Differential effects of progesterone and genital stimulation on sequential inhibition of estrous behavior and progesterone receptor expression in the rat brain.

The effect of genital stimulation, either by vaginocervical stimulation (VCS) using a calibrated vaginal probe combined with manual flank stimulation (FS), or by mounts performed by the male, on the hypothalamus and preoptic area concentration of the progesterone receptors A (PR-A) and B (PR-B) was assessed in ovariectomized (ovx) estrogen-primed rats. VCS/FS or stimulation provided by male mounts, even without intromission, significantly decreased PR-B concentration in the hypoythalamus. Down regulation of PR produced by genital stimulation was quantitatively similar to that elicited by progesterone (P) administration. Bilateral or unilateral transection of the pelvic or the pudendal nerves prevented down regulation elicited by VCS/FS. Repeated VCS/FS elicited lordosis behavior in most ovx estrogen primed rats, but the lordosis intensity was lower than that observed in response to P. P administered to ovx estrogen primed rats, induced sequential inhibition, i.e., failure to display estrous behavior in response to a second P injection (24h after the initial P injection). VCS/FS failed to elicit sequential inhibition, since rats responded with normal estrous behavior to the second injection of P. This suggests that down regulation by VCS, by contrast with P, failed to inhibit the subpopulation of PR involved in the facilitation of estrous behavior by P.

Nitric oxide and ERK/MAPK mediation of estrous behavior induced by GnRH, PGE2 and db-cAMP in rats.

We tested the hypothesis that GnRH, PGE2 and db-cAMP act via the nitric oxide (NO)-cGMP and MAPK pathways to facilitate estrous behavior (lordosis and proceptivity) in estradiol-primed female rats. Estradiol-primed rats received intracerebroventricular (icv) infusions of pharmacological antagonists of NO synthase (L-NAME), NO-dependent soluble guanylyl cyclase (ODQ), protein kinase G (KT5823), or the ERK1/2 inhibitor PD98059 15 min before icv administration of 50 ng of GnRH, 1 microg of PGE2 or 1 microg of db-cAMP. Icv infusions of GnRH, PGE2 and db-cAMP enhanced estrous behavior at 1 and 2 h after drug administration. Both L-NAME and ODQ blocked the estrous behavior induced by GnRH, PGE2 and db-cAMP at some of the times tested. The protein kinase G inhibitor KT5823 reduced PGE2 and db-cAMP facilitation of estrous behavior but did not affect the behavioral response to GnRH. In contrast, PD98059 blocked the estrous behavior induced by all three compounds. These data support the hypothesis that the NO-cGMP and ERK/MAPK pathways are involved in the lordosis and proceptive behaviors induced by GnRH, PGE2 and db-cAMP. However, cGMP mediation of GnRH-facilitated estrous behavior is independent of protein kinase G.

Facilitation of estrous behavior by vaginal cervical stimulation in female rats involves alpha1-adrenergic receptor activation of the nitric oxide pathway.

In estrogen-primed female rats, vaginal cervical stimulation (VCS) provided by male intromissions or by an experimenter enhances estrous behaviors exhibited by females during subsequent mating with a male. We tested the hypothesis that alpha(1)-adrenergic receptors, acting via the nitric oxide-cGMP-protein kinase G pathway, mediate VCS-induced facilitation of female reproductive behaviors. Ovariectomized, estradiol-primed rats received intracerebroventricular (icv) infusions of vehicle or pharmacological antagonists 15 or 60min before VCS. Estrous behaviors (lordosis and proceptivity) in the presence of a male were recorded immediately (0min), and 120min following VCS. First we verified that VCS, but not manual flank stimulation alone, enhanced estrous behaviors when females received icv infusion of the vehicles used to administer drugs. Increased estrous behavior was apparent immediately following VCS and persisted for 120min. We then infused prazosin, phenoxybenzamine (alpha(1)-adrenergic receptor antagonists), yohimbine, idaxozan (alpha(2)-adrenergic receptor antagonists), or propranolol (beta-adrenergic receptor antagonist) 15min prior to the application of VCS in females primed with 5mug estradiol benzoate. Only alpha(1)-adrenergic antagonists inhibited VCS facilitation of estrous behavior, apparent 120min after VCS. Finally, we administered specific inhibitors of soluble guanylyl cyclase, nitric oxide synthase or protein kinase G icv 15 or 60min before VCS. All three agents significantly attenuated VCS facilitation of estrous behavior. These data support the hypothesis that endogenously released norepinephrine, acting via alpha(1)-adrenergic receptors, mediates the facilitation of lordosis by VCS, and are consistent with a mechanism involving alpha(1)-adrenergic activation of the nitric oxide/cGMP/protein kinase G pathway.

Ontogeny of rat chondrocyte proliferation: studies in embryo, adult and osteoarthritic (OA) cartilage.

The aim of this work was to study the ontogeny of chondrocyte cell division using embryo, adult and osteoarthritic (OA) cartilage. We searched for mitosis phases and performed a comparative evaluation of mitotic index, basic fibroblast growth factor b (FGFb), transforming growth factor beta1 (TGF-beta1) receptors, cyclin dependent kinase (CDK1) and Cyclin-B expression in fetal, neonate, 3, 5, 8 weeks old rats and experimental OA. Our results showed that mitosis phases were observed in all normal cartilage studied, although, we found a decrease in mitotic index in relation to tissue development. No mitosis was detected in OA cartilage. We also found a statistical significant reduction in cell number in OA cartilage, compared with the normal tissue. Furthermore, FGFb and TGF-beta1 receptors diminished in relation to tissue development, and were very scarce in experimental OA. Western blot assays showed CDK-1 expression in all cases, including human-OA cartilage. Similar results were observed for Cyclin-B, except for 8 weeks, when it was not expressed. Our results suggest that cell division seems to be scarce, if not absent within the OA cartilage studied. Nevertheless, the existence of factors essential for cell division leaves open the question concerning chondrocyte proliferation in OA cartilage, which is likely to be present in the early stages of the disease.

[Publications: good or bad? Critical appraisal of scientific publications]. / Publikationen: Gut oder Schlecht? Kritische Betrachtung wissenschaftlicher Publikationen.

Doctors interested in medical research are flooded by publications in numerous scientific journals. Scientific manuscripts manifest, however, a wide range in terms of quality and conclusiveness, irrespective of their scientific context and the reader ought to be able to assess the value of the presented data and information. We have thus compiled a checklist in an attempt to provide the doctor with a relatively simple means of distinguishing between "good" and "bad" publications, even if he/she is not concerned with scientific methodology issues on a routine basis. Some aspects of "publication bias" are also touched upon in order to point out certain problems from the opposite perspective, namely that of the physician concerned with active scientific work.

[Diagnosis and treatment of thromboembolic diseases of the right heart]. / A jobbszívfél thromboemboliás betegségeinek diagnózisa és kezelése.

Right heart thrombosis (RHT) was found by 2D-echocardiography in 8 cases. Clinical suspicion of RHT could be documented in only 3 patients, while in the other 5 cases syncope, low output syndrome, essential pulmonary hypertension, cerebral embolism or congestive heart failure was the clinical diagnosis on first presentation. Out of the 4 cases of mobile RHT of extracardiac origin 1 patient had an emergency operation, 2 patients died shortly after the 2D-echo diagnosis before treatment could have been started and 1 patient improved on anticoagulant treatment. RHT of intracardiac origin was due to a central line or a ventriculoatrial shunt in 3 cases and no source could be found in 1 patient. Complete recovery was achieved in 2 cases by medical, in one case by surgical management and in 1 patient medical and surgical treatment resulted in clinical improvement. In conclusion authors 1. consider 2D echocardiography necessary in the clinical setting of acute or chronic pulmonary embolism or "primary" pulmonary hypertension and 2. they recommend emergency operation in case of mobile large RHT detected by 2D-echocardiography.

[Diagnosis of femoral pseudoaneurysm using 2-dimensional and Doppler echography]. / A femoralis álaneurysma diagnózisa 2-dimenziós és Doppler echographiával.

Femoral artery pseudoaneurysm was found by combined 2D, pulsed and continuous wave Doppler echography in 10 out of 16 patients with hematoma formation following cardiac catheterization. The typical features included an echofree area communicating with the femoral artery through a narrow neck. There was a low velocity systolic flow in the pseudoaneurysm and a high velocity systolic and reverse diastolic flow in the neck.

[Hemodynamic effects of lidocaine and mexiletine in acute heart infarction]. / Hämodynamische Effekte von Lidokain und Mexiletin beim akuten Herzinfarkt.

The effect of lidocaine (1.0 mg/kg body weight) and mexiletine (1.5 mg/kg body weight) on the arterial blood pressure, the pulmonary artery pressure, heart rate and relative stroke volume were investigated in 9 patients with acute myocardial infarction. The medicaments given as intravenous bolus did not influence significantly the arithmetical mean values of blood pressure, heart rate, pulmonary artery pressure and relative stroke volume. In two cases, however, the application of mexiletine resulted in a strong increase of the pulmonary artery pressure. In one case both drugs caused a significant decrease of the stroke volume.