42 research outputs found
Severe transient neonatal lactic acidosis during prophylactic zidovudine treatment
Zidovudine (ZDV) treatment during pregnancy, delivery and the postnatal period is effective in reducing the maternal-infant transmission of the human immunodeficiency virus. Reported adverse effects in the neonate during this long-term treatment are bone marrow suppression and elevation in aspartate aminotransferase activity. We report a case of severe ZDV-associated lactic acidosis in a neonate, which resolved rapidly following discontinuation of ZDV. The mechanisms leading to this side effect are poorly understoo
The primary headaches: genetics, epigenetics and a behavioural genetic model
The primary headaches, migraine with (MA) and without aura (MO) and cluster headache, all carry a substantial genetic liability. Familial hemiplegic migraine (FHM), an autosomal dominant mendelian disorder classified as a subtype of MA, is due to mutations in genes encoding neural channel subunits. MA/MO are considered multifactorial genetic disorders, and FHM has been proposed as a model for migraine aetiology. However, a review of the genetic studies suggests that the FHM genes are not involved in the typical migraines and that FHM should be considered as a syndromic migraine rather than a subtype of MA. Adopting the concept of syndromic migraine could be useful in understanding migraine pathogenesis. We hypothesise that epigenetic mechanisms play an important role in headache pathogenesis. A behavioural model is proposed, whereby the primary headaches are construed as behaviours, not symptoms, evolutionarily conserved for their adaptive value and engendered out of a genetic repertoire by a network of pattern generators present in the brain and signalling homeostatic imbalance. This behavioural model could be incorporated into migraine genetic research
Current and prospective pharmacological targets in relation to antimigraine action
Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon
Docteur, puis-je boire de l'alcool avec mes antibiotiques ?
Qui n'a pas été confronté, lors de la prescription d'antibiotiques, à la question : «Docteur, est-ce que je peux continuer à boire mon verre de vin ?». Cet article passe en revue les antibiotiques incriminés et les mécanismes connus ou suspectés de leur interaction avec l'éthanol. «L'effet antabuse» n'est pas l'exclusivité du métronidazole : certaines céphalosporines (céfamandole, céfazoline, etc.) et certains antifongiques (kétoconazole, griséofulvine) sont impliques. L'érythromycine, par son activité prokinétique, accélère l'absorption de l'éthanol et diminuerait son métabolisme de premier passage. L'alcool pourrait renforcer les effets des fluoroquinolones et des antimalariques sur le système nerveux central. Faut-il par principe déconseiller la prise d'alcool lors de traitement antibiotique ou faut-il prescrire des molécules ne présentant pas de risque d'interaction ? A chacun sa réponse
Severe transient neonatal lactic acidosis during prophylactic zidovudine treatment.
Zidovudine (ZDV) treatment during pregnancy, delivery and the postnatal period is effective in reducing the maternal-infant transmission of the human immunodeficiency virus. Reported adverse effects in the neonate during this longterm treatment are bone marrow suppression and elevation in aspartate aminotransferase activity. We report a case of severe ZDV-associated lactic acidosis in a neonate, which resolved rapidly following discontinuation of ZDV. The mechanisms leading to this side effect are poorly understood
Multiple and simultaneous phenotyping tests: beware of ascorbic acid when determining the mephenytoin (S)/(R) ratio
Pharmacokinetics and pharmacodynamics of IFN-beta 1a in healthy volunteers
The pharmacokinetics of recombinant human interferon-beta1a (IFN-beta1a) (Rebif, Ares-Serono, Geneva, Switzerland) were investigated in healthy volunteers following intravenous (i.v.) administration of increasing single doses of the drug (22 microg/6 million international units [MIU], 44 microg/12 MIU, and 66 microg/18 MIU); i.v., intramuscular (i.m.), and subcutaneous (s.c.) administration of a 66-microg dose; and repeated s.c. administration of four 66-microg doses at 48-h intervals. The disposition of IFN-beta1a followed triexponential decay after i.v. administration (half-lives 3 min, 42 min, and 22 h, respectively). After s.c. and i. m. administration, absorption was the rate-limiting factor in the terminal phase. The median absolute bioavailabilities were 30% and 27%, respectively. The accumulation ratio after repeated s.c. injections was 2.4, and a terminal half-life of 66 h was observed. Intracellular 2-5A synthetase activity and serum neopterin and beta2-microglobulin concentrations increased after all IFN-beta1a injections and remained elevated following every-other-day administration. The local tolerance was good, and the systemic tolerance was satisfactory
Mechanisms of Abruption-Induced Premature Rupture of the Fetal Membranes: Thrombin-Enhanced Interleukin-8 Expression in Term Decidua.
Recent evidence has linked preterm premature rupture
of the fetal membranes (PPROM) to placental abruption.
Because neutrophils are a rich source of proteases that
can degrade extracellular matrix in abruption-associated
PPROM,we examined whether decidual neutrophil
infiltration complicates abruption-associated PPROM.
Accordingly, immunostaining for the neutrophil
marker CD15 was performed in placentas obtained after
overt abruption (decidual hemorrhage) with or without
PPROM and in control placentas. Abruptions were associated
with a marked decidual neutrophil infiltration
that peaked after PPROM, whereas decidua from gestational
age-matched controls were virtually devoid of
neutrophils. Neutrophil infiltrates co-localized with fibrin
deposition. Because abruptions elicit intense decidua-
enhanced thrombin production, we examined the
regulation of abruption-induced neutrophil infiltration.
Expression of the primary neutrophil chemoattractant
interleukin-8 (IL-8) was evaluated in leukocyte-free term
decidual cells incubated with estradiol (E2; control) or
with E2medroxyprogesterone acetate (to mimic pregnancy)
thrombin. After 24 hours, enzyme-linked immunosorbent
assay measurements indicated that
thrombin (0.1 to 2.5 U/ml) elicited a dose-dependent
elevation in secreted IL-8 (P < 0.05) with 2.5 U/ml of
thrombin increasing IL-8 levels by >14-fold in E2 and
E2 medroxyprogesterone incubations. Results were
validated by Western blot and quantitative reverse
transcriptase-polymerase chain reaction. In summary,
thrombin-enhanced IL-8 expression in term decidual
cells may explain how abruption-associated PPROM
promotes decidual neutrophil infiltration
Mechanisms of leukocyte accumulation and activation in chorioamnionitis: interleukin 1 beta and tumor necrosis factor alpha enhance colony stimulating factor 2 expression in term decidua.
Chorioamnionitis is a major cause of prematurity as well as perinatal morbidity and mortality. The
present study observed a marked increase in immunohistochemical staining for Colony
Stimulating Factor 2 (CSF2; also known as granulocyte macrophage-colony stimulating factor), a
potent neutrophil and macrophage chemoattractant and activator, in the decidua of patients with
CAM compared with controls (n = 8; P = .001). To examine the regulation of this CSF2, cultured
decidual cells primed with estradiol (E2) or E2 plus medroxyprogesterone acetate, were exposed to
tumor necrosis factor-α or interleukin-1β and secreted CSF2 measured by ELISA. Levels of CSF2
in E2 plus MPA-treated cultures increased 18- and 245-fold following treatment with TNF or
IL1B (n = 7, P < .05). Quantitative RT-PCR demonstrated parallel changes in mRNA levels. This
study reveals that CSF2 is strongly expressed in decidua from patients with CAM and indicates
TNF or IL1B as important regulators of CAM-related decidual leukocyte infiltration and
activation