The influence of ethanol infusion on the effects of 35% CO2 challenge. A study in panic disorder patients and healthy volunteers.

UNLABELLED: Alcohol and panic disorders co-occur at a rate that exceeds chance significantly. Early experimental work suggests that alcoholic subjects, compared to non-alcoholics, are less sensitive to sodium lactate and that alcohol intake reduces the response to a 35% CO(2) challenge in Panic Disorder patients. The present study documents the direct pharmacological effect of ethanol infusion on CO(2) induced panic. METHODS: According to a placebo-controlled, double-blind, randomized, cross-over design 10 drug free panic disorder patients and 16 healthy volunteers underwent a 35% CO(2) challenge after intravenous infusion of a moderate dose of ethanol on one test day and of placebo on another test day. RESULTS: Compared to the placebo condition, the effect of the CO(2) challenge was significantly smaller after ethanol infusion (P = 0.041). DISCUSSION: A moderate dose of ethanol decreased the response to a 35% CO(2) without inducing pre challenge sedation. CONCLUSION: The results comfort earlier findings of a direct pharmacological effect of ethanol on panic.

Angiotensin II influences ovarian follicle development in the transgenic (mRen-2)27 and Sprague-Dawley rat.

There is accumulating evidence that local renin-angiotensin systems (RASs) influence cell growth and organ function in a variety of tissues including the ovary. The first aim of this study was to characterise the cellular location of RAS components in the rat ovary. This was facilitated by the use of the hypertensive transgenic (mRen-2)27 rat which overexpresses renin and angiotensin in extra-renal tissues. Comparisons were made with normal Sprague-Dawley (SD) rats. The second aim was to determine if the upregulated RAS of the transgenic (mRen-2)27 rat and infusion of angiotensin II (ANG II) in SD rats influences follicle number and litter size. Gene expression, immunohistochemical and autoradiographic techniques were used to identify a discrete RAS including ANG II receptors in the ovarian stroma, follicles (particularly atretic) and to a lesser extent corpora lutea. The RAS at these sites was most abundant in homozygous (HMZ) followed by heterozygous (HTZ) (mRen-2)27 rats and then SD rats. Large antral and preovulatory follicles and litter size were reduced in (mRen-2)27 rats. In HMZ (mRen-2)27 rats and SD rats infused with ANG II, angiotensin 1a (AT(1a)) receptor mRNA in the ovarian stroma was lower than control SD rats and was associated with a reduction in large antral and preovulatory follicles. These findings indicate that upregulation of the ovarian RAS in the rat influences follicular development and, potentially, reproductive capacity.

Parathyroid hormone(1-34) and parathyroid hormone-related protein(1-34) stimulate calcium release from human syncytiotrophoblast basal membranes via a common receptor.

The placental syncytiotrophoblast is the site for mineral and nutrient exchange across the maternal-fetal interface. It has been proposed that parathyroid hormone-related protein (PTHrP) is a key factor in the maintenance of a maternal-fetal calcium gradient. Using simultaneously prepared microvillous (maternal facing) and basal (fetal facing) syncytiotrophoblast membranes from term human placentae (n=8), we determined the relative contribution of PTH(1-34), PTHrP(1-34) and PTHrP(67-94) to the regulation of syncytiotrophoblast calcium efflux. The vesicles had correct right-side-out membrane orientation and specific markers validated the fractionation of microvillous and basal membrane vesicles. Calcium efflux was studied by preloading vesicles with calcium-45 in the presence of calcium and magnesium and then incubating the vesicles at 37 degrees C for 15 min with the peptides. In basal membranes, PTHrP(1-! 34) significantly stimulated calcium efflux at a dose of 12.5 nmol/l, whereas PTH(1-34)-stimulated efflux was significant at 50 nmol/l (P<0.05, ANOVA). This efflux was significantly reduced in the presence of the PTH/PTHrP receptor antagonist (PTHrP(7-34)). Midmolecule PTHrP(67-94) had no significant effect on basal membrane calcium efflux. PTH(1-34), PTHrP(1-34) or PTHrP(67-94) had no significant effects on MVM calcium efflux. This study, using the human syncytiotrophoblast in vitro membrane system, demonstrated that PTHrP(1-34) and PTH(1-34) stimulate calcium transport across the basal, but not microvillous, syncytiotrophoblast membrane vesicles, mediated via the PTH/PTHrP receptor.

Reduced intestinal epithelial cell brush border membrane calcium transport in spontaneously hypertensive rats.

OBJECTIVE: The present study aimed to determine whether there were alterations in intestinal calcium homeostasis in the spontaneously hypertensive rats (SHR) and to identify at which interface of the intestinal epithelial cell (brush border or basolateral) this occurs. DESIGN: Controversy exists as to whether intestinal calcium transport is altered in association with hypertension. Studies using perfused duodenal segments of the SHR have shed little light on the problem; other studies have only measured calcium transport in brush border membrane vesicles. This study allows specific focus on calcium transport mechanisms at both the brush border and basolateral membrane using simultaneously prepared membrane vesicles. METHODS: Calcium transport was studied by measuring radiolabelled calcium (45Ca) uptake in isolated brush border and basolateral membrane vesicles, prepared from the small intestines of SHR and Wistar-Kyoto (WKY) rats. Calcium uptake was measured when vesicles were incubated in solutions containing different concentrations of ATP and calcium. Orientation and membrane marker assays were used to confirm the phenotypes of the two membrane vesicle preparations. RESULTS: ATP-dependent calcium efflux was only observed in the basolateral membrane, which contains the Ca2+ -ATPase pump. SHR brush border membrane vesicles displayed no significant increase in calcium incorporation, whereas WKY brush border vesicles showed a 500% increase in uptake (ANOVA, P<0.05, n = 7). CONCLUSIONS: This study indicates that deficiencies exist in SHR intestinal calcium transport at the brush border membrane of intestinal epithelial cells. While further studies are required to ascertain the exact mechanisms involved, postulated deficiencies in the actions of calcium regulating hormones at this membrane suggest the need for concurrent intake of a calcitrophic agent to assist calcium uptake at the brush border membrane.