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P Vigil

Publications and source records attributed to P Vigil.

At least 19 recordsLinked to original sources

Update on the impact of Chlamydia trachomatis infection on male fertility.

With approximately 90 million cases annually, infection with Chlamydia trachomatis is the most prevalent sexually transmitted bacterial disease in the world. Considering that these infections are often asymptomatic and cause major complications like acute pelvic inflammatory disease, ectopic pregnancy, infertility or infant pneumonia, the estimated costs for diagnosis and treatment in the USA amounts to 2.2 million US dollars for each 500 cases. Therefore, there is a high need for correct, quick and cost-effective diagnosis and treatment of this urogenital tract infection. New innovative therapies provide good results with regard to efficacy and patients' compliance. The success rates of treatments are at least 95%. However, the occurrence of antibiotic resistance should not be ignored and new treatment schemes must be developed. The state-of-the-art of diagnosis and treatment of chlamydial infections as well as the pathophysiology is discussed in this review. In conclusion, infections with C. trachomatis is an important public health problem, especially in third world and developing countries, and more socio-economic studies linking secondary prevention of chlamydial infections, infertility and adverse pregnancy outcome are needed to understand more of its aetiology. In addition, diagnosis and treatment should be improved. Data in men revealed that past infections but not present infections are more related to male infertility. There is still controversial results. In future studies, function of the seminal vesicles and evaluation of the antioxidant capacity should be taken into account when role of C. trachomatis infection on male fertility is assessed.

Chlamydia Infections↗

Role of HLA-DR in the pathogenesis of abdominal aortic aneurysm.

OBJECTIVE: to establish a possible role for autoimmunity in the aetiology of abdominal aortic aneurysm (AAA) by examining human leukocyte antigen class II (HLA-II) immune response genes. MATERIALS AND METHODS: HLA-II typing was performed in a series of 72 AAA patients and a control group of 380 healthy subjects. RESULTS: a higher incidence of the allele subtype HLA-DR B1*0401 was detected in the AAA group with respect to the control group (12.5 vs 5.2%; p = 0.02, OR 2.59). In contrast, the HLA-DR B1*01 allele tended to behave as a protective factor for AAA (12.5% AAA vs 21.3% controls; p = 0.09, OR 0.5). CONCLUSIONS: the association observed here between HLA-DR B1*0401 and HLA-DR B1*01 and unspecific AAA is similar to that reported in several autoimmune diseases. This similarity suggests an essential role for autoimmune factors in the formation of the AAA.

Alleles↗

Chlamydia trachomatis infection in male partners of infertile couples: incidence and sperm function.

Chlamydia trachomatis infection is one of the most common sexually transmitted diseases. Its effect on male fertility, however, is still controversial. In this study, 284 male partners of infertile couples consulting the Center of Studies in Reproductive Biology (CEBRE) were analyzed. The incidence of C. trachomatis infection among male partners of infertile couples was 38.6%. There were no significant differences between infected and noninfected infertile men in any of the sperm parameters assessed (sperm concentration, motility and morphology). The results of the three bioassays developed to evaluate sperm physiology, namely spermatozoa-zona pellucida binding, acrosome reaction stimulated with human follicular fluid and zona-free hamster oocyte penetration, showed no differences between infected and noninfected men. Electron microscopy studies suggest that spermatozoa are active agents in the dissemination of the chlamydial infection; they could be acting as 'vehicles' for the pathogens. These, and other results, suggest that the possible effect of C. trachomatis on male fertility is not due to alterations in sperm 'quality' or function, but rather to the transmission of the disease to female partners, causing inflammatory processes and promoting the generation of antisperm antibodies.

Animals↗

First-trimester pregnancy loss and active Chlamydia trachomatis infection: correlation and ultrastructural evidence.

The incidence of Chlamydia trachomatis (Ct) infection and the possible correlation between couples presenting with first-trimester spontaneous abortions and active Ct infection was assessed. Additionally, the ability of Ct to infect zona-free hamster oocytes was explored by incubating the oocytes with spermatozoa from infected patients. A total of 961 women and 750 men consulting our reproductive medicine centre were screened for Ct using direct immunofluorescence. The general incidence of Ct infection was 9.4% in females (90 of 961) and 13.9% in males (104 of 750). In women with spontaneous abortions the incidence of Ct was 21.0% (14 of 66) compared with 8.9% (23 of 59) for women without spontaneous abortions and term pregnancies (chi-square, P < 0.05). When both partners of the couples were considered (one or both partners infected), the incidence rose to 68.8% (22 of 32) (chi-square, P < 0.001). In vitro studies using electron microscopy demonstrated the presence of Ct on the surface of and inside the oocyte. These results indicate a correlation between an active Ct infection and spontaneous abortion. Electron microscopy studies suggested the possibility of direct oocyte infection by Ct. Two models are proposed for the pathogenesis of Ct-related early abortions: (i) direct zygote infection, and (ii) immune response to heat shock proteins expressed by the zygote and triggered by previous Ct infections.

Abortion, Spontaneous↗

Celiac disease and TNF promoter polymorphisms.

The possibility that genetic susceptibility to celiac disease (CD) might be influenced by tumor necrosis factor (TNF) genes polymorphism has repeatedly been put forward. To date, this has only been investigated in case-control studies and results have been contradictory. In order to avoid any possible ethnic mismatching between patients and controls, we have approached this problem studying 71 celiac families, establishing the parental haplotypes and comparing CD versus control haplotypes (the so-called AFBAC or affected family-based controls). We used DNA-based methods to screen for HLA-DRB1, -DQA1, and -DQB1 alleles, TNFalpha promoter polymorphims and TNFa and b microsatellites. The guanine-to-adenine polymorphism at position -308 of the TNFalpha gene promoter region was found associated with CD as the TNF-308A allele appeared significantly increased in frequency in CD haplotypes, and this was shown to be independent of the association between CD and the DRB1*0301,DQA1*0501,DQB1*0201 alleles. Our results indicate that at least another gene, in addition to the known association of CD with HLA class II, has a susceptibility role in this disease. This should be either TNFalpha or another polymorphic gene in the telomeric end of the HLA class III region.

Celiac Disease↗

Tumor necrosis factor genomic polymorphism in Spanish IGA deficiency patients.

Selective IgA deficiency (IgAD) is the most common form of primary immunodeficiency. Its association with genes within the major histocompatibility complex (MHC) has been repeatedly reported. Recently the susceptibility gene has been located in the class III region, around the tumor necrosis factor (TNF) cluster. In this study we have examined IgAD association with TNF-alpha gene promoter polymorphisms and TNFa and b microsatellites. No significant association was found with the former polymorphisms and the observed associations with TNFa2 allele and haplotypes TNFa2b1 and TNFa2b3 were proven to be secondary to their occurrence on the B14-DR1 and B8-DR3 haplotypes, previously reported to be associated with susceptibility to IgAD. However, a primary negative (protective) association was found between the TNFa10 allele and IgAD.

Alleles↗

Gonadotropin-releasing hormone-stimulated sperm binding to the human zona is mediated by a calcium influx.

The mechanism by which GnRH increases sperm-zona pellucida binding in humans was investigated in this study. We tested whether GnRH increases sperm-zona binding in Ca(2+)-free medium and in the presence of Ca(2+) channel antagonists. We also examined the GnRH effect on the intracellular free Ca(2+) concentration ([Ca(2+)](i)). Sperm treatment with GnRH increased sperm-zona binding 300% but only when Ca(2+) was present in the medium. In Ca(2+)-free medium or in the presence of 400 nM nifedipine, 80 microM diltiazem, or 50 microM verapamil, GnRH did not influence sperm-zona binding. GnRH increased the [Ca(2+)](i) in the sperm in a dose-dependent manner. The maximum effect was reached with 75 nM GnRH. The GnRH-induced increase in [Ca(2+)](i) was fast and transient, from a basal [Ca(2+)](i) of 413 +/- 22 nM to a peak value of 797 +/- 24 nM. The GnRH-induced increase in [Ca(2+)](i) was entirely due to a Ca(2+) influx from the extracellular medium because the increase in [Ca(2+)](i) was blocked by the Ca(2+) chelator EGTA and by the Ca(2+) channel antagonists nifedipine and diltiazem. These antagonists, however, were not able to inhibit the progesterone-activated Ca(2+) influx. On the contrary, T-type calcium channel antagonists pimozide and mibefradil did not affect GnRH-activated Ca(2+) influx but inhibited the progesterone-activated Ca(2+) influx. Finally, the GnRH-induced Ca(2+) influx was blocked by two specific GnRH antagonists, Ac-D-Nal(1)-Cl-D-Phe(2)-3-Pyr-D-Ala(3)-Arg(5)-D-Glu(AA)(6)-GnRH and Ac-(3,4)-dehydro-Pro(1),-p-fluoro-D-Phe(2), D-Trp(3,6)-GnRH. These results suggest that GnRH increases sperm-zona binding via an elevation of [Ca(2+)](i) through T-type, voltage-operated calcium channels.

Calcium↗

Primary association of a TNF gene polymorphism with susceptibility to multiple sclerosis.

The associations of three promoter polymorphisms in the tumor necrosis factor (TNFA) gene have been studied in 238 patients and 324 control subjects. A significant correlation was found between MS susceptibility and the TNFA-376 polymorphism. This association was independent of the human leukocyte antigen (HLA) class II association and the combined inheritance of HLA-DRB1*1501 and the TNFA-376A allele more than additively increased susceptibility to MS.

Alleles↗

Susceptibility to multiple sclerosis mediated by HLA-DRB1 is influenced by a second gene telomeric of the TNF cluster.

Susceptibility to multiple sclerosis (MS) is clearly associated with human leukocyte antigen (HLA)-DRB1*1501, but some studies show associations with HLA-B7 and -B18. These are often co-expressed with DRB1*1501 in the ancestral haplotypes (AH) denoted 7.1 (HLA-A3, B7, tumor necrosis factor [TNF]a11b4, DRB1*1501) and 18.1 (HLA-A25, B18, TNFa10b4, DRB 1*1501). Here we present a systematic study of 218 patients and 274 controls typed at all standard class II and TNF microsatellite loci, and a novel non-synonymous polymorphism in the central major histocompatibility complex gene, inhibitor of kappa B-like protein (IKBL). The C allele at IKBL+738 is only found on the 7.1 haplotype. HLA-DRB1*1501 was associated with disease, as expected. When subjects expressing DRB 1*501 were analyzed separately, TNFa11b4 and IKBL+738C were less common in the patients and, hence, mark an allele that mediates resistance which lies telomeric of IKBL. TNFa10b4 and TNFa1b5 were more common in DRB1*1501 patients than in controls. These alleles have been associated with the 18.1 and 18.2 AH, respectively. Since no component of these haplotypes was an independent risk factor in this study, it appears likely that a gene linked to TNFa10b4 and TNFa1b5 modifies the effect of the susceptibility locus marked by HLA-DRB1*1501. Potential candidate genes telomeric of the TNF cluster are discussed.

Adaptor Proteins, Signal Transducing↗

Amino acid polymorphism at residue 71 in HLA-DR beta chain plays a critical role in susceptibility to ulcerative colitis.

The association of ulcerative colitis with distinct HLA-DRB1 alleles has not been easy to ascertain. Recent studies show that among HLA-DR2 alleles, DRB1*15 but not DRB1*16, is associated with the disease. Similarly, in the HLA-DR1 group, only DRB1*0103 is increased in ulcerative colitis patients. The aim of our study was to identify critical DRB1 residues that might account for these differences. We typed 121 patients with ulcerative colitis and 275 controls using gene amplification and sequence-specific oligonucleotide probing for HLA-DRB1 and DRB3. We observed a strong negative association between HLA-DRB1 alleles that encode lysine at position 71 in their beta-chain and susceptibility to ulcerative colitis. Differences in the prevalence among other alleles differing only in the third hypervariable region suggested a hierarchy of susceptible and protective class II alleles related to the presence of an acidic, neutral, or basic amino acid residue at position 71. These data implicate most strongly the amino acid residues in the third hypervariable region of the DRbeta chain, especially DRbeta71, in the association between ulcerative colitis and HLA. However, this does not exclude the contribution of other parts of the molecule and other immunoregulatory genes.

Adult↗

HLA class II homozygosity confers susceptibility to common variable immunodeficiency (CVID).

Most cases of CVID occur sporadically, but familial cases do also occur and 15% of the patients with the disease have first degree relatives with IgA deficiency (IgAD). Our purpose was to study CVID association with HLA class II alleles and to ascertain whether this disease shares a common genetic background with IgAD in our population. Patients with CVID (n = 42), were typed using gene amplification and sequence-specific oligonucleotide probing for HLA-DRB1, DRB3, DQA1 and DQB1 loci and their typing compared with that of 96 IgAD and 334 healthy controls. We observed a positive association between non-Asp residues at position 57 of the HLA-DQbeta chain and CVID, although much weaker than in IgAD. Further, we found an association between CVID and homozygosity for genes encoding HLA class II molecules, especially HLA-DQ, not seen in IgAD. The data support the hypothesis that a restricted diversity of HLA class II molecules may contribute to susceptibility to CVID.

Alleles↗

Pancolitis and genetic markers in the Spanish population.

BACKGROUND: although the etiology of ulcerative colitis disease remains an enigma, the importance of the major histocompatibility complex genes has been described, as in many other autoimmune diseases. AIM: we investigated the contribution of HLA-DRB1, DQA1 and DQB1 genes (HLA region) in patients with pancolitis. METHODS: we studied a total of 89 patients diagnosed as having ulcerative colitis (34 pancolitis and 55 left colitis) and 275 healthy control subjects. Complete information on sex, age, family history, age of onset, localization, complications, surgery and treatment was obtained from all patients. DNA was extracted from peripheral blood leukocytes and all individuals were HLA-DRB1 genotyped. RESULTS AND CONCLUSIONS: there was an association between pancolitis and the presence of DR4-Val86 (p = 0.009; OR = 3.3) and DRB1*0103 (p = 0.02; OR = 5.1) alleles. In patients with left colitis an association with DRB1*1501 (p = 0.03; OR = 1.9) and DRB1*0103 alleles (p = 0.03; OR = 3.8) was observed. We conclude that a strong association between DR4-Val86 and pancolitis exists.

Adult↗

Sperm binding to the human zona pellucida after migration through human cervical mucus.

During lactational amenorrhea a special type of cervical mucus, similar to that found during the luteal phase, is produced. This mucus, however, is able to support sperm migration. In the study described, the ability of spermatozoa to bind to the human zona pellucida (hZP) after migration through periovulatory and post-partum mucus was studied. Mucus was obtained from exclusively breastfeeding women in amenorrhea at 30, 60, 120 and 180 days post-partum. Periovulatory mucus samples from normally cycling women were used as a control. Flat capillary tubes were filled with BWW culture medium at the top and cervical mucus at the bottom. The tubes were immersed in a semen reservoir and the spermatozoa allowed to migrate through the mucus for 3 h into the culture media. Then the spermatozoa were coincubated with 3-4 hZP for 30 min and the number of bound spermatozoa per zona was counted. Periovulatory cervical mucus had an average Insler score of 14 +/- 0.5 as compared to 4.6 +/- 0.4 for post-partum mucus. Spermatozoa recovered from periovulatory mucus were always able to bind to the hZP in only 68 +/- 7% of the cases. Moreover, spermatozoa recovered from post-partum mucus bound to the ZP in lower numbers than did spermatozoa recovered fro periovulatory mucus (p < 0.03). These results suggest a greater ability of sperm-hZP binding after migration through periovulatory mucus and they also indicate that sperm binding to the ZP is possible even after sperm migration through a low quality mucus.

Cell Adhesion↗

Human cervical mucus: relationship between biochemical characteristics and ability to allow migration of spermatozoa.

Cervical mucus is produced throughout the menstrual cycle. Sperm migration, however, is possible only during the periovulatory period of the cycle. Cervical mucus is also produced during the amenorrhoeic post-partum period. Post-partum mucus is very similar to luteal phase mucus except that it can allow sperm migration. In this study, mucus samples obtained from all these periods were classified according to their capacity to allow sperm migration. The biochemical characteristics of mucus samples that did (peri-ovulatory and 40% of post-partum samples) and did not (luteal and 60% of post-partum samples) allow sperm migration were then compared. Mucus samples with positive sperm migration showed the highest percentage of water and lowest protein and glycoprotein concentration (per ml of mucus). In addition, post-partum mucus samples with positive sperm migration showed lower concentrations of proteins and glycoproteins than post-partum mucus samples that did not allow sperm migration. However, the amount of glycoproteins per mg of protein was similar between post-partum samples that were positive and negative for sperm migration. These data suggest that the carbohydrate composition of the glycoproteins is playing a key role in the ability of cervical mucus to accept spermatozoa.

Body Water↗

Inhibition of the acrosome reaction by trypsin inhibitors and prevention of penetration of spermatozoa through the human zona pellucida.

In this study we evaluated the effect of several trypsin inhibitors (p-aminobenzamidine: pAB; N-alpha-p-tosyl-L-lysine-chloromethyl-ketone: TLCK and p-nitrophenyl-p'-guanidino-benzoate: NPGM) on sperm binding and penetration of the human zona pellucida. Motile spermatozoa, selected by a two-step Percoll gradient, were incubated at 1 x 10(7) cells ml-1 at 37 degrees C and in 5% CO2 for 4.5 h. This was followed by the addition of 1 mmol pAB l-1 or phosphate-buffered saline (control) for 30 min. Three to four non-viable human oocytes were then added to each sperm suspension and incubated for 3 h. The numbers of spermatozoa bound to the human zona pellucida and in the perivitelline space were determined by phase contrast microscopy. The results showed that pAB significantly inhibited zona penetration by spermatozoa (56 +/- 8% oocytes penetrated, control versus 0 +/- 0% oocytes penetrated, pAB, mean +/- SEM), without modifying spermatozoa-zona pellucida binding. The inhibition of zona penetration was due to a block of the acrosome reaction normally induced by the human zona pellucida. In separate experiments, sperm suspensions pretreated with 1 mmol pAB l-1 or 10 mumol NPGB l-1 exhibited a marked decrease in the percentage of acrosome reactions on the zona surface (85 +/- 4% and 76 +/- 3% inhibition, respectively). In addition, the inhibitors prevented the acrosome reaction induced by human follicular fluid (percentage of acrosome-reacted spermatozoa: control 8 +/- 2; follicular fluid 25 +/- 3; pAB 6 +/- 2; NPGB 8 +/- 1; TLCK 12 +/- 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Benzamidines↗

The acrosome reaction-inducing activity of individual human follicular fluid samples is highly variable and is related to the steroid content.

In this study, we have evaluated the relationship between the acrosome reaction-inducing activity of individual human follicular fluid samples and their steroid content. Eighteen samples of follicular fluid were obtained during egg retrieval in six patients undergoing assisted fertilization. Motile spermatozoa were incubated in modified Tyrode's medium (26 mg/ml bovine serum albumin) for 20 h at 1 x 10(7) cells/ml. In a single experiment, aliquots of a semen specimen were simultaneously treated with an aliquot of each follicular fluid sample. The percentage of acrosome reacted spermatozoa was determined using fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA) lectin. The fluids were also analysed by radioimmunoassay to determine the levels of progesterone, 17 alpha-hydroxy-progesterone, testosterone and oestradiol. The results showed that there was a positive, highly significant correlation between the acrosome reaction-inducing activity and the progesterone level of each follicular fluid sample (r = 0.72, P less than 0.005). Additionally, treatment of the follicular fluid samples with charcoal-dextran caused both a decrease in progesterone concentration and the total loss of the acrosome reaction-inducing activity. The addition of progesterone restored the acrosome reaction-inducing ability in 88% of samples. These data support the idea that progesterone in follicular fluid is the molecule responsible for inducing the acrosome reaction in human spermatozoa.

Acrosome↗

Human spermatozoa selected by Percoll gradient or swim-up are equally capable of binding to the human zona pellucida and undergoing the acrosome reaction.

Several techniques have been used for selecting motile spermatozoa including Percoll and albumin gradients, swim-up, and glass wool filtration. A high yield of motile spermatozoa as well as an enhancement of motility are the most desirable features of a practical method. An equally important consideration is whether or not these techniques select functionally normal spermatozoa. In this study we have compared two methods for separation of motile cells, swim-up and Percoll gradient. Normal semen samples from 12 different men were used in this study. Each sample was simultaneously processed by swim-up and Percoll gradient using modified Tyrode's medium. After the sperm concentration was adjusted to 1 x 10(7) spermatozoa/ml, the suspensions were incubated at 37 degrees C, 5% CO2 in air. In each suspension the percentage of sperm recovery, percentage of motile spermatozoa, percentage of acrosome reacted spermatozoa (either spontaneously or stimulated with human follicular fluid), percentage of zona-free hamster oocytes penetrated, and number of spermatozoa bound to the human zona pellucida were determined. The results obtained indicated that the percentage of sperm recovery was higher with the Percoll gradient than with the swim-up procedure (P less than 0.001). However, no significant differences were found between these two sperm populations in the percentage of motile cells, in the percentage of acrosome reacted spermatozoa, and in the percentage of zona-free hamster oocytes penetrated. In addition, the number of spermatozoa bound per zona pellucida was similar for spermatozoa selected by Percoll or swim-up. We conclude that there were no functional differences between the spermatozoa selected by either method.

Acrosome↗