Food aversion conditioned in anesthetized sheep

We discovered that a food aversion could be conditioned in anesthetized sheep. Sheep were allowed to eat a familiar food (alfalfa-grain pellets) for 30 min, and 90 min later they were given either an intraruminal (IR) injection of water (C), an IR injection of LiCl (L), anesthesia followed by an IR injection of water (A), or anesthesia followed by an IR injection of LiCl (A+L). Induction of anesthesia was by an intravenous injection of pentobarbitone sodium, and maintenance of deep anesthesia was by halothane. Sheep were maintained in deep anesthesia for 2 h to ensure that the effects of LiCl on the acquisition of a food aversion, which occur within about 1 h, were completed before they awakened. When tested 5 days later, sheep that received LiCl (treatments L and A+L) consumed less alfalfa-grain pellets than sheep that did not receive LiCl (treatments C and A) (241 g vs. 306 g; p = 0.057). Intake of sheep that were anesthetized (treatments A and A+L) did not differ from that of sheep that were not anesthetized (treatments C and L) (295 g vs. 252 g; p = 0.183). Nor was there an interaction between LiCl and anesthesia (p = 0.423). Thus, we conclude that changes in preferences for foods caused by postingestive feedback occur automatically every time food is ingested (i.e., they are noncognitive), and the kind and amount of feedback is a function of the match between the food's chemical characteristics and its ability to meet the animal's current demands for nutrients.     

Effect of cyclosporin on the activity of cytidine deaminase and adenosine deaminase in the serum and polymorphonuclear leukocytes of patients with rheumatoid arthritis

Cytidine deaminase (CDA) and adenosine deaminase (ADA) were investigated in the serum and polymorphonuclear leukocytes (PMNLs) of healthy controls and ten patients with rheumatoid arthritis before and during cyclosporin therapy. CDA was significantly raised in the serum and decreased in the cells of patients. A dramatic increase (10-fold or more) in CDA activity was observed in the cells of some patients after only one month of cyclosporin therapy. Serum CDA significantly increased after three months' therapy. While the increase in serum CDA level during therapy was transient, the enzyme level in cells remained permanently raised, as shown in two patients evaluated for sixteen months. ADA in the serum of RA patients was somewhat higher as compared with healthy controls and remained almost unchanged during cyclosporin therapy. ADA activity in the cells also increased, but compared with the increase in CDA activity this increase was lower. Cyclosporin increased both CDA and ADA activities in PMNLs of RA patients. The dramatic increase in CDA observed in PMNLs of patients could be the cause of the transient increase in CDA in the serum. Further investigations will show to what extent this property of cyclosporin can reflect the immunoregulatory effect of this drug.     

Treatment of essential arterial hypertension with hypercholesterolemia. Effects of an alpha-adrenergic blocker and an inhibitor of the angiotensin converting enzyme

BACKGROUND: Hypertension and hypercholesterolemia are frequently associated with this leading to considerable cardiovascular risk. METHODS: An open parallel randomized study was performed in which the effects of doxazosin, an alpha-adrenergic blocker and enalapril, an inhibitor of the angiotensin converting enzyme were compared in 70 patients with essential high blood pressure and plasma cholesterol levels greater than 240 mg/dl. Following 2-4 weeks of placebo administration the patients were randomly treated with one of the two drugs. When required doses were increased and hydrochlorothiazide added until blood pressure lower than 160/95 mmHg was achieved. After this period the patients were observed for a minimum of 8 weeks. The mean length of the study was of 22 weeks. RESULTS: Both drugs significantly reduced blood pressure without modifying cardiac frequency. Doxazosin tended to favorably modify the lipid profile of the plasma while enalapril significantly reduced the levels of cholesterol, lipids and high density lipoproteins (HDL). Upon termination of the study the total HDL/cholesterol index increased 8.6% in those treated with doxazosin and decreased 5.5% in those receiving enalapril (p < 0.05). CONCLUSIONS: Although doxazosin and enalapril are potent antihypertensive drugs, the effects on plasma lipid obtained with doxazosin indicate that a reduction in cardiovascular risk was achieved with this drug in the patients included in this study.     

Dexamethasone perfusion of the labyrinth plus intravenous dexamethasone for Ménière's disease

Recent clinical and laboratory evidence indicates that Meniere's disease is an immune-mediated disease. Dexamethasone perfusion of the inner ear through the round window plus intravenous dexamethasone often will stop the dizzy spells, reduce the fullness and low-frequency tinnitus, and sometimes improve the hearing in patients with Meniere's disease. The dexamethasone must act mostly on the endolymphatic sac and, to a lesser extent, on the stria vascularis and spiral ligament, the known targets of immune response in the inner ear, to reduce the endolymphatic hydrops and restore the fluid dynamics of the endolymph. Despite the good results with streptomycin perfusion, the number of patients with further hearing loss is large, so dexamethasone perfusion with intravenous dexamethasone should be tried first. The initial response to dexamethasone perfusion plus intravenous dexamethasone has been very good, with very little risk of further hearing loss, and it holds great promise for the future.     

BCG vaccination

The author expounds the fairly obscure history of BCG vaccination. Summarises the efficiency of accomplished vaccinations of different geographical areas. He accounts the diversity of results by the distinction of technical and methodical conditions and disparity in virulence of BCG strains. Overviews the Inland and European routine and the risk of possible complications. The favourable position of domestic childhood tuberculosis is due to the effective preventive arrangements. Considering the international and national epidemiology of tuberculosis in adults the administration of BCG vaccine, by chance in modified form, is recommended further on.     

Solution structure of the superactive monomeric des-[Phe(B25)] human insulin mutant: elucidation of the structural basis for the monomerization of des-[Phe(B25)] insulin and the dimerization of native insulin

The three-dimensional solution structure of des-[Phe(B25)] human insulin has been determined by nuclear magnetic resonance spectroscopy and restrained molecular dynamics calculations. Thirty-five structures were calculated by distance geometry from 581 nuclear Overhauser enhancement-derived distance constraints, ten phi torsional angle restraints, the restraints from 16 helical hydrogen bonds, and three disulfide bridges. The distance geometry structures were optimized using simulated annealing and restrained energy minimization. The average root-mean-square (r.m.s.) deviation for the best 20 refined structures is 1.07 angstroms for the backbone and 1.92 angstroms for all atoms if the less well-defined N and C-terminal residues are excluded. The helical regions are more well defined, with r.m.s. deviations of 0.64 angstroms for the backbone and 1.51 angstroms for all atoms. It is found that the des-[Phe(B25)] insulin is a monomer under the applied conditions (4.6 to 4.7 mM, pH 3.0, 310 K), that the overall secondary and tertiary structures of the monomers in the 2Zn crystal hexamer of native insulin are preserved, and that the conformation-averaged NMR solution structure is close to the structure of molecule 1 in the hexamer. The structure reveals that the lost ability of des-[Phe(B25)] insulin to self-associate is caused by a conformational change of the C-terminal region of the B-chain, which results in an intra-molecular hydrophobic interaction between Pro(B28) and the hydrophobic region Leu(B11)-Leu(B15) of the B-chain alpha-helix. This interaction interferes with the inter-molecular hydrophobic interactions responsible for the dimerization of native insulin, depriving the mutant of the ability to dimerize. Further, the structure displays a series of features that may explain the high potency of the mutant on the basis of the current model for the insulin-receptor interaction. These features are: a change in conformation of the C-terminal region of the B-chain, the absence of strong hydrogen bonds between this region and the rest of the molecule, and a relatively easy accessibility to the Val(A3) residue.     

Abnormal behavioral responses to fenfluramine in patients with affective and personality disorders. Correlation with increased serotonergic responsivity

Serotonergic responsivity was assessed in 20 psychiatric patients by the prolactin response to a fenfluramine challenge test. During the fenfluramine challenge 6 of 20 patients (30%) spontaneously reported psychopathologic reactions that included: increased anxiety/agitation, psychotic symptoms, illusions, mood elevation, and anergia. The time of peak behavioral symptoms (2.5 +/- 0.8 hrs) corresponded closely to the time of peak increase in prolactin levels (3.0 +/- 1.1 hr). Abnormal behavioral responders had statistically significant greater increases in prolactin 1 to 4 hr after fenfluramine when compared to normal responders. Patients who developed an abnormal psychopathologic response to fenfluramine were characterized by higher levels of anxiety and agitation at the time of admission to the hospital but otherwise were not distinguishable on the basis of severity of other psychiatric symptoms. This study suggests that increased serotonergic transmission may trigger anxiety, psychosis, and mood elevation in specific vulnerable individuals, whereas other patients with similar psychiatric illnesses are not affected.     

Incidence of Lightspeed separation and the potential for bypassing

It is important for endodontic instruments to have a low fracture rate. If a fracture does occur, it would be desirable to have the ability to bypass the broken segment and complete the root canal treatment. One hundred sixty-two root canals in 52 maxillary and mandibular first molars were cleaned and shaped with Lightspeed instruments by three endodontists in their private practices. The canals were instrumented using the technique recommended by the manufacturer. All canals were instrumented to at least a size 45 at the working length. Six instruments separated during treatment. All six had been used more times than recommended by the manufacturer. Five of the six were easily bypassed and treatment completed.     

Electrophysiological properties and cholinergic responses of rat ventral oral pontine reticular neurons in vitro

This study analyses the relationship between the use of rotating instruments, the production of a smear layer and the presence of alterations to enamel microstructures. The rotating instruments used were carbide (8-12 blade) and diamond tipped (30-15 m) cutters. Cavities were made in extracted teeth. Subsequently, half the sample was analysed using the rugosimeter before and after the application of ortophosphoric acid at 35% for 15 and the other half suing a Scansion Electronic microscope (SEM). The results obtained showed on the one hand that carbide cutters leave a smoother surfacer than diamond tipped cutters, and on the other that the smear layer is eliminated better by carbide cutters compared to diamond tipped cutters. Moreover, there are no major traumatic-type alterations at the level of the enamel affecting the microstructure after the use of carbide cutters.