Calcium ionophore-induced acrosome reaction correlates with fertilization rates in vitro in patients with teratozoospermic semen

The aim of this study was to determine the relationship between calcium ionophore A23187-induced acrosome reaction (AR) and sperm fertilizing ability. Semen samples remaining after preparation for standard IVF were studied in 109 patients who had sperm concentrations > or =20 x 10(6)/ml. Ionophore-induced AR was performed on motile spermatozoa selected by centrifugation on a Percoll gradient. Semen analysis was performed using standard methods. Patients with higher (>50%, n = 76) fertilization rates had significantly higher ionophore-induced AR than patients with lower (<50%, n = 33) fertilization rates (49 +/- 14 versus 38 +/- 21%, P < 0.05). When the data from all patients were analysed by logistic regression, only the percentage sperm motility in insemination medium and ionophore-induced AR were significantly related to fertilization rates. Similar results were also obtained when the data from a subgroup of patients with poor (<15% normal) sperm morphology were analysed. However, when patients with normal sperm morphology > or =15% were analysed separately, only sperm count and the percentage of spermatozoa with progressive motility in semen were significantly related to fertilization rates. In conclusion, ionophore- induced AR was significantly related to fertilization rates in vitro mainly in patients with teratozoospermic semen. Tests for ionophore- induced AR may provide additional information about sperm fertilizing ability but may not indicate specific defects of the physiological AR.      

The CARD15 2936insC mutation and TLR4 896 A>G polymorphism in African Americans and risk of preterm premature rupture of membranes (PPROM)

Infection is believed to be a leading cause of preterm premature rupture of membranes (PPROM). The bacterial cell wall component, lipopolysaccharide (LPS), is thought to initiate tissue responses leading to PPROM in the setting of Gram negative infection. LPS is recognized by the innate immune system, including the proteins encoded by the CARD15 and TLR4 genes. A recently described mutation (2936insC) in CARD15 and a polymorphism in TLR4 896 A>G impair responses to LPS. The objective of this study was to determine if African Americans, who have a higher incidence of PPROM than Caucasians, have different frequencies of the mutant CARD15 allele and the TLR4 hyporesponsive variant, and if risk of PPROM is influenced by fetal carriage of these alleles. The allele frequencies for the CARD15 mutation and the TLR4 896G variant in African Americans were similar to those reported for Caucasians. There was no association between the TLR4 alleles examined and PPROM. However, the CARD15 mutation was only detected in controls and not in PPROM cases. We conclude that the CARD15 mutation and hyporesponsive TLR4 allele do not contribute to ethnic variation in the incidence of PPROM.     

p75(NTR) gene and suicide attempts in young adults with a history of childhood-onset mood disorder.

Recently, evidence has accumulated for the role of neurotrophic processes in mood disorders. Neurotrophins operate on receptors, one of which is the p75 neurotrophin receptor (p75(NTR)). We examined three p75(NTR) markers at the p75(NTR) gene, including a missense polymorphism that changes serine to leucine (S205L), for association with suicide attempt (SA) in 203 childhood-onset mood disorder (COMD) cases. There was no difference between COMD suicide attempters and COMD non-attempters with logistic regression models for any of the three markers. We also compared the three polymorphisms between 192 COMD cases and 192 matched healthy controls and found no significant differences between COMD and healthy controls. Our results do not support an association of the p75(NTR) S205L polymorphism with risk for COMD or SA in COMD.     

Differential long-term subcellular responses in heart and liver to adriamycin stress. Exogenous L-carnitine cardiac and hepatic protection

In order to evaluate the heart and liver responses after adriamycin (ADR) toxic aggression, with and without exogenous L-carnitine (CAR) protection, female Sprague-Dawley rats, body weight 40-60 g, were randomized into four groups: CON, ADR, CAR and CAR-ADR. ADR was injected i.v. at a dose of 15-18 mg/kg body wt (0.1 ml). CAR was administered i.v. at a dose of 20 mg (0.1 ml) before each subdose of ADR, and then orally at 180 mg/kg body wt daily for 12 weeks. Long-term cardiac and hepatic subcellular damage were determined by transmission electron microscopic analysis of ultrathin sections. The ADR-induced long-term cardiac subcellular pathology included loss, disruption and disassembly of myofibrils, and mitochondrial swelling and condensation. On the other hand, the ADR-induced subcellular hepatic alterations consisted of polymorphic mitochondria, cytoplasmic vacuolization and accumulation of lipid droplets. Apparently, cardiac tissue was more affected by ADR toxic aggression than hepatic tissue. However, these alterations were of less severity in protected groups, in both heart and liver, suggesting CAR as a possible hepatoprotector agent against ADR toxicity. Because of the liver-L-carnitine-heart relationship, studying ADR-hepatotoxicity could be helpful in the further understanding of severe ADR-cardiotoxicity.     

Role of the Phagocyte in Host-Parasite Interactions XXIV. Aldehyde Generation by the Myeloperoxidase-H(2)O(2)-Chloride Antimicrobial System: a Possible In Vivo Mechanism of Action

Myeloperoxidase (MPO), H₂O₂, and chloride ions in the presence of bacteria form aldehydes and are bactericidal. The use of heat-inactivated MPO prevented both killing and aldehyde generation. Decarboxylation and deamination of carboxyl and amino group substrates arising from the bacterial surface may participate in the reaction which yields aldehydes. Bacterial contact was essential for killing. Decarboxylation and bactericidal activities were noted when physiological concentrations of chloride were used. When MPO was replaced with horseradish peroxidase (HPO) in the chloride medium, decarboxylation and bactericidal activities were no longer noted. In contrast, iodide functioned in the antimicrobial system with either MPO or HPO. The iodide concentrations required were at least sixfold greater than circulating blood iodide levels. Moreover, decarboxylation did not occur in the presence of iodide with either enzyme. Thus, both halides function in the MPO-H₂O₂ system but by different mechanisms. It is likely that in vivo under most conditions chloride is the functional halide and that generation of aldehydes is the mechanism responsible for the antimicrobial activity of the MPO-H₂O₂-chloride system.     

Mycoplasmacidal Activity of Peroxidase-H2O2-Halide Systems

A mycoplasmacidal system consisting of myeloperoxidase (MPO)-containing granules, H(2)O(2), and a halide is described. In all parameters measured, it appears to be identical to the MPO-H(2)O(2)-halide bactericidal system previously reported. It has a pH optimum of approximately 5.5 and an optimal MPO:H(2)O(2) ratio of 1:25. The halide requirement can be satisfied by either chloride or iodide. Through the use of taurine or horseradish peroxidase substitution, chloride-mediated killing can be distinguished from iodide-mediated killing. The relationship of this mycoplasmacidal system to other mycoplasmacidal systems and to host surveillance of mycoplasma is discussed.