Sleep and bodily functions: the physiological interplay between body homeostasis and sleep homeostasis.

Body homeostasis and sleep homeostasis may both rely on the complex integrative activity carried out by the hypothalamus. Thus, the three main wake-sleep (WS) states (i.e. wakefulness, NREM sleep, and REM sleep) may be better understood if the different cardio-respiratory and metabolic parameters, which are under the integrated control of the autonomic and the endocrine systems, are studied during sleep monitoring. According to this view, many physiological events can be considered as an expression of the activity that physiological regulations should perform in order to cope with the need to fulfill body and sleep homeostasis. This review is aimed at making an assessment of data showing the existence of a physiological interplay between body homeostasis and sleep homeostasis, starting from the spontaneous changes observed in the somatic and autonomic activity during sleep, through evidence showing the deep changes occurring in the central integration of bodily functions during the different WS states, to the changes in the WS states observed when body homeostasis is challenged by the external environment and when the return to normal ambient conditions allows sleep homeo- stasis to run without apparent physiological restrictions. The data summarized in this review suggest that an approach to the dichotomy between NREM and REM sleep based on physiological regulations may offer a framework within which observations that a traditional behavioral approach may overlook can be interpreted. The study of the interplay between body and sleep homeostasis appears, therefore, to be a way to understand the function of complex organisms beyond that of the specific regulations.

Study of spontaneous recurrent seizures and morphological alterations after status epilepticus induced by intrahippocampal injection of pilocarpine.

Epileptic seizures are clinical manifestations of neuronal discharges characterized by hyperexcitability and/or hypersynchrony in the cortex and other subcortical regions. The pilocarpine (PILO) model of epilepsy mimics temporal lobe epilepsy (TLE) in humans. In the present study, we used a more selective approach: microinjection of PILO into the hilus of the dentate gyrus (H-PILO). Our main goal was to evaluate the behavioral and morphological alterations present in this model of TLE. Seventy-six percent of all animals receiving H-PILO injections had continuous seizures called status epilepticus (SE). A typical pattern of evolution of limbic seizures during the SE with a latency of 29.3 ± 16.3 minutes was observed using an analysis of behavioral sequences. During the subsequent 30 days, 71% of all animals exhibited spontaneous recurrent seizures (SRSs) during a daily 8-hour videotaping session. These SRSs had a very conspicuous and characteristic pattern detected by behavioral sequences or neuroethiological analysis. Only the animals that had SE showed positive Neo-Timm staining in the inner molecular layer of the dentate gyrus (sprouting) and reduced cell density in Ammon's horn pyramidal cell subfield CA1. However, no correlation between the intensity of sprouting and the mean number and total number of SRSs was found. Additionally, using Fluoro-Jade staining, we observed neurodegeneration in the hilus and pyramidal cell subfields CA3 and CA1 24 hours after SE. These data indicate that H-PILO is a reliable, selective, efficient, low-mortality model that mimics the acute and chronic behavioral and morphological aspects of TLE.

[Multivaried analysis of the interaction between quality of life and physical capacities for people occupationally intoxicated by mercury]. / Análise multivariada da interação entre qualidade de vida e capacidades físicas em intoxicados ocupacionais por mercúrio.

INTRODUCTION: One important aggression to human biology is constituted by metallic mercury intoxication, mainly expressed by neuropsychiatric disorders. OBJECTIVE: To explore interaction between the domains of Quality of Life (QoL.) and neuro-muscular evidences in intoxicated people by the metal within an urban-industrial environment. MATERIAL AND METHODS: 47 patients have been assessed, through SF36 application and semiological tests. Multiple regression was performed and, to test parameters estimated in adjustments, Student t test was used. RESULTS: Although there are low scores present in the instrument, there have been noticed good results in physical capacities. Muscular strength seems to be an influencing variable on physical and social functioning and mental health (p<0.05). Motor coordination influence on Vitality (p <0.05) was also remarked. As to equilibrium, it presents a negative interaction (p <0.03) with social functioning. CONCLUSIONS: Neuropsychiatric disorders influence negatively QoL perception, making people to subestime their motor performances. Complementarily, it is distinguished strength as physical capacity that presents positive interaction with the subjective perception of QV.

Cellular genetic therapy.

Cellular genetic therapy is the ultimate frontier for those pathologies that are consequent to a specific nonfunctional cellular type. A viable cure for there kinds of diseases is the replacement of sick cells with healthy ones, which can be obtained from the same patient or a different donor. In fact, structures can be corrected and strengthened with the introduction of undifferentiated cells within specific target tissues, where they will specialize into the desired cellular types. Furthermore, consequent to the recent results obtained with the transdifferentiation experiments, a process that allows the in vitro differentiation of embryonic and adult stem cells, it has also became clear that many advantages may be obtained from the use of stem cells to produce drugs, vaccines, and therapeutic molecules. Since stem cells can sustain lineage potentials, the capacity for differentiation, and better tolerance for the introduction of exogenous genes, they are also considered as feasible therapeutic vehicles for gene therapy. In fact, it is strongly believed that the combination of cellular genetic and gene therapy approaches will definitely allow the development of new therapeutic strategies as well as the production of totipotent cell lines to be used as experimental models for the cure of genetic disorders.

Time evolution of acoustic 'information' processing in the mesencephalon of Wistar rats.

A traditional analysis of intra-encephalic auditory evoked potentials does not highlight the dynamical evolution of the auditory 'information' processing in neither time nor space. This work presents a method for tracing such signal evolution throughout the primary auditory pathway in the mesencephalon of adult anesthetized Wistar rats, using a unilateral 3 kHz tone burst stimulus. The results of the acoustic evoked potentials mapping are presented as conventional 20 ms recordings and re-analyzed in intervals of 1 ms-time windows. The parameter used, as an 'activity' correlate, was the maximum/minimum voltage difference obtained from each time window. The methodology used clearly indicates sequential signal propagation from the dorsal and ventral nuclei of the lateral lemniscus up to the inferior colliculus.

Synthesis and pharmacological evaluation of indanpropionic acids as uterine relaxants.

The PGF2 alpha antagonist 5,6-bis(benzyloxy)-1-oxo-2-propyl-2-indanpropionic acid (1) had previously been shown to provide significant protection against the abortifacient actions of PGF2 alpha in mice. To explore further structural concepts in drug design employed for the development of 1, several mono(benzyloxy) ketones (3-10) and alcohols (11-15) as well as a diacid (22) were prepared. None of these structural modifications resulted in compounds of greater superiority to 1 as uterine relaxants and 22 was void of any antagonistic properties, suggesting that the original rationale requiring one carboxyl group and two benzyloxy functions appropriately placed for maximum PGF2 alpha antagonism in this series was a good assumption. A carbonyl rather than hydroxyl group at position C-1 of the indan is most beneficial for reversible antagonism. Reduction of the ketone to the alcohol is of synthetic interest and discussed in some detail.

Teratological evaluation of a novel antiabortifacient, dibenzyloxyindanpropionic acid--I. Dysmorphological and histopathological studies.

Dibenzyloxyindanpropionic acid (DIPA) is an anti-abortifacient prostaglandin F2 alpha(PGF2 alpha) antagonist. Significant protection against PGF2 alpha-induced abortion in Charles River CD-1 mice is afforded by 50 mg/kg DIPA, administered i.m. twice daily from day-15 of gestation; two days prior to PGF2 alpha challenge. In the present teratological evaluation, CD-1 mice were treated either daily throughout gestation with 50 mg/kg DIPA i.m., or only on day-15 of gestation with two doses each of 50 or 200 mg/kg DIPA i.m. Controls received saline injections. Some dams were delivered by cesarian section on day-19 of gestation, while others were allowed to deliver spontaneously at term. Parameters monitored in the offspring were litter sizes, body weights, sex ratios, viability of progeny, external malformations, cleft palate, skeletal anomalies, patency (prenatal) and closure (postnatal) of the ductus arteriosus, gross anatomy of organs, and histopathological examination of tissues. Consistent with a PGF2 alpha antagonistic mechanism of action, DIPA treatment throughout gestation prolonged pregnancy to the upper normal limit. Prenatal administration of DIPA increased the pseudopregnancy rate, but none of the treatment schedules produced any recognizable teratogenic effects.

Teratological evaluation of a novel antiabortifacient, dibenzyloxyindanpropionic acid. II. Postnatal morphological and behavioral development.

Dibenzyloxyindanpropionic acid (DIPA) is an antiabortifacient prostaglandin F2 alpha antagonist. Significant protection against prostaglandin F2 alpha-induced abortion in Charles River CD-1 mice is afforded by 50 mg/kg DIPA, administered intramuscularly twice daily from day-15 of gestation, two days prior to prostaglandin F2 alpha challenge. Furthermore, treatment of CD-1 mice with 50 mg/kg DIPA intramuscularly daily throughout gestation or with 50 or 200 mg/kg twice daily only on day-15 of pregnancy, revealed no structural teratological effects nor histopathological anomalies in the offspring. The present behavioral teratological investigation demonstrates that prenatal treatment of CD-1 mice with 50 mg/kg DIPA intramuscularly daily throughout gestation does not adversely affect postnatal morphological development (offspring viability; weight gain; timing of bilateral pinna detachment, eye opening, eruption of mandibular and maxillary incisors, appearance of mamillary ridges, vaginal opening, testicular descent, and appearance of downy fur), postnatal behavioral development (vocalization; auditory startle reflex; corneal reflex; righting reflex and subsequent air righting; cliff avoidance; limb placing response and grip strength; motor coordination; olfactory orientation; locomotion; motor activity; homing instinct; and acquisition and retention of an active avoidance task), or fertility of the progeny. It is concluded that DIPA is an effective and safe antiabortifacient in mice at the doses tested.

Antiabortifacient action of dibenzyloxyindanpropionic acid in mice.

DIPA [5,6-bis(dibenzyloxy)-1-oxo-2-propyl-2-indanpropionic acid] was evaluated for its antiabortifacient action in mice. PGF2 alpha administered intramuscularly twice daily at 525 micrograms/kg per dose starting on day-17 of gestation resulted in premature delivery (prior to day-19 of gestation) in 55% of the animals. This constituted an ED50 abortifacient dosage schedule of PGF2 alpha. Intramuscular administration of DIPA at a dose of 50 mg/kg twice daily, starting on day-15 of gestation, protected the mice against the premature delivery induced by the ED50 dosage schedule of PGF2 alpha in that only 20% of the animals delivered prematurely. In saline-treated controls, none of the animals delivered prior to day-19 of gestation. Thus, DIPA appears to be an effective antiabortifacient agent.

Influencia da quetamina sobre os potenciais evocados do nervo acustico e tronco cerebral: estudo experimental no cobaia. / Influence of ketamine on evoked potentials of acoustic nerve and brain stem: an experimental study in the guinea-pig

A quetamina em dose unica de 30 mg.Kg foi administrada por via intraperitonial em cobaias com eletrodos implantados no vertice,na mastoide e na fronte para registro dos potenciais evocados das vias auditivas por estimulacao com cliques. Foi utilizado um sistema acustico aberto com estimulacao binaural, com "cliques" de 60 e 70 dB SPL de intensidade e frequencia de repeticao igual a 10 estimulos por segundo, com registro dos potenciais atraves da derivacao vertice-mastoide, aplicando-se 128 estimulos em cada teste.Foi analisada a onda III por ser constante naquelas intensidades, bem como de maior amplitude. Os valores de latencia e amplitude nos testes realizados 15 e 40 minutos apos a administracao da droga foram semelhantes aos valores encontrados no teste controle dentro dos valores normais para cobaias. Conclui-se que a quetamina nao altera os potenciais auditivos ao nivel periferico e nas vias auditivas no tronco cerebral

[Development of the caudal portions of the Müllerian ducts in the rat (Rattus norvegicus)]. / Zur Entwicklung der kaudalen Abschnitte der Müllerschen Gänge bei der Ratte (Rattus norvegicus).

The development of the caudal portion of the Müllerian ducts was studied in rats. The following results were obtained: (1) In the female embryonic rat the proximal thirds of the caudal parts of the Müllerian ducts meet to form the anlage of the biluminal cervix uteri of the uterus duplex. The middle and the distal thirds of the Müllerian ducts fuse and become the canalis vaginalis. (2) In the female embryonic rat the canalis vaginalis represents the anlage of the cranial part of the vagina. (3) During embryonic life the epithelium of the sinus urogenitalis proliferates and develops into the vaginal plate. (4) At birth the vagina is closed by the vaginal plate. (5) In the male embryonic rat the caudal parts of the Müllerian ducts degenerate completely in their proximal and middle thirds. The distal third (canalis vaginalis) disintegrates cranially, caudally it gives rise to the prostatic vaginula. (6) In the male rat the prostatic vaginula is a remnant of the vaginal anlage, unlike the prostatic utriculus in man which contains a remnant of the uterine anlage.

[The early development of the cranial segment of the müllerian duct in the rat]. / Zur Frühentwicklung des kranialen Abschnitts des Müllerschen Ganges bei der Ratte (Rattus norvegicus).

In the rat the cranial part of the Muellerian duct (M-duct), i.e. the anlage of the uterine tube, is of dual origin. The different segments of the adult tube are already recognizable during embryogenesis and may be attributed to their original materials. The preampulla arises from the infundibular field of the coelomic epithelium (= MT). The isthmus is budding from the Wolffian duct (= MW). The middle segment of the tube, the ampulla, is organized by fusion of MT and MW. In the male rat embryo MW degenerates completely, whereas MT degenerates only partially. The remaining part of MT becomes to a solid structure close to the testis, namely the testicular appendage. In the rat testicular appendage is traceable until the first postnatal day.

[Experimental toxicological and pharmacodynamic studies of a triple drug association (adrenaline, atropine and papaverine) with anti-bronchospastic activity]. / Ricerche sperimentali tossicologiche e farmacodinamiche su una triplice associazione (adrenalina + atropina + papaverina) ad attività antibroncospastica.

The antibronchospastic value of the triple association adrenaline (1) + atropine (0,3) + papaverine (3) has been documented experimentally. Comparative investigations have been carried out with isoprenaline, metaproterenol, terbutaline and salbutamol. Toxicological and pharmacodynamic studies were done in the cardiovascular system and in vitro on certain muscles.

[Experimental analysis of the cardiovascular effects of acebutolol, a drug with beta-adrenolytic activity]. / Contributo sperimentale all'analisi delle azioni cardiovascolari dell'acebutololo, farmaco ad attività beta-adrenolitica.

In experiments at cardiovascular system level, acebutolol was found to possess beta-adrenolytic activity of cardioselective type associated with intrinsic beta-adrenergic, antiarrhythmic and anti-hypertensive activity. It was well tolerated systemically.