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1.
An. pediatr. (2003, Ed. impr.) ; 82(1): e68-e72, ene. 2015. tab
Article in Spanish | IBECS | ID: ibc-131673

ABSTRACT

OBJETIVO: Analizar las características de presentación, complicaciones y secuelas, de las fracturas de temporal ingresadas en UCIP.MATERIAL Y MÉTODOS: Análisis descriptivo retrospectivo de las historias clínicas y TC craneal. RESULTADOS: Veintisiete pacientes ingresados en UCIP presentaron fractura del temporal: 13 (48%) sin afectación de peñasco (grupo 1) y 14 (52%) con afectación de peñasco (grupo 2). El grupo 2 presentó mayor estancia en la UCIP: 4,5 días (RI: 2,75-22,25) vs. 2 (RI: 1-3) (p = 0,018), mayor frecuencia de secuelas (p = 0,04) y presencia de fístula del LCR (p < 0,02). Los scores de PRIMS III e índice de traumatismo pediátrico no mostraron diferencias significativas. El 31% presentó hipoacusia, 2 pacientes fallecieron y 4 (15%) presentaron secuelas permanentes. CONCLUSIONES: Las fracturas temporales pueden ser graves, especialmente si incluyen al peñasco, bien por las lesiones asociadas, que marcan el riesgo vital, como por las secuelas (déficit auditivo o fístula LCR). Los autores indican el seguimiento de estos pacientes a largo plazo por Otorrinolaringología


OBJECTIVES: To evaluate the clinical presentation, complications and sequelae in patients with temporal bone fracture in the last 11 years. MATERIAL AND METHODS: A total of 27 patient medical records were retrospectively analysed. RESULTS: Of the 27 patients who were admitted for temporal bone fracture from 2001 to 2012, 13 (48%) had no petrous involvement (Group 1), and 14 (52%) with petrous involvement (Group 2). Patients in Group 2 had a longer P-ICU stay: median 4.5 days (RI: 2.75-22.25 d) vs 2 (RI: 1-3 d) (P=.018); more days on mechanical ventilation support: median 3 days (RI: 1.50-17 d) vs 1 (RI: 1-1.25 d). This group also had a higher frequency in sequelae (P=.04 OR = 1.4 (95% CI: 1.05-1.95)) and a higher incidence in cerebrospinal fluid (CSF) fistula (P<.02; OR 2.33; 95% CI (1.27-4.27)). Severity scores (PRIMS III and PTI) showed no significant differences. Some degree of hearing loss was observed in 31% of the patients. Traffic accident was the main cause of trauma (33%), followed by falls (27%). There were 2 deaths and 4 (15%) had permanent sequelae. CONCLUSIONS: Isolated temporal bone fractures usually have a good outcome in children, but in some cases they can be fatal or have permanent sequelae. Long term follow up is recommendedby authors


Subject(s)
Humans , Male , Female , Child , Temporal Bone/abnormalities , Temporal Bone/injuries , Otolaryngology/instrumentation , Otolaryngology/methods , Peripheral Nervous System Agents/administration & dosage , Peripheral Nervous System Agents/analysis , Temporal Bone/growth & development , Temporal Bone/metabolism , Otolaryngology/standards , Peripheral Nervous System Agents/adverse effects , Peripheral Nervous System Agents/chemical synthesis
2.
ChemMedChem ; 7(3): 452-63, 2012 Mar 05.
Article in English | MEDLINE | ID: mdl-22302767

ABSTRACT

The unwanted psychoactive effects of cannabinoid receptor agonists have limited their development as medicines. These CB1-mediated side effects are due to the fact that CB1 receptors are largely expressed in the central nervous system (CNS). As it is known that CB1 receptors are also located peripherally, there is growing interest in targeting cannabinoid receptors located outside the brain. A library of chromenopyrazoles designed analogously to the classical cannabinoid cannabinol were synthesized, characterized, and tested for cannabinoid activity. Radioligand binding assays were used to determine their affinities at CB1 and CB2 receptors. Structural features required for CB1/CB2 affinity and selectivity were explored by molecular modeling. Some compounds in the chromenopyrazole series were observed to be selective CB1 ligands. These modeling studies suggest that full CB1 selectivity over CB2 can be explained by the presence of a pyrazole ring in the structure. The functional activities of selected chromenopyrazoles were evaluated in isolated tissues. In vivo behavioral tests were then carried out on the most effective CB1 cannabinoid agonist, 13 a. Chromenopyrazole 13 a did not induce modifications in any of the tested parameters on the mouse cannabinoid tetrad, thus discounting CNS-mediated effects. This lack of agonistic activity in the CNS suggests that this compound does not readily cross the blood-brain barrier. Moreover, 13 a can induce antinociception in a rat peripheral model of orofacial pain. Taking into account the negative results obtained with the hot-plate test, the antinociception induced by 13 a in the orofacial test could be mediated through peripheral mechanisms.


Subject(s)
Analgesics/chemical synthesis , Benzopyrans/chemical synthesis , Pain/drug therapy , Peripheral Nerves/drug effects , Peripheral Nervous System Agents/chemical synthesis , Pyrazoles/chemical synthesis , Receptor, Cannabinoid, CB1/agonists , Receptor, Cannabinoid, CB2/agonists , Analgesics/administration & dosage , Analgesics/therapeutic use , Animals , Benzopyrans/administration & dosage , Benzopyrans/therapeutic use , Binding, Competitive , Blood-Brain Barrier/metabolism , Cannabinoids/metabolism , HEK293 Cells , Humans , Injections, Intraperitoneal , Male , Mice , Models, Molecular , Pain/metabolism , Pain Measurement , Peripheral Nerves/metabolism , Peripheral Nervous System Agents/administration & dosage , Peripheral Nervous System Agents/therapeutic use , Pyrazoles/administration & dosage , Pyrazoles/therapeutic use , Rats , Receptor, Cannabinoid, CB1/metabolism , Receptor, Cannabinoid, CB2/metabolism
3.
Peptides ; 31(8): 1617-24, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20434497

ABSTRACT

Morphiceptin (Tyr-Pro-Phe-Pro-NH(2)), a tetrapeptide present in the enzymatic digest of bovine beta-casein, is a selective ligand of the mu-opioid receptor. In the present study, we describe the synthesis of a series of novel morphiceptin analogs modified in positions 1-3. Two of the obtained analogs, [Dmt(1), D-Ala(2), D-1-Nal(3)]morphiceptin and [Dmt(1), D-NMeAla(2), D-1-Nal(3)]morphiceptin (Dmt-2',6'-dimethyltyrosine and d-1-Nal-3-(1-naphthyl)-D-alanine)) displayed very high mu-receptor affinity, resistance to enzymatic degradation, and remarkable supraspinally mediated analgesia, as shown in the hot-plate test after intracerebroventricular but not intravenous administration, which indicated that they could not cross the blood-brain barrier. Therefore, these two analogs were further tested in vitro and in vivo towards their possible peripheral analgesic activity and inhibitory effect on gastrointestinal (GI) motility. We report that both peptides showed strong antinociceptive effect in the writhing test after intraperitoneal administration, inhibited smooth muscle contractility in vitro and GI motility in vivo. Taken together, these findings indicate that the novel morphiceptin analogs which induce peripheral, but not central antinociception, inhibit GI transit, and possess exceptional metabolic stability, may provide an interesting approach to the development of peripherally restricted agents for the treatment of GI motility disorders, such as diarrhea or diarrhea-predominant irritable bowel syndrome.


Subject(s)
Endorphins/chemistry , Endorphins/chemical synthesis , Endorphins/pharmacology , Neurotransmitter Agents/chemical synthesis , Neurotransmitter Agents/pharmacology , Oligopeptides/chemical synthesis , Oligopeptides/pharmacology , Peripheral Nervous System Agents/chemical synthesis , Peripheral Nervous System Agents/pharmacology , Analgesics, Opioid/chemical synthesis , Analgesics, Opioid/chemistry , Analgesics, Opioid/metabolism , Analgesics, Opioid/pharmacology , Animals , Antidiarrheals/chemical synthesis , Antidiarrheals/chemistry , Antidiarrheals/metabolism , Antidiarrheals/pharmacology , Colon/drug effects , Colon/metabolism , Drug Design , Drug Stability , Endorphins/administration & dosage , Endorphins/metabolism , Female , Gastrointestinal Motility/drug effects , In Vitro Techniques , Injections, Intraperitoneal , Injections, Intraventricular , Ligands , Male , Mice , Mice, Inbred C57BL , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Neurotransmitter Agents/chemistry , Neurotransmitter Agents/metabolism , Oligopeptides/chemistry , Oligopeptides/metabolism , Pain Measurement , Peripheral Nerves/drug effects , Peripheral Nervous System Agents/chemistry , Peripheral Nervous System Agents/metabolism , Receptors, Opioid, mu/agonists , Receptors, Opioid, mu/antagonists & inhibitors , Receptors, Opioid, mu/metabolism , Structure-Activity Relationship
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