PubMed Health⌕ Search

Biomedical subjects

B G Green

Publications and source records attributed to B G Green.

At least 37 records · Page 2Linked to original sources
PubMed1996

Sensitization and desensitization to capsaicin and menthol in the oral cavity: interactions and individual differences.

It was reported in a recent study that, like capsaicin, menthol is capable of producing a desensitization to sensory irritation in the oral cavity. Whereas capsaicin is known to be able to cross-desensitize with other chemical irritants, no such information exists for menthol. To address this question, the first experiment was designed to reveal whether cross-desensitization would occur between menthol and capsaicin. After a pretest on the tongue tip in which subjects rated the intensity of irritation and cold produced by 3.5 ppm capsaicin or 0.3% l-menthol, five samples of the same stimuli were sipped and swished at 1-min intervals for 5 min. Fifteen minutes later subjects were tested on the tongue tip with either capsaicin or menthol. The results 1) confirmed self-desensitization for both chemicals, 2) demonstrated cross-desensitization of menthol by capsaicin, and 3) revealed cross-sensitization of capsaicin by menthol. This series of outcomes suggests that menthol produces much of its sensory irritation via capsaicin-sensitive pathways, but that it excites and/or desensitizes those pathways via different mechanisms than does capsaicin. Analysis of the individual data revealed large differences in sensitization, and desensitization that were significantly correlated across chemicals, which suggests the possibility that the perceptual response to repeated exposures to irritants may be idiosyncratic. Contrary to earlier findings, the first experiment also revealed apparent self- and cross-desensitization of the menthol sensation of coolness. The latter outcome was investigated in a second experiment in which the effect of capsaicin desensitization on the perception of physical as well as chemical (menthol) cooling was measured when the stimuli were presented as oral rinses. No desensitization was found for either form of stimulation, which implied the apparent desensitization of coolness in Experiment I may have been due to the difficulty of discriminating sensations of cold from sensations of chemical irritation. The overall findings are discussed in terms of the complex sensory and perceptual interactions that take place within the chemesthetic modality.

Adult↗
PubMed1996

Rapid recovery from capsaicin desensitization during recurrent stimulation.

Topical desensitization of the tongue was assessed during multiple bouts of exposure to capsaicin. In the first experiment subjects rated perceived irritation as 30 capsaicin stimuli (33 microM) were applied to the tongue tip in three blocks of 10, with 15 min breaks between blocks. Significant desensitization was measured at the beginning of the second and third blocks within each session. However, as stimulation continued within those blocks sensations of irritation grew toward undesensitized levels ('stimulus-induced recovery' (SIR)). Desensitization did not extend across days. The second experiment employed a 10-fold higher concentration of capsaicin (330 microM) to determine if SIR was limited to low levels of desensitization. SIR occurred as before within sessions, and the higher concentration produced desensitization across days that also exhibited recovery during the first block of stimuli on days 2 and 3. The third experiment included piperine, zingerone and citric acid as stimuli to determine if SIR was specific to capsaicin. Piperine produced SIR under conditions of both self- and cross-desensitization with capsaicin, whereas recovery failed to materialize with zingerone. Citric acid was not significantly cross-desensitized by capsaicin, so recovery could not be measured. Overall the results demonstrate that desensitization of the tongue produced by either capsaicin or piperine can be temporarily reversed if stimulation with either chemical is resumed for only a few minutes. The implications these findings may have for hypotheses about the mechanisms of capsaicin desensitization and sensitization as well as for clinical applications of capsaicin as a topical analgesic are discussed.

Administration, Oral↗
PubMed1996

Epidemiology of current treatment for sexual dysfunction in spinal cord injured men in the USA model spinal cord injury centers.

This study is a prospective multicenter cooperative survey of the evaluation and treatment of erectile dysfunction in men with spinal cord injury (SCI). Uniform database questionnaires were completed prospectively by patients seeking therapy for erectile dysfunction. Eighty-five SCI men aged 17-68 years (mean age = 26 +/- 17) were enrolled. Mean duration of traumatic SCI was 3 +/- 3.2 years (Range = 0.3-18 years). The level of injury was cervical in 20 patients, thoracic in 31, lumbar in 29 and sacral in five. Patients were fully evaluated and then counseled as to their therapeutic options. Twenty-eight chose to use a vacuum erection device (VED), 26 preferred pharmacological penile injection and five used both intracorporeal therapy and VED. The remainder were managed with marriage and sexual counseling in 10 patients, three underwent penile prosthesis placement and two used topical pharmacotherapy. Four patients used other forms of treatment and in nine no therapy was recommended. Of the patients that used pharmacologic injection only, 74 percent used papaverine as a single agent, 20 percent used papaverine with phentolamine, five percent used prostaglandin E (PGE1) alone and one percent used a mixture. Patients using injection therapy report sexual intercourse a mean of 3 +/- 3.4 times per month as compared with 5 +/- 3.2 times per month in those using VED. Five intracorporeal injection patients developed priapism while two patients using the VED developed subcutaneous bleeding and one developed penile ischemia. We conclude that although a spectrum of erectile dysfunction treatment is present among SCI centers, VED and pharmacological penile injection are by far the two most popular methods of treatment and papaverine is the most common drug. The incidence of complications is small in the model centers.

Adolescent↗
PubMed1996

Evaluating the 'Labeled Magnitude Scale' for measuring sensations of taste and smell.

The Labeled Magnitude Scale (LMS) is a semantic scale of perceptual intensity characterized by a quasi-logarithmic spacing of its verbal labels. The LMS had previously been shown to yield psychophysical functions equivalent to magnitude estimation (ME) when gustatory, thermal and nociceptive stimuli were presented and rated together, and the upper bound of the LMS was defined as the 'strongest imaginable oral sensation'. The present study compared the LMS to ME within the more limited contexts of taste and smell. In Experiment 1, subjects used both methods to rate either taste intensity produced by sucrose and NaC1 or odor intensity produced by acetic acid and phenyl ethyl alcohol, with the upper bound of the LMS defined as either the 'strongest imaginable taste' or the 'strongest imaginable odor'. The LMS produced psychophysical functions equivalent to those produced by ME. In, Experiment 2 a new group of subjects used both methods to rate the intensity of three different taste qualities, with the upper bound of the LMS defined as the 'strongest imaginable [sweetness, saltiness, or bitterness]'. In all three cases the LMS produced steeper functions than did ME. Experiment 3 tested the hypothesis that the LMS yields data comparable to ME only when the perceptual domain under study includes painful sensations. This hypothesis was supported when the LMS again produced steeper functions that ME after subjects had been explicitly instructed to omit painful sensations (e.g. the 'burn' of hot peppers) from the concept of 'strongest imaginable taste'. We conclude that the LMS can be used to scale sensations of taste and smell when they are broadly defined, but that it should be modified for use in scaling specific taste (and probably odor) qualities. The implications of these results for theoretical issues related to ME, category-ratio scales and the size of the perceptual range in different sensory modalities are discussed.

Acetic Acid↗
PubMed1996

Proteoglycan-degrading activity of human stromelysin-1 and leukocyte elastase in rabbit joints. Quantitation of proteoglycan and a stromelysin-induced HABR fragment of aggrecan in synovial fluid and cartilage.

The objective of this study was to compare the specificity and potency of recombinant human SLN-1 (rhSLN) and human leukocyte elastase (HLE) as proteoglycan (PG)-degrading enzymes after intraarticular injection into rabbits. Another objective was to evaluate the elicitation of a rhSLN-induced hyaluronan-binding region (HABR) fragment from rabbit aggrecan in joints using a polyclonal antiserum (anti-FVDIPEN) against the synthetic peptide, Phe-Val-Asp-Ile-Pro-Glu-Asn (FVDIPEN). The intraarticular injection of either activated rhSLN or HLE resulted in enzyme-specific quantitative release of PG fragments into synovial fluid. Based on the criteria used herein, HLE appears to be a more potent PG-degrading enzyme than SLN. Intraarticular injection of rhSLN also resulted in time- and dose-dependent release of a new HABR fragment of aggrecan (HABR-FMDIPEN) into both articular cartilage and synovial fluid. HABR-FVDIPEN is likely to be a good marker of matrix metalloproteinase (MMP)-induced degradation of aggrecan.

Aggrecans↗
PubMed1996

Reversible clinical outcome after sphincter stent removal.

PURPOSE: We determined whether the self-expanding sphincter stent, a potential alternative to conventional external sphincterotomy for the treatment of detrusor external sphincter dyssynergia, causes a permanent effect on the lower urinary tract. MATERIALS AND METHODS: Four spinal cord injured men with voiding symptoms of detrusor external sphincter dyssynergia as noted by complete urological evaluation, including a video urodynamic study, were treated with the self-expanding sphincter stent. However, the device was explanted 6 months or longer after insertion in all 4 cases due to stent migration (3) and difficulty with condom catheter urinary drainage (1). RESULTS: All stents were removed completely without damage to the urethra. Mean voiding pressure decreased from 62.5 +/- 39.4 to 20.7 +/- 6.5 cm. water after sphincter stent placement. One year after stent explantation mean voiding pressure remained unchanged from preoperative values of 58.5 +/- 21.5 cm. water. No patient had stress urinary incontinence or endoscopically apparent urethral strictures. CONCLUSIONS: The stent can be removed even after complete epithelialization and an extended interval without damage to external sphincter function or urethral stricture formation. The urinary sphincter stent is an effective, reversible treatment for patients with detrusor external sphincter dyssynergia.

Adult↗
PubMed1995

Mechanism of inhibition of human leucocyte elastase by beta-lactams. 2. Stability, reactivation kinetics, and products of beta-lactam-derived E-I complexes.

The monocyclic beta-lactams reported by Knight et al. [Knight, W. B., et al. (1992) Biochemistry 31, 8160; Chabin, R., et al. (1993) Biochemistry 32, 8970] as inhibitors of human leucocyte elastase (HLE) produce stable HLE-inhibitor complexes that slowly reactivate with half-lives ranging from less than 1 to 15 h at 37 degrees C. The complexes produced between PPE and two C-3 dimethyl-substituted beta-lactams are less stable than those produced between HLE and analogous C-3 diethyl-substituted lactams. The stability of the HLE-I complexes is governed primarily by the structure of the substituted urea portion of the inhibitors and not by the identity or presence of a leaving group at C-4 of the lactam ring. In some cases substitutions on the urea portion of the inhibitors yielded complexes that displayed biphasic reactivation kinetics. This suggests the presence of at least two different complexes. The stereochemistry of the leaving group at C-4 has a small effect on the stability of the final complex (1.3-2-fold); therefore, the identity of the final complex is dependent upon the initial stereochemistry at that position. The stability of the complexes was relatively insensitive to hydroxylamine, which suggests that the acyl-enzymes are protected from nucleophilic "rescue". The rate of reactivation of the complex derived from L-680,833,[S-R*,S*)]-4-[(1-(((1-(4- methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-2-oxo-4-azetidinyl)ben zeneacetic acid, was pH independent, while the L-684,481, (R)-(1-(((1-(4-methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-2-azeti din one generated complex displayed a pH-dependent reactivation rate. In the latter case, the increase in reactivation rate with pH displayed a pKa of 7.2. This is consistent with the requirement for base catalysis by the active site histidine to regenerate enzymatic activity. Reactivation of the L-680,833-derived complex produced different products as a function of pH, suggesting two different pH-dependent routes of reactivation. At low pH a route that produced primarily the substituted urea is favored, while at higher pH production of two six-membered ring diastereomers competes with urea generation. Thus, the apparent pH independence of the return of activity is the result of two offsetting pathways. Other compounds such as L-670,258, (S)-4-[((((2-naphthylmethyl)amino)carbonyl)-3,3-diethyl-4-oxo-2- azetidinyl)oxy]benzoic acid, reactivate by these two routes as well as by aminolysis by the other urea nitrogen to produce an additional regioisomer. The temperature dependence of the reactivation of the complexes derived from L-684,481 and L-680,833 suggests different mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1995

Mechanism of inhibition of human leucocyte elastase by beta-lactams. 3. Use of electrospray ionization mass spectrometry and two-dimensional NMR techniques to identify beta-lactam-derived E-I complexes.

A combination of NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS) was used to probe the identity of beta-lactam-derived complexes with serine proteases. The carbon and proton NMR chemical shifts of the human leucocyte elastase (HLE)-inhibitor complex derived from [4-13C]-L-680,833, [S-(R*,S*)]-4-[(1-(((1-(4- methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-2-oxo-4- azetidinyl)oxy]benzeneacetic acid, were consistent with an sp3 hybridized carbon. The ESI-MS spectrum of the L-680,833-derived HLE-I complex indicated an increase of 333 Da over the mass of the free enzyme. The data are consistent with acylation of the active site serine, loss of p-hydroxybenzeneacetic acid, and formation of a carbinolamine at the carbon deriving from C-4 of the lactam ring. The complexes produced from HLE and the diastereomers of L-680,833 display identical masses. Since the 4R-isomers produce more stable complexes [Green et al. (1995) Biochemistry 34, 14331-14343], these data suggest that these complexes differ in their stereochemistry or conformation. The structural model of the HLE-I complexes derived from the diastereomers predicts that the hydroxyl of the carbinolamine derives from a structurally observed water molecule yielding S-stereochemistry in all cases. In this model, the 4S- and 4R-diastereomers produce complexes that differ by the location of the side chain of a phenylalanine residue. The mass of HLE was increased by that of L-684,481, (R)-1-(((1-(4-methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-2-azetidino ne, which lacks a leaving group at C-4 in the complex derived from this compound. L-691,886, [S-(R*,S*)]-4-[(1-(((1-(4-ethoxyphenyl)butyl)amino)carbonyl)- 3,3-diethyl-4-oxo-2-azetidinyl)-oxy]benzeneacetic acid, produces two complexes of different mass that reactivate with different rates. The mass of the less stable complex is consistent with the acyl-enzyme of 2,2-ethyl-3-oxopropanoic acid while the mass of the more stable complex is analogous to the carbinolamine observed during L-680,833 inactivation. Porcine pancreatic elastase (PPE) produces a complex with a mass consistent with replacement of the C-4 leaving group by water to produce a carbinolamine from L-684,248, [S-(R*,S*)]-4-[(1-(((1-(4-methylphenyl)butyl)amino)carbonyl)-3,3-dimethy l - 2-oxo-4-azetidinyl)oxy]benzoic acid. The C-4 diastereomer, L-684,249, produces two PPE-I complexes with different masses. One of these complexes has a mass identical to the mass of the complex derived from L-684,248 while the mass of the other complex indicates the presence of the entire inhibitor molecule.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1995

The nonrefluxing ileal conduit: a new form of urinary diversion.

PURPOSE: We describe a variation of the ileal conduit that includes a nonrefluxing nipple valve designed to protect the upper urinary tracts. MATERIALS AND METHODS: A total of 13 patients underwent urinary diversion with the nonrefluxing ileal conduit. The nonrefluxing nipple valve is created by intussuscepting the ileum into the conduit. RESULTS: Followup ranged from 3 to 35 months. No patient demonstrated radiographic deterioration of the upper tracts or a clinically significant increase in serum creatinine level during followup. CONCLUSIONS: The nonrefluxing ileal conduit appears to be a viable treatment option in select patients with neurogenic bladder dysfunction.

Adult↗
PubMed1995

Collagen injections for intrinsic sphincter deficiency in the neuropathic urethra.

Twelve subjects experiencing stress urinary incontinence caused by spinal injury or myelomeningocele were treated by periurethral injection of a bulking agent, glutaraldehyde cross-linked (GAX) collagen. Of the 11 subjects who completed the program, seven were either cured or improved and four were only slightly improved or no better following injection. The valsalva (abdominal) leak point pressure (LPP) rose an average of 57 cm H2O (pre-treatment mean of 60 cm H2O versus post-treatment mean of 117 cm H2O) and none of the patients experienced significant complications during the mean follow-up period of 24 months. Every subject injected was able to maintain an intermittent catheterization program after treatment. These data support the use of GAX collagen as an alternative or adjunct therapy to pharmacotherapy, surgical reconstruction or implantation of a prosthesis in the management of stress urinary incontinence in the neuropathic urethra.

Adult↗
PubMed1995

Management of sphincter dyssynergia using the sphincter stent prosthesis in chronically catheterized SCI men.

This effort represents a subset analysis of the long-term Multicenter North American Trial of the UroLume sphincter stent prosthesis to determine the effect of the sphincter stent prosthesis in SCI men afflicted with detrusor-external sphincter dyssynergia (DESD) and chronically managed with an indwelling urinary catheter. Forty-one of 153 male patients in this study were evaluated urodynamically before and after placement of the sphincter stent prosthesis. Of the 41 patients, 34 (81 percent) suffered cervical-level injury while 10 patients (25 percent) had been treated previously with external sphincterotomy. Forty patients (98 percent) were troubled with recurrent urinary tract infections (UTI), with a mean of 4.6 +/- 3 episodes of UTI per year. Seven patients (17 percent) demonstrated hydronephrosis prior to stent placement. Follow-up ranged from six to 44 months. Voiding pressures decreased from a mean of 77 +/- 23 cmH2O preoperatively to 35 +/- 18 cmH2O at 12 months (n = 34) and 33 +/- 20 cmH2O at 24 months (n = 22) after stent insertion (p = 0.001). Post-void residual urinary volume decreased from 202 +/- 187 ml preinsertion to 64 +/- 69 ml at 24 months (p = 0.001) postinsertion. Maximum cystometric capacity remained constant at 201 +/- 144 ml preinsertion to 203 +/- 79 ml at 24 months (p = 0.75) postinsertion. No significant changes in any of the urodynamic parameters occurred after 24 months of follow-up between patients with (n = 10) and without (n = 31) previous external sphincterotomy. Neither hemorrhage requiring blood transfusion, obstructive hyperplastic epithelial overgrowth, stent encrustation or stone formation, nor soft tissue erosion occurred in any patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

2-Iminobiotin is an inhibitor of nitric oxide synthases.

Nitric oxide synthase (NOS, EC 1.14.23) catalyzes the oxidation of the guanidino-nitrogen of L-arginine to form nitric oxide and L-citrulline. 2-Iminobiotin was found to be a reversible inhibitor of murine iNOS and rat n-cNOS with Ki values of 21.8 and 37.5 microM, respectively. The urea and thiourea analogs, biotin and thiobiotin, were not inhibitors of NOS, indicating that the guanidino group of 2-iminobiotin is essential for binding. 2-iminobiotin carboxy derivatives were also inhibitors of iNOS which indicates that the free carboxyl group is not required for binding. 2-Iminobiotin is a novel, potent inhibitor of NO biosynthesis and may be a useful reagent in the understanding of binding-site interactions for this important class of enzymes.

Amino Acid Oxidoreductases↗
PubMed1994

Sensory irritation and coolness produced by menthol: evidence for selective desensitization of irritation.

The temporal characteristics of the oral perception of menthol solutions were explored in two experiments. In Experiment 1, 10 samples of either 0.03% or 0.30% menthol were presented at 1 min intervals and rated for the perceived intensity of cooling and irritation. Reports of sensation quality (burning, tingling, stinging and numbing) and pain were also collected. At the higher concentration, a significant decrease in perceived intensity was observed over time for irritation, but not for cooling. Experiment 2 was designed to explore further the nature of the decline in irritation observed in Experiment 1. Employing 1-min and 5-min inter-stimulus intervals between solutions, it was found that the decrease in menthol irritation more closely resembled desensitization than adaptation. Decreases in the frequency of reports of the burning and stinging qualities, but not the tingling, numbing or cooling qualities, suggested that menthol has a specific desensitizing effect on a population of mucosal nociceptive fibers.

Adult↗
PubMed1993

Effect of nitric oxide synthase substrate analog inhibitors on rat liver arginase.

Nitric oxide synthase (EC 1.14.23) substrate analog inhibitors NG-monomethyl-L-Arg, NG-nitro-L-Arg, NG-nitro-L-Arg methyl ester, and aminoguanidine were examined as potential inhibitors of rat liver arginase (EC 3.5.3.1). NG-nitro-L-Arg was found to inhibit arginase catalyzed conversion of L-Arg to L-Orn at pH 7.5 with an IC50 = 27.2 +/- 4.3 mM, compared to L-Val and L-Lys with IC50 values of 6.2 +/- 0.4 mM and 31.3 +/- 2.7 mM, respectively. Inhibition was stereospecific for the L-amino acid, not NG-nitro-D-Arg, and required a free alpha-carboxyl group. NG-nitro-L-Arg was not a substrate for rat liver arginase. These results suggest that arginase inhibition should also be evaluated when studying the effects of NOS substrate analog inhibitors in vivo.

Amino Acid Oxidoreductases↗
PubMed1993

Mechanism of inhibition of human leucocyte elastase by monocyclic beta-lactams.

The kinetic and catalytic mechanisms of time-dependent inhibition of human polymorphonuclear leukocyte elastase (HLE) by the monocyclic beta-lactams described by Knight et al. [Knight, W.B., et al. (1992) Biochemistry 31, 8160] are investigated in this work. The dependence of the pseudo-first-order rate constant (k(obs)) on inhibitor concentration was saturable. The individual kinetic constants for the inhibition by L-680,833, [S-(R*,S*)]-4-[(1-(((1-(4- methylphenyl)butyl)amino)carbonyl)-3,3-diethyl-4-oxo-2- azetidinyl)oxy]benzeneacetic acid, and L-683,845, [S-(R*,S*)]-4-[(1-(((1-(5-benzofuranyl)butyl)amino)carbonyl)- 3,3-diethyl-4-oxo-2-azetidinyl)oxy]benzeneacetic acid, at pH 7.5 were k(inact) = 0.08 and 0.06 s-1 and Ki = 0.14 and 0.06 microM, respectively. The relative potency of this class of compounds as measured by k(inact)/Ki is primarily controlled by the Ki, term which ranged from 6 nM to 8 mM, while K(inact) was relatively insensitive to structural changes and varied by only an order of magnitude. Inactivation by the beta-lactams was efficient, requiring only 1.3 and 1.7 equiv of L-680,833 and L-683,845 to inactivate HLE. These values are indicative of some partitioning between turnover of inhibitor and inactivation. The partition ratio ranged as high as 3.5:1 depending upon the structure of the inhibitors, but this ratio was essentially independent of the availability and identity of a leaving group at C-4 of the lactam ring. Inactivation and partitioning liberate the leaving group when present at C-4. p-Hydroxy-m-nitrophenylacetic acid is liberated from this position at a rate similar to that for enzyme inactivation, suggesting kinetic competence of this process. Other products observed during the interaction of L-680,833 with HLE include a substituted urea, a species previously observed during the base-catalyzed decomposition of this class of compounds, and small amounts of products observed during reactivation of beta-lactam-derived HLE-I complexes. Both the pH dependence of k(inact)/Ki for the inactivation of HLE by [S-(R*,S*)]-4-[(1-(((1-(4-methylphenyl)butyl)amino)carbonyl)-3,3-diethyl - 4-oxo-2-azetidinyl)oxyl]benzoic acid and V/K for HLE-catalyzed substrate hydrolysis indicate that a single ionizable group with a pK of approximately 7 must be deprotonated for both processes. This group is likely the active site histidine. The data are consistent with initial formation of a Michaelis complex, acylation of the catalytic serine, and loss of the leaving group at C-4 of the original beta-lactam ring followed by partitioning between regeneration of active enzyme and production of a stable enzyme-inhibitor complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Catalysis↗
PubMed1993

Electrospray ionization mass spectrometry as a mechanistic tool: mass of human leucocyte elastase and a beta-lactam-derived E-I complex.

We have utilized liquid chromatography electrospray ionization mass spectrometry (ESI-MS) to probe the nature of the covalent E-I complex of human leucocyte elastase (HLE) and a beta-lactam. The mass spectrum of HLE isozyme 4 displayed one major and two minor components with masses of 25,202, 25,043, and 24,522 Da, respectively. Isozyme 3 displayed three components, with masses of 25,180, 24,030, and 24,523 Da. These data suggest that the isozymes differ in the type and not the content of carbohydrate. The minor components represent decreases in carbohydrate content. Inactivation of isozyme 4 with trans-4-(ethoxycarbonyl)-3-ethyl-1-[(4-nitrophenyl)sulfonyl]-azetidin -3-one increased the mass of the three components by that of the parent compound. Similar results were obtained with the mixture of HLE isozymes. These observations demonstrate that HLE does not catalyze the beta-elimination of p-nitrophenylsulfinate as Firestone et al. [(1990) Tetrahedron 46, 2255) suggested. In addition, it suggests that a "double hit" of both the active-site serine and histidine is not required to form a stable acyl-enzyme. Noncovalent complexes between HLE and either the tight-binding secretory leucoprotease inhibitor (SLPI) or a slow tight-binding peptide difluoroketone inhibitor were not observed by ESI-MS. SLPI displayed a mass of 11,710 Da in the absence and presence of HLE. These data demonstrate the utility of ESI-MS to probe the mechanism of inhibition of enzymes by mechanism-based inhibitors.

Anti-Bacterial Agents↗
PubMed1993

Evidence that removal of capsaicin accelerates desensitization on the tongue.

It has previously been shown that repeated presentations of a moderate concentration of capsaicin could either sensitize or desensitize the tongue, depending upon the temporal pattern of stimulation. Only when stimulation was halted for 5 min or longer did sensitization begin to give way to desensitization. The apparent necessity of a hiatus in stimulation led to the hypothesis that desensitization involved an inability to re-excite quiescent fibers rather than a progressive suppression of stimulated fibers. This hypothesis was tested in the present study by measuring the perceptual response to a non-desensitizing irritant, zingerone, when it was presented at the rate of l/min following a series of capsaicin conditioning stimuli. After an initial, brief period of cross-hyper-sensitization, cross-desensitization developed at a rate equivalent to that observed when no stimulus was presented. Thus, the results disproved the hypothesis that desensitization cannot occur if capsaicin-sensitive fibers continue to be stimulated, and suggested that after an initial period of excitation, the removal of capsaicin accelerates the desensitization process. This seeming paradox is discussed in terms of the neural mechanisms that may underlie capsaicin desensitization.

Capsaicin↗