Efecto del embarazo en la formación hepática de insulina no-suprimibile

Riassunto Allo scopo di studiare l'attività insulinica non sopprimibile durante la gravidanza, si è prelevata bile da coniglie gravide dopo somministrazione i.v. di insulina omologa ed eterologa. Dosando la concentrazione dell'IRI con un metodo radioimmunologico, si può dimostrare che, a parità di concentrazione, l'insulina presente nella bile di animali gravidi esplica un effetto più marcato sulla captazione del glucosio da parte del grasso epididimale di ratto. La bile stessa non influisce sulla permeabilità della membrana cellulare degli adipociti. Nel dosaggio biologico, l'aggiunta al mezzo d'incubazione di un siero antinsulina specifico in quantità sufficiente per sopprimere tutta l'attività IRI, non annulla l'ILA biliare, il che dimostra che l'insulina non sopprimibile è aumentata; tale aumento è più marcato nella bile di femmine gravide.

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Summary In order to study non-suppressible insulin during pregnancy, bile was obtained from pregnant rabbits after i.v. administration of homologous and heterologous insulin. After estimation of the immunoreactive insulin concentration by a radioimmunological method, it may be shown that, for the same concentration, the insulin found in the bile from pregnant females exhibitis a more significant effect on glucose uptake by the rat epididymal fat pad. Bile itself does not affect the permeability of the fat cell membrane. In the bio-assay, the addition to the incubation medium of specific AIS, of a concentration high enough to cover the whole IRI, does not suppress biliary ILA, which demonstrates an increase in non-suppressible insulin, this increase being more significant in the bile from pregnant females.

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Zusammenfassung In der Absicht das nicht unterdrückbare Insulin während der Schwangerschaft zu untersuchen wurde Galle von schwangeren Kaninchen nach intravenöser Verabreichung homologen und heterologen Insulins gewonnen. Durch Bestimmung der IRI-Konzentration mittels einer radioimmunologischen Methode kann gezeigt werden, dass bei gleichbleibender Insulinkonzentration die Galle der schwangeren Tiere die Glukoseaufnahme seitens des epididymalen Fettpolsters der Ratte stärker beeinflusst. Galle allein hat keine Wirkung auf die Durchlässigkeit der Fettzellmembran. Bei der biologischen Bestimmung unterdrückt der Zusatz von spezifischem Antilymphozytenserum in Mengen die ausreichen um die ganze IRI zu unterdrücken, nicht, um die Galle-ILA zu unterdrücken. Das zeigt, dass ein Anstieg des nicht unterdrückbaren Insulins erfolgt ist. Dieser ist in der Galle schwangerer Kaninchen ausgesprochener.

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Resumen Para el estudio de la insulina no suprimible en el embarazo a término, la bilis fué obtenida en conejas preñadas después de la administración i.v. de insulina homóloga y heteróloga. Después de comprobada la concentración de insulina immuno-reactiva por un metodo radioinmunológico se puede demostrar que para la misma concentración de insulina detectada, la alícuota de bilis procedente de la hembra preñada muestra un efecto más significativo en el consumo de glucosa por el epididímo de rata. La bilis por sí misma no muestra ningún efecto en la permeabilidad de la membrana de la célula del tejido adiposo. En el bio-ensayo, la incorporación en el medio de la incubación de AIS específicos en concentración sufficientemente alta para cubrir toda la IRI, no suprime el efecto ILA de la bilis, lo que representa un incremento de la insulina no suprimible que aparece con más significación en la bilis de la hembra preñada.

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Résumé Afin d'étudier l'insuline qu'on ne peut pas supprimer pendant la grossesse, de la bile a été prélevée de certaines lapines grosses après avoir administré par injection intraveineuse de l'insuline homologue et hétérologue; après avoir évalué la concentration d'insuline immuno-réactive par la méthode radio-immunologique, il est possible de prouver que pour la même concentration d'insuline vérifiée la bile des lapines grosses révèle un effet significatif sur la consommation de glucose par l'épididyme du rat. La bile n'influence pas la perméabilité de la membrane des cellules du tissu adipeux. Dans l'analyse biologique, l'addition au moyen d'incubation de l'AIS spécifique, d'une concentration suffisamment élevée à couvrir l'IRI tout entier, n'élimine pas l'ILA de la bile, qui manifeste un accroissement de l'insuline ne pouvant pas être suppromée. Cette augmentation est plus significative dans la bile des lapines grosses.

     

Migraine and cerebrovascular disease: still a dangerous connection?

Migraine is a common type of headache in young adults, with an estimated prevalence of 4% before puberty and as high as 25% in women by their mid to late 30s. About one third of migraineurs experience transient neurological symptoms known as auras, which characterize a variant known as migraine with aura. Many evidences have shown an increased risk of vascular events in patients affected by migraine, particularly among women and among migraine patients with aura. Potential underlying mechanisms include endothelial dysfunction, hypercoagulability, platelet aggregation, vasospasm, cardiovascular risk factors, paradoxical embolism, spreading depolarization, shared genetic risk, use of non-steroidal anti-inflammatory drugs, and immobilization. The risk of vascular events in migraine patients is also linked by concomitant oral contraception; moreover, the common finding of increased incidence of right to left cardiac shunt in migraine patients might have a pathogenetic role. Finally, many MRI studies in migraine patients, particularly in migraine with aura, have shown subcortical lesions particularly in the cerebellum as a common finding. In this review, we analyzed the more recent findings regarding the topic of migraine as a risk factor in stroke.     

In vivo characterization of emerging white matter microstructure in the fetal brain in the third trimester

The third trimester of pregnancy is a period of rapid development of fiber bundles in the fetal white matter. Using a recently developed motion‐tracked slice‐to‐volume registration (MT‐SVR) method, we aimed to quantify tract‐specific developmental changes in apparent diffusion coefficient (ADC), fractional anisotropy (FA), and volume in third trimester healthy fetuses. To this end, we reconstructed diffusion tensor images from motion corrected fetal diffusion magnetic resonance imaging data. With an approved protocol, fetal MRI exams were performed on healthy pregnant women at 3 Tesla and included multiple (2–8) diffusion scans of the fetal head (1–2 b = 0 s/mm² images and 12 diffusion‐sensitized images at b = 500 s/mm²). Diffusion data from 32 fetuses (13 females) with median gestational age (GA) of 33 weeks 4 days were processed with MT‐SVR and deterministic tractography seeded by regions of interest corresponding to 12 major fiber tracts. Multivariable regression analysis was used to evaluate the association of GA with volume, FA, and ADC for each tract. For all tracts, the volume and FA increased, and the ADC decreased with GA. Associations reached statistical significance for: FA and ADC of the forceps major; volume and ADC for the forceps minor; FA, ADC, and volume for the cingulum; ADC, FA, and volume for the uncinate fasciculi; ADC of the inferior fronto‐occipital fasciculi, ADC of the inferior longitudinal fasciculi; and FA and ADC for the corticospinal tracts. These quantitative results demonstrate the complex pattern and rates of tract‐specific, GA‐related microstructural changes of the developing white matter in human fetal brain.     

Spatiotemporal changes in diffusivity and anisotropy in fetal brain tractography

Population averaged diffusion atlases can be utilized to characterize complex microstructural changes with less bias than data from individual subjects. In this study, a fetal diffusion tensor imaging (DTI) atlas was used to investigate tract‐based changes in anisotropy and diffusivity in vivo from 23 to 38 weeks of gestational age (GA). Healthy pregnant volunteers with typically developing fetuses were imaged at 3 T. Acquisition included structural images processed with a super‐resolution algorithm and DTI images processed with a motion‐tracked slice‐to‐volume registration algorithm. The DTI from individual subjects were used to generate 16 templates, each specific to a week of GA; this was accomplished by means of a tensor‐to‐tensor diffeomorphic deformable registration method integrated with kernel regression in age. Deterministic tractography was performed to outline the forceps major, forceps minor, bilateral corticospinal tracts (CST), bilateral inferior fronto‐occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), and bilateral uncinate fasciculus (UF). The mean fractional anisotropy (FA) and mean diffusivity (MD) was recorded for all tracts. For a subset of tracts (forceps major, CST, and IFOF) we manually divided the tractograms into anatomy conforming segments to evaluate within‐tract changes. We found tract‐specific, nonlinear, age related changes in FA and MD. Early in gestation, these trends appear to be dominated by cytoarchitectonic changes in the transient white matter fetal zones while later in gestation, trends conforming to the progression of myelination were observed. We also observed significant (local) heterogeneity in within‐tract developmental trajectories for the CST, IFOF, and forceps major.     

Combined pharmacological and short-term psychodynamic psychotherapy for probable medication overuse headache: a pilot study

We studied the effects of short-term psychodynamic psychotherapy (STPP) and pharmacological therapy in 26 consecutive patients with probable medication overuse headache (pMOH). Patients underwent a standard in-patient detoxification protocol, lasting a mean of 7 days. Eleven patients overused non-steroidal anti-inflammatory drugs (NSAIDs), five a combination of NSAIDs and triptans, four triptans, four a combination of NSAIDs, and three triptans and ergot derivates. Preventive therapy was initiated during detoxification. The STPP protocol comprised the Brief Psychodynamic Investigation (BPI) and psychoanalysis-inspired psychotherapy. All patients (groups A and B) underwent the BPI and pharmacological therapy. Half of the patients (group B) also not randomly underwent psychoanalysis-inspired psychotherapy. We found a significant interaction between time and group for headache frequency and medication intake. At 12-month follow-up, a statistically greater decrease in headache frequency and medication intake was observed in group B than in group A ( P  = 0.0108 and P  = 0.0097, respectively). The relapse rate was much lower in group B patients at both 6 and 12 months [15.3%, odds ratio (OR) 0.11, P  = 0.016, and 23%, OR 0.18, P  = 0.047, respectively] than in group A. The risk of developing chronic migraine (CM) during follow-up was higher in group A than in group B at 6 (OR 2.0, P  = 0.047) and 12 months (OR 2.75, P  = 0.005). Our study suggests that STPP in conjunction with drug withdrawal and prophylactic pharmacotherapy relieves headache symptoms in pMOH, reducing both long-term relapses and the burden of CM.     

Denervation-activated inward rectifier in frog slow skeletal muscle fibers

We tested whether the absence of an inward rectifier channel in slow skeletal muscle fibers of the frog is regulated by innervation. Normal and denervated slow fibers were identified according to their passive electrical properties. In current-clamp experiments, anomalous rectification was quantified as the ratio of effective resistances for hyperpolarizing and depolarizing pulses. In isotonic potassium solution, this ratio was 0.45 +/- 0.1 (n = 14) for twitch fibers, whereas slow fibers displayed linear behavior [ratio = 1.0 +/- 0.05 (n = 15)]. However, denervated slow fibers showed anomalous rectification (ratio, 0.48 +/- 0.07; n = 5). This finding was supported by voltage-clamp experiments in which denervated slow fibers displayed (1) an inward rectifier current during hyperpolarizing pulses, (2) an increase in this current when [K(+)](o) was increased, and (3) a current inhibition after application of Ba(2+). These results suggest that frog slow fibers, which normally do not possess inward rectifier channels, can express them after denervation.     

Directly applied low intensity direct electric current enhances peripheral nerve regeneration in rats

The influence of direct electric stimulation on nerve regeneration was studied in a model of crush injury of the sciatic nerve of rats. Forty-three rats were used and distributed in four groups according to the procedure: (1) intact nerve, inactive circuit; (2) crush injury, inactive circuit; (3) intact nerve, active circuit; (4) crush injury, active circuit. The low intensity continuous current circuit (1 microA) was implanted in the lumbar region, the anode being fixed to the muscles proximally and the cathode below the nerve distally to the lesion site. The Sciatic Functional Index (SFI) was evaluated at weekly intervals for 3 weeks, the sciatic nerve being resected on the 21st day for histologic and morphometric studies. The SFI progressively improved and the average fiber nerve density recovered to a nearly normal value in Group 2 and increased in Group 4 compared with the control groups (1 and 3), but this was accompanied by a decreased average fiber nerve diameter. Both number and diameter of inter and intra-fascicular blood vessels increased in the stimulated nerves. We conclude that low intensity direct electric stimulation enhances nerve regeneration following a controlled nerve crush injury and increases blood supply by increasing number and diameter of vasa nervorum.     

The rapid diagnosis of HIV-1 infection in mothers in Puerto Rico: a crucial testing strategy for maximal reduction of perinatal transmission

This study was designed to evaluate early post partum rapid HIV testing of infants as surrogates for their mothers. In a screening of 971 infants whose mother's HIV-1 status was not known at delivery, 22 (= 2.26%) were found positive for antibodies by ELISA. Five were new cases and two (40%) were from transmitting mothers. This is in contrast with the UPR Women and Infants Transmission Study (UPR WITS) in which of 186 HIV-1 infected mothers none were transmitters. These were selected among thousands screened for anti-HIV-1 antibodies over a period of almost 5 years studied (September, 1996 through August, 2001). These results clearly indicate that all mothers at delivery should have a rapid test to determine their HIV-1 status to allow in the positive cases rapid intervention strategies to prevent perinatal transmission.