Kisspeptin and fertility

The kisspeptins are a family of peptide hormones, which in recent years have been shown to play a critical role in the regulation of the hypothalamic-pituitary-gonadal axis, thus in turn influencing fertility and reproduction. This review examines the physiological role of kisspeptin and the kisspeptin receptor in the control of gonadotrophin and gonadal steroid hormone secretion and the implications of these findings with respect to fertility. In addition, the potential therapeutic use of kisspeptin in the treatment of reproductive disorders will be examined.     

A Short Insert in the Leader Sequence of RNA 3L,A Long Variant of <Emphasis Type="Italic">Alfalfa mosaic virus</Emphasis> RNA3, Introduces Two Unidentified Reading Frames

N20-RNA 3L, a large form of RNA 3 associated with Alfalfa mosaic virus (AMV) strain N20 comprises 2281nt and has approximately 97% overall sequence similarity to the longest previously described RNA 3 of AMV strain YSMV (YSMV-RNA 3; 2188nt). Compared with YSMV-RNA 3, N20-RNA 3L contains an additional 97nt in the 5' leader upstream of the open reading frames for movement protein (MP) and coat protein (CP). Two overlapping unidentified reading frames (URF1 and URF2) result from this modification, each of which code for putative translation products of 21 amino acids. The URF1 putative peptide has a hydrophilic N-terminus and a hydrophobic C-terminus, indicating a possible association with both host cell membrane and cytosol whereas the putative URF2 product is predominantly hydrophobic. A further structural modification found in N20-RNA 3L is a new tandem repeat of 243nts which overlaps with the MP open reading frame.     

Efficacy of eletriptan in migraineurs with persistent poor response to nonsteroidal anti-inflammatory drugs

BACKGROUND/OBJECTIVE: Nonsteroidal anti-inflammatory drugs continue to be one of the most widely used therapies for migraine, but their efficacy in treating moderate to severe migraine headache has not been well documented. In contrast, the efficacy of triptans in this group of patients is well documented, although no systematic research is available that evaluates the effectiveness of switching to a triptan in patients who respond poorly to nonsteroidal anti-inflammatory drugs. METHODS: One hundred thirteen patients who met International Headache Society criteria for migraine and who did not experience satisfactory response to nonsteroidal anti-inflammatory drugs, received open-label treatment with a 40-mg dose of eletriptan for one migraine attack. Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of headache and pain-free response rates, absence of associated symptoms, and functional response. Global ratings of treatment effectiveness and preference were obtained at 24 hours. RESULTS: The pain-free response rate at 2 hours postdose was 25% and at 4 hours postdose, 55%; the headache response rate at 2 hours was 66% and at 4 hours, 87%. At 2 hours postdose, relief of baseline associated symptoms was achieved by 41% of patients with nausea compared to 82% of patients at 4 hours; for patients with phonophobia, 67% were relieved at 2 hours and 93% at 4 hours, and for patients with photophobia, 70% were relieved at 2 hours and 91% at 4 hours. Functional response was achieved by 70% of patients by 2 hours postdose. The high level of acute response was maintained over 24 hours, with only 24% of patients experiencing a headache recurrence and only 10% using rescue medication. At 24 hours postdose, 74% of patients rated eletriptan as preferable to any previous treatment for migraine. The most frequent reasons cited for this treatment preference were faster headache improvement (83%) and functional response (78%). Overall, eletriptan was well tolerated; most adverse events were transient and mild to moderate in severity. No serious adverse events were reported. CONCLUSION: Results of this open-label trial found the 40-mg dose of eletriptan to have a high degree of efficacy and tolerability among patients who responded poorly to nonsteroidal anti-inflammatory drugs.     

Effects of sumatriptan and eletriptan on diseased epicardial coronary arteries

Background: Triptans are contraindicated in patients with known or suspected coronary artery disease (CAD); however, few studies have evaluated triptans in patients with obstructive CAD to quantify the vasoconstrictive effect on diseased coronary vessels. Methods: Patients undergoing percutaneous transluminal coronary angioplasty for symptomatic single-vessel CAD were randomised to one of three parallel cohorts to receive (1) 6 mg intravenously (IV) infused eletriptan plus subcutaneous (SC) placebo, (2) IV infused placebo plus 6 mg SC sumatriptan or (3) IV infused placebo plus SC placebo, as simultaneous administrations in a double-blind manner. Serial arteriograms, hemodynamic indices, electrocardiography and triptan plasma concentrations were obtained. Results:. Fifteen minutes after triptan challenge, median (95% confidence interval) changes in coronary artery diameter (CADM) at the focal point of the stenosed segment were: dilation of 2.6% (−5.0, 11.4), eletriptan 6 mg IV (n=18); constriction of 6.8% (−12.6, 0.4), sumatriptan 6 mg SC (n=17), and constriction of 4.5% (−7.0, 7.9), placebo (n=10). One patient had angiographic evidence of a new thrombus at the stenosis site, necessitating termination of study infusion and successful stenting of the lesion. There was no correlation between effects on CADM and triptan concentration, or between hemodynamic or electrocardiograph changes and the presence (n=13) or absence (n=33) of chest pain. Conclusions: Triptans had very little effect on diseased epicardial coronary arteries in a small group of angina sufferers with established CAD. Results should be interpreted cautiously since there may be instances where even modest triptan-associated epicardial constriction is sufficient to precipitate myocardial ischemia in patients with severe obstructive CAD.     

The distribution of proteins that bind neurohypophysial hormones

1. Protein fractions were prepared from serum and various organs of pigs following the methods used to extract and purify neurophysin from posterior pituitaries.2. Protein fractions extracted from porcine kidney, uterus, mammary gland or serum, which contain antigen reacting with anti-neurophysin serum, form non-dialysable complexes with oxytocin and/or lysine vasopressin.3. Protein from uterus or mammary gland bound oxytocin but not lysine vasopressin, while protein extracted from kidney bound lysine vasopressin but not oxytocin: protein from serum bound both hormones.4. Protein fractions prepared in the same way from porcine liver, spleen, skeletal muscle and brain, which do not contain antigen reacting with anti-neurophysin serum, did not form complexes with neurohypophysial hormone.5. The formation of complexes between the renal or uterine protein fractions and lysine vasopressin or oxytocin is inhibited by the addition of 1.0 x 10(-6)M-CaCl(2).6. 1-Desamino 8-arginine vasopressin is not bound by neurophysin prepared from porcine posterior pituitaries or the protein from porcine kidneys, while 8-arginine vasopressin does form non-dialysable complexes with proteins from both sources.7. A protein fraction extracted from guinea-pig kidney by similar preparative methods also bound lysine vasopressin and the binding was inhibited by addition of CaCl(2).     

Preparation and in‐vitro/in‐vivo evaluation of surface‐modified poly (lactide‐co‐glycolide) fluorescent nanoparticles

Objective The aim was to develop biodegradable nanoparticles suitable for cellular delivery of chemotherapeutic drugs. Methods Poly (lactide‐co‐glycolide) (PLGA) nanoparticles were prepared using a modified solvent evaporation method. Chitosan and calcium chloride were tested as surface modifiers. Coumarin‐6 was incorporated into some formulations as a fluorescent marker. Key findings The median size of the particles was between 400 nm and 7 μm, and scanning electron microscope pictures showed that the particles were smooth and spherical. The zeta potentials of the particles with and without surface modifier ranged between ‐25.7 mV and ‐7.0 mV, respectively. Fluorescence microscopy and flow cytometry (FACS) analysis showed that smaller surface‐modified particles were efficiently internalised by neoplastic 4T1 cells. Image analysis of frozen tissue sections from Balb/c mice given nanoparticles via the tail vein showed that the particles were distributed preferentially into the lungs, followed by the liver, spleen, kidney and heart. Conclusions Chitosan‐modified PLGA nanoparticles showed significant uptake by neoplastic 4T1 cells, and were distributed to several major organs frequently seen as sites of cancer metastasis in mice.