Hypothalamic paraventricular nucleus lesions differentially affect serotonin-1A (5-HT1A) and 5-HT2 receptor agonist-induced oxytocin, prolactin, and corticosterone responses

A number of receptor subtypes mediate hormonal responses to serotonin (5-HT). To test the hypothesis that the hypothalamic paraventricular nucleus (PVN) mediates 5-HT1A and 5-HT2 receptor-mediated oxytocin, PRL, and corticosterone responses, we studied the effects of the 5-HT1A agonist ipsapirone and the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI) after surgical PVN lesions or sham operations. Chronically cannulated, conscious, freely moving, male Wistar rats were injected iv (1 mg/kg) shortly after (3-4 days) and 5 weeks after (35-37 days) the operations. In sham-operated rats, ipsapirone caused marked elevations in plasma PRL and corticosterone, but not oxytocin concentrations, whereas DOI increased plasma concentrations of all three hormones. Short term PVN lesions prevented ipsapirone-induced corticosterone and DOI-induced oxytocin responses. DOI-induced PRL and corticosterone responses were also markedly inhibited 3-4 days after lesioning, although small rises over the baseline values were still observed. The ipsapirone-induced PRL response was unaffected by the lesioning. Five weeks after PVN lesioning, partial recoveries were observed in ipsapirone- and DOI-induced corticosterone and DOI-induced oxytocin responses, whereas DOI-induced PRL responses remained suppressed. The present findings suggest that the PVN or neural pathways close to it mediate oxytocin, PRL, and corticosterone responses to the 5-HT2 receptor agonist DOI as well as corticosterone, but not PRL, responses to the 5-HT1A receptor agonist ipsapirone. The results after long term PVN lesioning show that the oxytocin and corticosterone responses may be partially restored with time after lesioning.     

Chronic pancreatitis prevalence in liver cirrhosis. Morphological and functional study

In the present study we have examined the ability of the beta-amyloid peptide (A beta(25-35)) to modulate the respiratory burst activity of human monocytes in vitro. Incubation of the cells for 24 h with A beta(25-35) as well as with A beta(1-42) resulted in an enhanced production of reactive oxygen radicals (ROI) in response to phorbol 12-myristate 13-acetate (PMA). Such effect was additively increased by coincubation with interferon-gamma (IFN gamma), and was paralleled by modulation of gene and protein expression of some components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system. Since the effects of A beta(25-35) were also reproduced in primary rat microglia, our findings indicate that A beta(25-35) can potentiate the ability of mononuclear phagocytes to produce ROI, and add further insights into its biological effects.     

Dietary risk factors for pre-eclampsia among women attending Harare Maternity Hospital, Zimbabwe

OBJECTIVE: To identify specific foods that predispose Zimbabwean women to a higher or lower risk of pre-eclampsia and/or eclampsia. DESIGN: A case control study was implemented. Participants were asked by questionnaire to recall the specific amounts of meats, poultry, fruits, fish, vegetables and dairy products they had consumed in the month prior to giving birth. SETTING: Harare Maternity Hospital, Harare, Zimbabwe between June of 1995 and April of 1996. SUBJECTS: 180 women clinically diagnosed with pre-eclampsia (144) or eclampsia (36), and 194 normotensive women without these conditions. MAIN OUTCOME MEASURES: Pre-eclampsia/eclampsia. RESULTS: There were few associations between consumption of specific food items and the occurrence of pre-eclampsia/eclampsia. Meat and fruit were the only foods found to be significantly associated with pre-eclampsia. Women who consumed 12 or more servings of meat per month were more likely to have pre-eclampsia/eclampsia when compared to women eating 11 servings of meat or less per month. While intake of bananas and mangos was unrelated to risk, women who consumed other fruits (i.e. apples, oranges, grapes, peaches, apricots, paw paw, and plums), were 1.7 (95% CI = 1.0 to 3.1) times more likely to develop pre-eclampsia/eclampsia as women who ate none of these fruits. However, women who consumed relatively large quantities of these fruits were not at a particularly high risk. Increased consumption of kapenta was modestly associated with a decrease in disease risk, but this finding was well within the limits of chance and no association was present with intake of other types of fish. CONCLUSIONS: Our findings suggest that variation in consumption of specific foods do not have a strong effect on the incidence of pre-eclampsia in this population. However, further research involving the use of a more comprehensive dietary measure, biochemical measurements of nutrients, pre-pregnancy assessment and ascertainment of dietary intake prior to the development of pre-eclampsia are needed.     

Quantitative evaluation of chronological ageing and photoageing in vivo: studies on skin echogenicity and thickness

Skin ageing is divided into chronological ageing and photoageing due to the cumulative effects of solar ultraviolet radiation. It is, however, difficult to measure the degree of photoageing and chronological ageing in humans in vivo. Here, we have evaluated the usefulness of ultrasonography for measurement of chronological ageing and photoageing in vivo. Twenty megahertz ultrasonography was performed in 90 individuals (29 men, 61 women, age 18-94) to describe age-related changes in sun-exposed regions with different levels of sun exposure (dorsal and ventral forearm, forehead, ankle) and non-exposed buttock skin. Skin thickness and skin echogenicity in different layers of the dermis were measured in ultrasound images. Additionally, cutaneous photodamage was scored clinically. Age-related changes were dependent on body site as well as layer of the dermis. A progressive, age-related decrease in echogenicity of the upper dermis was found in sun-exposed regions (dorsal forearm, forehead), but not in moderately exposed regions (ventral forearm, ankle). In the buttock an increase in echogenicity was observed. The echogenicity of the lower dermis increased in all examined sites. Skin thickness increased with age in the forehead and buttock, but decreased in the extremity skin. Our findings show that photoageing causes a decrease in echogenicity in the upper dermis. In contrast, chronological ageing is associated with an increase in echogenicity in the lower dermis. Although both increases and decreases in skin thickness were observed in different anatomical regions, there was no general relationship between skin thickness and age. Dermal echogenicity was deemed valuable for in vivo study of chronological ageing and photoageing.     

Phosphatidylinositol 3-kinase is required for CD28 but not CD3 regulation of the TEC family tyrosine kinase EMT/ITK/TSK: functional and physical interaction of EMT with phosphatidylinositol 3-kinase

Ligation of the TCR or CD28 induces activation of phosphatidylinositol 3-kinase (PI3K), the TEC family protein tyrosine kinase, EMT/ITK/TSK (EMT), and the SRC family tyrosine kinase, LCK. LCK is required for the activation and phosphorylation of EMT induced by ligation of the TCR or CD28 placing LCK upstream of EMT in T cell signaling cascades. We report herein that inhibition of PI3K activity with the specific inhibitors LY294002 and wortmannin markedly decreased EMT activation induced by CD28 cross-linking but not by CD3 cross-linking. Further, inhibition of PI3K markedly decreased EMT in vitro autokinase activity induced by activated LCK. In contrast, PI3K inhibitors did not alter CD28 or CD3 cross-linking or LCK-induced EMT phosphorylation. Consistent with the requirement of PI3K activity for CD28 but not CD3-induced stimulation of the EMT in vitro autokinase activity, a small but significant portion of cellular EMT associates with PI3K following CD28 cross-linking but not following CD3 cross-linking. CD28-induced association of EMT with PI3K also requires functional expression of LCK. Fusion proteins containing the SRC homology 2 domain of EMT interact with PI3K or a PI3K-associated molecule in a tyrosine phosphorylation-dependent manner. Taken together, the data suggest that EMT is differentially regulated and recruited to different signaling complexes following ligation of CD28 or the TCR complex, perhaps contributing to the disparate roles that EMT appears to play downstream of CD28 and the TCR.     

Functional outcome after myocardial revascularization in ischemic left ventricular failure

BACKGROUND: Myocardial revascularization in patients with left ventricular failure (ejection fraction < 30%) offers survival comparable to heart transplantation. The functional outcome, however, has yet to be determined. In order to assess the clinical results in patients with LVEF < 30% undergoing coronary artery bypass grafts (CABG), 101 consecutive patients operated between 1/91 and 1/97 were reviewed retrospectively. METHODS: The patients were stratified according to presentation: 65 pts had angina (Group 1) and 36 congestive failure (Group 2). Mean age (62 +/- 7 vs 60 +/- 8 yrs), sex (90 vs 88% male), LVEF (0.28 +/- 0.04 vs 0.29 +/- 0.04), prior myocardial infarction (1.2 +/- 0.4 vs 1.2 +/- 0.5 episodes/pt), presence of vital myocardium at scintiscan or low-dose dobutamine echocardiography (92 vs 93%), need for preoperative IABP (3.1 vs 8.3%), aortic cross-clamp (53 +/- 21 vs 60 +/- 21 min) and cardiopulmonary bypass (104 +/- 31 vs 114 +/- 36 min) times were comparable. RESULTS: There was only 1 (1%) perioperative death due to low-output syndrome. Eleven pts (6 vs 5, Group 1 vs Group 2) had postoperative low-output syndrome, requiring IABP in 7 pts (4 vs 3). There were 14 (10 vs 4, Group 1 vs Group 2) deaths during follow-up (29 +/- 19 months, range 2-67), with an overall actuarial survival of 91 +/- 4 vs 100% at 1 yr and 74 +/- 9 vs 78 +/- 10% at 5 yrs in Group 1 vs Group 2, respectively (p = ns). Actuarial symptom-free survival was 89 +/- 4 vs 84 +/- 6% at 1 yr and 49 +/- 9 vs 28 +/- 11% at 5 yrs, respectively (p = 0.05). Despite the high recurrence of congestive failure (22 vs 66% in Group 1 vs Group 2, p = 0.004), improvement in functional class (3.1 +/- 0.8 vs 1.5 +/- 0.7 in Group 1 and 2.7 +/- 0.7 vs 1.8 +/- 0.5 in Group 2) and LVEF (0.28 +/- 0.04 vs 0.38 +/- 0.04 in Group 1 and 0.29 +/- 0.04 vs 0.40 +/- 0.06 in Group 2) was found in both groups at follow-up. CONCLUSIONS: In spite of improving early and late survival after revascularization for ischemic left ventricular failure, patients presenting with congestive failure have an unsatisfactory symptom-free survival. Further studies are necessary to ascertain the relative indications to revascularization or transplantation in this specific patient subgroup.