Distribution of gene mutations associated with familial normosmic idiopathic hypogonadotropic hypogonadism

Objective: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH. Methods: In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH. Results: Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency. Conclusions: Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty.     

Multiple sulfatase deficiency: A case series of four children

Multiple sulfatase deficiency is biochemically characterized by the accumulation of sulfated lipids and acid mucopolysaccharides. The gene sulfatase-modifying factor 1 (SUMF1), recently identified, encodes the enzyme responsible for post-translational modification of a cysteine residue, which is essential for the activity of sulfatases. We describe clinical findings and mutation analysis of four patients. The patients presented with hypotonia, developmental delay, coarse face, ichthyosis, and hepatosplenomegaly. The diagnosis was made through clinical findings, enzymatic assays, and mutation analysis. We were detected to be homozygous for a novel missense mutation c. 739G > C causing a p.G247R amino acid substitution in the SUMF1 protein.Key Words: Child, multiple sulfatase deficiency, sulfatase-modifying factor 1 gene     

Rehydration of a reattached fractured tooth fragment after prolonged dehydration

Crown fractures of the anterior teeth are one of the most common outcomes of trauma to the orofacial region. The reattachment of dental fragments is a conservative treatment and should be considered a primary treatment choice in the restoration of anterior tooth fractures. This article presents a clinical technique for the restoration of a fractured maxillary lateral incisor by reattaching the tooth fragment that was kept in dry conditions for five days with the aid of adhesive dentistry. The esthetic compromise of white color (due to excessive dehydration of the segment) was reconciled after one month of service in the mouth by regaining the natural color by rehydration. The one-year clinical evaluation revealed a successful outcome for this technique, and the patient was pleased with the esthetic results of the conservative treatment modality.     

Is late adolescence a real risk factor for an adverse outcome of pregnancy?

Objective: To compare the obstetrical and neonatal outcomes of late adolescent (LA) and adult pregnancies.

Methods: Between January 2012 and December 2012, a total of 313 late adolescent pregnant aged between 16 and 19 years and 418 adult pregnant women aged between 20 and 35 years having given birth in our maternity service were enrolled into this case–control study. The demographic and clinical data were reviewed from hospital database and patients’ medical records.

Results: The incidence of preterm birth (PB) in the LA group was significantly higher than in the adult group (p?=?0.001), while the incidence of gestational diabetes mellitus was significantly lower (p?=?0.001). The mean birth weight and the rate of delivered macrosomic fetuses in the study group were lower than in the control group (p?=?0.03). The LA group had significantly higher rate of vaginal delivery when compared to the adult group (p?=?0.001). Both the rate of pregnancy induced hypertensive disorders and postpartum hemorrhage were not statistically different between the two groups (p?=?0.31; p?=?0.38, respectively). The LA group had lower rate of stillbirth when compared to the adult group; however, the difference was statistically insignificant (0.3% versus 1.2%) (p?=?0.24).

Conclusions: The LA pregnancy should be closely followed up during their antenatal care period due to the significantly higher rate of PB.     

Effects of aging on the male reproductive system

The study aims to discuss the effects of aging on the male reproductive system. A systematic review was performed using PubMed from 1980 to 2014. Aging is a natural process comprising of irreversible changes due to a myriad of endogenous and environmental factors at the level of all organs and systems. In modern life, as more couples choose to postpone having a child due to various socioeconomic reasons, research for understanding the effects of aging on the reproductive system has gained an increased importance. Paternal aging also causes genetic and epigenetic changes in spermatozoa, which impair male reproductive functions through their adverse effects on sperm quality and count as, well as, on sexual organs and the hypothalamic-pituitary-gonadal axis. Hormone production, spermatogenesis, and testes undergo changes as a man ages. These small changes lead to decrease in both the quality and quantity of spermatozoa. The offspring of older fathers show high prevalence of genetic abnormalities, childhood cancers, and several neuropsychiatric disorders. In addition, the latest advances in assisted reproductive techniques give older men a chance to have a child even with poor semen parameters. Further studies should investigate the onset of gonadal senesce and its effects on aging men.     

Melatonin protects against epirubicin-induced cardiotoxicity

We investigated the cytoprotective effect of melatonin in epirubicin-induced cardiotoxicity using four experimental groups of male Wistar rats: untreated control rats, epirubicin-treated rats, epirubicin+melatonin-treated rats, and melatonin-treated rats. We examined the histopathological and biochemical effects of melatonin on the epirubicin-induced changes and measured the levels of the lipid peroxidation end-product (malondialdehyde, MDA), an indicator of nitric oxide (NO) synthesis (nitrite/nitrate production), and reduced glutathione (GSH) in the heart. We also studied the extracellular matrix components (fibronectin, laminin) in the heart. Vacuole formation, mitochondrial deformation and degeneration, and disordered myofibrillary structures were detected ultrastructurally in the epirubicin-treated group. The degeneration was reduced in the heart tissues of the epirubicin+melatonin group. Epirubicin increased the nitrite/nitrate production, but did not change the MDA and GSH levels significantly. Melatonin treatment lowered the nitrite/nitrate concentrations, while increasing the GSH levels, which exceeded the levels in epirubicin+melatonin-treated rats. We conclude that the epirubicin increased the nitrozative stress, not the oxidative stress, in heart tissue, and the cardioprotective effect of melatonin was partially attributed to the suppression of epirubicin-induced nitrozative stress. These results suggest that melatonin partially protects against epirubicin-induced cardiotoxicity.     

Influence of previous provisional cementation on the bond strength between two definitive resin-based luting and dentin bonding agents and human dentin

This study evaluated the effect of two different types of provisional luting agents (RelyX Temp E, eugenol-based; RelyX Temp NE, eugenol-free) on the shear bond strengths between human dentin and two different resin-based luting systems (RelyXARC-Single Bond and Duo Link-One Step) after cementation with two different techniques (dual bonding and conventional technique). One hundred human molars were trimmed parallel to the original long axis, to expose flat dentin surfaces, and were divided into three groups. After related surface treatments for each specimen, the resin-based luting agent was applied in a silicone cylindrical mold (3.5 x 4 mm), placed on the bonding-agent-treated dentin surfaces and polymerized. In the control group (n = 20), the specimens were further divided into two groups (n = 10), and two different resin-based luting systems were immediately applied following the manufacturer's protocols: RelyX ARC-Single Bond (Group I C) and Duo Link-One Step (Group II C). In the provisionalization group (n = 40), the specimens were further divided into four subgroups of 10 specimens each (Group I N, I E and Group II N, II E). In Groups I N and II N, eugenol-free (RelyX NE), and in groups I E and II E, eugenol-based (RelyX E) provisional luting agents (PLA), were applied on the dentin surface. The dentin surfaces were cleaned with a flour-free pumice, and the resin-based luting systems RelyX ARC (Group I N and E) and Duo Link (Group II N and E) were applied. In the Dual bonding groups (n = 40), the specimens were divided into four subgroups of 10 specimens each (Group I ND, ED and Group II ND, ED). The specimens were treated with Single Bond (Groups I ND and ED) or One Step (Groups II ND and ED). After the dentin bonding agent treatment, RelyX Temp NE was applied to Groups I ND and II ND, and RelyX Temp E was applied to Groups I ED and II ED. The dentin surfaces were then cleaned as described in the provisionalization group, and the resin-based luting systems were applied: RelyX ARC-Single Bond (Group I ND and ED) and Duo Link-One Step (Group II ND and ED). After 1,000 thermal cycles between 5 degrees C and 55 degrees C, shear bond testing was conducted at a crosshead speed of 0.5 mm/minutes. One-way ANOVA, followed by a post hoc Tukey test (alpha = 0.05) was done. The dentin-resin-based luting system interfaces were evaluated under a scanning electron microscope. There was a significant reduction in the mean shear bond strength values of groups subjected to the provisionalization compared to the control and dual bonding technique groups (p < 0.05). The composition of provisional luting did not create a significant difference with regard to reducing shear bond strength values (p > 0.05). With regard to resin based luting systems, the shear bond strength values of the double-bond technique groups were not significantly different from the controls (p > 0.05).     

Relationship between the G protein–coupled oestrogen receptor and spermatogenesis,and its correlation with male infertility

The aim of this study was to investigate the diagnostic value of serum G protein–coupled oestrogen receptor (GPER) levels and their correlation with semen parameters in men with infertility. The participants were divided into two groups as follows: 76 fertile control men (Group 1) and 77 infertile men (Group 2). Semen analysis, hormonal evaluation, serum GPER level and scrotal ultrasound of the participants were evaluated. Follicle-stimulating hormone and total testosterone levels were not significantly different between the groups (p = .413 and p = .535 respectively). The oestradiol level in Group 1 was significantly lower than that in Group 2 (p < .001). The serum GPER level was found to be significantly higher in Group 1 than that of Group 2 (p < .001). GPER levels were positively correlated with the total sperm count, sperm concentration, motility and morphology in Group 2 (r = 0.303, 0.345, 0.260 and 0.322, respectively, p < .001). In this study, GPER levels were positively correlated with sperm parameters, and it was hypothesised that the decrease in GPER expression might be associated with male infertility by adversely affecting spermatogenesis.