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Biomedical subjects

Samuel Finkielman

Publications and source records attributed to Samuel Finkielman.

10 recordsLinked to original sources
PubMed2005

Parathyroid hormone-related protein overexpression decreases blood pressure in spontaneously hypertensive rats.

We have recently demonstrated that arterial PTHrP expression and cardiovascular responses to this protein are altered in SHR compared with normotensive animals, Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats. To investigate whether the slightly, but significantly decreased, aortic PTHrP gene expression observed in SHR, compared to that of normotensive animals, may play a causative role in the maintenance of the elevated arterial blood pressure (ABP) of the SHR, we transfected a hepatic lobe with a PTHrP expression vector in a sense and antisense orientation. At 24 and 48 hours, sense pSV2neo-ECE induced a significant five-fold increase in PTHrP mRNA abundance with respect to antisense pSV2neo-ECE and vehicle. This increment in the PTHrP mRNA induced by the sense PTHrP expression vector was totally inhibited by the co-administration of the antisense PTHrP expression vector. At the same time, we observed a significant decrease of mean ABP (MABP) in SHR transfected with the sense pSV2neo-ECE to similar values as those obtained in the normotensive strain. Neither antisense PTHrP expression vector nor vehicle had any significant effect in any strain. Again, the effect of the sense PTHrP expression vector on MABP was blocked by the simultaneous treatment with the antisense PTHrP expression vector. At 48 hours, the hypotensive effect of the sense pSV2neo-ECE in SHR was reverted by the i.v. bolus injection of a specific competitive PTHrP receptor antagonist such as Nle8,18,Tyr34-bPTH(3-34)amide. We propose that a defect of this potent local vasodilator may contribute to the development and/or maintenance of arterial hypertension in SHR. This defect can be ameliorated by transfecting tissues with protein-exporting capabilities, such as the liver. Finally, our work adds additional data to a cumulative body of evidence suggesting that it might be possible to design an effective gene therapy to treat the common polygenic and multifactorial form of hypertension by increasing the activity of potent and physiological vasodilators.

Animals↗
PubMed2003

[Yawning and temporal lobe epilepsy].

Temporal lobe epilepsy is a partial epileptic disorder in which mesial structures are responsible for the principal ictal symptoms. Its characteristic feature is the recurrence of simple and complex partial seizures, associated with postictal confusion and amnesia of the event. The facilitating effect of NREM sleep on the propagation of the seizure, as well as the sleep abnormalities provoked by epilepsy were evident in our two patients. Yawning is a physiological reflex induced by arousal and drowsiness and may appear in different neurological conditions. Its relation with epilepsy of limbic origin has been rarely reported. We describe in a 95 year old male patient, the occurrence of yawning followed by complex partial seizure during a state of drowsiness. His EEG showed independent bilateral interictal foci of temporal sharp waves and after being medicated with carbamazepine 400 mg/day, the episode did not recur. Another patient, a 17 year old female, displayed complex partial seizures and secondarily generalized seizures with yawning during the posictal period, after naps. The EEG was normal and her polysomnography showed bilateral synchronous temporal spikes and slow waves with secondarily generalization during stage 2 of NREM sleep that produce paroxysmal microarousals and increased stages 1 and 2 of NREM sleep and REM sleep diminished. After being medicated with divalproex sodium 750 mg/day, she suffered no further seizures. Temporal lobe epilepsy, sleep-wake cycles and yawning seem not only to share the same anatomic structures but also the same neurochemical mechanisms. The fact that endogenous opiods are considered as part of a protective system that stop and prevent seizures may allow us to postulate that yawning would be the expression of the endogenous opiods induced mechanisms that stop and prevent the recurrence of the temporal lobe epilepsy. Another hypothesis may be that this is only a particular form of temporal lobe epilepsy.

Adolescent↗
PubMed2003

[Yawning].

Yawning is a normal reflex triggered by arousal, drowsiness, boredom, hunger and emotional conditions and it is associated to several neurological diseases and drug abuse. Its wide presence in the phylogenetic vertebrate scale and even in human fetuses as young as 12 weeks directed the search for the common anatomic and biochemical mechanisms involved. The demonstration that yawning is not connected with high CO2 or low O2 blood levels left aside a prevalent metabolic hypothesis. Its close relationship with the sleep-wake cycle, specially in moments previous to falling asleep and after awaking has been related to changes in personal situation and activity. A single component of this reflex which is to be found exclusively in humans, is the fact that yawning is contagious. Thus, it is considered a component of the adaptative mechanism that is part of the surveillance reflex, becoming a significant paralinguistic evolutive expression aimed at protection and social cohesion. The common anatomical structures and neurochemical systems taking part in yawning, the sleep-wake cycle and the temporal lobe epilepsy may imply that yawning results from a set of protective systems induced by endogenous opiods which intervene in the inhibition and prevention of the temporal lobe epileptic seizures.

Epilepsy, Temporal Lobe↗
PubMed2002

Thyrotropin-releasing hormone decreases leptin and mediates the leptin-induced pressor effect.

Leptin, an adipocyte-released hormone, modifies food intake and energy expenditure regulating hypothalamic-pituitary-thyroid axis function. We previously reported that thyrotropin-releasing hormone (TRH) precursor gene overexpression induces hypertension in the normal rat and that spontaneously hypertensive rats have central TRH hyperactivity with increased TRH synthesis and release and an elevated TRH receptor number. In both models, intracerebroventricular antisense (AS) treatment against the TRH precursor produced a dose-dependent reduction of the increased diencephalic TRH content while normalizing high arterial blood pressure. In this article, we report that male Wistar rats that were made hypertensive by intracerebroventricular injection of a eucaryotic expression plasmid containing the pre-TRH cDNA showed decreased leptin plasma levels and that pre-TRH AS treatment reversed this phenomenon. In addition, male and female spontaneously hypertensive rats showed lower levels of circulating leptin than did sex-matched Wistar-Kyoto control rats. This difference also was abated by the pre-TRH AS treatment. Conversely, 20 microg ICV leptin induced a long-lasting pressor effect (18 +/- 5 mm Hg, n=6, P<0.01, >60 minutes) that was not observed in pre-TRH AS pretreated rats (2 +/- 3 mm Hg, n=6) but persisted in rats used as controls that were treated with inverted oligonucleotide (20 +/- 6 mm Hg, n=4, P<0.01). These data suggest that in rats with TRH-induced hypertension, leptin is decreased, inducing compensatory adiposity. We propose that because leptin produces central TRH synthesis and release, obesity may induce hypertension through TRH system activation and that the TRH-leptin interaction may thus contribute to the strong association between hypertension and obesity.

Animals↗