Adrenomedullin increases the short-circuit current in the mouse seminal vesicle: actions on chloride secretion.

Adrenomedullin (ADM) may regulate seminal vesicle fluid secretion, and this may affect sperm quality. In this study, we investigated the effect of ADM on chloride secretion in the mouse seminal vesicle. The presence of ADM in mouse seminal vesicle was confirmed using immunostaining, and the molecular species was determined using gel filtration chromatography coupled with enzyme-linked assay for ADM. The effects of ADM on chloride secretion were studied by short-circuit current technique in a whole-mount preparation of mouse seminal vesicle in an Ussing chamber. The effects of specific ADM and calcitonin gene-related peptide (CGRP) receptor antagonists were investigated. Whether the ADM effect depended on the cAMP- and/or calcium-activated chloride channel was also studied using specific chloride channel blockers. The results showed that ADM was present in seminal vesicle epithelial cells. The major molecular species was precursor in the mouse seminal vesicle. ADM increased short-circuit current through the calcium-activated chloride channel in mouse seminal vesicle, and CGRP receptor was involved. We conclude that ADM may regulate chloride and fluid secretion from the seminal vesicle, which may affect the composition of the seminal plasma bathing the sperm and, hence, fertility.

Adrenomedullin increases the short-circuit current in the rat prostate: Receptors, chloride channels, the effects of cAMP and calcium ions and implications on fluid secretion.

In this study, we have investigated the effects of adrenomedullin on chloride and fluid secretion in the rat prostate. The presence of adrenomedullin (ADM) in rat prostate was confirmed using immunostaining, and the molecular species was determined using gel filtration chromatography coupled with an enzyme-linked assay for ADM. The effects of ADM on fluid secretion were studied by short-circuit current technique in a whole mount preparation of the prostate in an Ussing chamber. The results indicated that the ADM level was higher in the ventral than the dorso-lateral prostate and the major molecular species was the active peptide. ADM increased the short-circuit current through both the cAMP- and calcium-activated chloride channels in the ventral lobe, but only through the calcium-activated channels in the dorso-lateral lobe. These stimulatory effects were blocked by the calcitonin gene-related peptide (CGRP) receptor antagonist, hCGRP8-37. We conclude that ADM may regulate prostatic fluid secretion through the chloride channels, which may affect the composition of the seminal plasma bathing the spermatozoa and hence fertility.

Adrenomedullin increased the short-circuit current in the pig oviduct through chloride channels via the CGRP receptor: mediation by cAMP and calcium ions but not by nitric oxide.

The oviduct serves as a site for the fertilization of the ovum and the transport of the conceptus down to the uterus for implantation. In this study, we investigated the presence of adrenomedullin (ADM) and its receptor component proteins in the pig oviduct. The effect of ADM on oviductal secretion, the specific receptor, and the mechanisms involved were also investigated. The presence of ADM and its receptor component proteins in the pig oviduct were confirmed using immunostaining. Short-circuit current (I(sc)) technique was employed to study chloride ion secretion in the oviductal epithelium. ADM increased I(sc) through cAMP- and calcium-activated chloride channels, and this effect could be inhibited by the CGRP receptor antagonist, hCGRP8-37. In contrast, the nitric oxide synthase inhibitor, L-NG-nitroarginine methyl ester (L-NAME), could not block the effect of ADM on I(sc). In summary, ADM may increase oviductal fluid secretion via chloride secretion independent of the nitric oxide pathway for the transport of sperm and the conceptus.

Effects of adrenomedullin on tumour necrosis factor alpha, interleukins, endothelin-1, leptin, and adiponectin in the epididymal fat and soleus muscle of the rat.

Adrenomedullin (ADM) is a peptide hormone, which participates in the development of metabolic syndrome. In this study, we have investigated the interaction of ADM and cytokines, endothelin-1 (EDN-1) and adipokines in the epididymal fat and the soleus muscle. Epididymal fat and soleus muscles from adult male Sprague-Dawley rat were incubated with ADM at concentration of 100 nM for the study of the gene expression and secretion of tumour necrosis factor (TNF-α), EDN-1, leptin, adiponectin, interleukin 1ß (IL-1ß), and IL-6. The effects of TNF-α and EDN-1 on ADM gene expression and secretion were also investigated. The results showed that ADM decreased the gene expression and protein secretion of TNF-α in both the epididymal fat and the soleus muscle and decreased IL-1ß gene expression and secretion in the soleus muscle. It also decreased endothelin gene expression and adiponectin gene expression and release and increased IL-6 and leptin gene expression and secretion in the epididymal fat. These effects were effectively blocked by the calcitonin gene-related peptide (CGRP) receptor antagonist, hCGRP8-37, but not by the ADM receptor antagonist, hADM22-52. The reduction of inflammatory cytokines and EDN-1 may help to decrease insulin resistance and increase glucose uptake. As TNF-α also increases ADM levels in the epididymal fat and the soleus muscle and EDN-1 also increases ADM levels in the epididymal fat, they may form a feedback loop with ADM in these tissues. The increase in leptin and the decrease in adiponectin by ADM in the epididymal fat may have opposite effects on metabolism.

Possible role of adrenomedullin in the pathogenesis of tubal ectopic pregnancy.

CONTEXT: Tubal ectopic pregnancy (tEP) is currently the leading cause of pregnancy-related deaths during the first trimester. Our current knowledge on the molecular pathogenesis is limited. OBJECTIVE: The objective of the study was to find out the possible role of adrenomedullin (ADM) in the pathogenesis of tEP. DESIGN: This was an experimental in vitro study on oviductal tissue. SETTING: The study was conducted at a university teaching hospital. PATIENTS AND INTERVENTIONS: Patients included those having oviducts removed surgically during salpingectomy for tEP or hysterectomy for benign gynecological conditions. Oviductal tissues were incubated in hormonal condition mimicking early pregnancy before used for in vitro experiments. MAIN OUTCOME MEASURES: Plasma ADM concentration, oviductal expression of ADM and its receptors, ciliary beat frequency, smooth muscle contraction were measured. RESULTS: The ciliary beat frequency and frequency of muscle contraction were lower in the oviducts from patients with tEP than those from simulated normal pregnancy. The plasma and oviductal tissue ADM levels were also lower. The decreases in ciliary beat and frequency of contraction were restored to normal after ADM treatment. CONCLUSIONS: The results suggest that the lower ADM level in the oviducts of tEP may lead to the decrease in ciliary beating and muscle contraction, with the result that the embryo is retained and implanted in the oviduct. Our findings explain for the first time the etiology of tubal pregnancy on the basis of an impairment of the transport of the fertilized ovum resulting from an ADM deficiency and raise the possibility of using the plasma ADM level as a predictor for tubal ectopic pregnancy.

Adrenomedullin increases ciliary beat frequency and decreases muscular contraction in the rat oviduct.

Our laboratory previously showed that oviduct produced the greatest amount of adrenomedullin (ADM) in the rat female reproductive tract. The aim of this study is to investigate the changes in ADM levels resulting from the contact between the sperm and the oviduct and the possible roles of ADM in ciliary beating and oviductal contractility. Oviducts from Sprague-Dawley rats removed at pre- and post-ovulatory stages were cut open longitudinally and treated with ADM and/or receptor blockers before ciliary beat frequency (CBF) was measured. The effects of sperm on ADM production and CBF in the oviduct were also determined. The contraction of the oviduct after treatment with ADM and receptor antagonists was measured using the organ-bath technique. The results showed that ADM increased the CBF in rat oviduct and this stimulating effect was blocked by the calcitonin-gene-related peptide (CGRP) receptor antagonist, hCGRP(8-37). CBF was lower in post-ovulatory than pre-ovulatory oviducts. The presence of sperm in the oviduct increased both the ADM level and CBF. ADM treatment was shown to inhibit the contractility of the oviduct by lowering the basal tone and decreasing the contraction amplitude. The ADM receptor antagonist, hADM(22-52), was effective in counteracting the relaxation effect of ADM in the oviduct. All in all, these results indicate that ADM may play a crucial role in transporting the gametes/embryos by regulating ciliary beating and muscular contraction.

Spontaneous subconjunctival orbital fat prolapse: report of three cases.

Spontaneous subconjunctival orbital fat prolapse is an uncommon but benign entity. It is seldom discussed in the literature, and is sometimes confused with other ocular surface tumors, such as dermolipoma. We present 3 cases, two of which are bilateral, the other being unilateral. Two cases underwent surgical excision due to ocular irritation, and the pathology proved mature adipose tissue compatible with the diagnosis. Computed tomography (CT) was available for 1 case and revealed a fat-compatible radiolucent mass continuous with the intraconal fat. Some other reports have presumed that the intraconal fat was prolapsed from a dehiscence of Tenon's capsule. However, according to our surgical findings, we suggest that the possible weak point for intraconal orbital fat prolapse is between the regions where the rectus muscle tendons penetrate into Tenon's capsule. The fat just bulges anteriorly, but not penetrates the Tenon's capsule and the intermuscular septum.

Bilateral endogenous Klebsiella pneumoniae endophthalmitis associated with meningitis-useful vision regained after treatment: case report.

Endogenous endophthalmitis is a rare but devastating complication of bacteremia. Klebsiella pneumoniae is reported to be the leading organism of endogenous endophthalmitis in Taiwan, and the prognosis of endogenous Klebsiella pneumoniae endophthalmitis is extremely poor. A 46-year-old male patient was hospitalized because of fever, chills, and consciousness disturbance for 1 day. Meningitis was the impression by clinical presentation and findings of cerebrospinal fluid analysis. Parenteral ceftriaxone (4 g/day) and gentamicin (180 mg/day) were given, and his consciousness gradually cleared. On hospital day 6, he complained of blurred vision in both eyes and floaters in the left eye for 1 day. After ophthalmic examination, bilateral endogenous endophthalmitis was diagnosed. After aggressive treatment with intravitreal antibiotics and trans pars plana vitrectomy, the visual outcome of both eyes was better than those of other reported cases.