Clinical aspects of infertile 47,XYY patients: a retrospective study

47,XYY syndrome is a sex chromosomal anomaly in men, which may be associated with infertility and has an incidence of 0.1% of male births. The clinical and paraclinical characteristics of men suffering from this anomaly have not been fully described. In this retrospective study, we present 37 cases of 47,XYY infertile men with sperm counts varying from normal to azoospermia, referred to the Genetics Laboratory at the Royan Institute, Iran. Thirteen individuals were mosaic and 24 non-mosaics. Non-mosaic patients were classified as azoospermic (nine cases) and normospermic/oligozoospermic men (15 cases). Two of the non-mosaic and three mosaic patients had secondary infertility. In addition, 13 of them underwent IUI, IVF or ICSI, and in seven cases, there was a biochemical pregnancy. The remaining 14 patients did not have ART. The 47,XYY syndrome is relatively unusual and can be missed clinically because of the lack of symptoms and of diverse phenotypes. Diagnosis of this aneuploidy can provide valuable data for counselling and early management of the patients who undergo fertility evaluation.     

Clinical and laboratory findings in Iranian children with cyclic neutropenia

Cyclic neutropenia is a rare immunodeficiency syndrome, characterized by regular periodic oscillations in the circulating neutrophil count from normal to neutropenic levels through 3 weeks period, and lasting for 3-6 days. In order to determine the clinical features of cyclic neutropenia, this study was performed. Seven patients with cyclic neutropenia (3 males and 4 females), who experienced neutropenic periods every 3 weeks (5 with severe and 2 with moderate neutropenia), were investigated in this study. They had been referred to Iranian Primary Immunodeficiency Registry during 23 years (1980-2003). The range of patients' ages was from 7 to 13 years (median 11 years). The median age at the onset of the disease was 12 months (1 month- 2 years) and the median age of diagnosis was 2 (1.5-5) years, with a median diagnosis delay of 1 year (2 months- 5 years). Neutropenia was associated with leukopenia (3 patients), anemia (3 patients), and thrombocytopenia (1 patient). Patients were asymptomatic in healthy phase, but during the episode of neutropenia suffered from aphthous ulcers, abscesses and overwhelming infections. The most commonly occurred manifestations were: otitis media (6 cases), oral ulcers (5 cases), abscesses (4 cases), pneumonia (3 cases), diarrhea (3 cases), oral candidiasis (3 cases), cutaneous infections (2 cases), and periodontitis (2 cases). One of these patients subsequently died because of recurrent infections. Unusual, persistent or severe infections should be the initiating factors to search for an immune deficiency syndrome such as cyclic neutropenia, because a delay in diagnosis may result in chronic infection, irretrievable end-organ damage or even death of the patient.     

Usefulness of Serum Brain Natriuretic Peptide Level for Screening Hemodynamically Significant Patent Ductus Arteriosus in Preterm Neonates

Objective:

We studied usefulness of serum B-type natriuretic peptide level as a screening tool for detecting hemodynamically significant patent ductus arteriosus in the preterm neonates.

Methods:

Sixty admitted preterm neonates with gestational age ≤34 weeks, birth weight ≤2500 gr, and age of >3 days have been enrolled in this study. We measured serum B-type natriuretic peptide levels at the beginning and after completion of drug therapy for ductus occlusion.

Findings:

Mean±SD gestational age and weight was 31±1.9 weeks and 1680±350 gr, respectively. The peptide levels in the neonates with significant duct (n=13) were significantly higher than in those with insignificant duct (n=17) or no duct (n=30) (1667±821 pg/ml versus 667±666 and 309±171, respectively). The peptide level dropped significantly after ibuprofen administration in the neonates with significant PDA (n=13), (1667±1165 pg/ml to 429±386).

Conclusion:

At a cutoff point of 450 pg/ml, B-type natriuretic peptide level had a sensitivity of 92% and specificity of 87%, the negative predictive value of 98.5%, the positive likelihood ratio of 6.92 and the negative likelihood ratio of 0.089 for detecting significant patent duct. Levels below this can eliminate the need for echocardiography.     

Effect of heterotopic noxious conditioning stimulation on electrical and pressure pain thresholds in two different anatomical regions

Objectives. The aims of the study were to investigate the influence of heterotopic noxious conditioning stimulation (HNCS) on pain thresholds in the orofacial and spinal regions and to find out whether there are gender differences in this respect. Material and Methods. Thirty healthy subjects (15 of each sex) with a mean (SD) age of 25.1 (4.4) years participated. Pain thresholds to electrical (EPT) and pressure stimuli (PPT) were recorded in the masseter muscle and 1st upper incisor (tooth), as well as in the fingertip, before, during, and 5 and 15 min after a cold pressor task to the contralateral hand immersed in ice-cold water for a maximum of 5 min. Results. With the exception of the EPT in the orofacial region, all pain thresholds increased during the HNCS and then returned to baseline during the 15 min follow-up. The significant changes in EPT were greater in the finger than in the tooth, while the changes in PPT were greater in the masseter muscle than in the finger. Electrical stimuli in the finger induced greater significant changes of pain thresholds than pressure. In the orofacial region, pressure induced greater significant changes in pain thresholds during HNCS than electrical stimuli did. The HNCS induced pain of high intensity and unpleasantness, i.e. varying between 5 and 10 on the numeric rating scale (NRS). There were no gender differences in the response to the HNCS. Conclusion. We conclude that, in general, HNCS induced by cold pressor stimulation increases pain thresholds, but the magnitude of the effect differs between the orofacial region and the finger and is influenced by the tissue and type of test stimuli.     

Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals

IntroductionGoblet cell hyperplasia (GCH) and mucus hypersecretion in the airway is recognized as an important contributor to morbidity and mortality in asthma and COPD. Verapamil is a calcium channel blocker that binds to the alpha-subunit of L-type calcium channels and inhibits the mucin gene via the calmodulin and CaM kinase pathway. The objective of this study was to determine the in vivo effect of verapamil on GCH and eosinophilic inflammation in sensitized mice.MethodsMale BALB/c mice were sensitized to ovalbumin using the standard method. Two groups of animals were received verapamil via an intramuscular injection: 1-low dose (0.5 mg/kg/day for two weeks), 2-high dose (1.5 mg/kg/day for two weeks). Serum and bronchoalveolar lavage fluid (BALF) was collected and analyzed for inflammatory cells, interferon-γ and IL-4. The left lung was sent for histopathological evaluation, especially for periodic acid-Schiff (PAS), to identify goblet cells in the epithelium. The degree of inflammatory cell infiltration, including eosinophils, mucus plugging, and smooth muscle thickness of the airways were classified on a semi quantitative scale.ResultsInflammatory cell infiltration in peribronchial and perivascular areas was observed in all sensitized groups. Eosinophils percentage in the BALF significantly decreased in verapamil-treated mice compared with sensitized mice (from 19.8% in asthmatic to 5.4% for low dose and 4.4% for high dose). The ratio of airway goblet cells per epithelial cells were significantly lower in verapamil-treated mice versus sensitized mice (1.57 ± 1.30% for low dose; 1.50 ± 0.93% for high dose versus 12.93 ± 7.55%, P < 0.05, respectively). Mucus production of goblet cells decreased significantly in verapamil-treated mice versus sensitized mice (mean score was 1.45 ± 0.30 for low dose; 0.81 ± 1.00 for high dose versus 2.85 ± 0.86 in the sensitized control group, P < 0.05, respectively). The concentration of serum and BALF-IFN-γ in verapamil-treated mice markedly increased by the verapamil treatment when compared to sensitized mice (15.1 ± 0.43 versus 4.7 ± 0.96, P < 0.05 and 91.8 ± 47.7 versus 14.8 ± 4.6, P < 0.01, respectively).ConclusionVerapamil is a useful drug with therapeutic targeting on GCH and a potential way to limit mucous production and improve bronchial inflammation.     

Evaluation of corneal topographic, tomographic and biomechanical indices for detecting clinical and subclinical keratoconus: a comprehensive three-device study

AIM:To evaluate the diagnostic ability of topographic and tomographic indices with Pentacam and Sirius as well as biomechanical parameters with Corvis ST for the detection of clinical and subclinical forms of keratoconus(KCN).METHODS:In this prospective diagnostic test study,70 patients with clinical KCN,79 patients with abnormal findings in topography and tomography maps with no evidence on clinical examination(subclinical KCN),and 68 normal control subjects were enrolled.The accuracy of topographic,tomographic,and biomechanical parameters was evaluated using the area under the receiver operating characteristic curve(AUC)and cross-validation analysis.The Delong method was used for comparing AUCs.RESULTS:In distinguishing KCN from normal,all parameters showed statistically significant differences between the two groups(P<0.001).Indices with the perfect diagnostic ability(AUC≥0.999)were Sirius KCN vertex of back(KVb),Pentacam random forest index(PRFI),Pentacam index of height decentration(IHD),and Corvis integrated tomographic/biomechanical index(TBI).In distinguishing subclinical KCN from normal,Sirius symmetry index of back(SIb;AUC=0.908),Pentacam inferior-superior difference(IS)value(AUC=0.862),PRFI(AUC=0.847),and Corvis TBI(AUC=0.820)performed best.There were no significant differences between the highest AUCs within keratoconic groups(De Long,P>0.05).CONCLUSION:In clinical KCN,all topographic,tomographic,and biomechanical indices have acceptable outcomes in terms of sensitivity and specificity.However,in differentiating subclinical forms of KCN from normal corneas,curvature-based parameters(SIb and IS value)followed by integrated indices(PRFI and TBI)are the most powerful tools for early detection of KCN.     

Catalytic C–H aerobic and oxidant-induced oxidation of alkylbenzenes (including toluene derivatives) over VO2+ immobilized on core–shell Fe3O4@SiO2 at room temperature in water

Direct C–H bond oxidation of organic materials, and producing the necessary oxygenated compounds under mild conditions, has attracted increasing interest. The selective oxidation of various alkylbenzenes was carried out by means of a new catalyst containing VO²⁺ species supported on silica-coated Fe₃O₄ nanoparticles using t-butyl hydroperoxide as an oxidant at room temperature in H₂O or solvent-free media. The chemical and structural characterization of the catalyst using several methods such as FTIR spectroscopy, XRD, FETEM, FESEM, SAED, EDX and XPS showed that VO²⁺ is covalently bonded to the silica surface. High selectivity and excellent conversion of various toluene derivatives, with less reactive aliphatic (sp³) C–H bonds, to related benzoic acids were quite noticeable. The aerobic oxygenation reaction of these alkylbenzenes was studied under the same conditions. All the results accompanied by sustainability of the inexpensive and simple magnetically separable heterogeneous catalyst proved the important criteria for commercial applications.

A highly efficient, recoverable, sustainable, economic and eco-friendly catalyst containing VO²⁺ species supported on SiO₂@Fe₃O₄ nanoparticles for selective oxidation of alkylbenzenes using TBHP or O₂ at room temperature in H₂O or solvent-free media.     

Wound healing by topical application of antioxidant iron chelators: kojic acid and deferiprone

Kojic acid and deferiprone are iron chelators used for skin lightening and iron‐overload treatment, respectively. As iron chelation and free radical scavenging are principal factors for wound healing, it was hypothesised that the local application of these compounds might accelerate wound healing in rats. Ointments of 3%, 6% and 9% of deferiprone and kojic acid were prepared and topical treatment was performed on in vivo wound models for 12 days twice in day for test and control groups. Topical treatment with 3%, 6% and 9% showed significant improvement in wound healing after 4 days (P < 0·001). Topical application of 3% and 6% deferiprone enhanced wound healing after 8 days (P < 0·026 and P < 0·001, respectively). Accelerated wound healing was seen using 3% and 6% deferiprone after 12 days (P = 0·003 and P < 0·001, respectively). DPPH scavenging assay was also performed to compare the antioxidant potencies of kojic acid and deferiprone. Deferiprone had more free radical scavenging power than kojic acid. Generally, deferiprone topical treatment, accelerated wound healing more than kojic acid because of its higher antioxidant and iron chelation abilities.     

Effect of vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms: A randomized,double blind,placebo-controlled trial

Objectives: Previous studies have shown that serum levels of vitamin D were lower in attention deficit hyperactivity disorder (ADHD) children compared to healthy controls. The aim of the study was to determine the effect of vitamin D supplementation as adjunctive therapy to methylphenidate on symptoms of children with ADHD.

Methods: Sixty-two children aged 5–12 years with a diagnosis of ADHD based on DSM-IV criteria were randomly assigned into two groups to receive either 2000IU vitamin D or placebo in addition to methylphenidate for 8 weeks. Symptoms severity was assessed by Conner's Parent Rating Scale-Revised[S] (CPRS), ADHD rating scale-IV (ADHD-RS), and Weekly Parent Ratings of Evening and Morning Behavior (WPREMB) at weeks 0, 4, and 8. Serum levels of 25(OH)D were measured at baseline and after 8 weeks. Anthropometric variables, dietary intake, physical activity, sun exposure, and side effects were assessed.

Results: Fifty-four participants completed the trial. After 8 weeks of supplementation, serum levels of 25(OH)D significantly increased in the vitamin D group. ADHD symptoms decreased significantly in both groups (P?P?=?0.013, 0.016, respectively), but no differences were found in symptoms by CPRS and ADHD-RS scales.

Discussion: Vitamin D supplementation as adjunctive therapy to methylphenidate improved ADHD evening symptoms. Future research is needed to clarify vitamin D effects as monotherapy in ADHD and its mechanism.

The trial was registered in www.irct.ir is (IRCT201404222394N10).