Comment: risk of drug-disease and disease-drug interactions with anticonvulsants in HIV-positive patients.
Explore the source record for details and available documents.
Anticonvulsants↗
Biomedical subjects
F Romanelli
Publications and source records attributed to F Romanelli.
The use of valproic acid in HIV-positive patients.
OBJECTIVE: To review the use of valproic acid in HIV-positive patients. DATA SOURCES: Clinical literature was accessed through a MEDLINE search (January 1966-November 1998). Key search terms included HIV, AIDS, seizures, valproic acid, and glutathione. DATA SYNTHESIS: Patients with HIV often develop neurologic manifestations; therefore, valproic acid may be considered in the management of this population. It has been demonstrated that valproate may increase viral burden by potentiating replication. An evaluation of studies addressing the use of valproic acid in HIV-positive patients was conducted. CONCLUSIONS: The potential for valproate-induced increases in viral replication exists. Although further studies are warranted, clinicians should exercise caution when using valproate in HIV-positive patients.
Anticonvulsants↗
Hydroxyurea to inhibit human immunodeficiency virus-1 replication.
Treatment of human immunodeficiency virus (HIV) infection continues to be a challenge. Drug regimens that include two nucleoside reverse transcriptase inhibitors and a protease inhibitor are now the standard of care. These regimens require strict patient adherence and have numerous adverse effects at a high cost, so clinicians must continue to explore other therapeutic options. Hydroxyurea is a ribonucleotide reductase inhibitor that may have efficacy against HIV. We conducted a critical review of the literature to examine the utility of hydroxyurea-based drug combinations.
Anti-HIV Agents↗
Galanin stimulates steroidogenesis in rat Leydig cells.
The present study was designed to evaluate whether galanin could play a role in the regulation of testicular steroidogenesis. To this purpose, using purified rat Leydig cells, we examined the effects of galanin on basal and hCG- or LHRH-induced testosterone production and the interference of a specific galanin receptor antagonist, galantide, on galanin activity. Moreover, since it has been shown that galanin-induced stimulation of LHRH secretion appears to involve the release of prostaglandin E2 (PGE2) as intracellular mediator, we evaluated also the effect of galanin on Leydig cells PGE2 output and the interference of indomethacin, a cycloxygenase blocker, on its activity. Furthermore, the effect of nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, was also examined. Data obtained indicate that galanin amplified testosterone response to hCG or LHRH whilst galantide prevented its potentiating activity. Moreover, galanin stimulated PGE2 output though this fatty acid is not involved in galanin activity on Leydig cells as indomethacin failed to affect its amplification of testosterone production. The possible involvement of leukotrienes should also be excluded as NDGA did not modify galanin action. In summary, the present study indicates that galanin potentiates acute gonadotropin or LHRH steroidogenic action on Leydig cells and that this activity is specific and receptor-mediated as it is prevented by a specific receptor antagonist.
Animals↗
Stimulatory action of endothelin-1 on rat Leydig cells: involvement of endothelin-A subtype receptor and phospholipase A2-arachidonate metabolism system.
In a previous report we have observed that endothelin-1 (ET-1) is able to stimulate testosterone (T) production by rat Leydig cells revealing an interaction with human chorionic gonadotropin (hCG). The present study was designed to further characterize the stimulatory action of ET on testicular steroidogenesis, to evaluate which subtype of ET receptors is involved in this activity and to examine the role of phospholipase A2 (PLA2)-arachidonate metabolism system in ET-1 transduction mechanism. To this purpose we investigated: i) the interaction of ET-1 with another secretagogue of T, like luteinizing hormone releasing hormone (LHRH); ii) the interference of ET(A) and ET(B) receptor antagonists (BQ-123 and BQ-788, respectively) and of inhibitors of PLA2 (quinacrine) and arachidonate lipoxygenase pathway (nordihydroguaiaretic acid:NDGA) on ET-1-induced T and PGE2 secretion from purified rat Leydig cells. Data obtained indicate that ET-1 amplified T and PGE2 response to LHRH and this secretagogue in turn potentiated testicular steroidogenesis stimulated by endothelin. The ET(A) antagonist, BQ-123, inhibited in a dose-related fashion ET-1-induced T production whereas ET(B) antagonist, BQ-788, failed to affect T response to the peptide. Furthermore, ET(A) antagonist inhibited the stimulatory effect of ET-1 on hCG- or LHRH-induced T secretion and it was able to exert a dose-dependent inhibition of ET-1-stimulated PGE2 output. Moreover, a PLA2 inhibitor quinacrine inhibited the stimulatory action of ET-1 on T production and suppressed basal and ET-1-induced PGE2 release whilst a lipoxygenase blocker NDGA did not modify T response to the peptide. Taken together these findings i) indicate additivity of effects between ET-1 and LHRH in stimulating T and PGE2 production; ii) confirm that ET(A) subtype receptors mediate the stimulatory action of ET-1 on rat Leydig cells; iii) strongly suggest that PLA2-arachidonate metabolism system is involved in endothelin transduction mechanism.
Animals↗
Pituitary adenylate cyclase-activating polypeptide regulates rat Leydig cell function in vitro.
The present study was designed to evaluate the effects of both pituitary adenylate cyclase-activating polypeptide (PACAP)-27 and PACAP-38 on testosterone, cAMP and prostaglandin E2 (PGE2) production by purified rat Leyding cells. Because PACAP-38 shares homology with vasoactive intestinal peptide (VIP), the effects of VIP and both PACAP and VIP receptor antagonists on testicular steroidogenesis were also examined. PACAP-38 potentiated testosterone response to a low effective dose of human chorionic gonadotropin (hCG), while PACAP-27 was without effect. Furthermore, PACAP-38 amplified testosterone response to a wide concentration range of hCG until the submaximal dose. VIP evoked a dose-dependent increase of both basal and hCG-induced testosterone production. PACAP potentiation of steroidogenesis was nullified in the presence of a PACAP antagonist, but was not modified by a VIP antagonist. Moreover, while VIP antagonist blunted testosterone response to VIP, PACAP antagonist was without effect. Increasing concentrations of PACAP-38 evoked a dose-response enhancement of both cAMP and PGE2 production. However, this fatty acid is not involved in PACAP activity, as a prostaglandin blocker indomethacin did not modify the effect of PACAP on steroidogenesis. Taken together these findings: (i) demonstrate that PACAP-38 is able to activate both cAMP- and phosphatidylinositol-dependent mechanisms in Leydig cells; (ii) indicate that the peptide exerts an amplificatory action on testicular steroidogenesis stimulated by hCG and that this activity is receptor-mediated, as it is prevented by a PACAP receptor antagonist; (iii) predict the existence of specific PACAP receptors (type 1 binding sites) on Leydig cells.
Animals↗
Growth hormone and insulin-like growth factor I responses to moderate submaximal acute physical exercise in man: effects of octreotide, a somatostatin analogue, administration.
We evaluated growth hormone (GH) and insulin-like growth factor I (IGF-I) response to moderate submaximal acute short-term physical exercise under basal conditions and after the administration of octreotide, a somatostatin analogue (SA), in a double-blind, counter-balanced experimental protocol. Seven untrained male volunteers performed two identical exercise tests, each on a treadmill (2.5% slope) for 30 minutes (min) at 60% of VO2max. Before starting the exercise test all the subjects received a single administration of placebo or octreotide and vice versa at two different sessions. Plasma GH, IGF-I and lactate assays were evaluated before starting, during, at the end and in the recovery phase. In the placebo-treated group GH rose significantly both during exercise and recovery whereas no significant modifications in IGF-I levels were observed. SA administration inhibited the exercise-dependent GH secretion, which showed a small rise only during exercise and returned to basal levels during recovery. In the same group, IGF-I decreased significantly after exercise compared to basal values. The results suggest that 1) in our experimental conditions acute physical exercise at aerobic threshold does not modify IGF-I concentration 2) SA is able to inhibit the exercise-dependent GH secretion and to decrease post-exercise IGF-I concentration.
Adult↗
[Diagnostic imaging and therapeutic implications in lung infections in patients with HIV-1 infection].
We studied retrospectively 132 episodes of infectious pneumonias in 89 patients examined from 1990 to 1995. Pneumocystis carinii was found to be the most common cause of pneumonia (33 patients). The other causes were: Streptococcus pneumoniae (15), Mycobacterium tuberculosis (14), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Cytomegalovirus (4), Haemophilus influentiae (4), Mycobacterium avium intracellulare (2), Klebsiella pneumoniae (2), E. coli (2), Serratia marcescens (1). No etiologic agent was found in 40 cases. We stress the need of a more frequent use of invasive diagnostic procedures in the study of focal lung consolidations because this radiologic sign is highly aspecific and may be caused by too many different pathogenic agents, needing different therapies-i.e., Streptococcus pneumoniae (15 cases), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Klebsiella pneumoniae (2), Escherichia coli (2), Pneumocystis carinii, Serratia marcescens and Haemophilus influentiae (1). Since there is an increase in mortality among patients treated with empiric antibiotic therapy, we stress the need of the routinary use of bronchoalveolar lavage in HIV+ patients with lung consolidation to perform specific therapy. Moreover, Pneumocystis carinii is by far the most frequent cause of diffuse interstitial infiltrates, and PCP has very suggestive clinical (dyspnea), radiologic (diffuse perihilar interstitial infiltrates; ground glass opacities; pneumatoceles) and laboratory (CD3+CD4 < 200/mcl; LDH > 600 UI/dl; PO2 < 70 mmHg) patterns, always related to the discovery of Pneumocystis carinii in escreatum. Thus, we decided to treat 15 patients with specific therapy for Pneumocystis carinii pneumonia with the above diagnostic algorithm, obtaining in all of them complete clinical and radiologic recovery. To conclude, in critical patients, invasive procedures should be performed only in the cases in which PCP is clinically improbable.
Acquired Immunodeficiency Syndrome↗
Lattice Boltzmann algorithm for three-dimensional simulations of plasma turbulence.
Explore the source record for details and available documents.
Journal Article↗
Possible paroxetine-induced bruxism.
OBJECTIVE: To report the case of a patient with possible paroxetine-induced bruxism that was effectively treated with buspirone. CASE SUMMARY: A 20-year-old woman with no active medical conditions besides acne and no history of dental problems was seen in an outpatient psychiatry clinic for the evaluation of ongoing depression. The patient was prescribed paroxetine 10 mg every morning. After 5 days of therapy the patient reported no adverse effects, and the paroxetine dosage was increased to 20 mg every morning. Due to increased somnolence, the dosing schedule was subsequently changed to 20 mg hs. Two months later during a dental visit for a tooth extraction, the dentist noted that the patient's teeth appeared damaged in what he believed to be a pattern consistent with the grinding and clenching of teeth. Prior to this time, dental examinations had not revealed any tooth damage. The patient was thought to have paroxetine-induced bruxism and, based on earlier case reports, was treated with buspirone 5 mg hs. On day 4 of buspirone therapy the patient reported a significant reduction in the extent of gritting, tooth pain, and jaw tenderness. DISCUSSION: The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline have been associated with bruxism in previous reports. This case suggests paroxetine-induced bruxism. The exact mechanism of SSRI-induced bruxism remains unclear. Many theories have been proposed, including sleep disturbance, serotonergic-mediated inhibition of dopamine manifesting as akathisia, and SSRI-induced anxiety. According to published reports, SSRI-induced bruxism may respond to therapy with buspirone. Consistent with these reports, this patient responded favorably to buspirone therapy. CONCLUSIONS: Clinicians should be aware that the potential for paroxetine-induced bruxism exists and that buspirone may be an appropriate therapeutic intervention.
Adult↗
Aspirin inhibition of naloxone-induced luteinizing hormone secretion in man.
It is well known that endogenous opioid peptides exert a tonic inhibitory control on GnRH release, leading to the inhibition of LH secretion, whereas eicosanoids, particularly prostaglandin E2(PGE2), stimulate GnRH output. Furthermore, in vitro studies suggest the existence of an interaction between these two regulatory systems in animals. The present work was designed to evaluate the acute effect of the prostaglandin blocker aspirin on plasma LH response to the opiate antagonist naloxone or GnRH in normal volunteers in a placebo-controlled, single-blind study. To exclude a hypothetical action of aspirin directly at the testis level, plasma testosterone concentrations were monitored during basal sampling after acetylsalicylic acid ingestion, whereas the efficacy of the drug as a prostaglandin blocker was tested by the determination of seminal PGE2 levels. Aspirin pretreatment significantly lowered seminal PGE2 levels (from 86 +/- 5 before to 11 +/- 2 micrograms/mL [corrected] after drug administration; P < 0.001) without affecting testosterone concentrations. Moreover, the drug induced a significant reduction of LH response to naloxone, assessed as the mean integrated area under the curve, from 1666.5 +/- 116 to 1197.5 +/- 98 mUI/mL per min (P < 0.05), whereas it did not influence GnRH-induced LH release. We conclude that the effective cycloxygenase blockade inhibits the stimulatory activity of naloxone on LH release, suggesting that the inhibitory tone of opioids on GnRH secretion may be caused by the block of hypothalamic prostaglandin biosynthesis with consequent inhibition of PGE2-induced GnRH secretion.
Adult↗
Nonlinear Saturation of Toroidal Alfvén Eigenmodes.
Explore the source record for details and available documents.
Journal Article↗
Arachidonic acid and its metabolites effects on testosterone production by rat Leydig cells.
Arachidonic acid (AA) seems to play an important role in testicular steroidogenesis, although controversial data exist in the literature. In the present study AA induced a dose related increase of testosterone (T) formation and, at the highest dose, stimulated the production of prostaglandin E2 (PGE2), leukotrienes B4 (LTB4) and C4 (LTC4) by purified rat Leydig cells. The contemporary addition of the prostaglandin synthesis blocker, indomethacin (IND), and AA further increased T formation, decreased PGE2 levels and did not modify LTB4 and LTC4 concentrations. The addition of a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA, 5 microM), did not influence the stimulatory effect of AA on T and PGE2 formation while it decreased the output of LTB4 and LTC4. When 20 microM NDGA was used in addition to AA the expected reduction of leukotrienes release was observed together with a surprising impairment of T and PGE2 secretion. PGE2 and PGF2 alpha did not modify basal T production but reduced HCG-stimulated T secretion at the 10 nM dose. When 5-12- and 15-HETE were tested an enhancement of basal T formation was observed at the 10nM dose. 5-HETE (10nM) stimulated HCG-induced T production. LTA4, LTB4 and LTE4 did not influence basal T output while LTC4 and LTD4 inhibited it. LTC4 (10nM) induced a decrease of HCG-stimulated T production. These findings suggest that: 1) exogenous AA stimulates T secretion; 2) conversion of AA to cycloxygenated and lipoxygenated metabolites is not required for its steroidogenic effect; 3) cycloxygenated and lipoxygenated compounds play a diverse modulatory role on testicular steroidogenesis.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Endothelin stimulates testosterone secretion by rat Leydig cells.
The present study was designed to evaluate the effects of endothelin (ET) on rat testicular steroidogenesis in vitro and the involvement of prostaglandins (PG) and extracellular calcium in its mechanism of action. To this purpose we examined the effects of ET-1 and ET-3 on basal testosterone secretion, the influence of ET-1 on PGE2 release, the interaction of ET-1 and ET-3 with human chorionic gonadotrophin (hCG) and the interference of indomethacin (an inhibitor of cyclooxygenase) and nifedipine (a calcium-channel blocker) in purified rat Leydig cells. The data indicate that ET-1 and ET-3 stimulate basal and hCG-induced testosterone production although the effects of ET-3 were less marked. In addition, a concomitant release of PGE2 was observed after exposure to ET-1. A synergistic interaction between ET-1 and hCG in stimulating testicular steroidogenesis was revealed. Indomethacin was ineffective in modifying ET-1 evoked testosterone output, while in the presence of nifedipine the stimulatory effect of ET-1 was completely abolished. Since it has been shown by others that ET-1 is produced by rat Sertoli cells and specific binding sites are present in Leydig cells, the results of our study indicate that such a peptide may be regarded as a new paracrine factor able to influence steroidogenesis in Leydig cells. The action of ET-1 requires the activity of voltage-operated Ca2+ channels, while PGE2 activation is not essential for its steroidogenic effect.
Animals↗
High- beta, sawtooth-free tokamak operation using energetic trapped particles.
Explore the source record for details and available documents.
Journal Article↗
Role of arachidonate metabolism on the in vitro release of luteinizing hormone and prolactin from the anterior pituitary gland: possible involvement of lipoxygenase pathway.
The aim of the present study was to evaluate whether arachidonic acid metabolism may play a role on luteinizing hormone (LH) and prolactin (PRL) release directly at the pituitary level. To this purpose, exogenous arachidonic acid, alone or in presence of inhibitors of cyclooxygenase (indomethacin:IND) and lipoxygenase pathways (nordihydroguaiaretic acid:NDGA), was added to perfused rat anterior pituitary cells. PGE, PGF alpha, LH and PRL levels present in the eluate were assayed with specific RIA methods. Both PGE and PGF alpha show a dose-related response after the addition of increasing doses of arachidonic acid. The addition of 0.05 mM arachidonic acid induces an increase of LH and PRL. The addition of IND to the perfusion medium highly potentiates the stimulatory effects induced by arachidonic acid on LH and PRL release. On the contrary, the addition to the medium of either NDGA or IND plus NDGA completely reverses the stimulatory action induced by arachidonic acid alone. The present results suggest that: adenohypophyseal cells are able to metabolize exogenous arachidonic acid; arachidonic acid induces an elevation in LH and PRL levels; lipoxygenase pathway metabolite(s) are likely involved in these activities, and the site of action of arachidonic acid is at the pituitary level.
Animals↗
Role of seminal prostaglandins in male fertility. II. Effects of prostaglandin synthesis inhibition on spermatogenesis in man.
The effect of prostaglandin biosynthesis inhibition has been studied in two groups of infertile oligozoospermic patients with high or normal-low seminal prostaglandin (PG) levels. PGE and 19-OH PGE were assayed by means of a gas chromatographic method and the most important seminal parameters (volume, concentration, motility and morphology of spermatozoa) were evaluated in basal conditions and at the end of indomethacin treatment, at a daily oral dose of 100 mg for thirty days. A drop in prostaglandin levels following indomethacin was observed in both groups of patients but only in the group with high concentrations of prostanoid derivates the prostaglandin inhibition was correlated with a significant improvement in sperm count and motility.
Adult↗
Effects of the "vascular factor" on platelet and vascular arachidonic acid metabolism in man.
The effects of a drug with hemostatic action, "Vascular Factor" (V.F.), on platelet and vascular arachidonic acid metabolism were evaluated in man to establish the lack of side effects on platelet aggregation. Plasma levels of 6-keto PGF1 alpha and thromboxane B2 were determined by RIA in healthy volunteers undergoing treatment with V.F. Results indicate that basal values obtained in these compounds do not present significant variations following treatment with V.F. On the basis of these results, the possibility of administering this drug in atherosclerotic patients is further confirmed.
6-Ketoprostaglandin F1 alpha↗