The effects of male age on sperm analysis by motile sperm organelle morphology examination (MSOME)

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate the influence of age on sperm quality, as analysed by motile sperm organelle morphology examination (MSOME).</p> <p>Methods</p> <p>Semen samples were collected from 975 men undergoing evaluation or treatment for infertility. Sperm cells were evaluated at 8400× magnification using an inverted microscope equipped with Nomarski (differential interference contrast) optics. Two forms of spermatozoa were considered: normal spermatozoa and spermatozoa with large nuclear vacuoles (LNV, defined as vacuoles occupying > 50% of the sperm nuclear area). At least 200 spermatozoa per sample were evaluated, and the percentages of normal and LNV spermatozoa were determined. The subjects were divided into three groups according to age: Group I, less than or equal to 35 years; Group II, 36-40 years; and Group III, greater than or equal to 41 years.</p> <p>Results</p> <p>There was no difference in the percentages of normal sperm between the two younger (I and II) groups (<it>P ></it>0.05). The percentage of normal sperm in the older group (III) was significantly lower than that in the younger (I and II) groups (<it>P </it>< 0.05). There was no difference in the percentage of LNV spermatozoa between the younger (I and II) groups (<it>P ></it>0.05). The percentage of LNV spermatozoa was significantly higher in the older group (III) than in the younger (I and II) groups (<it>P </it>< 0.05). Regression analysis demonstrated a significant decrease in the incidence of normal sperm with increasing age (<it>P </it>< 0.05; r = -0.10). However, there was a significant positive correlation between the percentage of spermatozoa with LNV and male age (<it>P </it>< 0.05, r = 0.10).</p> <p>Conclusion</p> <p>The results demonstrated a consistent decline in semen quality, as reflected by morphological evaluation by MSOME, with increased age. Considering the relationship between nuclear vacuoles and DNA damage, these age-related changes predict that increased paternal age should be associated with unsuccessful or abnormal pregnancy as a consequence of fertilisation with damaged spermatozoa. Given that sperm nuclear vacuoles can be evaluated more precisely at high magnification, these results support the routine use of MSOME for ICSI as a criterion for semen analysis.</p

Motile sperm organelle morphology examination (MSOME): intervariation study of normal sperm and sperm with large nuclear vacuoles

<p>Abstract</p> <p>Background</p> <p>Although the motile sperm organelle morphology examination (MSOME) was developed only as a selection criterion, its application as a method for classifying sperm morphology may represent an improvement in evaluation of semen quality, with potential clinical repercussions. The present study aimed to evaluate individual variations in the motile sperm organelle morphology examination (MSOME) analysis after a time interval.</p> <p>Methods</p> <p>Two semen samples were obtained from 240 men from an unselected group of couples undergoing infertility investigation and treatment. Mean time interval between the two semen evaluations was 119 +/- 102 days. No clinical or surgical treatment was realized between the two observations. Spermatozoa were analyzed at greater than or equal to 8400× magnification by inverted microscope equipped with DIC/Nomarski differential interference contrast optics. At least 200 motile spermatozoa per semen sample were evaluated and percentages of normal spermatozoa and spermatozoa with large nuclear vacuoles (LNV/one or more vacuoles occupying >50% of the sperm nuclear area) were determined. A spermatozoon was classified as morphologically normal when it exhibited a normal nucleus (smooth, symmetric and oval nucleus, width 3.28 +/- 0.20 μm, length 4.75 +/- 0.20 μm/absence of vacuoles occupying >4% of nuclear area) as well as acrosome, post-acrosomal lamina, neck and tail, besides not presenting cytoplasm around the head. One examiner, blinded to subject identity, performed the entire study.</p> <p>Results</p> <p>Mean percentages of morphologically normal and LNV spermatozoa were identical in the two MSOME analyses (1.6 +/- 2.2% vs. 1.6 +/- 2.1% <it>P </it>= 0.83 and 25.2 +/- 19.2% vs. 26.1 +/- 19.0% <it>P </it>= 0.31, respectively). Regression analysis between the two samples revealed significant positive correlation for morphologically normal and for LNV spermatozoa (r = 0.57 95% CI:0.47-0.65 <it>P </it>< 0.0001 and r = 0.50 95% CI:0.38-0.58 <it>P </it>< 0.0001, respectively).</p> <p>Conclusions</p> <p>The significant positive correlation and absence of differences between two sperm samples evaluated after a time interval with respect to normal morphology and LNV spermatozoa indicated that MSOME seems reliable (at least for these two specific sperm forms) for analyzing semen. The present result supports the future use of MSOME as a routine method for semen analysis.</p

Intestinal Epithelial Stem/Progenitor Cells Are Controlled by Mucosal Afferent Nerves

Background: The maintenance of the intestinal epithelium is of great importance for the survival of the organism. A possible nervous control of epithelial cell renewal was studied in rats and mice. Methods: Mucosal afferent nerves were stimulated by exposing the intestinal mucosa to capsaicin (1.6 mM), which stimulates intestinal external axons. Epithelial cell renewal was investigated in the jejunum by measuring intestinal thymidine kinase (TK) activity, intestinal H-3-thymidine incorporation into DNA, and the number of crypt cells labeled with BrdU. The influence of the external gut innervation was minimized by severing the periarterial nerves. Principal Findings: Luminal capsaicin increased all the studied variables, an effect nervously mediated to judge from inhibitory effects on TK activity or H-3-thymidine incorporation into DNA by exposing the mucosa to lidocaine (a local anesthetic) or by giving four different neurotransmitter receptor antagonists i.v. (muscarinic, nicotinic, neurokinin1 (NK1) or calcitonin gene related peptide (CGRP) receptors). After degeneration of the intestinal external nerves capsaicin did not increase TK activity, suggesting the involvement of an axon reflex. Intra-arterial infusion of Substance P (SP) or CGRP increased intestinal TK activity, a response abolished by muscarinic receptor blockade. Immunohistochemistry suggested presence of M3 and M5 muscarinic receptors on the intestinal stem/progenitor cells. We propose that the stem/progenitor cells are controlled by cholinergic nerves, which, in turn, are influenced by mucosal afferent neuron(s) releasing acetylcholine and/or SP and/or CGRP. In mice lacking the capsaicin receptor, thymidine incorporation into DNA and number of crypt cells labeled with BrdU was lower than in wild type animals suggesting that nerves are important also in the absence of luminal capsaicin, a conclusion also supported by the observation that atropine lowered thymidine incorporation into DNA by 60% in control rat segments. Conclusion: Enteric nerves are of importance in maintaining the intestinal epithelial barrier.Original Publication:Ove Lundgren, Mats Jodal, Madeleine Jansson, Anders T Ryberg and Lennart Svensson, Intestinal Epithelial Stem/Progenitor Cells Are Controlled by Mucosal Afferent Nerves, 2011, PLOS ONE, (6), 2, 16295.http://dx.doi.org/10.1371/journal.pone.0016295Copyright: Public Library of Science (PLoS)http://www.plos.org

Tacrolimus once daily (ADVAGRAF) versus twice daily (PROGRAF) in de novo renal transplantation: a randomized phase III study.

This multicenter, 1:1-randomized, parallel-group, noninferiority study compared the efficacy and safety of twice-daily tacrolimus (Tacrolimus BID; Prograf) and once-daily tacrolimus prolonged release (Tacrolimus QD; Advagraf), combined with steroids and low-dose mycophenolate mofetil without antibody induction, in 667 de novo kidney transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension of up to 12 months posttransplant. Biopsy-proven acute rejection rate at 24 weeks (primary endpoint, per-protocol analysis) was 15.8% for Tacrolimus BID versus 20.4% for Tacrolimus QD (p = 0.182; treatment difference 4.5%, 95% confidence interval-1.8%, 10.9%, just outside the prespecified 10% noninferiority margin). Kaplan-Meier 12-month patient and graft survival rates were 97.5% and 92.8% for Tacrolimus BID and 96.9% and 91.5% for QD. Both treatment groups showed equally well-maintained renal function at 12 months (mean creatinine clearance approximately 67 mL/min) and similar adverse event profiles. Overall results obtained with either Tacrolimus QD or BID, without antibody induction, were good, supporting use of the once-daily formulation as an effective alternative to the established twice-daily formulation

Technological Insights on the Philistine Culture: Perspectives from Tell es-Safi/Gath

More than a century of study of the Philistines has revealed abundant remains of their material culture. Concurrently, our understanding of the origins, developmental processes, and socio-political matrix of this fascinating culture has undergone major changes. Among other facets, Philistine technology has been discussed, but in our opinion, a broad view of its importance for understanding Philistine culture is still lacking. The more than twenty years of excavation at Tell es-Safi/Gath, one of the central sites in Iron Age Philistia, offers an opportunity to review a broad range of technologically-related evidence from this site, and from this to offer a current interpretation of Philistine technology within the broader picture of the Iron Age and the processes, mechanisms, interactions, and identity politics of this culture