Medicine use among HIV/AIDS Patients in public hospitals, Kwara State

Background: The prognosis of HIV/AIDS and HIV-related comorbidities has been revolutionized by the use of medicines. However, World Health Organization reported that 50% of patients do not use their medicines as prescribed.Objective: To assess HIV/AIDS patients' knowledge of the use of medicines dispensed to them.Method: This study was conducted in seven public hospitals in six local government areas, Kwara State. Exit interviews of 780 eligible HIV/AIDS patients were conducted through use of structured questionnaire. Additionally, there were exit observational checks of medicines dispensed to these patients. Descriptive statistics and Fisher Exact test were used for data analyses.Results: Of the 780 study participants, 36.1% had no formal education, 99.9% knew the 'quantity' of medicines to be administered, while 99.2% knew the frequency of administration. All the patients knew the route of administration, 96.7% and 94.3% knew the general precautions to avoid concomitant use of dispensed medicines with alcohol or herbal products respectively, while 93.7% of those who received co-trimoxazole knew of the precaution to use "plenty of water" as the vehicle for its administration. There were no significant associations between the patients' knowledge of these precautions and duration of antiretroviral therapy (P>0.05). However, the patients lacked knowledge of specific precautions of some dispensed medicines.Conclusion: Most of the patients knew of the administration and the general precautions of dispensed medicines. However, lack of knowledge of specific precautions of some dispensed medicines calls for intervention

Differential effects of selective vagotomy and tropisetron in aminoprivic feeding.

Both total subdiaphragmatic vagotomy (TVAGX) and serotonin(3) receptor blockade with tropisetron or ondansetron attenuate amino acid-imbalanced diet (Imb) anorexia. Total vagotomy is less effective than tropisetron in reducing Imb-induced anorexia and also blunts the tropisetron effect. With the use of electrocautery at the subdiaphragmatic level of the vagus, we severed the ventral and dorsal trunks as well as the hepatic, ventral gastric, dorsal gastric, celiac, and accessory celiac branches separately or in combination to determine which vagal branches or associated structures may be involved in these responses. Rats were prefed a low-protein diet. On the first experimental day, tropisetron or saline was given intraperitoneally 1 h before presentation of Imb. Cuts including the ventral branch, i.e., TVAGX, ventral vagotomy (above the hepatic branch), and hepatic + gastric vagotomies (but not hepatic branch cuts alone) caused the highest (P < 0.05) Imb intake on day 1 with or without tropisetron. The responses to tropisetron were not affected significantly. On days 2-8, groups having vagotomies that included the hepatic branch recovered faster than sham-treated animals. Because the hepatic and gastric branches together account for most of the vagal innervation to the proximal duodenum, this area may be important in the initial responses, whereas structures served by the hepatic branch alone apparently act in the later adaptation to Imb.

Design and development of selective muscarinic agonists for the treatment of Alzheimer's disease: characterization of tetrahydropyrimidine derivatives and development of new approaches for improved affinity and selectivity for M1 receptors.

Cholinergic neurons degenerate in Alzheimer's disease, resulting in cognitive impairments and memory deficits, and drug development efforts have focused on selective M1 muscarinic agonists. 5-(3-Ethyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine trifluoroacetic acid (CDD-0102) stimulates M1 muscarinic receptors in rat brain [Messer, W.S., Jr., Abuh, Y.F., Liu, Y., Periyasamy, S., Ngur, D.O., Edgar, M.A., El-Assadi, A.A., Sbeih, S., Dunbar, P.G., Roknich, S., Rho, T., Fang, Z., Ojo, B., Zhang, H., Huzl, J.J., III, Nagy, P.I., 1997a. J. Med. Chem. 40, 1230-1246.] and improves memory function in rats with lesions of the basal forebrain cholinergic system. Moreover, CDD-0102 exhibits oral bioavailability, few side effects and low toxicity, and thus represents a viable candidate for clinical studies. Despite the development of functionally selective agonists such as xanomeline and CDD-0102, there is room for improvements in ligand affinity and selectivity. The high degree of amino acid homology within transmembrane domains has hindered the development of truly selective agonists. Site-directed mutagenesis, biochemical and molecular modeling studies have identified key amino acid residues such as Thr192 and Asn382 in the binding of agonist to M1 receptors [Huang, X.P., Nagy, P.I., Williams, F.E., Peseckis, S.M., Messer, W.S., Jr., 1999. Br. J. Pharmacol. 126, 735-745.]. Recent work has implicated residues at the top of transmembrane domain VI in the binding of muscarinic agonists and activation of M1 receptors [Huang, X.P., Williams, F.E., Peseckis, S.M., Messer, W.S., Jr., 1998. J. Pharmacol. Exp. Ther. 286, 1129-1139.]. Thus, residues such as Ser388 represent molecular targets for the further development of agonists with improved M1 receptor affinity, selectivity and activity.

Differential modulation of agonist potency and receptor coupling by mutations of Ser388Tyr and Thr389Pro at the junction of transmembrane domain VI and the third extracellular loop of human M(1) muscarinic acetylcholine receptors.

Transmembrane domain VI of muscarinic acetylcholine receptors plays an important role in ligand binding and receptor function. A human M(1) (HM(1)) mutant receptor, HM(1)(S388Y, T389P), displayed significantly enhanced agonist potency, binding affinity, and G protein coupling. The mutations are located at the top of transmembrane domain VI and about two helical turns above Tyr381 and Asn382, which are important for ligand binding and receptor function. To determine the functional role of individual mutations of Ser388Tyr and Thr389Pro, we created stable A9 L cell lines expressing HM(1)(S388Y) or HM(1)(T389P) receptors. In phosphatidylinositol hydrolysis assays, muscarinic agonists showed greater potency at the HM(1)(S388Y) and HM(1)(S388Y, T389P) mutants compared with the wild-type and HM(1)(T389P) receptors. Acetylcholine demonstrated 105-fold higher potency at HM(1)(S388Y) receptors than at HM(1)(T389P) receptors. Choline (30 microM, the concentration found in Dulbecco's modified Eagle's medium) exhibited 90% stimulation at HM(1)(S388Y) receptors but was inactive at HM(1)(T389P) receptors. In ligand binding experiments, mutation of Ser388Tyr resulted in significantly increased agonist binding affinity. In contrast, mutation of Thr389Pro did not change agonist binding affinity but rendered multiple agonist binding sites, and the high-affinity binding was sensitive to GTP analogs. These results demonstrate that the Ser388Tyr mutation is responsible for enhanced agonist potency and binding affinity, whereas the Thr389Pro mutation alters G protein interactions. The data suggest that Ser388 and Thr389 are potential targets for modulation of agonist binding and G protein coupling.

Roles of threonine 192 and asparagine 382 in agonist and antagonist interactions with M1 muscarinic receptors.

Conserved amino acids, such as Thr in transmembrane domains (TM) V and Asn in TM VI of muscarinic receptors, may be important in agonist binding and/or receptor activation. In order to determine the functional roles of Thr192 and Asn382 in human M1 receptors in ligand binding and receptor activation processes, we created and characterized mutant receptors with Thr192 or Asn382 substituted by Ala. HM1 wild-type (WT) and mutant receptors [HM1(Thr192Ala) and HM1(Asn382Ala)] were stably expressed in A9 L cells. The Kd values for 3H-(R)-QNB and Ki values for other classical muscarinic antagonists were similar at HM1(WT) and HM1(Thr192Ala) mutant receptors, yet higher at HM1(Asn382Ala) mutant receptors. Carbachol exhibited lower potency and efficacy in stimulating PI hydrolysis via HM1(Thr192Ala) mutant receptors, and intermediate agonist activity at the HM1(Asn382Ala) mutant receptors. The Asn382 residue in TM VI but not the Thr192 residue in TM V of the human M1 receptor appears to participate directly in antagonist binding. Both Thr192 and Asn382 residues are involved differentially in agonist binding and/or receptor activation processes, yet the Asn382 residue is less important than Thr192 in agonist activation of M1 receptors. Molecular modelling studies indicate that substitution of Thr192 or Asn382 results in the loss of hydrogen-bond interactions and changes in the agonist binding mode associated with an increase in hydrophobic interactions between ligand and receptor.

Pharmacological characterization of human m1 muscarinic acetylcholine receptors with double mutations at the junction of TM VI and the third extracellular domain.

A mutant human m5 receptor containing the mutations of Ser465 to Tyr and Thr466 to Pro showed constitutive activity. By replacing the equivalent Ser388 with Tyr and Thr389 with Pro, we created a mutant human m1 (Hm1) receptor with comparable double mutations. The mutant receptor, Hm1(Ser388Tyr, Thr389Pro), was stably expressed in A9 L cells and displayed enhanced responses to classical muscarinic agonists with significantly increased potencies. Choline, a normal component of growth media, showed an efficacy comparable to acetylcholine and carbachol at Hm1(Ser388Tyr, Thr389Pro) receptors. Methylcarbachol, a selective nicotinic agonist, exhibited partial agonist activity at human m1 wild-type receptors and full agonist activity at Hm1(Ser388Tyr, Thr389Pro) receptors. l-Hyoscyamine inhibited the activities of choline and methylcarbachol. Muscarinic antagonists displayed small reductions in binding affinities, although muscarinic agonists showed greatly increased binding affinities for Hm1(Ser388Tyr, Thr389Pro) receptors. All agonists, including choline and methylcarbachol, showed multiple affinity states at Hm1(Ser388Tyr, Thr389Pro) receptors in the absence of GppNHp. The high affinity binding sites for acetylcholine, arecoline and choline were shifted in the presence of GppNHp. These results suggest that Hm1(Ser388Tyr, Thr389Pro) is conformationally favorable for agonist binding and receptor activation.

Feasibility of obtaining pulmonary venous flow velocity in cardiac patients using transthoracic pulsed wave Doppler technique.

The purpose of this study was to determine, in an adult population, the percentage of patients in whom high quality pulmonary venous flow velocity recordings can be obtained using current transthoracic pulsed wave Doppler techniques. Pulmonary venous and mitral flow velocity variables obtained with a pulsed wave Doppler method were used for the indirect assessment of left ventricular (LV) diastolic function and LV filling pressures. The general clinical use of these methods, however, remains uncertain because the transthoracic success rate of obtaining all components of pulmonary venous flow velocity has been variable, and sometimes reported to be as low as 30% to 60%. Mitral and pulmonary venous flow velocity variables were obtained using pulsed wave Doppler signals in 200 consecutive adult patients (mean age 68.2 +/- 11.4 years) in normal sinus rhythm who were referred for echocardiographic study. Six cardiac sonographers and five ultrasound systems were used. The success rate for obtaining pulmonary venous systolic and diastolic flow velocity was 95%, reverse flow velocity at atrial contraction was 90%, and the duration of reverse flow at atrial contraction was 89%. In the 5% to 11% of patients in whom pulmonary flow velocities could not be adequately recorded, the most common reasons were depth limitations of the pulsed wave Doppler machine, marked cardiac enlargement, or left atrial wall motion artifact. The success rate also was influenced by the ultrasound equipment used, individual variation among sonographers, and even the type (impaired, pseudonormal, restricted) of associated mitral filling pattern. Given current machine technology, sonographer education, and daily practice, high quality, complete recordings of pulmonary venous flow velocity can be obtained in approximately 90% of adult patients using the precordial transthoracic Doppler technique. These results suggest that using these variables as an aid for evaluating LV diastolic function and filling pressures may have broader clinical applicability than previously appreciated.

Influence of three membrane types on healing of bone defects.

OBJECTIVES: To determine and compare osseous regeneration associated with three guided tissue regeneration membrane types (expanded polytetrafluoroethylene, dense polytetrafluoroethylene, and an absorbable polylactic acid/citric acid ester base) and removal forces required for expanded and dense polytetrafluoroethylene membranes. STUDY DESIGN: Bilateral osseous defects were created in 30 adult rat calvaria; one defect was covered with a test membrane and the other received no membrane (control). After 2 or 4 weeks, forces required for membrane removal from the tissues were electronically determined, and the calvaria removed and decalcified. Sections through the defects were stained and evaluated electronically and microscopically. Data were analyzed statistically. RESULTS: Microscopic evaluation with Mann-Whitney U test revealed that dense polytetrafluoroethylene was associated with significantly greater bone formation than expanded polytetrafluoroethylene (p = 0.02) at 2 weeks and absorbable polylactic acid/citric acid ester base (p = 0.004) at 4 weeks. Electronic evaluation of the linear degree of fill with one way ANOVA and Tukey's test found no significant difference (p > 0.05) among the experimental or the control groups. In addition, the Mann-Whitney U test indicated that removal forces required for dense polytetrafluoroethylene were significantly less than for expanded polytetrafluoroethylene (p = 0.003). CONCLUSIONS: The use of dense polytetrafluoroethylene as a membrane barrier deserves further investigation as it allows osseous regeneration, it is easier to remove from healing soft tissues, and it is inexpensive. A study with larger sample sizes should be conducted.

Liver denervation attenuates the hypophagia produced by an imbalanced amino acid diet.

We observed previously that totally liver denervated (TLD) rats consumed more of an imbalanced amino acid diet (IAAD) than sham-operated controls (CON). For the present study rats were either CON, TLD, had only the hepatic-vagal branch cut (HVX), or had all nerves on the hepatic artery and portal vein removed (HAPV) (n = 10-11). The rats were prefed a purified basal diet for 9 days then switched to an isoleucine IAAD for 7 days. On days 2-5 all experimental groups consumed more (p < 0.05) of the IAAD than the CON; they also showed less (p < 0.01) weight loss on days 3-7. This experiment showed that either total or partial liver denervations enhanced the intake of an IAAD compared to CON. However, when one considers the anatomical arrangement of the nerves and the surgery technique employed the vital neural pathway may involve the hepatic vagal branch.

Meal patterns and plasma liver enzymes and metabolites after total liver denervations.

The liver by way of afferent nerves has been suggested to be a controller of food intake. However, long term meal pattern analysis of chow intake by rats has revealed that total liver denervation (TLD) did not affect the patterns. Nevertheless, these studies have been criticized because they may have missed initial subtle difference in meal patterns that were corrected later by redundant mechanisms. TLD also can alter physiological regulator mechanisms that could secondarily affect feeding behavior. Furthermore, the TLD procedure itself can produce pathologic changes if extreme care is not taken; if pathology does occur it could subsequently affect food intake measurements. In Experiment 1, male rats were given TLD or sham operations (SHAM) at the beginning of the light phase and food withheld until the onset of the dark period. Using a computer operated system, postsurgery onset on feeding, meal size, duration, and frequency were found to be comparable between the groups from the first meal onward. In Experiment 2, 21 days after TLD or SHAM feeding patterns were recorded; all meal parameters were similar between the groups. The rats were then killed and plasma analyzed for liver enzymes (a reflection of liver damage), nutrients and metabolites: no differences were found between the groups. The data suggests that TLD doesn't affect normal regulation of chow intake from the rats' first postsurgery meal onwards. The second study showed that the TLD technique, in our hands, did not produce an adverse effect on normal liver function.

Ingestive patterns of liver-denervated rats presented with several diets.

The liver by way of afferent nerves is suggested to be a controller of food intake. In experiment 1, male rats were given a 15% fructose solution during the first 4 h of the dark phase, while chow was available the rest of the time, for 10 days, before total liver denervation (TLD) or sham operation. Postsurgery ingestion patterns (15-min measurements for 4 h) of fructose were similar in the two groups. However, chow intake in the TLD group was slightly attenuated the first 2 days after surgery. In experiment 2, rats were given chow in cups and vegetable oil in bottles for 8 days before TLD or sham operation. After surgery, hourly ingestion of chow and oil did not differ between the groups; however, there was a trend for the TLD group to take more oil in the dark phase on the first-day diet exposure. In experiment 3, rats were fed a high-protein diet for 21 days before TLD or sham operation. With the use of a computer-operated system, postsurgery meal size, meal duration, and frequency patterns were found to be comparable between the groups. In experiment 4, rats were given a diet of sweetened condensed milk mixed with water (3:1 vol/vol) and vitamins for 14 days before hepatic vagal branch transection (HVBX) or sham operation. After surgery the first-day milk intake of both groups was similar up to 3.5 h and then depressed at 4 and 24 h in the HVBX rats, but was again comparable over the next 13 days; body weights were similar throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Validation study of a total body electrical conductive (TOBEC) instrument that measures fat-free body mass.

Validation of the model SA-2's (EM-SCAN, Inc.) ability to measure fat-free body mass (FFM) and indirectly predict body fat mass using total body electrical conductivity (TOBEC) methodology was investigated. To simulate changes in FFM (6.8 to 27.2 g) and fat mass (5 to 20 g), saline and oil, respectively, were injected into multiple sites of male Sprague-Dawley rats in separate trials. Two identical experiments were conducted; only the body weights differed. In Experiment 1 the rats' starting body weight averaged 171.8 +/- 3.4 g, while it averaged 214.0 +/- 2.8 g in Experiment 2. In Experiments 1 and 2, model SA-2 was used, and theoretical changes in FFM had correlations of r = 0.88 and r = 0.82, respectively. There was a tendency of the machine to consistently overpredict FFM as greater amounts of saline were injected. In Experiment 1, when oil was injected, FFM remained extremely stable, whereas in Experiment 2, it consistently overpredicted the amount of fat added in these heavier rats. Because the overpredictions in both the cases were consistent, an adjustment to the prediction equation can possibly correct these problems. Until this is done, caution must be used in interpreting data gather from the model SA-2.

Liver denervation, 5-HT3 receptor antagonist, and intake of imbalanced amino acid diet.

The serotonin3 receptor antagonist ICS 205-930 (ICS) may act peripherally to attenuate the anorectic response of rats given an imbalanced amino acid (IMB) diet. Rats were divided into four groups: SHAM+saline (sal); SHAM+ICS; total liver denervation (TLD) + sal; and TLD+ICS. Rats were then given a purified basal diet for 16 days. Next, the groups were injected with sal or 9 mg/kg BW of ICS at 0800 h and at 0900 h (lights out) an isoleucine IMB diet was presented. By 12 h postinjection, the food intake (FI) of TLD and SHAM rats receiving ICS was similarly higher (p < 0.02) than sal-injected counterparts whose FI was also similar; BW followed FI. By day 3, the SHAM groups had similar low FI, whereas the FI of the TLD groups was increasing. The above study was repeated with similar results. Liver innervation is not required for ICS attenuation of IMB diet-induced hypophagia. Also, while sal-injected TLD rats show a normal attenuation of consumption of the IMB diet on the first day of exposure, they subsequently consume more of the IMB diet than SHAM rats. The reason for this difference in TLD rats is not clear but may be related to metabolism of the IMB diet or possibly learning.

Rapid Activation of Phenylpropanoid Metabolism in Elicitor-Treated Hybrid Poplar (Populus trichocarpa Torr. & Gray x Populus deltoides Marsh) Suspension-Cultured Cells.

Elicitor induction of phenylpropanoid metabolism was investigated in suspension-cultured cells of the fast-growing poplar hybrid (Populus trichocarpa Torr. & Gray x Populus deltoides Marsh) H11-11. Treatment of cells with polygalacturonic acid lyase or two fungal elicitors resulted in rapid and transient increases in extractable l-phenylalanine ammonia lyase and 4-coumarate:coenzyme A ligase enzyme activities. The substrate specificity of the inducible 4-coumarate:coenzyme A ligase enzyme activity appeared to differ from substrate specificity of 4-coumarate:coenzyme A ligase enzyme activity in untreated control cells. Large and transient increases in the accumulation of l-phenylalanine ammonia-lyase and 4-coumarate:coenzyme A ligase mRNAs preceded the increases in enzyme activities and were detectable by 30 minutes after the start of elicitor treatment. Chalcone synthase, cinnamyl alcohol dehydrogenase, and coniferin beta-glucosidase enzyme activities were unaffected by the elicitors, but a large and transient increase in beta-glucosidase activity capable of hydrolyzing 4-nitrophenyl-beta-glucoside was observed. Subsequent to increases in l-phenylalanine ammonialyase and 4-coumarate:coenzyme A ligase enzyme activities, cell wall-bound thioglycolic acid-extractable compounds accumulated in elicitor-treated cultures, and these cells exhibited strong staining with phloroglucinol, suggesting the accumulation of wall-bound phenolic compounds.

Molecular events in the membrane transport of methotrexate in human CCRF-CEM leukemia cell lines.

A variant line (CEM-7A) "overproducing" the reduced folate/MTX carrier system was isolated from human CCRF-CEM leukemia cells grown under selective conditions in medium containing 0.25 nM 5-formyl-THF as the sole folate source. This line exhibits a 95-fold increased Vmax for [3H]-MTX influx as compared to parental cells. The values for [3H]-MTX influx Km, efflux t1/2 and structural specificity for other (anti)folate compounds were unchanged. The amount of carrier protein, estimated by NHS-[3H]-MTX affinity labeling, was approximately 30-fold higher in CEM-7A cells than in parental cells. Influx of [3H]-MTX in CEM-7A cells was found to be down-regulated 6-7-fold after preincubation of cells with adenosine, 5-formyl-THF or 5-methyl-THF, but could be prevented exclusively by inhibitors of dihydrofolate reductase. The underlying mechanism(s) of these effects have not as yet been elucidated. A radioiodinated photoaffinity analog of MTX was used to prove the molecular events in carrier-mediated MTX uptake in parental CCRF-CEM cells, CEM-7A cells, and a line exhibiting a MTX-transport defect (CEM-MTX). Specific labeling of an 80-85 kDa membrane protein was observed in parental cells, but not in CEM/MTX cells. Uptake of photoprobe and levels of the 80-85 kDa membrane protein were significantly increased in CEM-7A cells. Due to extensive glycosylation the MW of the carrier protein in human cells seems to be substantially higher than that of its counterpart in murine L1210 leukemia cells (46-48 kDa). Pulse-labeling experiments at 37 degrees C demonstrated that in CEM-7A cells photoprobe uptake proceeds via a specific pathway. The 80-85 kDa membrane protein is involved in the initial binding and translocation of photoprobe, after which a 38 kDa cytosolic protein is responsible for further intracellular distribution. At this time, the combination of photoaffinity labeling techniques and the availability of variant cell lines overexpressing the reduced folate/MTX carrier protein has provided new insights into the MTX transport process in human leukemia cell lines. In the near future this approach should also allow a further elucidation of the regulatory aspects of carrier function.

The CYC8 and TUP1 proteins involved in glucose repression in Saccharomyces cerevisiae are associated in a protein complex.

Mutations of yeast CYC8 or TUP1 genes greatly reduce the degree of glucose repression of many genes and affect other regulatory pathways, including mating type. The predicted CYC8 protein contains 10 copies of the 34-amino-acid tetratricopeptide repeat unit, and the predicted TUP1 protein has six repeated regions found in the beta subunit of heterotrimeric G proteins. The absence of DNA-binding motifs and the presence of these repeated domains suggest that the CYC8 and TUP1 proteins function via protein-protein interaction with transcriptional regulatory proteins. We raised polyclonal antibodies against TrpE-CYC8 and TrpE-TUP1 fusion proteins expressed in Escherichia coli. The CYC8 and TUP1 proteins from yeast cells were detected as closely spaced doublets on Western immunoblots of sodium dodecyl sulfate-polyacrylamide gels. Western blots of nondenaturing gels revealed that both proteins are associated in a high-molecular-weight complex with an apparent size of 1,200 kDa. In extracts from delta cyc8 strains, the size of the complex is reduced to 830 kDa. The CYC8 and TUP1 proteins were coprecipitated by either antiserum, further supporting the conclusion that they are associated with each other. The complex could be reconstituted in vitro by mixing extracts from strains with complementary mutations in the CYC8 and TUP1 genes.

Characterization of TUP1, a mediator of glucose repression in Saccharomyces cerevisiae.

The TUP1 and CYC8 (= SSN6) genes of Saccharomyces cerevisiae play a major role in glucose repression. Mutations in either TUP1 or CYC8 eliminate or reduce glucose repression of many repressible genes and induce other phenotypes, including flocculence, failure to sporulate, and sterility of MAT alpha cells. The TUP1 gene was isolated in a screen for genes that regulate mating type (V.L. MacKay, Methods Enzymol. 101:325-343, 1983). We found that a 3.5-kb restriction fragment was sufficient for complete complementation of tup1-100. The gene was further localized by insertional mutagenesis and RNA mapping. Sequence analysis of 2.9 kb of DNA including TUP1 revealed only one long open reading frame which predicts a protein of molecular weight 78,221. The predicted protein is rich in serine, threonine, and glutamine. In the carboxyl region there are six repeats of a pattern of about 43 amino acids. This same pattern of conserved residues is seen in the beta subunit of transducin and the yeast CDC4 gene product. Insertion and deletion mutants are viable, with the same range of phenotypes as for point mutants. Deletions of the 3' end of the coding region produced the same mutant phenotypes as did total deletions, suggesting that the C terminus is critical for TUP1 function. Strains with deletions in both the CYC8 and TUP1 genes are viable, with phenotypes similar to those of strains with a single deletion. A deletion mutation of TUP1 was able to suppress the snf1 mutation block on expression of the SUC2 gene encoding invertase.

The effect of portal infusions of epinephrine on ingestion, plasma glucose and insulin in dogs.

Preabsorptive satiety has been hypothesized to occur as the result of food activating oral and gastrointestinal receptors that cause the release of catecholamines in the liver. The catecholamines were then proposed to hyperpolarize hepatic glucoreceptors and produce satiety. In the present study the hepatic portal vein was chronically cannulated in six mongrel dogs. Upon recovery the dogs were infused, over three minutes, with either saline or epinephrine (0.83 and 1.5 micrograms/kg b. wt.). Infusions ended 10 minutes prior to the animals' daily one-hour feeding period. The epinephrine infusions resulted in physiological increases in plasma glucose and insulin, but did not inhibit food consumption. The animals were next prefed 20% of their normal daily food intake 30 minutes prior to infusion of epinephrine at the above noted doses. Again plasma glucose and insulin increased, but food consumption was not affected. These data show that epinephrine infusions which produce physiological changes in plasma glucose and insulin do not alter feeding behavior of mongrel dogs. These findings are in agreement with previous data that question the physiological importance of the preabsorptive catecholamine satiety hypothesis.

Gingival crevicular fluid prostaglandins and gingival phospholipids in experimentally-induced periodontitis in the dog.

Prostaglandins are known to be mediators of inflammation in many tissues. Their fluctuations in gingival crevicular fluid during experimentally induced periodontitis were investigated, together with the possible role of phospholipids, which were measured in normal gingiva and gingiva associated with the chronic periodontitis. Periodontitis was induced in 5 dogs in the lower premolar quadrant; the opposite quadrant was used as a control. A small amount of inter-radicular bone was removed and then a cotton-wrapped stainless steel ligature was placed around each of 3 premolar teeth below the gingival margin to provide an inflammatory irritant. Pocket depth was measured by periodontal probe; crevicular fluid was collected on absorbent paper points. PGs were analysed by HPLC and the results expressed as ng PG/microliter crevicular fluid. Measurements were taken in both quadrants at 1, 3 and 6 weeks after placement of the ligatures; PGI2, 6 keto-F1 alpha, F2 alpha, E2, E1 and D2 were detected in the crevicular fluid. At 1 week, there was no difference in PG levels between experimental and control sides. During week 3, PGI2 and PGE2 increased in the experimental crevicular fluid [214.1 +/- 49.3 (SEM) vs control 87.0 +/- 39.7; p less than 0.05 and 350.0 +/- 115 vs 162.0 +/- 14.7; p less than 0.05, respectively]. At week 6, only PGE2 was elevated in crevicular fluid (207.7 +/- 68.1 vs 99.2 +/- 45; p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)