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1.
Public Health ; 145: 7-19, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28359394

ABSTRACT

OBJECTIVES: We assessed preferences of social media-using young black, Hispanic and white men-who-have-sex-with-men (YMSM) for oral fluid rapid HIV self-testing, as compared to other currently available HIV testing options. We also identified aspects of the oral fluid rapid HIV self-test that might influence preferences for using this test instead of other HIV testing options and determined if consideration of HIV testing costs and the potential future availability of fingerstick rapid HIV self-testing change HIV testing preferences. STUDY DESIGN: Anonymous online survey. METHODS: HIV-uninfected YMSM across the United States recruited from multiple social media platforms completed an online survey about willingness to use, opinions about and their preferences for using oral fluid rapid HIV self-testing and five other currently available HIV testing options. In a pre/post questionnaire format design, participants first indicated their preferences for using the six HIV testing options (pre) before answering questions that asked their experience with and opinions about HIV testing. Although not revealed to participants and not apparent in the phrasing of the questions or responses, the opinion questions concerned aspects of oral fluid rapid HIV self-testing (e.g. its possible advantages/disadvantages, merits/demerits, and barriers/facilitators). Afterward, participants were queried again about their HIV testing preferences (post). After completing these questions, participants were asked to re-indicate their HIV testing preferences when considering they had to pay for HIV testing and if fingerstick blood sample rapid HIV self-testing were an additional testing option. Aspects about the oral fluid rapid HIV self-test associated with increased preference for using the test (post-assessment vs pre-assessment of opinion topics) were identified through multivariable regression models that adjusted for participant characteristics. RESULTS: Of the 1975 YMSM participants, the median age was 22 years (IQR 20-23); 19% were black, 36% Hispanic, and 45% white; and 18% previously used an oral fluid rapid HIV self-test. Although views about oral fluid rapid HIV self-testing test were favorable, few intended to use the test. Aspects about the oral fluid rapid HIV self-test associated with an increased preference for using the test were its privacy features, that it motivated getting tested more often or as soon as possible, and that it conferred feelings of more control over one's sexual health. Preferences for the oral fluid rapid HIV self-test were lower when costs were considered, yet these YMSM were much more interested in fingerstick blood sampling than oral fluid sampling rapid HIV self-testing. CONCLUSIONS: Despite the perceived advantages of the oral fluid rapid HIV self-test and favorable views about it by this population, prior use as well as future intention in using the test were low. Aspects about oral fluid rapid HIV self-testing identified as influential in this study might assist in interventions aimed to increase its use among this high HIV risk population as a means of encouraging regular HIV testing, identifying HIV-infected persons, and linking them to care. Although not yet commercially available in the United States, fingerstick rapid HIV self-testing might help motivate YMSM to be tested more than oral fluid rapid HIV self-testing.


Subject(s)
Black People/psychology , Black or African American/psychology , HIV Infections/diagnosis , Hispanic or Latino/psychology , Homosexuality, Male/psychology , Mass Screening/methods , Mouth/virology , Social Media , Adolescent , Adult , Black or African American/statistics & numerical data , Black People/statistics & numerical data , Cross-Sectional Studies , HIV Infections/prevention & control , HIV Infections/psychology , Hispanic or Latino/statistics & numerical data , Homosexuality, Male/statistics & numerical data , Humans , Internet , Male , Mass Screening/trends , Sexual Behavior , Surveys and Questionnaires , United States , Young Adult
2.
Int J STD AIDS ; 24(4): 323-8, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23970665

ABSTRACT

Routine screening is a key component of sexually transmitted infection (STI) prevention and control; however, traditional programmes often fail to effectively reach men and women in hidden communities. To reduce prevalence, we must understand the programmatic features that would encourage utilization of services among asymptomatic individuals. Using incentivized snowball sampling, 44 women and men recently engaging in transactional sex were recruited (24 women, 20 men); median age 37 years. Respondents were offered the opportunity to collect genital, oropharyngeal and rectal samples for STI testing and completed a face-to-face interview about their experience with self-obtained sampling. Interviews were analysed using qualitative methods. Participants were unaware of potential risk for STI, but found self-sampling in non-clinical settings to be acceptable and preferable to clinic-based testing. All participants collected genital specimens; 96% and 4% collected oropharyngeal and rectal specimens, respectively. The burden of disease in this population was high: 38% tested positive for at least one STI. We detected multiple concomitant infections. Incorporating field collection of self-obtained samples into STI control programmes may increase utilization among high-risk populations unlikely to access clinic-based services. High infection rates indicate that individuals engaging in transactional sex would benefit from, and be responsive to, community-based self-sampling for STI screening.


Subject(s)
Mass Screening/methods , Patient Acceptance of Health Care , Patient Participation , Sex Work , Sexually Transmitted Diseases/diagnosis , Adult , Feasibility Studies , Female , Health Knowledge, Attitudes, Practice , Humans , Interviews as Topic , Male , Middle Aged , Patient Preference , Prevalence , Qualitative Research , Self Care , Sex Workers/statistics & numerical data , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/prevention & control , Specimen Handling , Surveys and Questionnaires , Young Adult
3.
Int J STD AIDS ; 22(8): 442-8, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21742813

ABSTRACT

HIV/AIDS disproportionately impacts men who have sex with men (MSM) in the USA. Most existing literature on MSM with HIV focuses on transmission risk, but does not acknowledge health-promoting sexual behaviours men may undertake. This study examined sex toy use within this population to describe the extent to which using toys is incorporated into their sexual repertoires as a risk reduction practice. Data regarding sociodemographics, sexual/health-related behaviours and sex toy use were collected from 2275 MSM using an online survey. Most participants reported being sexually active (88.5%), and the majority (70.2%) of participants reported sex toy use within the previous year. Sex toy users were more likely to be white, in sexual relationships with others, and reported higher levels of sexual satisfaction. Given that sex toy use is common among this population, room for discussion exists about sex toys as tools to enhance pleasure and reduce HIV/sexually transmitted infection (STI) transmission.


Subject(s)
HIV Seropositivity/epidemiology , Homosexuality, Male , Sexual Behavior , Adult , Aged , Chi-Square Distribution , Humans , Male , Middle Aged , Play and Playthings , Sexual Partners , United States/epidemiology
4.
Sex Transm Infect ; 86(5): 400-3, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20448100

ABSTRACT

BACKGROUND: Condom use is a key part of sexually transmitted infection (STI) prevention for young men. Yet little is known about how younger adolescent boys initially learn about and use condoms. We examined sources of information, attitudes towards, acquisition, practice and early use of condoms among 14-16-year-old boys. METHODS: Thirty 14-16-year-old boys were recruited from a teen clinic serving a community with high STI rates and were asked open-ended questions about condoms, such as, "Where did you learn about condoms?" and "In what situations would you/would you not, use condoms." Interviews were audio recorded, transcribed and coded. Qualitative analysis focused upon key concepts and shared social cognitions related to condom use. RESULTS: Both sexually inexperienced and experienced participants perceived that sex feels or would feel less pleasurable with condoms. For almost all participants, families were the primary source of both information about condoms and of condoms themselves. This information focused on pregnancy prevention, with STIs secondary. Participants' views of condoms fell into three developmental groups: not interested in condoms and equating their use with interest in sex; exploring condoms out of either curiosity or in preparation for sex; and experienced with condom use. Exploring included behaviours such as checking condoms out and trying them on. CONCLUSIONS: Our findings of existing negative perceptions of condoms, the importance of families in learning about condoms and the developmental need to test and try on condoms before use have implications for adolescent STI prevention programmes.


Subject(s)
Adolescent Development , Attitude to Health , Condoms/statistics & numerical data , Patient Education as Topic , Adolescent , Family Health , Humans , Interpersonal Relations , Male , Sexual Behavior , Time Factors
5.
Int J STD AIDS ; 21(4): 260-4, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20378897

ABSTRACT

Rectal sexually transmitted infections (STIs) are common in men at risk for urethral infections with these pathogens, particularly men who have sex with men (MSM). However, for those individuals not regularly seen by a clinician, screening for rectal STI is not currently a widespread option. Qualitative data and samples (i.e. self-obtained rectal specimens) were collected from 75 MSM in a variety of venues. Upon completion of the rectal self-sampling, each participant completed a brief interview regarding their overall experience with the process. Participants reported an overall high level of acceptability and comfort-level involved with self-sampling for rectal STI. Of the majority of men who agreed to provide a rectal self-sample, all reported that they would provide a sample again in the future. However, many men also appreciated the interaction with a health-care provider that a clinical setting offered. In conclusion, self-sampling is a feasible and acceptable option when offered to MSM in a range of community-based venues. Further research is needed to determine which combinations of STI testing and treatment methods (including self-sampling) are most appropriate for diverse groups of men.


Subject(s)
Chlamydia Infections/diagnosis , Chlamydia trachomatis/isolation & purification , Feces/microbiology , Gonorrhea/diagnosis , Homosexuality, Male , Specimen Handling , Adolescent , Adult , Feasibility Studies , Humans , Male , Middle Aged , Self Care , Young Adult
6.
Can J Physiol Pharmacol ; 76(3): 278-83, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9673791

ABSTRACT

Chronic continuous cocaine administration for 3 days has been shown to upregulate the level of mu opioid receptor (MOR) mRNA in the nucleus accumbens (n. acc.) of rat brain. Dopamine (DA) antagonists, SCH 23390, eticlopride, and nafadotride, blocked, and DA agonists, SKF 38393, R(+)-6-bromo-APB hydrobromide, and bromocriptine, mimicked the cocaine-induced upregulation of MOR mRNA, suggesting involvement of both subfamilies of DA receptors in the effect of cocaine. In the present study the time course of cocaine-induced and DA agonist induced alterations in the level of MOR mRNA in n. acc. has been determined and compared with the changes in the level of MOR binding sites. Male Sprague-Dawley rats were treated with saline, cocaine (50 mg.kg-1.day-1), or DA agonists for periods between 24 and 336 h. Expression of MOR mRNA in n. acc. was estimated using quantitative competitive polymerase chain reaction assays following reverse transcription. The cocaine-induced upregulation of MOR mRNA in n. acc. was transient, developing 2 days after exposure, and peaking at 3 days with return to baseline levels by 4 days of chronic continuous cocaine treatment. The temporal characteristics of DA agonist induced increase in the levels of MOR mRNA in n. acc. were similar to those of cocaine, with maximum effect after 3 days of treatment. The density of [3H]DAMGO binding sites in n. acc. was 30% higher after 3 days of cocaine administration than in saline-treated control animals, but returned toward baseline levels after 4 days of cocaine treatment. No changes in the binding of [3H]DAMGO were detected after 7 or 14 days exposure to cocaine. The affinity of [3H]DAMGO to n. acc. membranes (approximately 2.0 nM) was unchanged during the cocaine treatment.


Subject(s)
Cocaine/pharmacology , Nucleus Accumbens/drug effects , Receptors, Opioid, mu/metabolism , 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/analogs & derivatives , 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology , Analgesics, Opioid/pharmacology , Animals , Benzopyrans/pharmacology , Bromocriptine/pharmacology , Cocaine/administration & dosage , Dopamine Agonists/pharmacology , Dopamine Uptake Inhibitors/administration & dosage , Dopamine Uptake Inhibitors/pharmacology , Enkephalin, Ala(2)-MePhe(4)-Gly(5)- , Enkephalins/pharmacology , Gene Expression Regulation , Male , Nucleus Accumbens/metabolism , Oxazines/pharmacology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Time Factors , Up-Regulation/drug effects
7.
Life Sci ; 52(16): PL141-5, 1993.
Article in English | MEDLINE | ID: mdl-8464332

ABSTRACT

Binding of the potent cocaine analog [3H]WIN 35,428 (2 beta-carbomethoxy-3 beta-(4-fluoro-phenyl)-tropane) was examined in membrane homogenates prepared from fresh rat caudate-putamen. The number of rinses of the membranes following incubation with the ligand was varied. After one wash, only a single binding site was evident. With an increasing number of washes, however, two binding sites were observed. Additional rinses, up to a total of four, led to a decrease in the number of low affinity binding sites, with no change in the number of high affinity sites. These results suggest that the methodology used in these binding assays may be important for interpretation of the results.


Subject(s)
Caudate Nucleus/metabolism , Cocaine/analogs & derivatives , Putamen/metabolism , Animals , Binding Sites , Cocaine/metabolism , In Vitro Techniques , Male , Radioligand Assay , Rats , Rats, Sprague-Dawley
8.
Life Sci ; 50(8): 541-7, 1992.
Article in English | MEDLINE | ID: mdl-1736024

ABSTRACT

Cocaine inhibits both [3H]dopamine and [3H]serotonin uptake in rat striatum and nucleus accumbens. In a chopped tissue slice preparation, the inhibition curve for [3H]dopamine uptake is biphasic, suggesting two components of uptake, whereas the curve for [3H]serotonin uptake is steep and apparently monophasic. In synaptosomal preparations, both curves are monophasic. Monensin, a sodium ionophore, inhibits uptake but does not change the shape of the cocaine inhibition curve in synaptosomes, suggesting that the biphasic inhibition curves in slices are not likely due to differential sodium gradients across the slices. In tissue slices, only the component which is more sensitive to inhibition by cocaine and related drugs is inhibitable by nicotine. This suggests that the two components of dopamine uptake in tissue slices may be differentially regulated.


Subject(s)
Cocaine/pharmacology , Dopamine/pharmacokinetics , Serotonin/pharmacokinetics , Synaptosomes/metabolism , Animals , Corpus Striatum/metabolism , Dose-Response Relationship, Drug , In Vitro Techniques , Male , Monensin/pharmacology , Rats , Rats, Inbred Strains , Tritium
9.
J Neurochem ; 56(2): 603-10, 1991 Feb.
Article in English | MEDLINE | ID: mdl-1988558

ABSTRACT

The effects of both (-)- and (+)-nicotine isomers were examined on in vitro uptake and release of [3H]dopamine in rat striatum. Both isomers inhibited uptake of [3H]dopamine in chopped tissue at concentrations well below those necessary for promoting release of preloaded [3H]dopamine. (-)-Nicotine was more potent than (+)-nicotine both at inhibiting uptake and at promoting release. Unlike other dopamine uptake inhibitors, however, nicotine inhibited only 50% of the total uptake. In the presence of 1 nM nicotine, the residual [3H]dopamine uptake was less sensitive to inhibition by cocaine than uptake in the absence of nicotine. Nicotine did not compete against the binding of [3H]GBR 12935, a selective dopamine uptake inhibitor. The nicotinic receptor agonists carbachol and 1,1-dimethyl-4-phenylpiperazinium iodide also inhibited uptake, whereas the nicotinic antagonists chlorisondamine and mecamylamine blocked nicotine's effect. Thus, the effect of nicotine on dopamine uptake appears to be mediated by a receptor similar to the nicotinic acetylcholine receptor. These receptors do not seem to be on the terminals that are accumulating dopamine, however, since tetrodotoxin prevented the effect of nicotine on [3H]dopamine uptake and nicotine had no effect on uptake in a synaptosomal preparation.


Subject(s)
Corpus Striatum/metabolism , Dopamine/metabolism , Nicotine/pharmacology , Animals , Binding, Competitive , Carbachol/pharmacology , Chlorisondamine/pharmacology , Cocaine/pharmacology , Corpus Striatum/drug effects , Dimethylphenylpiperazinium Iodide/pharmacology , Dose-Response Relationship, Drug , Male , Mecamylamine/pharmacology , Nicotine/administration & dosage , Nicotine/metabolism , Piperazines/metabolism , Rats , Rats, Inbred Strains , Receptors, Nicotinic/drug effects , Receptors, Nicotinic/physiology , Synaptosomes/drug effects , Synaptosomes/metabolism
10.
Neuropharmacology ; 29(11): 1017-24, 1990 Nov.
Article in English | MEDLINE | ID: mdl-2087254

ABSTRACT

The binding characteristics of [3H]GBR 12935 (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine), a selective dopmaine uptake inhibitor, were examined in intact membrane preparations and solubilized extracts of terminal field regions of dopamine pathways in the brain of the rats. There were many similarities in the properties of binding sites for [3H]GBR 12935 in the striatum, nucleus accumbens and olfactory tubercle. The binding of [3H]GBR 12935 was saturable and the affinity constants were not significantly different between regions of the brain. The binding of [3H]GBR 12935 was inhibited by amfonelic acid, GBR 12909, mazindol, methylphenidate and cocaine, with comparable affinities in each region of the brain and with the same order of potency in both preparations. Furthermore, the rank order of potencies for inhibiting the binding of [3H]GBR 12935 was the same as for inhibiting the uptake of [3H]dopamine in these regions of the brain. There did appear to be some degree of heterogeneity of binding sites for [3H]GBR 12935 in each of these regions of the brain, as both amfonelic acid and mazindol were best fitted by two-site models. Whether this apparent heterogeneity was due to the existence of two distinct binding sites or to two components of a single site is unclear. It did not, however, appear to be due to binding to uptake sites for norepinephrine or serotonin, as neither nisoxetine nor fluoxetine, selective inhibitors of the uptake of norepinephrine and serotonin, respectively, inhibited the binding of [3H]GBR 12935, at concentrations which inhibit the uptake of norepinephrine or serotonin.


Subject(s)
Brain/metabolism , Dopamine/metabolism , Piperazines/metabolism , Animals , Binding Sites , Binding, Competitive , Cell Membrane/metabolism , Cerebral Cortex/metabolism , Corpus Striatum/metabolism , Kinetics , Limbic System/metabolism , Male , Nucleus Accumbens/metabolism , Olfactory Bulb/metabolism , Organ Specificity , Rats , Rats, Inbred Strains , Solubility , Substantia Nigra/metabolism
11.
Peptides ; 10(3): 621-6, 1989.
Article in English | MEDLINE | ID: mdl-2780421

ABSTRACT

The possible existence in rat brain tissues of shorter peptides related to VIP has been examined. VIP and PHI both contain paired basic amino acid residues at which posttranslational cleavage of these peptides might occur. Antiserum to VIP(22-28) was raised in rabbits. The antiserum was carboxy-terminus directed, showing cross-reactivity with all tested peptides containing the VIP carboxy-terminus sequences. Chromatographic analysis of rat brain extracts demonstrated that recovered VIP(22-28) immunoreactivity [VIP(22-28)-ir] was heterogeneous, consisting of a major fraction [60-70% of total VIP(22-28)-ir] which eluted as authentic VIP(1-28) on gel filtration and on reversed phase high performance liquid chromatography (HPLC) columns. A second fraction (30-35% of total VIP(22-28)-ir] eluted from gel filtration columns in the position of VIP(22-28). HPLC analysis of this fraction from extracts of rat cortex, hippocampus, and midbrain indicated that it was heterogeneous. One component corresponded to authentic VIP(22-28). The other two components have not been identified; one appears to be a VIP fragment intermediate in size between VIP(1-28) and VIP(22-28).


Subject(s)
Brain Chemistry , Peptide Fragments/analysis , Vasoactive Intestinal Peptide/analysis , Animals , Chromatography, Gel , Male , Organ Specificity , Radioimmunoassay , Rats , Rats, Inbred Strains
12.
Regul Pept ; 19(1-2): 1-12, 1987 Oct.
Article in English | MEDLINE | ID: mdl-2891155

ABSTRACT

Tissues of the reproductive tract have been shown to contain mRNAs coding for pro-opiomelanocortin (POMC), pro-enkephalin and pro-dynorphin. However, the amounts of immunoreactive opioid peptides in these tissues are low, and in the case of the enkephalins and dynorphin, the molecular species responsible for the immunoreactivities have not been characterized. The chromatographic properties of dynorphin and enkephalin immunoreactivities in extracts of guinea pig and rat testis have therefore been determined. Dynorphin A and dynorphin B immunoreactivity was heterogeneous, with a significant amount attributable to high-molecular-weight forms. About 20% of the dynorphin A immunoreactivity, and about 40% of the dynorphin B immunoreactivity, in guinea pig testis extracts behaved as authentic dynorphin A or B, respectively during fractionation by ion exchange, gel filtration and high-performance liquid chromatography. Both high- and low-molecular-weight forms of [Leu5]enkephalin immunoreactivity were also present, with roughly 50-70% of the immunoreactivity attributable to low-molecular-weight forms. In extracts of guinea pig testis only a small part of this immunoreactivity eluted as authentic [Leu5]enkephalin during high-performance liquid chromatography. In rat testis most of the low-molecular-weight [Leu5]enkephalin immunoreactivity behaved as the authentic peptide. These results confirm that opioid peptides are produced in guinea pig and rat testis, and demonstrate that immunoreactive forms of the peptides similar to those found in brain and pituitary are present in the tissue.


Subject(s)
Dynorphins/analysis , Enkephalin, Leucine/analysis , Testis/analysis , Animals , Chromatography, Gel , Chromatography, High Pressure Liquid , Chromatography, Ion Exchange , Dynorphins/immunology , Enkephalin, Leucine/immunology , Guinea Pigs , Male , Radioimmunoassay , Rats , Species Specificity
13.
Endocrinology ; 119(5): 2297-305, 1986 Nov.
Article in English | MEDLINE | ID: mdl-2876888

ABSTRACT

The total content of rat pituitary anterior lobe (AL) immunoreactive (ir) dynorphin A (ir-Dyn A) and ir-dynorphin B (Dyn B) increased in male rats between 15 and 58 days of age, but there was little alteration in the concentration of ir-Dyn A or B expressed relative to protein content. Adult rats (90 days of age) had lower concentrations of these peptide immunoreactivities in the AL. Castration of 58-day-old male rats produced a testosterone-reversible loss of ir-Dyn A and B by 50-60% 3 days after surgery. Thereafter, the levels of these peptides gradually increased to 2.5 times the levels found in control animals at 1 month after castration. These effects of castration on AL dynorphin were not seen in 15-day-old rats and were much less marked in adults. Similar changes were seen in the levels of other prodynorphin products, alpha- and beta-neo-endorphin (ir-alpha-nEnd and ir-beta-nEnd), and ir-[Leu5]enkephalin (ir-LE). Administration of testosterone (100 micrograms/100 g BW) to castrated rats for 2 days largely prevented the drop in the levels of AL ir-Dyn A and B. Ovariectomy produced an increase in the levels of ir-Dyn A, Dyn B, alpha-nEnd, beta-nEnd, and LE 2 weeks after surgery, but, in contrast to castration, no significant decrease was seen 3 days after ovariectomy. These changes in AL content of dynorphin-related peptides after castration or ovariectomy directly reflect those previously reported for AL content of LH. The mechanisms regulating storage (and perhaps secretion) of AL peptides derived from prodynorphin may be similar to those regulating storage and secretion of LH and FSH in rat AL. AL ir-LE could potentially arise from proenkephalin A or prodynorphin (proenkephalin B). Ir-LE levels in AL were approximately 10 times higher than the levels of ir-[Met5]-enkephalinyl-Arg-Gly-Leu (ME-RGL) in male rat AL, and changes in ir-LE content after castration were very similar to those observed in other prodynorphin-derived peptides, but different from the effects of castration on ir-ME-RGL. It is possible that prodynorphin is a major source of AL ir-LE.


Subject(s)
Enkephalins/metabolism , Gonadal Steroid Hormones/physiology , Pituitary Gland, Anterior/metabolism , Protein Precursors/metabolism , Animals , Dynorphins/analogs & derivatives , Dynorphins/metabolism , Endorphins/metabolism , Enkephalin, Leucine/metabolism , Female , Male , Orchiectomy , Ovariectomy , Rats , Testosterone/pharmacology
14.
Am J Physiol ; 249(3 Pt 1): E244-50, 1985 Sep.
Article in English | MEDLINE | ID: mdl-2863984

ABSTRACT

The effect of hemorrhagic shock (40% of blood vol) on the distribution of immunoreactive dynorphin A (Dyn A-IR), [Arg8]vasopressin (AVP-IR), and [Leu5]enkephalin (LE-IR) in the pituitary and brain nuclei was studied in the conscious rat. At 24 h after hemorrhage, the neurointermediate lobe (NIL) showed a reduction in Dyn A-IR (52%) and AVP-IR (32%) and an increase in LE-IR (72%); at this time, the anterior lobe also showed decreased Dyn A-IR (50%) and increased LE-IR (210%). Dyn A-IR, but not LE-IR, was also significantly depleted in some forebrain nuclei in all experimental groups as compared with intact controls, whereas Dyn A-IR in the hypothalamic ventromedial nucleus was elevated only in the sham-control rats. AVP-IR was elevated in the supraoptic nucleus and median eminence (200 and 31%, respectively) 2 and 24 h after bleeding, although plasma AVP returned to normal levels. These data indicate that stress and hypovolemic hypotension produce site and time-dependent change in distribution of dynorphins, AVP, and LE in the central nervous system.


Subject(s)
Arginine Vasopressin/analysis , Brain Chemistry , Dynorphins/analysis , Enkephalin, Leucine/analysis , Pituitary Gland/analysis , Shock, Hemorrhagic/physiopathology , Animals , Arginine Vasopressin/blood , Blood Pressure , Heart Rate , Hematocrit , Male , Radioimmunoassay , Rats , Rats, Inbred Strains , Tissue Distribution
15.
Regul Pept ; 11(1): 35-41, 1985 May.
Article in English | MEDLINE | ID: mdl-2861626

ABSTRACT

Opiate antagonists, at high doses, have been shown to improve physiological variables and outcome after experimental spinal injury. Dynorphin appears to be unique amongst opioids in producing hindlimb paralysis after intrathecal injection. Taken together, these findings suggest a possible pathophysiological role for endogenous opioids, particularly dynorphin, in spinal injury. In the present studies we examined the relationship between changes in dynorphin immunoreactivity (Dyn-ir) in rat spinal cord after traumatic injury and the subsequent motor dysfunction. Trauma was associated with significantly increased Dyn-ir at the injury site, but not distant from the lesion. Dyn-ir was found elevated as early as 2 h and as late as 2 weeks after trauma, and was significantly correlated with the degree of injury. These data are consistent with the hypothesis that dynorphin systems may be involved in the secondary injury that follows spinal trauma.


Subject(s)
Dynorphins/analysis , Spinal Cord Injuries/physiopathology , Animals , Dynorphins/physiology , Male , Naloxone/pharmacology , Naloxone/therapeutic use , Narcotic Antagonists/pharmacology , Narcotic Antagonists/therapeutic use , Paraplegia/etiology , Paraplegia/prevention & control , Rats , Rats, Inbred Strains , Receptors, Opioid/drug effects , Receptors, Opioid, kappa , Spinal Cord/analysis , Spinal Cord Injuries/complications , Spinal Cord Injuries/metabolism
16.
Ann Neurol ; 17(4): 386-90, 1985 Apr.
Article in English | MEDLINE | ID: mdl-2860844

ABSTRACT

It has been postulated that endogenous opioids play a pathophysiological role in spinal cord injury, based on the therapeutic effects of the opiate receptor antagonist naloxone in certain experimental models. The high doses of naloxone required to exert a therapeutic action suggest that naloxone's effects may be mediated by non-mu opiate receptors, such as the kappa receptor. This notion is supported by recent pharmacological studies demonstrating that an opiate antagonist more active at kappa sites is effective and far more potent than naloxone in improving outcome after spinal cord injury. Moreover, dynorphin--postulated to be the endogenous ligand for the kappa receptor--is unique among opioids in producing hindlimb paralysis following intrathecal administration in the rat. In the present studies we have examined changes in endogenous opioid immunoreactivity following traumatic spinal cord injury in the rat. Dynorphin A was found to increase progressively with graded injury; changes were restricted to the injury segment and adjacent areas and were time dependent. Dynorphin A-(1-8) showed no marked changes. Methionine and leucine enkephalin were either unaltered or reduced at the injury site; changes were not well localized and were not clearly related to the injury variables. These findings provide further support for a potential pathophysiological role of prodynorphin-derived peptides in spinal cord injury.


Subject(s)
Endorphins/analysis , Spinal Cord Injuries/metabolism , Animals , Dynorphins/analysis , Enkephalin, Methionine/analysis , Leucine/analysis , Peptide Fragments/analysis , Radioimmunoassay , Rats , Rats, Inbred Strains , Spinal Cord/metabolism , Time Factors
17.
Neuropeptides ; 5(4-6): 571-4, 1985 Feb.
Article in English | MEDLINE | ID: mdl-2860614

ABSTRACT

Traumatic spinal cord injury in rats resulted in a significant eleation of dynorphin A immunoreactivity in spinal cord tissue at the level of, and below, the site of injury. [Leu5]enkephalin levels in the same tissue samples were not significantly altered following severe injury. Dynorphin A immunoreactivity was found in the fraction relatively enriched in synaptosomes after subcellular fractionation of spinal cord tissue. The dynorphin A content of this fraction was not significantly changed following injury, suggesting that dynorphin containing nerve terminals and axons are not severely damaged as a result of the injury.


Subject(s)
Dynorphins/analysis , Enkephalin, Leucine/analysis , Spinal Cord Injuries/metabolism , Spinal Cord/analysis , Animals , Male , Rats , Rats, Inbred Strains , Subcellular Fractions/analysis , Synaptosomes/analysis
18.
J Neurochem ; 43(6): 1616-23, 1984 Dec.
Article in English | MEDLINE | ID: mdl-6149267

ABSTRACT

Homogenates of rat anterior lobe (AL) and neurointermediate lobe (NIL) pituitary and rat hypothalamus were subjected to subcellular fractionation and density gradient centrifugation. The subcellular distribution of immunoreactive dynorophin A (ir-Dyn A) in NIL was found to be similar to that of ir-arginine vasopressin (ir-AVP). ir-Dyn A migrated as a discrete band on sucrose density gradients, which corresponded in sedimentation rate to that of ir-AVP, suggesting that these two peptides are stored within organelles of similar size and density. Two other products of prodynorphin, ir-alpha-neoendorphin (ir-alpha-nEND) and ir-Dyn A-(1-8) also comigrated with ir-AVP. ir-[Leu5]-enkephalin (ir-LE), which may be a product of prodynorphin or proenkephalin, was also found to migrate in this region of the gradient. When a homogenate of rat hypothalamus was prepared using a method that has been developed for synaptosome isolation, ir-Dyn A was found to comigrate with Na+/K+-activated adenosine triphosphatase (Na/K-ATPase), a synaptosomal marker enzyme. Using a more concentrated homogenate ir-Dyn A was found to migrate to a less dense region where peptide-containing synaptic vesicles have previously been localized. When a synaptosomal preparation was lysed in hypotonic solution a shift was seen in the migration rate of ir-Dyn A to this region of the gradient (containing putative synaptic vesicles). Thus the bulk of hypothalamic dynorphin appears to be present within synaptosome-like structures which, upon lysis, release a less dense, smaller subcellular organelle corresponding in sedimentation characteristics to other types of peptide-containing synaptic vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Endorphins/metabolism , Hypothalamus/ultrastructure , Pituitary Gland/ultrastructure , Animals , Arginine Vasopressin/metabolism , Centrifugation, Density Gradient , Dynorphins/metabolism , Enkephalin, Leucine/metabolism , Enkephalin, Methionine/analogs & derivatives , Enkephalin, Methionine/metabolism , Male , Peptide Fragments/metabolism , Protein Precursors/metabolism , Rats , Rats, Inbred Strains , Subcellular Fractions/metabolism , Synaptic Vesicles/metabolism , Synaptosomes/metabolism
20.
Peptides ; 4(2): 225-9, 1983.
Article in English | MEDLINE | ID: mdl-6622288

ABSTRACT

The distribution of dynorphin 1-13 (Dyn-1-13, Dyn-(1-8) and Leu5-enkephalin (LE) immunoreactivities (ir) were determined in discrete brain nuclei of normotensive (WKY) and hypertensive (SHR) rats. The concentration of ir-Dyn-(1-13) and ir-Dyn-(1-8) varied markedly among the various nuclei studies with a predominance of ir-Dyn-(1-13) over ir-Dyn-(1-8) in all the nuclei of both WKY and SHR rats. Ir-LE also showed large variations in different sites and no consistent relationships were found between the distribution of ir-Dyn-(1-8), Dyn-(1-13) and LE. SHR rats had lower levels of ir-Dyn-(1-13), Dyn-(1-8) and LE in the suprachiasmatic nucleus compared with WKY rats. In addition, SHR rats had lower levels of ir-Dyn-(1-8)- in the paraventricular and central amygdala, and higher ir-Dyn-(1-13) levels in the substantia nigra. The level of ir-Dyn-(1-13) in the neurointermediate lobe (NIL) of SHR rats was decreased substantially compared with that of WKY rats. The localization of these opioid peptides suggests that dynorphin-like peptides may serve a variety of hypothalamic and extrahypothalamic functions which might differ between SHR and WKY rats.


Subject(s)
Brain Chemistry , Dynorphins , Endorphins/analysis , Enkephalin, Leucine/analysis , Hypertension/metabolism , Peptide Fragments/analysis , Pituitary Gland/analysis , Animals , Male , Radioimmunoassay/methods , Rats , Rats, Inbred Strains , Species Specificity
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