Adrenergic influences on coeliac ganglion affect the release of progesterone from cycling ovaries: characterisation of an in vitro system

The superior ovarian nerve (SON) arrives at the ovary through the suspensory ligament and innervates mainly the ovarian stroma. Most neurones from which the SON fibres originate are located in the complex coeliac and mesenteric ganglia. Taking into account that other ganglia have been shown to have alpha- and beta-adrenergic receptors, and that the coeliac ganglion receives adrenergic fibres from other sympathetic paravertebral and preaortic ganglia, we utilised adrenergic agonists and antagonists specific to the ganglion, to analyse the role of the alpha and beta receptors in ovarian physiology. To that end, it was necessary to develop and standardise an in vitro coeliac ganglion-SON-ovary (coeliac ganglion-SON-O) experimental system that would enable study of the release of steroids in the ovary in the absence of humoral factors. We investigated the effect of adrenergic agents on the liberation of progesterone in the different stages of the oestrous cycle.To this end we placed the coeliac ganglion and the ovary in different compartments, connected through the SON, to produce a system being studied as a whole. Combined neural and hormonal (luteinising hormone (LH)) effects were also examined. Non-specific stimulation with KCl in the ganglion compartment evoked different responses in terms of release of progesterone, depending on the physiological conditions of the cycle; this demonstrated the sensitivity and viability of the system. During pro-oestrus, stimulation of the ganglion compartment with adrenergic agents such as the agonist noradrenaline or the beta-adrenergic antagonist propranolol, did not modify the release of progesterone. In contrast, the alpha-adrenergic antagonist, phentolamine, induced a strong inhibitory response. During the oestrous stage, noradrenaline was inactive, but phentolamine and propranolol exerted a strong stimulus throughout the experiment. On dioestrus day 1 (D1), both noradrenaline and propranolol increased the release of ovarian progesterone, whereas phentolamine had the opposite effect. Finally, on dioestrus day 2 (D2), what was noteworthy was the pronounced inhibitory effect of noradrenaline, whereas phentolamine was inactive and propranolol showed its greatest stimulatory effect. In order to compare the combined neural and endocrine effects on the ovarian release of progesterone, the experiment was carried out during stages D1 and D2, when the corpora lutea are at their peak of activity. Adrenergic agents were added to the ganglion and LH in a final concentration of 50 ng/ml was added to the ovarian comparment. Different effects were observed indicating a differential response to these agents in stimulated and basal conditions. We conclude that the in vitro coeliac ganglion-SON-ovary system is a functional entity because it possesses its own autonomic tone. This is verified because different basal values of progesterone appear in the different stages of the oestrous cycle. In similar fashion, variations of progesterone induced via the neural pathway were observed under different experimental conditions. In contrast, on D2, noradrenaline added to the ganglion compartment had an inhibitory effect on the liberation of ovarian progesterone.This would indicate that, during this phase, noradrenaline may not be the neurotransmitter released in the ovarian compartment, but that other inhibitory molecules might participate in the observed effects. Finally, during D2, the neural input would condition the ovarian response to LH, facilitating the decrease in progesterone necessary to start a new cycle. The experimental scheme is, in our opinion, a valuable tool for the study of peripheral neural participation in ovarian physiology.     

Anti-inflammatory sesquiterpene lactones from Lourteigia ballotaefolia

Three sesquiterpene lactones were isolated from Lourteigia ballotaefolia (H. B. K.). 9beta-hydroxy-atripliciolide-8- O-tiglate ( 1) was isolated for the first time from this plant and was previously reported in Conocliniopsis prasiifolia (DC) K. et R., 9beta-hydroxy-atripliciolide-8- O-(5'-acetoxytiglate) ( 2) had been already reported in this species. The minor component, 9beta-(tigloyloxy)-atripliciolide, is a new compound. The anti-inflammatory activity of compounds 1 and 2 was evaluated using the croton oil ear test in mice.     

Determinants of willingness to donate living related and cadaveric organs: identifying opportunities for intervention

BACKGROUND: Although low rates of cadaveric organ donation have been attributed to potential cadaveric donors' concerns regarding their religious beliefs and mistrust of the health care system, it is unclear whether similar concerns are important to potential living related donors. It is also not known which factors might be most responsible for low rates of cadaveric and living related donation among the general public. METHODS: We conducted a cross-sectional study of households in Maryland, using a standardized telephone questionnaire, to assess factors associated with willingness to donate cadaveric and living related organs. We compared factors (demographic, cultural, attitudinal, and clinical) related to willingness to donate cadaveric organs with factors related to willingness to donate living related organs. In multivariate analyses, we assessed the independent relation of factors to willingness to donate cadaveric and living related organs, and we assessed the relative importance of these factors in explaining variation in the general public's willingness to donate. RESULTS: Of 385 participants (84% of randomized homes), 254 (66%) were extremely willing to donate to a sibling but only 179 (47%) had designated themselves a cadaveric donor on their drivers' licenses. In bivariate analysis, older age, comorbid conditions, mistrust in hospitals, and concerns about discrimination in hospitals were statistically significantly associated with less willingness to donate living related organs, although African-Americans, older age, lower education, lack of insurance, unemployment, comorbid conditions, and religion/spirituality were associated with less willingness to donate cadaveric organs. After adjusting for potential confounders, only mistrust in hospitals and concerns about discrimination remained strongly and independently associated with 50 to 60% less odds of willingness to donate living related organs [[relative odds [95% confidence intervals (CI)]: 0.4 (0.2-0.7) to 0.5 (0.3-1.0) and 0.4 (0.2-0.9), respectively]] although presence of dependents was associated with 70% higher odds of willingness to donate living related organs [relative odds (95% CI): 1.7 (1.0-3.0)]. In contrast, older age, employment status, religion/spirituality, and mistrust in hospitals were associated with 50 to 90% less odds of willingness to donate living related organs cadaveric organs [relative odds (95% CI): 0.3 (0.1-0.8), 0.4(0.2-0.8), 0.1 (0.1- 0.5) to 0.5 (0.2-0.9), and 0.3 (0.2-0.6), respectively]. Mistrust in hospitals and concerns about the surgical donation procedure contributed most to the variation in willingness to be a living related donor, although race contributed most to the variation in willingness to be a cadaveric donor. CONCLUSIONS: Many factors affect the general public's willingness to donate organs, but their relative contribution is different for living related versus cadaveric donation. Efforts to improve organ donation rates should be directed toward factors that are most important in explaining the existing variation in willingness to donate.     

Aldosterone acts on the kidney,not the brain,to cause mineralocorticoid hypertension in sheep

OBJECTIVE : To determine the extent to which mineralocortioid hypertension depends on a direct action of aldosterone on the kidney or on the brain. METHODS : Studies were performed in conscious sheep that were previously uninephrectomized, implanted with silastic cannulae in the renal artery of the remaining kidney, and had guide tubes implanted over the lateral cerebral ventricles. The effect of aldosterone, infused either intrarenally (i.r.; 2 microg/h) or intravenously (i.v.; 2 and 10 microg/h) for 10 days (n = 5), on arterial pressure and fluid and electrolyte balance was determined. The i.r. (2 microg/h) and i.v. (10 microg/h) doses were calculated to give similar intrarenal concentrations of aldosterone. In a further study, the effect of intracerebroventricular (i.c.v.) infusion of aldosterone (2 microg/h for 21 days) on arterial pressure was examined (n = 5). RESULTS : Infusion of aldosterone caused a progressive increase in mean arterial pressure from 83 +/- 3 mmHg to a maximum of 100 +/- 4 mmHg (P < 0.001) with 2 microg/h i.r. and from 84 +/- 3 mmHg to a maximum of 104 +/- 4 mmHg (P < 0.001) with 10 microg/h i.v., both by day 7. With both infusions there were similar increases in plasma [Na+] and decreases in plasma [K+] and total protein concentration (P < 0.05) between days 3 and 5; these were maintained throughout the infusion. There were no significant changes with i.v. aldosterone (2 microg/h). Long-term i.c.v. infusion of aldosterone (2 microg/h for 21 days) caused no change in arterial pressure. CONCLUSIONS : In conscious sheep the hypertensive response to aldosterone resulted from an action on the kidney, with no evidence for a direct action on the brain.     

Coeliac ganglion adrenergic activity modifies ovarian progesterone during pregnancy: its inter-relationship with LH

Most of the fibres that constitute the superior ovarian nerve (SON) originate at the neuronal bodies of the coeliac ganglion and innervate rat ovarian stroma cells. The purpose of this work was to study the part played by innervation on ovarian release of progesterone on day 15 and at the end of pregnancy in an integrated in vitro system known as the coeliac ganglion-SON-ovary system. We also investigated, in the same system, whether there is some kind of inter-relationship between the effect of adrenergic agents and LH on progesterone release on day 15 of pregnancy. The coeliac ganglion and the ovary were incubated in separate compartments, linked by the SON. The ovary was immersed in 2 ml buffer solution (ovarian compartment) and the coeliac ganglion was immersed in 2 ml of a different buffer solution (ganglion compartment). Under these conditions, the accumulation of progesterone in the ovarian compartment medium was used as an endpoint. Conditions were standardised on day 15 of pregnancy, when the decrease in the release of ovarian progesterone caused by non-specific stimulation on the ganglion with KCl (56 mM) demonstrated the functional integrity of the system. Neural influence was evaluated by the addition of adrenergic agents at a concentration of 10(-6)M to the coeliac ganglion. On day 15 of pregnancy, noradrenaline and propranolol increased progesterone release while phentolamine diminished it. The existence of ganglionic tone was assessed by analysing progesterone basal levels at different stages of pregnancy. The highest secretion of progesterone was found to take place on day 15, diminishing as pregnancy advanced. In addition, adrenergic neural participation was studied during the physiological luteolysis occurring at the end of pregnancy. Major findings were that noradrenaline increased ovarian accumulation of progesterone on day 19 and decreased it on day 20, while propranolol and phentolamine diminished progesterone release on both days. In additional studies, some neuroendocrine aspects were investigated at a peripheral level. The addition of LH only to the ovarian compartment did not affect progesterone secretion. However, when LH in the ovarian compartment was accompanied by noradrenaline, propranolol or phentolamine in the ganglion compartment, the release of progesterone decreased. It can be concluded that modifications of the neural state of the coeliac ganglion affect ovarian progesterone secretion and the physiology of pregnancy via the SON. The results may confirm that the coeliac ganglion-SON-ovary system provides a direct link between the autonomic nervous system and physiological events during pregnancy.     

Capillary refill test--a possible auxiliary diagnostic method in obliterative arteriosclerosis.

Values of capillary refill time (CRT) were used for evaluation of skin microcirculation in the lower extremities severed by arteriosclerotic disease. The authors examined 133 extremities in 83 arteriosclerotic patients and 84 extremities of 50 healthy volunteers as a control group. To define the stage of the disease, walking distance, rest pain, level of arterial occlusion and the ankle/arm Doppler index (AAI) were considered. On each leg CRT was measured three times on the foot dorsum and pulp of the hallux. The mean value was calculated. The capillary refill index (CRI) was defined from the values of CRT as a proportion of compression time and time of skin recolouration. Twenty three extremities were examined before and after surgical treatment. The results suggest that values of CRI lower than 0.80 may be considered pathological. In advanced forms of the disease, low values of CRI were found in a significant number of extremities (p less than 0.01). A correlation was found among AAI, walking distance and CRI (r = 0.50). An extremely low CRI (under 0.55) was found on extremities without palpable femoral pulsations. After operation, a significant increase of CRI was observed (p less than 0.01).