Male infertility: pathogenesis and clinical diagnosis

Infertility affects about 7% of all men. The etiology of impaired sperm production and function can be related to factors acting at pre-testicular, post-testicular or directly at the testicular level. Primary testicular failure accounts for about 75% of all male factor infertility. Genetic factors can be identified in about 15% of cases (congenital hypogonadotrophic hypogonadism, congenital absence of vas deferens, primitive testicular failure). Despite progresses, mainly in the field of genetics, the etiology is still unknown in about 50% cases and it is termed "idiopathic infertility". A part from few exceptions, the only available therapy for male factor infertility is assisted reproduction which allows conception also in severe male factor, including azoospermia following testicular sperm extraction. The complete diagnostic workup is important for: i) the identification of treatable/reversible or health-threatening conditions; ii) selection of patients for assisted reproductive techniques; iii) for appropriate genetic counselling including preventive measures (preimplanatation or prenatal diagnosis) to safeguard the health of future offspring.     

Conus magus vs. Irukandji syndrome: a computational approach of a possible new therapy

The Irukandji syndrome is caused by the sting of some small jellyfish species. The syndrome has severe life-threatening consequences. The exacerbating pain and cardiovascular symptoms (tachycardia and hypertension) are hard to control in many cases. We suggest a way to experiment a new possible therapy with an FDA approved analgesic, ziconotide, a synthetic derivative from a marine cone snail (Conus magus) venom component, which is administrated intravenously. The proposed experimental plasma concentration of ziconotide for rats is in the range of 0-6μgml(-1). Based on a molecular biological scenario of the venom action mechanism at cellular level, we suggest that the proposed method should be functional in re-establishing the normal cardiovascular parameters of the experimental animals and concomitantly it should abolish the severe pain caused by envenomation. We expect that positive experimental results in agreement with our theory will lead to the possibility of a new therapy for the Irukandji syndrome and possibly for other envenomations with similar ethyology.     

Triglyceride Level-Influencing Functional Variants of the ANGPTL3, CILP2, and TRIB1 Loci in Ischemic Stroke

Stroke is a common multifactorial disease, and the third leading cause of death worldwide, which results in serious long-term mental and physical disability among survivors. The role of affected triglyceride metabolism in the development of ischemic stroke is under extensive investigations. Here, we examined three SNPs, rs12130333 located within the ANGPTL3 locus; rs16996148 residing at the CILP2 gene locus; and rs17321515 at the TRIB1 locus, which were originally reported in association with decreased triglyceride levels; therefore, we investigated their possible protective effect against the development of ischemic stroke. A total of 459 Caucasian stroke patients, stratified as large-vessel, small-vessel, and mixed stroke groups, and 168 control subjects were genotyped using PCR-RFLP methods. As a result, we could not detect any differences in triglyceride or total cholesterol levels in relation to any allelic variants of rs16996148, rs17321515, or rs12130333 SNPs. No correlation was found between the minor alleles rs16996148-T (P?=?0.881), rs17321515-G (P?=?0.070), or rs12130333-T allele (P?=?0.757) and the risk for development of stroke. The data presented here suggest different scale of effect of triglyceride modifier alleles and also their variable susceptibility or protective nature.     

Distribution of mRNAs encoding transforming growth factors‐β1, ‐2, and ‐3 in the intact rat brain and after experimentally induced focal ischemia

Transforming growth factors‐β1 (TGF‐β1), ‐2, and ‐3 form a small group of related proteins involved in the regulation of proliferation, differentiation, and survival of various cell types. Recently, TGF‐βs were also demonstrated to be neuroprotective. In the present study, we investigated their distribution in the rat brain as well as their expression following middle cerebral artery occlusion. Probes were produced for all types of TGF‐βs, and in situ hybridization was performed. We demonstrated high TGF‐β1 expression in cerebral cortex, hippocampus, central amygdaloid nucleus, medial preoptic area, hypothalamic paraventricular nucleus, substantia nigra, brainstem reticular formation and motoneurons, and area postrema. In contrast, TGF‐β2 was abundantly expressed in deep cortical layers, dentate gyrus, midline thalamic nuclei, posterior hypothalamic area and mamillary body, superior olive, areas of monoaminergic neurons, spinal trigeminal nucleus, dorsal vagal complex, cerebellum, and choroid plexus, and a high level of TGF‐β3 mRNA was found in cerebral cortex, hippocampus, basal amygdaloid nuclei, lateral septal nucleus, several thalamic nuclei, arcuate and supramamillary nuclei, superior colliculus, superior olive, brainstem reticular formation and motoneurons, area postrema, and inferior olive. Focal brain ischemia induced TGF‐βs with markedly different expression patterns. TGF‐β1 was induced in the penumbral region of cortex and striatum, whereas TGF‐β2 and ‐β3 were induced in different layers of the ipsilateral cortex. The expression of the subtypes of TGF‐βs in different brain regions suggests that they are involved in the regulation of different neurons and bind to different latent TGF‐β binding proteins. Furthermore, they might have subtype‐specific functions following ischemic attack. J. Comp. Neurol. 518:3752–3770, 2010. © 2010 Wiley‐Liss, Inc.     

Assessment of lung development in isolated congenital diaphragmatic hernia using signal intensity ratios on fetal MR imaging

Objectives

To investigate developmental changes in the apparently unaffected contralateral lung by using signal intensity ratios (SIR) and lung volumes (LV), and to search for correlation with clinical outcome.

Methods

Twenty-five fetuses (22–37 weeks’ gestation) were examined. Lung/liver signal intensity ratios (LLSIR) were assessed on T1-weighted and T2-weighted sequences for both lungs, then together with LV compared with age-matched controls of 91 fetuses by using the U test. Differences in LLSIRs and lung volumes were correlated with neonatal outcomes.

Results

LLSIRs in fetuses with congenital diaphragmatic hernia (CDH) were significantly higher in both lungs on T1-weighted images and significantly lower on T2-weighted images, compared with normals (p?<?0.05), increasing on T2-weighted imaging and decreasing on T1-weighted imaging during gestation. Total LV were significantly smaller in the CDH group than in controls (p?<?0.05). No significant differences in LLSIR of the two lungs were found. Outcomes correlated significantly with total LV, but not with LLSIR.

Conclusion

Changes in LLSIR seem to reflect developmental impairment in CDH; however, they provide no additional information in predicting outcome. LV remains the best indicator on fetal MR imaging of neonatal survival in isolated, left-sided CDH.     

Genetic Risk Factors in Male Infertility

The etiopathogenesis of testicular failure remains unknown in about half of the cases and is referred to as “idiopathic infertility”. “Idiopathic” testicular failure is of probable genetic origin since the number of genes involved in human spermatogenesis is likely thousands and only a small proportion of them have been identified and screened in infertile men. In parallel with studies aimed to identify mutations with a clear cause-effect relationship in spermatogenesis candidate genes, there is an increasing interest towards genetic susceptibility factors to male infertility. Despite many efforts, only a few clinically relevant polymorphisms have been identified. This is mainly related to the multifactorial nature of male infertility and to the inappropriate study design of the majority of the studies. The most promising polymorphisms are in genes involved in the endocrine regulation of spermatogenesis and on the Y chromosome, the “gr/gr” deletions. Polymorphisms are generally considered as co-factors. Their final effect on testis function and fertility is probably modulated by the genetic background of each individual and/or by the presence of certain environmental factors. In this review, recent findings concerning some of the most widely studied polymorphisms and male infertility will be discussed.     

Background data about the high dental fear scores of Hungarian 8-15-year-old primary school children

Free associations (coupling) of 139 Hungarian primary school children about their teeth was collected. Dental fear (DAS, DFS) and general anxiety scores were measured. Typical dental events (i.e.: loss of deciduous teeth, simple and traumatising dental treatments, tooth fractures) were coupled by the participants in 41.0% of the cases. Functions and importance of the teeth and oral hygiene were described in 20.1% of the cases. Simple, grotesque, or magical stories and tales about teeth were found in 8.6% of the cases. No answer was given in 30.2% of the cases. Highest dental fear and general anxiety scores were found in the group coupled traumatising dental treatment. Traumatising loss of deciduous teeth was caused by the dentist or by the father of the child, and was associated with higher dental fear and general anxiety comparing to simple loss of deciduous teeth. Higher dental fear and general anxiety scores were found in the group coupled functions and importance of the teeth comparing to the group coupled simple, grotesque, or magical stories and tales, or the group giving no answer.     

Work-related stress factors and menstrual pain: a nation-wide representative survey

While imposing research has been conducted with respect to the biological determinants of painful menstruation, little is known about the psychosocial factors, including work-related stress that might influence menstrual pain. We conducted a study in which we aimed to determine besides the prevalence of dysmenorrhoea whether menstrual pain was associated with job control, co-worker social support, job security and dissatisfaction with the job. Data of 2772 working women aged 18–55 years, participants in the Hungarostudy 2002 nation-wide representative survey was analyzed. Binary logistic regression was used to determine the association between work stress factors and menstrual pain. Altogether 15.5% of women reported to experience menstrual pain that limits their daily activity. Low job control, low co-worker social support and low job security were found to be associated with a higher risk for menstrual pain even after controlling for the effect of age, educational attainment, parity status, smoking, body-mass index and treatment for gynecological problems. Job dissatisfaction was also related to dysmenorrhoea, albeit not significantly. The relationship between work-related psychosocial factors and painful menstruation deserves further investigation in order to determine the possible pathways of this association.