Biomedical subjects

J Pitha

Publications and source records attributed to J Pitha.

At least 73 records · Page 4Linked to original sources

PubMed1988

Epididymal sperm profiles in young adult, middle-aged, and testosterone-supplemented old rats.

Both ejaculated semen and epididymal contents from an individual male contain sperm that differ in various physicochemical characteristics. An experiment is reported in which epididymides from rats 5-24 months old were subjected to density gradient centrifugation to separate gametes of different stages of maturity. The research was designed to examine typical changes in "profiles" of sperm maturity during the reproductive lifetime of rats. Also, testosterone complexed with cyclodextrin that mimics the episodic release of the endogenous hormone was used to supplement the decreased circulating titers of some of the old males. Results revealed clear ontogenetic patterns of gradually decreasing reproductive competence as measured by absolute numbers of sperm, circulating levels of testosterone, and various other physiological markers of fertility. Sperm profiles also revealed age-specific changes with a shift toward progressively more mature, perhaps senile, gametes that begins at middle age. Testosterone supplementation (400 micrograms/kg b.w./day for 30 days) failed to restore sperm numbers or other measures of physiology in the old males, but the steroid modified sperm profiles to approximate more closely the profiles characteristic of young adult males than either untreated middle-aged or old males. The data were interpreted as suggesting that epididymal sperm profiles clearly identify males of different ages, and that the aging epididymis retains its capacity to respond to manipulations that modify the endocrine milieu.

Aging↗

PubMed1988

Drug solubilizers to aid pharmacologists: amorphous cyclodextrin derivatives.

Conversion of crystalline alpha-, beta-, or gamma-cyclodextrins into amorphous mixtures of water soluble derivatives yields non-toxic solubilizers which dissolve drugs through the formation of inclusion complexes. From these types of compounds 2-hydroxypropyl ethers of cyclodextrins have presently been investigated and the ranges for the safe use in working with (a) receptor binding assays on membrane preparations, (b) cells in vitro, and (c) parenteral use in mice were established for these compounds. The drugs which were investigated were dissolved in amounts linearly proportionate to the concentration of the solubilizers used and did not precipitate upon dilution by aqueous media. These solubilizers may considerably facilitate pharmacological evaluation of new, water insoluble potential drugs.

Adenylyl Cyclases↗

PubMed1988

Amorphous water-soluble cyclodextrin derivatives: 2-hydroxyethyl, 3-hydroxypropyl, 2-hydroxyisobutyl, and carboxamidomethyl derivatives of beta-cyclodextrin.

The pharmaceutical usefulness of natural, crystalline cyclodextrins can be improved by chemical conversions into water-soluble, amorphous mixtures of their derivatives. Reaction of beta-cyclodextrin with 2-chloroethanol, 3-chloropropanol, isobutylene oxide, or iodoacetamide yielded the title compounds. Distributions of the substitution degree were close to symmetrical and relatively narrow. The average substitution degrees increased with the amount of alkylating reagent used in the preparation. The number of components (half-width of distribution) increased with increasing average substitution degree. Further, distributions of the substitution degree were measured in glucose derivatives after hydrolysis of 2-hydroxyethyl, 2-hydroxypropyl, and 2-hydroxyisobutyl-beta-cyclodextrin. The results show an uneven distribution of substituents around the cyclodextrins, suggesting that growth of oligoglycol side chains and/or clustering of substituents on one glucose residue occurs.

Chemical Phenomena↗

PubMed1988

Irreversible binding and recovery of the norepinephrine uptake system using an alkylating derivative of norepinephrine.

The effects of bromoacetylaminomenthylnorepinephrine (BAAN) on the sodium-dependent, high-affinity norepinephrine (NE) uptake system in rat brain synaptosomes and CNS neuronal cultures were investigated. BAAN inhibited [3H]NE uptake into synaptosomes in a dose- and time-dependent manner (IC50, 6.5 microM). Pretreatment of cortical synaptosomes or neuronal cells with BAAN alone, followed by washing to remove free drug, reduced the Vmax but did not alter the Km value for [3H]NE uptake. The BAAN-induced reduction in Vmax was attenuated by concurrent pretreatment with desipramine and blocked by the reaction of BAAN with dithiothreitol or cysteine. In contrast, BAAN was 19-fold less potent at inhibiting [3H]dopamine uptake in striatal synaptosomes, and no change in the Vmax or Km value for [3H]dopamine uptake was observed after a pretreatment with BAAN followed by washing. Furthermore, the irreversible beta-antagonist, bromoacetylalprenololmentane, was equipotent to BAAN for inhibiting [3H]NE uptake into cortical synaptosomes, but did not alter the Vmax or Km for [3H]NE after pretreatment. In neuronal cultures, BAAN inhibited sodium-dependent uptake of [3H]NE (IC50, 5.6 microM) with no effect on sodium-independent uptake. After pretreatment of cultures with 30 microM BAAN followed by washing, there was a 74% decrease in the Vmax for [3H]NE uptake. Following a 24-h lag period, uptake recovered to the control level within 48 h; however, recovery was completely blocked by cycloheximide. The data indicate that BAAN irreversibly binds to the [3H]NE uptake system in both CNS synaptosomes and neuronal cultures and may be a useful probe for studying the turnover of the [3H]NE uptake system.

Adrenergic beta-Antagonists↗

PubMed1988

Percutaneous catheter ablation at the mitral annulus in canines using a bipolar epicardial-endocardial electrode configuration.

For potential application in ablating left free-wall accessory AV pathways with direct current shocks, a new epicardial-endocardial electrode configuration, designed to focus the current field across the mitral annulus, was tested in dogs. A catheter electrode in the coronary sinus (epicardial electrode) was used as the cathode, and a catheter electrode in the left ventricle (endocardial electrode) placed beneath the mitral valve, high against the mitral annulus and directly across from the epicardial electrode formed the anode. Two shocks, each of 30, 40, or 50 joules (J) were delivered in nine, three, and four dogs, respectively. The first shock was applied to the anterior or lateral wall and the second shock to the posterior wall, except in one dog which received one anterior and one lateral shock. Two dogs receiving 50 J shocks died acutely, one due to rupture of the coronary sinus and cardiac tamponade and the other had unexplained electromechanical dissociation. The remaining 14 dogs tolerated the two shocks well and were sacrificed 3-5 days later for pathological examination of the heart. Shocks in the anterior and lateral regions produced atrial necrosis (height 1.5-11 mm, width 1.5-12 mm and depth 1-3 mm) in 10 of 14 dogs and ventricular necrosis (height 4-27 mm, width 4-33 mm, and depth 5-14 mm) in all 14 dogs. Ideal lesions with atrial necrosis extending down to the annulus and ventricular necrosis extending to the epicardial aspect of the ventricular crest occurred in five dogs in which the endocardial electrode was positioned high against the annulus. In the other nine dogs, the endocardial electrode was located 6-18 mm below the annulus, as estimated by the center of ventricular necrosis. In these dogs, the ventricular lesions did not extend to the epicardial aspect of the crest and, in four dogs, no atrial necrosis was found. Shocks delivered to the posterior wall produced no atrial or ventricular necrosis except in one dog receiving a 50 J shock. It is concluded that, using the epicardial-endocardial electrode configuration with the LV catheter positioned high against the annulus, shocks of less than 50 J in dogs safely produce atrial and ventricular necrosis adjacent to the mitral annulus in the anterior and lateral regions but not in the posterior regions. Similar lesions in man may be capable of interrupting left anterior and lateral accessory AV pathways.

Animals↗

PubMed1988

Radiofrequency current directed across the mitral anulus with a bipolar epicardial-endocardial catheter electrode configuration in dogs.

This study tested the capability of low-power radiofrequency current delivered through a bipolar "epicardial-endocardial" catheter electrode configuration to produce discrete epicardial left atrial (LA) and left ventricular (LV) necrosis adjacent to the mitral anulus for potential application in ablating left free-wall accessory atrioventricular pathways. In 15 anesthetized, closed-chest dogs, a 6F electrode catheter was inserted via the jugular vein into the coronary sinus (CS). A second catheter was inserted via the femoral artery into the left ventricle and positioned beneath the mitral valve, high against the anulus, and directly opposite the CS electrode. The LV tip electrode was positioned to record the largest LA potential to ensure proximity to the anulus. Thirty-four sites were tested (five anterior, 14 lateral, and 15 posterior). Radiofrequency current (continuous wave, 625 kHz) was delivered between the CS and LV electrodes at 37-55 V (median, 41 V) for 4-60 seconds (median, 20 seconds). Current ranged from 0.10 to 0.35 A (median, 0.18 A), resulting in power ranging from 4.3 to 19.2 W (median, 7.3 W) and total energy of 51-446 J (median, 152 J). Dogs were sacrificed 2-9 days later. The CS was grossly intact in all dogs and thrombosed in one dog. The circumflex artery was grossly normal in all dogs. Necrosis of a small segment of the arterial wall was found microscopically in one dog. Lesions were identified at 30 of the 34 sites. Twenty-two (73%) of the 30 lesions consisted of a cylindrical-shaped area of necrosis extending between the anulus and CS with diameter ranging from 2.1 to 15.0 mm (median, 4.0 mm). Atrial and ventricular epicardial necrosis extended 0-7.0 mm (median, 2.5 mm) and 0-6.8 mm (median, 2.6 mm) beyond the anulus, respectively. At the remaining eight (27%) sites, little or no epicardial injury occurred, possibly because of downward displacement of LV electrode (four sites) or positioning of LV electrode within a trabecular recess (four sites). We conclude that 1) radiofrequency current delivered between CS and LV produced, at 22 (65%) of 34 sites, LA and LV necrosis adjacent to the anulus without rupture of the CS and that 2) large, sharp LA potentials help identify an optimal anular location of LV electrode. This technique may have clinical usefulness for ablating left free-wall accessory atrioventricular connections.

Animals↗

PubMed1988

Alkylation of alpha-1 receptors with a chemically reactive analog of prazosin reveals low affinity sites for norepinephrine in rabbit aorta.

The effect of a newly synthesized irreversible blocker of the alpha-1 receptor [1-(4-amino-6,7-dimethoxy-2-quinazolnyl)-4-(2-bicyclo[2,2,2] octa-2,5-dienylcarbonyl)-piperazine; SZL-49] has been evaluated in contractile studies in rabbit aorta and binding studies in aorta and brain. SZL-49 produced long lasting inhibition of norepinephrine-induced contractions which was apparent 21 hr after drug washout. The inhibition, which was dose and time dependent, was characterized by progressive shift to the right in the norepinephrine dose-response curve. The ED50 for norepinephrine was shifted from 10(-7) M to 8 X 10(-7), 3 X 10(-6), 1 X 10(-5) and 5 X 10(-4) M after incubation (30 min) and washout of increasing concentrations of SZL-49. Surprisingly, SZL-49, irrespective of the dose or incubation time, did not decrease the maximal response of aortic rings to norepinephrine. This resulted in a norepinephrine dose-response curve after SZL-treatment that is parallel to the control. SZL-49 had no effect on the spasmogenic actions of histamine, serotonin, KCl or CaCl2. In contrast to the inhibitory pattern seen with SZL-49, incubation with 10(-7) M phenoxybenzamine shifted the norepinephrine dose-response curve to the right in a nonparallel manner and significantly depressed the maximal response obtainable with norepinephrine. Incubation with 10(-6) M phenoxybenzamine for 30 min virtually abolished the response to norepinephrine. Phenoxybenzamine (10(-7) M) was without effect on aortic rings treated with a maximally effective dose of SZL-49. Prazosin weakly antagonized the contractile actions of norepinephrine observed after SZL-49 treatment, whereas yohimbine was without effect on these norepinephrine-induced contractions. In control binding studies [3H]prazosin bound to two classes of sites in both aorta and brain preparations. Affinities and densities for these sites were K1 = 67.5 pM, K2 = 309 pM; R1 = 38.2 fmol/mg, R2 = 46.47 fmol/mg in aorta and K1 = 29.6 pM, K2 = 182 pM; R1 = 6.6 fmol/mg and R2 = 30.4 fmol/mg in brain. Treatment with increasing amounts of SZL-49 (10(-10) to 10(-8) M) progressively reduced the number of [3H]prazosin sites without altering the affinity of the sites remaining. At 10(-7) M, SZL-49 eliminated completely all specific [3H]prazosin binding. Our results indicate that the site mediating norepinephrine contraction after treatment with SZL-49 does not possess the characteristics of an alpha-1 receptor and supports the hypothesis that a low affinity site for norepinephrine and prazosin exists in vascular smooth muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkylation↗

PubMed1988

Bilateral elastofibroma dorsi.

Elastofibroma, a rare, noncapsulated, benign entity (pseudotumor), is characterized by the proliferation of fibrous tissue with elastin and scattered islands of adipose tissue that occurs most often in the infrascapular area of elderly women. We report on a 44-year-old man with bilateral infrascapular elastofibromas.

Fibroma↗

PubMed1987

Reaction of cyclodextrins with propylene oxide or with glycidol: analysis of product distribution.

Reaction of cyclomalto-hexaose, -heptaose, or -octaose with propylene oxide in strong aqueous alkali gave products in which distribution of the degrees of substitution was relatively narrow and nearly symmetrical, and increased with the average degree of substitution. When an equimolar mixture of cyclomalto-hexaose, heptaose, or -octaose was used, the average degrees of substitution of all three carbohydrates were close to each other. These findings indicate that the reactivities of the hydroxyl groups of cyclomalto-hexaose, -heptaose, or -octaose, and of all their (2-hydroxypropyl) ethers formed in the reactions, are quite similar. Reaction of cyclomaltoheptaose with glycidol also yielded a product having a narrow distribution of degree of substitution, but which was slightly skewed towards the higher degrees. Thus, as it proceeds, this etherification leads to products having higher reactivity towards the epoxide.

Cyclodextrins↗

PubMed1987

A bromoacetylated analogue of cyanopindolol: an irreversible antagonist at rat beta-adrenoceptors.

A high affinity, chemically reactive cyanopindolol derivative. N8-bromoacetyl-N1-3'-(2-cyano-4-indolyloxy)-2'-hydroxypropyl-[Z]-1 ,8-diamino-p-menthane (Br-CYP) was synthesized and its interaction with beta-adrenoceptors characterized. Studies with rat heart, lung, brain, and red blood cell membranes indicated that the compound displaced 3H-dihydroalprenolol (3H-DHA) from beta-adrenoceptors with IC50 values in the nanomolar range. The concentration of functional beta-adrenoceptors in membranes was markedly reduced when membranes were preincubated with Br-CYP and then extensively washed prior to assay. (+/-)Alprenolol and (-)isoproterenol, but not (+)isoproterenol, when included in the preincubation prevented this reduction in binding sites by Br-CYP. Br-CYP was active in vivo when injected intraperitoneally into rats. A dose of 10 micrograms/kg reduced the concentration of binding sites in membranes from heart by 30%, lung by 36%, and RBC by 70%, but did not affect sites on brain membranes 16 hours after injection. Higher doses blocked virtually all the 3H-DHA binding sites in the peripheral organs studied. Br-CYP reduced the concentration of beta-adrenoceptors in membranes from these same tissues (but not brain tissue) as long as two weeks after injection with recovery of binding occurring more rapidly in heart tissue than lung and red blood cells. These results suggest that Br-CYP may be a useful compound for in vivo studies of the biochemistry and pharmacology of beta-adrenergic systems.

Adrenergic beta-Antagonists↗

PubMed1987

Inhibition of alpha 1-adrenergic responsiveness in intact cells by a new, irreversible receptor antagonist.

A novel alpha 1-adrenoreceptor antagonist, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-bicyclo [2.2.2] octa-2,5-dienylcarbonyl) piperazine, was synthesized and shown to potently block alpha 1-adrenoceptor-induced Ca2+ mobilization in intact rat parotid acinar cells. Irreversible inhibition was complete in less than 5 min. This alkylating prazosin derivative blocked Ca2+ release (IC50 approximately 5 X 10(-10)M) and [3H]-prazosin membrane binding (IC50 approximately 3 X 10(-10)M) in a concentration dependent fashion and increased the EC50 of epinephrine for Ca2+ efflux by approximately 35 fold. The agent however had no effect on muscarinic receptor-induced Ca2+ mobilization, or beta-adrenoreceptor-induced protein secretion, from cells. These findings suggest that this irreversible alpha 1-adrenoreceptor antagonist will be a valuable tool in probing alpha 1-adrenoreceptor function and metabolism in intact cells.

Adrenergic alpha-Antagonists↗

PubMed1987

Two beta-adrenergic pharmacophores on the same molecule. A set of agonist-antagonist combinations.

A series of compounds containing combinations of one or two pharmacophores of the agonist type (isoproterenol) or the antagonist type (propranolol or alprenolol) on the same molecule were prepared. The pharmacophores were connected by a derivative of polyethylene glycol with an average length of six atoms (carbon and oxygen). Furthermore, compounds containing two alprenolol residues, separated by chains of average lengths of 70 or 145 atoms, were synthesized. The abilities of these compounds to interact with beta-adrenoceptors of rat heart and lung tissues were examined by measuring the following parameters: competitive binding with [3H]dihydroalprenolol, activation of adenylate cyclase, and inhibition of isoproterenol-stimulated adenylate cyclase. The affinity of the compound with two isoproterenol pharmacophores for receptor was about the same as that with one isoproterenol pharmacophore and between 30 and 200 times weaker than that of (+/-)isoproterenol. Both mono- and bis-pharmacophore compounds partially stimulated catecholamine sensitive adenylate cyclase and at high concentrations inhibited the stimulation produced by (-)isoproterenol. The affinity of the compound with antagonist (propranolol) and agonist (isoproterenol) pharmacophores on the same molecule was intermediate between that of propranolol and isoproterenol. The compound was only able to inhibit adenylate cyclase activity. Compounds containing two antagonist (alprenolol) pharmacophores bound to receptors with affinities from an order of magnitude lower to about equal to that of the compound containing one pharmacophore. When membranes were preincubated with compounds containing two antagonist pharmacophores and then washed extensively, there were persistent effects of all of these compounds on the binding constants of [3H]dihydroalprenolol. All of these compounds were only able to inhibit adenylate cyclase activity and none exhibited any subtype selectivity at beta-adrenoceptors. The results suggest that, in the beta-adrenergic system, compounds with agonist and antagonist substituents on the same molecule exhibit properties of the substituent with the higher affinity for beta-adrenoceptor, and no agonist activity is evident when two antagonist pharmacophores are linked on the same molecule. All of the above results may be explained without recourse to cross-linking of beta-adrenoceptors with two pharmacophores, a phenomenon cited in similar studies of receptors for opiates and gonadotropin-releasing hormone.

Adrenergic beta-Agonists↗

PubMed1987

gamma-Cyclodextrin:testosterone complex suitable for sublingual administration.

A crystalline complex of testosterone with gamma-cyclodextrin was evaluated for solubility and dissolution rate. Whereas these parameters were at least an order of magnitude lower than those of testosterone complexes with amorphous derivatives of cyclodextrins, the properties of the crystalline complex enabled the preparation of a suitable pharmaceutical form for the sublingual administration of hormone to humans. This is in contrast to the situation with similar beta-cyclodextrin complexes, in which such administration was ineffective. Sublingual administration of the gamma-cyclodextrin complex, as shown in previous work using amorphous complexes, avoided rapid first-pass loss of hormone and directed it effectively into the circulation; administration of the complex into the stomach resulted in much lower circulatory hormone levels.

Administration, Sublingual↗

PubMed1987

Severe hypervitaminosis A in siblings: evidence of variable tolerance to retinol intake.

A 2-year-old boy had signs and symptoms of chronic hypervitaminosis A. A course of increasing severity led to eventual death. A younger brother later had similar clinical features. Chicken liver spread containing up to 420 IU/g vitamin A was the likely source of intoxication. Markedly elevated circulating retinyl ester levels have persisted in the surviving sibling for 3 subsequent years despite severe restriction of vitamin A intake. A therapeutic trial of the carbohydrate-derived complexing agent 2-hydroxypropyl-beta-cyclodextrin was initiated. Circulating retinyl esters transiently increased during the infusion (from 407 to 4791 micrograms/dL), and urinary total vitamin A excretion, undetectable before infusion, increased to 23 micrograms/dL after infusion. The frequency of hypervitaminotic episodes has decreased somewhat in the 2 years since the infusion, probably related to dietary vitamin A restriction. The occurrence of this syndrome in two brothers, while a sister ingesting the same diet remains completely healthy, suggests an inherited variance in tolerance to vitamin A intake.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1987

Affinity labels for beta-adrenoceptors: preparation and properties of alkylating beta-blockers derived from indole.

New alkylating ligands derived from indole with high affinity for beta-adrenoceptors were synthesized and their properties examined. N8-(Bromoacetyl)-N1-[3-(4-indolyloxy)-2-hydroxypropyl]-(Z)-1,8-dia mino-p- menthane (8) and its N1,N8 isomer (9) were prepared by the reaction of bromoacetyl bromide with a product of the condensation of 4-indolyl glycidyl ether with (Z)-1,8-diamino-p-menthane. A similar reaction employing 2-cyano-4-indolyl glycidyl ether yielded the respective cyano derivatives 10 and 11. Apparent affinities (Ki, M) for beta-adrenoceptors on membrane preparations from rat heart and lung were 4.6 X 10(-10) and 1.34 X 10(-9) for 8, 2.3 X 10(-8) and 4.5 X 10(-9) for 9, 6.1 X 10(-10) and 1.49 X 10(-9) for 10, and 1.83 X 10(-9) and 2.78 X 10(-9) for 11, respectively. When membranes were preincubated with the above ligands (1 X 10(-8) M, 30 min, 30 degrees C) and then washed extensively, reduction in the concentration of specific binding sites of [3H]dihydroalprenolol ranged from 7% to 76% and there was no change in KD of the remaining binding sites. (+/-)-Alprenolol and (-)-isoproterenol, but not (+)-isoproterenol, when included with the alkylating ligands in the preincubation mixtures, prevented the reduction in concentration of [3H]dihydroalprenolol binding sites. Compounds 8-11 alone did not stimulate adenylate cyclase activity in rat heart homogenates. However, these compounds inhibited (-)-isoproterenol-stimulated adenylate cyclase activity with Ki values ranging between 5 X 10(-9) and 60 X 10(-9) M. These results suggest that high-affinity irreversible beta-adrenergic antagonists were obtained that may be useful for in vivo studies of beta-adrenoceptors.

Adenylyl Cyclases↗

PubMed1987

Carbostyril derivatives having potent beta-adrenergic agonist properties.

Derivatives carrying a substituent in the para position of the phenyl group of 8-hydroxy-5-[2-[(1-phenyl-2-methylprop-2-yl)amino]-1-hydroxyethyl] carbostyril (10) were prepared and their effects on beta-adrenoceptors evaluated in vitro. Unsubstituted compound 10, iodo 11, amino 12, and bromoacetamido 13 derivatives (all racemic) bound to the receptor with 15-100-fold lower dissociation constants than that of (-)-isoproterenol. All the above compounds stimulated adenylate cyclase more potently than (-)-isoproterenol. The intrinsic activities of compounds 10 and 12 were equal to that of (-)-isoproterenol. The intrinsic activities of compounds 11 and 13 were 1.3 and 1.2 times that of (-)-isoproterenol, respectively. Treatment of membrane preparations with bromoacetamido derivative 13 resulted in an irreversible loss of binding sites, and thus, 13 seems to be an alkylating affinity label for beta-adrenoceptors.

Adenylyl Cyclases↗

PubMed1986

A new photoaffinity probe, 4-amino-2-[4-(4-azidocinnamoyl)piperazino]-6,7-dimethoxyqu inazoline, for alpha 1-adrenoceptors.

A photoaffinity probe for alpha 1-adrenoceptors was synthesized and its properties examined on rat brain membrane preparations. The binding of 4-amino-2-[4-(4-azidocinnamoyl)piperazino]-6,7-dimethoxyquin azoline (ACP) to these receptors was of high affinity (KD = 1.05 nM) and reversible in the dark. A dose-dependent decrease in the concentration of [3H]prazosin binding sites without a change in KD was observed when membranes were preincubated with ACP, photolyzed, and then extensively washed prior to assay. This reduction in receptor concentration was prevented by alpha 1-adrenergic ligands. The specificity of ACP for alpha 1-receptors was further demonstrated by its inability to compete with [3H]dihydroalprenolol and [3H]yohimbine binding in these same membranes. Also, the concentrations and affinity constants of beta-adrenoceptors and alpha 2-adrenoceptors were unaffected in membranes which had been photolyzed after preincubation with ACP. No reduction in concentration of alpha 1-adrenoceptors was detected if ACP was photolyzed prior to incubation with receptors or if ACP was maintained in darkness throughout the experiment. The results suggest that ACP is a specific and sensitive photoprobe that may be useful for further studies on alpha 1-adrenoceptor coupled systems and that may be particularly suited for use in cell culture work.

Affinity Labels↗

PubMed1986

Hydrophilic cyclodextrin derivatives enable effective oral administration of steroidal hormones.

Condensation products of beta-cyclodextrin with propylene oxide or epichlorohydrin, which are amorphous and thus very soluble in water, were used to form complexes with testosterone, progesterone, and estradiol. Sublingual/buccal administration of tablets of these complexes led to effective absorption and entry of the hormones into the systemic circulation, followed by gradual elimination; rapid first-pass loss was avoided. beta-Cyclodextrin itself, its 2,6-dimethyl derivative, and a nonionic detergent did not enable effective buccal absorption. Absorption from the GI tract of hormones complexed with hydrophilic cyclodextrins was also less effective. Effective absorption of drugs from the oral cavity requires (a) that the drug and solubilizer form a complex of the inclusion type which dissolves completely and rapidly and (b) that the solubilizer neither enters nor damages oral tissue.

Administration, Oral↗