleep has been preserved during evolutionary history and is found in all mammalian species and birds. Despite the apparent strong survival advantage of sleep, and the observation in experimental animals that persistent sleep deprivation leads to rapid physical deterioration and death, the function of sleep is poorly understood. Modern neurophysiologic techniques have shown that sleep is not a homogeneous state but rather is divided into rapid eye movement and non-rapid eye movement stages. These two sleep states are as different from one another as sleep is from wakefulness. The advent of polysomnography has led to the recognition of a variety of sleep disorders; some, such as sleep apnoea, have potentially fatal consequences. Bruxism is an example of a parasomnia, viz a disorder which intrudes in normal sleep but does not lead to a primary sleep complaint. Recent improvements in diagnostic and therapeutic approaches to sleep disorders has led to the development of multidisciplinary Sleep Disorders Clinics.


Determination of occlusal facial height in oral reconstructive procedures. A review is provided of the methods that have been employed for the determination of occlusal facial height in oral reconstructive procedures. Details are provided in relation to a modified form of the patient's own assessment of a preferred vertical dimension of occlusion (PVDO) in dentate subjects exhibiting overclosure, edentulous subjects and in those patients requiring full mouth oral rehabilitation.


The influence of modified cavity design and finishing techniques on the margin region of amalgam restorations: a simulated clinical study. The use of high copper amalgams has substantially reduced the marginal fracture around amalgam restorations. Modified cavity designs and finishing techniques have been proposed for occlusal amalgam restorations in order to reduce further the long-term marginal fracture around these restorations. Clinical and laboratory studies are required before these techniques can be recommended to clinicians and taught to dental students with confidence. Using eighty extracted third molar teeth, this in vitro study examines four combinations of cavity design and finishing technique. After finishing, the restorations were photographed for evaluation of the initial marginal fracture attributable to the finishing technique, and sectioned twice to enable examination of the margin regions to determine the cavo-surface angles, amalgam margin angles and the occurrence of amalgam excess at and beyond the cavo-surface angle. Although careful application of the modified cavity design provided a mean cavo-surface angle of 100-110 degrees and assisted in achieving a mean amalgam margin angle of at least 70 degrees, long-term clinical and further laboratory studies are required before the cavity design modification can be recommended for routine use.


To vent or not to vent?

To vent or not to vent? The complete seating of full coronal restorations during cementation is hindered by the inability of cement to flow from the internal surface of the crown, and possible binding of the crown on the tooth. Perforation venting is an effective technique to allow full seating but requires repair of the perforation. Provision of space between the crown and the tooth for cement flow is also an effective technique, and does not require repair of a perforation. Such spacing is commonly achieved with die spacer, and has the added possibility of decreasing crown deformation during cementation by diminishing binding between the crown and the tooth. A disclosing agent is effective in aiding complete seating by identifying areas of binding. These areas can subsequently be adjusted, which will allow more complete seating. The placement of an appropriate amount of cement in the crown or on the preparation is an important addition to cementation technique.


Restoration of a dentition affected by dentinogenesis imperfecta using In-Ceram: a case report. A patient suffering from dentinogenesis imperfecta and consequent noncarious tooth destruction was rehabilitated using In-Ceram crowns. The problems encountered in the diagnosis, treatment planning and treatment are discussed.


Abrasion: an evolutionary and clinical view. Abrasion is the type of wear produced on the tooth by the friction of exogenous material forced over the surface by incisive, masticatory and grasping functions. It is one of the four common processes that have affected the morphology of newly erupted teeth from the time they first evolved millions of years ago. While some observers have regarded tooth reduction as pathological, there is evidence from comparative and palaeontological studies which demonstrates that these processes are an essential part of the normal, continually changing relationship between the form and function of the dentition. To understand these precise mechanisms is important if one is to replicate nature's 'intentions' in clinical dental procedures.


The priming effect of ultraviolet B radiation on retinoic acid-stimulated collagen synthesis in the mouse photodamage model. We have demonstrated previously that all-trans retinoic acid (tRA) stimulates collagen synthesis in ultraviolet B (UVB)-exposed but not in nonirradiated hairless mouse skin, suggesting that UVB exposure is required to prime certain tRA-induced events. The current study investigated further whether this tRA stimulatory effect on collagen synthesis could be regulated quantitatively by the accumulative dose of UVB. Mice were irradiated with the total amount of 0.25 (low), 0.77 (medium) or 1.43 J/cm2 (high) UVB radiation over 2, 5 and 10 weeks, respectively. Post-irradiation, 50 microliters of 0.1% tRA was applied topically 5 times a week. An initial delay was observed before tRA-induced collagen stimulation was detected in all 3 treatment groups. The first statistically significant increase in collagen synthesis was observed at the 6th week of tRA treatment in the high-UVB group. In the groups receiving medium and low UVB doses, onset occurred at the 8th week. Furthermore, at the end of tRA treatment, the degree of collagen stimulation correlated positively with the total UVB dose applied (increasing 183%, 224% and 250% over the vehicle control in the low-, medium- and high-UVB groups). By contrast, no collagen stimulation was detectable in the non-irradiated animals treated with tRA for 10 weeks, as previously reported. Although the mechanism by which UVB exposure primes skin to respond to tRA for collagen synthesis still remains unknown, the data indicate that the accumulative UVB dose positively affects the length of the initial delay and the magnitude of the stimulatory effect of tRA on collagen synthesis in photodamaged skin.


Prediagnostic serum levels of 1,25-dihydroxyvitamin D and malignant melanoma. A prospective nested case-control study of the relationship between prediagnostic serum levels of 1,25-dihydroxyvitamin D and subsequent development of malignant melanoma was done to test the hypothesis that increased levels are protective. Serum from 23 cases of malignant melanoma that developed between 1975 and 1987 in donors to the Washington County, Maryland serum bank was assayed along with that from 46 matched controls. There were no demonstrable differences among controls by sex, age, smoking or use of multivitamin supplements. The mean serum levels of 1,25-dihydroxyvitamin D were only 5% lower among cases than controls, a difference that could easily have occurred by chance.


Photoprotective effects of sunscreens in cosmetics on sunburn and Langerhans cell photodamage. It has become common practice to add sunscreening agents of variable potency to cosmetics to protect against the adverse effects of ultraviolet (UV) radiation exposure. The purpose of this study was to determine whether cosmetic preparations containing sunscreening agents protected against the adverse effects of acute UV radiation exposure and, if so, to identify the components responsible for the photoprotective effects. Pretreatment of skin with one such cosmetic product provided complete protection against UV-induced erythema, sunburn cell formation and Langerhans cell damage in volunteers, skin types II and III, whose skin was exposed to a 1.5 minimal erythema dose daily for 4 consecutive days. When individual components of the cosmetic preparation were analyzed for their photoprotective activities, it was found that both the cinnamate and benzophenone sunscreen combination and an extract of baker's yeast present in the preparation had photoprotective properties. These studies indicate that incorporation of photoprotective agents into cosmetic preparations provides a beneficial function and should therefore be encouraged.


The biological interaction of cis- and trans-urocanic acid and DNA. The potential for the cis and trans isomers of urocanic acid to produce DNA damage was measured by assays for DNA binding (32P-postlabeling assay), for induction of DNA repair (unscheduled DNA synthesis assay) and induction of mutations (Salmonella typhimurium and Escherichia coli plate-incorporation assays). These assays did not detect any evidence of a direct effect of either isomer of urocanic acid on DNA over a wide range of concentrations. These results suggest that neither isomer of urocanic acid alone, nor ultraviolet-irradiation of either cis or trans-urocanic acid produces significant DNA damage under conditions that permit cell survival.


Urocanic acid isomers, immunosuppressive cytokines and the induction of human immunodeficiency virus. The ability of cis-urocanic acid to mimic the effects of ultraviolet (UV) was tested in two systems that show cellular responses to direct UV irradiation. First, cultured mouse keratinocytes were treated with cis-urocanic acid and the cell culture supernatants were injected into mice to test for the ability to block spleen cell proliferation in the mixed lymphocyte reaction. Second, human fibroblasts carrying the chloramphenicol acetyltransferase gene under the control of the human immunodeficiency virus (HIV) long terminal repeat promoter were tested for the ability of cis-urocanic acid to induce gene expression. In these tests cis-urocanic acid did not induce a response comparable with UV irradiation alone, although at toxic concentrations cis-UCA did induce low expression from the viral promoter. These data suggest that, unlike UVB radiation, cis-urocanic acid does not activate keratinocytes to produce immunosuppressive cytokines nor does it induce expression of the HIV promoter.


Experimental models for primary melanoma. The nonmelanoma skin cancers squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) are by far the most common malignancies that occur in the United States each year. The third most common skin cancer, malignant melanomas (MM), accounted for 3% of all reportable cancers in the United States in 1991. The incidence of and mortality due to MM have been increasing at an alarming rate over at least the past 4 decades. As a result of this epidemic, there have been intense efforts to develop appropriate experimental models to examine the etiology and biology of this cancer. Benign and malignant melanocytic tumors have been produced in dogs, mice, guinea pigs, hamsters and gerbils with chemical carcinogens such as 7,12 dimethyl(a)benzanthracene (DMBA) and chemical promoters. Perhaps the most extensive and thorough studies using these chemicals were accomplished in the Weiser-Maple guinea pig model, in which radial and vertical stage growth occurred similar to human MM growth patterns. However, such stimuli are unlikely to be related to the human experience. Many investigators have considered ultraviolet radiation (UVR) from the sun to be intimately involved with the melanoma epidemic. Thus, a number of models have been developed to examine this possible relationship. These have included irradiation of DMBA-induced benign melanocytic tumors in pigmented hairless mice, chemical promotion of UVR-induced tumors in haired mice and the induction of melanomas by UVR in the South American opossum. In addition, a melanocytic growth was produced with psoralens plus UVA in a haired mouse. All of these melanomas required chronic UVR exposure.(ABSTRACT TRUNCATED AT 250 WORDS)