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Biomedical subjects

C Bianchi

Publications and source records attributed to C Bianchi.

At least 145 records · Page 8Linked to original sources
PubMed1996

Renal effects of prolonged antihypertensive treatment with diltiazem.

The effects of diltiazem (DTZ) treatment on blood pressure, renal function and renal hemodynamics over a six week period of therapy were evaluated in 14 adult patients with mild to moderate hypertension. Their creatinine clearances were 64 to 153 ml/min. After a week of treatment with placebo, DTZ was administered orally at a daily dose of 120 mg b.i.d. Blood pressure decreased from a mean value of 152/99 mm Hg (+/-13/6 SD) up to 144/91 (+/-17/8, P < 0.005) in the supine position and from 149/107 (+/-14/9) to 141/96 (+/-16/9, P < 0.005) in standing position. Heart rate decreased from 74 (+/-9) to 69 (+/-8). Plasma urea, creatinine, uric acid and their clearances as well as GFR and ERPF remained stable throughout the trial. Plasma glucose increased from 81 (+/-15) mg/dl to 98 (+/-30, P < 0.05) and plasma potassium decreased from 4.0 mEq/liter to 3.7 (+/-0.3, P < 0.005). Plasma cholesterol and triglycerides were unmodified. DTZ is an effective antihypertensive agent which does not significantly affect renal function. The effects on plasma glucose and potassium require periodical check-ups of these parameters.

Adult↗
PubMed1996

Antihypertensive activity and renal effects of benazepril in humans.

The effects of the treatment with benazepril (BEN) on blood pressure and renal function have been evaluated in nine adult patients affected by mild to moderate hypertension. BEN was administered orally, at a single daily dose of 10 mg for four weeks. BEN induced a clinically significant decrease in blood pressure, from a mean basal value of 155/98 mm Hg (+/- 15/7 SD) to 146/92 (+/- 12/9) after seven days of therapy and 139/88 (+/- 11/10) after 28 days in supine position and from 152/104 (+/- 17/6) to 144/97 (+/- 14/6) after seven days and 145/99 (+/- 16/9) after 28 days in a standing position. Plasma urea, creatinine, uric acid and their clearances as well as urine enzymes (GGT, ALP, LDH) remained stable throughout the duration of the therapy. GFR showed a modest increase, from 61.3 +/- 13.2 ml/min to 65.3 +/- 18.3 ERPF showed a slightly more evident increase, from 246.7 +/- 68.1 ml/min to 276.9 +/- 75.6. Plasma levels of glucose, cholesterol and triglycerides were not influenced by BEN. Plasma potassium increased from 4.0 +/- 0.3 to 4.4 +/- 0.5 mEq/liter. The results of this study indicate that BEN is a safe and effective antihypertensive agent that does not cause any adverse renal or metabolic effects.

Adult↗
PubMed1996

Laparoscopic cholecystectomy in the third trimester of pregnancy.

Laparoscopic cholecystectomy has become the method of choice for symptomatic cholelithiasis. Laparoscopic cholecystectomy during pregnancy is also becoming more accepted, as illustrated by several recent publications on this subject. In the third trimester, however, laparoscopic cholecystectomy has been less commonly attempted, with only a few case reports. We present a series of four patients who underwent laparoscopic cholecystectomy during the third trimester of pregnancy without complication. We describe a safe and effective technique for this procedure, and review the literature on this topic.

Adolescent↗
PubMed1996

[Quality assurance in radiology: quality control of radiographic cassettes].

A "quality team" in radiology, whose members are the authors of this paper, has implemented a quality control program to test the cassettes with intensifying screen systems used in radiology departments. 149 systems-124 of them for general purpose radiology and 25 for mammography-were submitted to the following tests: visual inspection of radiographic cassettes and intensifying screens, screen-film contact, intensifying screen cleanliness and relative sensitivity of the intensifying screens. The results of each type of test are reported in detail in the paper, on a 3-point scale: good, sufficient and poor. The overall results of the quality control tests show 78% of general purpose radiology cassettes to qualify as good (69%) or sufficient (9%), while 22% were of poor quality. 88% of the mammographic cassettes qualified as good (76%) or sufficient (12%), while 12% were of poor quality. All tests were easy to perform and required limited resources. The necessary procedures to keep quality high over time are also reported. To conclude, the results obtained with our quality control program could be used as an effective tool to address and plan the turnover of the cassettes with intensifying screens which are usually used in diagnostic radiology practice.

Evaluation Studies as Topic↗
PubMed1996

[Myocarditis in legionellosis. A case report].

Cardiac involvement during Legionnaires' disease has been rarely described; few cases of myocarditis, pericarditis and endocarditis were reported. We describe a case of myocarditis associated to pneumonia, with high antibody title suggesting a disease due to Legionella pneumophila. The patient had severe myocardial damage, with overt heart failure and important ECG and Doppler-echocardiographic abnormalities, without associated multiorgan involvement.

Antibodies, Bacterial↗
PubMed1995

LEW-to-F344 carotid artery allografts: analysis of a rat model of posttransplant vascular injury involving cell-mediated and humoral responses.

A key manifestation of chronic rejection is an obliterative arteriosclerosis. Myointimal thickening in the vessel is preceded by an endothelialitis involving accumulation of host mononuclear cells in the perivascular and intimal spaces. We report a paratopic LEW-to-F344 rat carotid artery transplantation model developed to study the cells, cytokines, and inflammatory response associated with this early phase of vascular immune injury. Compared with contralateral control arteries and isografts, LEW-to-F344 carotid allografts develop intimal thickening with mononuclear cell infiltration that persists (days 20, 45, 75, 90, and 120). Allografted vessels had dense collections of intimal and adventitial leukocytes (CD45+) consisting of equal numbers of T cells and macrophages. There were small but variable numbers of intimal smooth muscle cells. Intimal cells showed dense staining for tumor necrosis factor-alpha, interleukin-8, platelet-derived growth factor, iNOS, and ICAM and weaker labeling for interleukin-1 beta and interleukin-6. There was also prominent staining for interleukin-4 and interleukin-7 with no detectable interferon-gamma or interleukin-2 staining and high titer labeling for IgG1 (but not IgG2). The predominance of the T cell infiltrate coupled with interleukin-4 and IgG1 expression in carotid allografts is consistent with a TH2 response. This contrasts with balloon-injured rat carotids, which evoke a macrophage-dependent proliferative response. These findings demonstrate that there are distinct as well as common activation pathways in various forms of vascular injury and the LEW-to-F344 carotid model provides the opportunity to gain insight into molecular mechanisms regulating alloimmune injury in the vessel.

Animals↗
PubMed1995

Early changes in prodynorphin mRNA and ir-dynorphin A levels after kindled seizures in the rat.

Prodynorphin mRNA and immunoreactive dynorphin A (ir-dynorphin A) levels were measured in different brain areas at various time points after amygdala kindled seizures. In the hippocampus, striatum and hypothalamus, prodynorphin mRNA levels were not significantly changed in kindled rats (killed 1 week after the last stimulus-evoked seizure), but they were significantly increased 1 h after seizures. The relative increase was the highest in the hippocampus (approximately 3-fold). In the brainstem, midbrain and cerebral cortex no changes in prodynorphin mRNA were detected in kindled rats, 1 h or 1 week after a kindled seizure. ir-Dynorphin A levels were significantly reduced in the hippocampus and in the striatum of kindled rats, as well as 5 and 60 min after kindled seizures, but they were increased back to control levels after 120 min. In the hypothalamus, ir-dynorphin A levels were significantly increased 120 min after a kindled seizure. ir-Dynorphin A levels were also significantly reduced in the brainstem and in the frontal, parietal and temporal cortex 120 min, but not 5 or 60 min, after a kindled seizure. Taken together, these data support the hypothesis that the dynorphinergic system is activated after amygdala kindled seizures, with different kinetics in different brain areas.

Amygdala↗
PubMed1995

Noninvasive localization of experimental atherosclerotic lesions with mouse/human chimeric Z2D3 F(ab')2 specific for the proliferating smooth muscle cells of human atheroma. Imaging with conventional and negative charge-modified antibody fragments.

BACKGROUND: A murine monoclonal antibody designated Z2D3 (IgM) generated against homogenized human atherosclerotic plaques was demonstrated to be highly specific for proliferating smooth muscle cells. The primary clone subsequently was genetically engineered to provide a mouse/human chimeric antibody with human IgG1 constant region expressed in a rat myeloma cell line. The resulting Z2D3-73.30 chimeric retained the immunoreactivity relative to the parent Z2D3-IgM and was pepsin-digested to yield F(ab')2. 111In-labeled chimeric Z2D3 F(ab')2 was then used for noninvasive imaging of experimental atherosclerotic lesions. To improve the imaging characteristics, we modified chimeric Z2D3 F(ab')2 fragments to carry a high negative charge. Improved visualization of targets with 111In-labeled, negatively charged, polymer-modified antibodies most probably is the result of faster blood clearance and a decrease in nontarget background activity. METHODS AND RESULTS: Experimental atherosclerotic lesions were induced in rabbits by deendothelialization of the infradiaphragmatic aorta followed by a 6% peanut oil-2% cholesterol diet. After 12 weeks, localization of the conventionally labeled 111In-Z2D3 F(ab')2 (24 Mbq [650 microCi]/500 to 750 micrograms) (n = 4) was compared with 111In-labeled, negatively charged, polymer-modified Z2D3 F(ab')2 (24 Mbq [650 microCi]/25 to 50 micrograms) in eight atherosclerotic rabbits. Three control rabbits also received radiolabeled polymer-modified Z2D3. Ten rabbits with atherosclerotic lesions received 111In-labeled nonspecific human IgG1 F(ab')2 with (n = 6) or without (n = 4) negative charge modification. Atherosclerotic lesions were visualized in all rabbits with the conventional Z2D3 F(ab')2 at 48 hours. However, unequivocal lesion visualization was possible at 24 hours only with negatively charged, polymer-modified Z2D3 F(ab')2. Quantitative uptake of F(ab')2 fragments was essentially determined by the presence of atherosclerotic lesions (F1.37 = 69.8; P < .0001) and the specificity of the antibody (F1.37 = 36.6; P < .0001). Uptake of the conventional Z2D3 in atherosclerotic lesions (mean +/- SEM percent injected dose per gram, 0.112 +/- 0.024%) was six times higher than background activity in the normal aortic segments (nondenuded thoracic aorta; mean percent injected dose per gram, 0.019 +/- 0.003%). Uptake of the conventional Z2D3 was also significantly higher than that of nonspecific human IgG1 F(ab')2 (0.027 +/- 0.004%). Specific uptake of the conventional Z2D3 in the lesions was comparable to the charge-modified Z2D3 uptake (0.084 +/- 0.017; P = .20). Uptake of negative charge-modified Z2D3 in the lesions was significantly higher than in the corresponding background activity in normal thoracic aorta (0.021 +/- 0.002). Uptake of negative charge-modified Z2D3 F(ab')2 in the lesions was higher than the uptake of negative charge-modified nonspecific IgG1 F(ab')2 (0.020 +/- 0.002) in the lesions. Uptake of charge-modified Z2D3 in the atherosclerotic lesions was also significantly higher than the corresponding regions of the aorta of the control rabbits (0.017 +/- 0.002; F1.18 = 27.9; P = .0001). There was, however, no difference in the specific lesion uptake of negative charge-modified Z2D3 at 24 hours (0.079 +/- 0.014) and 48 hours (0.084 +/- 0.0017; P = .99) after intravenous administration. Nontarget organ activities were lower with negative charge-modified 111In-labeled Z2D3 F(ab')2 than with the conventional Z2D3 F(ab')2. Mean kidney activity was fourfold less with the modified (0.45 +/- 0.06) than with the conventionally radiolabeled (1.67 +/- 0.264; P = .001) Z2D3 F(ab')2.

Animals↗
PubMed1995

AMPA receptor activation regulates the glutamate metabotropic receptor stimulated phosphatidylinositol turnover in human cerebral cortex slices.

The effect of excitatory amino acids (EAA) on phosphatidylinositol (PI) turnover in human cerebral cortical slices was investigated. Trans-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) increased inositol phosphate (IP) formation in the 1-1000 microM range. Quisqualic acid (QA) was maximally effective at 10-100 microM, showing an inverse correlation between concentration and effect in the 100-1000 microM range. The glutamate metabotropic receptor antagonist 2-amino-3-phosphonopropionic acid (AP3), the ionotropic non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the NMDA channel blocker dizolcipine (MK-801) failed to prevent the PI response to ACPD (1000 microM). However, CNQX (100 microM) modified the concentration-response curve of QA reducing the effect of QA 10 microM by approx. 50% and enhancing that of QA 1000 microM by 2-fold. In addition, CNQX (100 microM) together with MK-801 (100 microM) unmasked the ability of L-glutamate (L-GLU) 3000 microM to stimulate PI turnover. The effect of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) on the EAA-induced PI turnover was also studied. AMPA (0.1-1 microM) potentiated the response to submaximal (30 microM) ACPD and (1 microM) QA concentrations. However, higher AMPA concentrations (10 microM) failed to synergize with ACPD 30 microM and, in addition, inhibited the PI turnover maximally stimulated by QA 10 microM. These results further support the presence of the glutamate metabotropic receptor in the human neocortex. In addition, they show the occurrence of a concentration-related dual interaction between AMPA and glutamate metabotropic receptor activation in the IP formation in this brain area.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Detection by polymerase chain reaction of BCR/ABL transcripts in myeloproliferative diseases at time of diagnosis and for monitoring chronic myelogenous leukaemia patients after bone marrow transplantation.

The Philadelphia chromosome t(9;22)(q34;q11) is a cytogenetic marker for chronic myelogenous leukaemia (CML), and is also present in some acute leukaemias. The translocation in CML gives rise to two BCR/ABL chimeric transcripts (b3a2 and b2a2) encoding a 210-kD tyrosine kinase protein. These leukaemia-specific transcripts can be detected easily by the reverse transcriptase polymerase chain reaction (PCR). PCR has improved the possibility of detecting minimal residual leukaemia cells in Ph-positive patients, especially after bone marrow transplantation (BMT). With PCR, we looked for BCR/ABL transcripts in 30 patients with CML and 4 with essential thrombocythaemia at time of diagnosis, finding a significant difference in the platelet counts of CML patients carrying b3a2 or b2a2 transcripts. The BCR/ABL transcript was monitored by PCR in 6 CML patients after BMT. The usefulness of PCR in clinical practice at time of diagnosis, and the biological and clinical significance of positive/negative PCR results, in patients with transplants, are discussed.

Adult↗
PubMed1995

Number of sexual partners, condom use and risk of human immunodeficiency virus infection.

BACKGROUND: To analyse the relation between number of sexual partners, selected sexual habits and the risk of human immunodeficiency virus (HIV) infection. METHODS: We conducted a case-control study nested in a cross-sectional survey conducted among subjects attending sexually transmitted diseases (STD) clinics in Northern Italy. Eligible for the study were 1711 subjects (1259 males, 452 females) who referred themselves for the first time between September 1988 and March 1993 to three STD clinics in Northern Italy for suspected STD or STD treatment. A total of 145 subjects (113 males and 32 females) were HIV positive. RESULTS: In comparison with subjects reporting no or one sexual partner over the 3 years before the interview, the estimated odds ratios (OR) of HIV serum positivity were 1.2 (95% confidence interval [CI]: 0.6-2.3), 0.8 (95% CI: 0.4-1.8) and 0.3 (95% CI: 0.4-2.5) in subjects reporting 2-3, 4-5, and > or = 6 partners, respectively. The results were similar considering separately males and females and in men reporting only homosexual partners. Regular condom use decreased the risk of HIV infection: in comparison with subjects reporting no or occasional use of condoms, the OR of HIV infection was 0.5 (95% CI: 0.4-0.8) for regular users. Considering men only, compared with men with no homosexual intercourse, the OR of HIV infection was 2.3 (95% CI: 1.4-3.9) in those reporting bisexual intercourse and 2.2 (95% CI: 1.2-4.2) in men reporting only homosexual intercourse (among homosexuals). There was no relation between HIV infection risk and receptive anal sex. CONCLUSIONS: The risk of HIV infection does not increase linearly with the number of sexual partners in this population. This is reasonable, as the prevalence of HIV infection in this population is essentially determined by drug use. Caution is needed in the interpretation of these results since the analysis of role of number of sexual partners in male intravenous drug users is impaired by low statistical power.

Adult↗
PubMed1995

Single diastereomeric desaminotyrosylalanyl tetra- and heptapeptides with opioid antagonistic activity.

The N-terminal dipeptide Tyr-d-Ala of a mu-selective agonist, dermorphin tetrapeptide (DT, H-Tyr-D-Ala-Phe-Gly-NH2) and delta-selective agonist deltorphin C (DEL-C, H-Tyr-D-Ala-Phe-Asp-Val-Val- Gly-NH2) was changed into an aminodiacyl moiety. The relevant synthetic step is a nucleophilic substitution of bromine from a chiral 2-bromopropanamide by the amino group of tyrosine, with overall retention of configuration. The resulting pseudo tetra- and heptapeptides I-VI were characterized for mu- and delta-opioid receptor binding properties using [3H]DAGO and [3H]DPDPE, respectively, and in a bioassay using guinea pig ileum (GPI) and mouse vas deferens (MVD). As a result of chemical alteration of N-terminal depeptide moiety, all synthesized analogs showed considerable reduction in opioid receptor affinity compared to mu- and delta-prototypes (500-fold on the mu-site, analog I, and 125-fold on the delta-site, analog IV). Interestingly, analogs I and IV showed moderate antagonist activity, respectively, on GPI and MVD, with pA2 values of 6.05 and 6.82. Analog IV did not exhibit the delta-antagonist potency and delta-selectivity of TIPP peptides.

Amino Acid Sequence↗
PubMed1995

Changes in [3H]-UK 14304 binding to alpha 2-adrenoceptors in morphine-dependent guinea-pigs.

1. The aim of this study was to investigate the effect of a noradrenergic input in the cortex of morphine-dependent animals. Binding of the alpha 1-adrenoceptor ligand [3H]-prazosin did not change in cortical membranes taken from morphine-dependent as compared to control guinea-pigs. However, binding of the alpha 2-adrenoceptor ligand [3H]-UK 14304 showed decreased KD (-30%) in the absence of significant changes in Bmax, either in cortical membranes or in synaptosomes. 2. Several characteristics of this phenomenon were identified. First, it occurs in a time-dependent fashion, in that it takes 5 days of chronic morphine treatment to start developing. Second, it can be observed after acute administration of high doses of morphine (100 mg kg-1). Third, it does not require a connection with the locus coeruleus or with other subcortical structures, in that it can be reproduced in vitro in isolated cortical slices. Fourth, it requires the integrity of cortical structures, since it cannot be reproduced in vitro in cortical synaptosomes. 3. Release studies were run to attempt identification of a functional correlate of the above observations. No changes were observed in the ability of the alpha 2-adrenoceptor agonist UK 14304 to inhibit 35 mM K(+)-evoked [3H]-noradrenaline outflow from cortical synaptosomes taken from morphine-dependent as compared to control guinea-pigs. However, a large decrease in the IC50 of UK 14304 for the inhibition of 35 mM K(+)-evoked [3H]-gamma-aminobutyric acid ([3H]-GABA) outflow (41 vs. 501 nM) was observed in morphine-dependent as compared to control animals. 4. These data suggest that, in the guinea-pig, chronic morphine treatment is associated with a shift from a low to high affinity agonist state in alpha 2-adrenoceptors on cortical GABA terminals.

Adrenergic alpha-Agonists↗
PubMed1995

5-Hydroxytryptamine-mediated effects of nicotine on endogenous GABA efflux from guinea-pig cortical slices.

1. The effect of nicotine on endogenous basal GABA outflow was studied in guinea-pig cerebral cortex slices. 2. Nicotine 1.86-18.6 mumol l-1 significantly decreased the basal, tetrodotoxin-sensitive GABA efflux, whereas at higher concentrations (186-620 mumol l-1) nicotine increased it. The inhibition was prevented by mecamylamine while the facilitation was blocked by mecamylamine, (+)-tubocurarine and tetrodotoxin. 3. The effect of nicotine was due to an indirect 5-hydroxytryptaminergic action. In fact, MDL 72222 (1 mumol l-1) completely prevented the alkaloid inhibition and methysergide (1 mumol l-1) reversed the facilitation into inhibition; concomitant treatment with methysergide and MDL 72222 antagonized the effect of nicotine at 186 mumol l-1 4. Lower concentrations of 5-HT (3-10 mumol l-1) decreased, whereas higher concentrations (30-100 mumol l-1) increased, spontaneous GABA outflow. The inhibition of GABA efflux was prevented by MDL 72222 whereas the facilitation was reversed by methysergide (1 mumol l-1) into inhibition, and prevented by MDL 72222 1 mumol l-11. 5. These results suggest that, by activating nicotinic receptors present on 5-hydroxytryptaminergic terminals, nicotine releases 5-HT which, in turn, inhibits or increases the secretory activity of cortical GABA interneurones via 5-HT3 and methysergide-sensitive receptors, respectively.

Animals↗
PubMed1995

Dipyridamole echocardiography and 99mTc-MIBI spect dipyridamole scintigraphy for cardiac evaluation prior to peripheral vascular surgery.

Coronary artery disease accounts for most of the early and late mortality and morbidity associated with vascular surgery. Cardiac pre-operative evaluation is mandatory for the assessment of cardiac risk. The aim of this study is to compare dipyridamole scintigraphy with 99mTc-MIBI (MIBI-dipy) and dipyridamole echocardiography (ECHO-dipy) and to evaluate their capability in identifying cardiac risk for strong events such as death, unstable angina or myocardial infarction. METHODS. Sixty consecutive patients (mean age 67 +/- 7) were enrolled. 52 performed ECHO-dipy, 51 MIBI-dipy. 40 patients went to aorto-femoral or aorto-iliac graft replacement and 15 to vascular angioplasty. Five patients did not undergo surgery. RESULTS. Eighteen patients (30%) had stress defects and 9 patients also rest defects with MIBI-dipy. Six patients new asinergic areas at ECHO-dipy. Three pts died in the first year follow-up for a cerebrovascular event, a myocardial infarction and a sudden death respectively. Sensitivity and specificity, positive and negative predictive value were 100%, 69%, 16%, 100% for MIBI-dipy and 66%, 94%, 40%, 98% for ECHO-dipy. CONCLUSIONS. As other authors reported, stress scintigraphy is a pre-operative test showing high sensitivity but with no satisfying specificity. Stress echocardiography, in our population, can produce a good negative predictive value. It is a less expensive and widespread clinical tool useful in the evaluation of preoperative patients. Its positive predictive power is not satisfying but it is shared with all non-invasive pre-operative tests available now.

Aged↗
PubMed1995

Intracavitary cisplatin (CDDP) in the treatment of metastatic pericardial involvement from breast and lung cancer.

Seven patients with lung cancer and two with breast cancer developed a symptomatic pericardial effusion and were treated with intrapericardial cisplatin (CDDP). In all of the patients, cytological confirmation of metastatic effusion was achieved. A single cycle with 10 mg of cisplatin diluted in 20 ml of normal saline was administered for five consecutive days via an intrapericardial catheter. Control of recurrent effusions was obtained in eight of the nine patients. No significant side-effects were observed.

Breast Neoplasms↗
PubMed1995

Delta opioidmimetic antagonists: prototypes for designing a new generation of ultraselective opioid peptides.

BACKGROUND: Tyr-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) and Tyr-Tic-Ala were the first peptides with delta opioid antagonist activity lacking Phe, considered essential for opioid activity based on the N-terminal tripeptide sequence (Tyr-D-Xaa-Phe) of amphibian skin opioids. Analogs were then designed to restrain the rotational flexibility of Tyr by the substitution of 2,6-dimethyl-L-tyrosine (Dmt). MATERIALS AND METHODS: Tyr and Dmt peptides were synthesized by solid phase and solution methods using Fmoc technology or condensing Boc-Dmt-OH or Boc-Tyr(But)-OH with H-L-Tic-OBut or H-D-Tic-OBut, respectively. Peptides were purified (> 99%) by HPLC and characteristics determined by 1H-NMR, FAB-MS, melting point, TLC, and amino acid analyses. RESULTS: H-Dmt-Tic-OH had high affinity (Ki delta = 0.022 nM) and extraordinary selectivity (Ki mu/Ki delta = 150,000); H-Dmt-Tic-Ala-OH had a Ki delta = 0.29 nM and delta selectivity = 20,000. Affinity and selectivity increased 8700- and 1000-fold relative to H-Tyr-Tic-OH, respectively. H-Dmt-Tic-OH and H-Dmt-Tic-NH2 fitted one-site receptor binding models (eta = 0.939-0.987), while H-Dmt-Tic-ol, H-Dmt-Tic-Ala-OH and H-Dmt-Tic-Ala-NH2 best fitted two-site models (eta = 0.708-0.801, F 18.9-26.0, p < 0.0001). Amidation increased mu affinity by 10- to 100-fold and acted synergistically with D-Tic2 to reverse selectivity (delta-->mu). Dmt-Tic di- and tripeptides exhibited delta antagonist bioactivity (Ke = 4-66 nM) with mouse vas deferens and lacked agonist mu activity (> 10 microM) in guinea-pig ileum preparations. Dmt-Tic analogs weakly interacted with kappa receptors in the 1 to > 20 microM range. CONCLUSIONS: Dmt-Tic opioidmimetic peptides represent a highly potent class of opioid peptide antagonists with greater potency than the nonopioid delta antagonist naltrindole and have potential application as clinical and therapeutic compounds.

Amino Acid Sequence↗