Seminal plasma alpha-glucosidase activity and male infertility

Measurement of alpha-glucosidase (alpha-GLUC) activity by means of a simple colorimetric test using a commercial kit (EpiScreen; FertiPro, Lotenhulle, Belgium) yielded results that were strongly correlated with the values obtained for the neutral iso-enzyme measured by a fluorimetric reference method (r=0.85, P=0.003, n=13). The former method was characterized by a low intra- and inter-coefficient of variation (6.6 and 4.3% respectively). Vasectomized men with azoospermia (n=27) had a significantly lower alpha-GLUC activity in semen than vasectomized men with residual spermatozoa present (n=11, P < 0.01) and men with azoospermia of primary testicular origin (n=33, P < 0.01). Receiver operating curve (ROC) analysis showed alpha-GLUC measurement to be reasonably accurate in differentiation between cases with obstructive versus testicular azoospermia at criterion value 13.5 U/l (sensitivity=82%, specificity= 70%). In cases with spermatozoa present, alpha-GLUC activity and output per ejaculate were positively correlated with sperm concentration (r=0.53 and 0.38, n=472), linear velocity (r=0.35 and 0.30, n=224), curvilinear velocity (r=0.32 and r=0.29, n=224), semen adenosine triphosphate (r=0.35 and 0.26, n=64), the concentration of 5alpha-dihydrotestosterone (r=0.31 and 0.29, n=74), and gamma-glutamyltransferase activity (r=0.62 and 0.32, n=275) in seminal plasma. The activity of alpha-GLUC was inversely correlated with ROS generation after 12-myristate, 13-acetate phorbol ester stimulation (r=-0.27, n=104), and both alpha-GLUC activity and total output were inversely correlated with the concentration of peroxidase- positive white blood cells among samples with > or =1x10(6)/ml of these cells (r=-0.30 and -0.19, n=165). It is concluded that simple photometric measurement of alpha-GLUC activity in seminal plasma reflects the functional state of the epididymis and may be helpful for the differential diagnosis of certain cases with azoospermia.      

Hereditary leiomyomatosis and renal cell cancer in families referred for fumarate hydratase germline mutation analysis

Smit DL, Mensenkamp AR, Badeloe S, Breuning MH, Simon MEH, van Spaendonck KY, Aalfs CM, Post JG, Shanley S, Krapels IPC, Hoefsloot LH, van Moorselaar RJA, Starink TM, Bayley J‐P, Frank J, van Steensel MAM, Menko FH. Hereditary leiomyomatosis and renal cell cancer in families referred for fumarate hydratase germline mutation analysis. Heterozygous fumarate hydratase (FH) germline mutations cause hereditary leiomyomatosis and renal cell cancer (HLRCC), an autosomal dominant syndrome characterized by multiple cutaneous piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer. The main objective of our study was to evaluate clinical and genetic data from families suspected of HLRCC on a nationwide level. All families referred for FH mutation analysis in the Netherlands were assessed. We performed FH sequence analysis and multiplex ligation‐dependent probe amplification. Families with similar FH mutations were examined for haplotype sharing. In 14 out of 33 families, we identified 11 different pathogenic FH germline mutations, including 4 novel mutations and 1 whole‐gene deletion. Clinical data were available for 35 FH mutation carriers. Cutaneous leiomyomas were present in all FH mutation carriers older than 40 years of age. Eleven out of 21 female FH mutation carriers underwent surgical treatment for symptomatic uterine leiomyomas at an average of 35 years. Two FH mutation carriers had papillary type 2 renal cancer and Wilms' tumour, respectively. We evaluated the relevance of our findings for clinical practice and have proposed clinical diagnostic criteria, indications for FH mutation analysis and recommendations for management.     

Lack of correlation between maximum early follicular phase serum follicle stimulating hormone concentrations and menstrual cycle characteristics in women under the age of 35 years

The gradual increase in follicle stimulating hormone (FSH) concentrations in women approaching menopause results from the depletion of the ovarian follicular pool, a process referred to as 'ovarian ageing'. This study investigates whether variable endogenous FSH concentrations, as have been observed in normo-ovulatory young women, are related to menstrual cycle characteristics, including predictors of ovarian ageing. Serum concentrations of immunoreactive FSH, oestradiol, and inhibin-A and inhibin-B were measured, and follicular growth was assessed by transvaginal ultrasound throughout the follicular phase in 39 healthy volunteers (20-35 years) with regular menstrual cycles. Median serum FSH concentration on cycle day 3 was 5.1 IU/l (range 3.6-11.2), and median maximum follicular phase FSH was 6.2 IU/l (range 4.3-11.2), observed on cycle day 6 (range 2-15). Maximum FSH concentrations were not correlated with age or cycle length, nor with maximum inhibin-B. The number of small (<10 mm) antral follicles on cycle day 3 was 11 (range 4-21) and was not correlated with age, nor with maximum FSH. Inhibin-A remained low until a significant rise on cycle day 9 (range 3-12), which was significantly correlated with the late follicular rise in oestradiol (r = 0.56, P = 0.01). These observations indicate a lack of correlation between maximum follicular phase serum FSH concentrations and parameters of ovarian ageing in women under the age of 35 years. In addition, FSH concentrations assessed on cycle day 3 represent an underestimation of maximum early follicular phase FSH. Distinct individual differences in intra-ovarian modification of FSH action, resulting in differences in the FSH threshold for stimulation of ovarian function, may be operative.      

Zweipunktediskrimination bei Phantomschmerzen

There is evidence that phantom pain is associated with a disrupted organization of the sensory cortex and that this organization can be normalized by training with two-point discrimination (TPD). In this case study a reduction in all three phantom modalities (i.e. phantom pain, phantom feeling and painful phantom sensation) and a reduction in pain level from m=?4.13/10 visual analogue scale (VAS) to m=?0.67/10 (VAS) could be observed in a patient with an upper limb amputation during a test period of 28 days with TPD. The quality of life and performance increased significantly. This can be a promising indication for a better social and work reintegration.     

Acute cervical spine trauma: evaluation with 1.5-T MR imaging

Twenty-one patients with acute neurologic deficits following cervical spine trauma were evaluated with magnetic resonance (MR) imaging (n = 21), computed tomography enhanced with intrathecal contrast material (CT myelography) (n = 18), myelography (n = 13), cervical spine radiography (n = 21), and intraoperative sonography (n = 7). MR imaging proved superior to other modalities in demonstrating parenchymal spinal cord injuries and cervical intervertebral disk herniation. Although both T1- and T2-weighted studies appear necessary to evaluate the anatomic relationship of the spinal cord, thecal space, intervertebral disks, and surrounding osseous and ligamentous structures, T2-weighted sequences were more sensitive than T1-weighted studies for detection of spinal cord injury. CT myelography was superior to MR imaging in demonstrating cervical spine fractures. In most cases, myelography revealed no information that was not apparent from both CT and MR imaging studies. Preliminary experience with MR imaging of acute cervical spine trauma suggests that it should be the study of choice in symptomatic patients who are otherwise clinically stable. CT may still be required in selected patients to evaluate complex fractures.     

Tooth root dentin mineralization defects in a mouse model of hypophosphatasia

Tissue‐nonspecific alkaline phosphatase (TNAP) is expressed in mineralizing tissues and functions to reduce pyrophosphate (PP_i), a potent inhibitor of mineralization. Loss of TNAP function causes hypophosphatasia (HPP), a heritable disorder marked by increased PP_i, resulting in rickets and osteomalacia. Tooth root cementum defects are well described in both HPP patients and in Alpl^?/? mice, a model for infantile HPP. In Alpl^?/? mice, dentin mineralization is specifically delayed in the root; however, reports from human HPP patients are variable and inconsistent regarding dentin defects. In the current study, we aimed to define the molecular basis for changes in dentinogenesis observed in Alpl^?/? mice. TNAP was found to be highly expressed by mature odontoblasts, and Alpl^?/? molar and incisor roots featured defective dentin mineralization, ranging from a mild delay to severely disturbed root dentinogenesis. Lack of mantle dentin mineralization was associated with disordered and dysmorphic odontoblasts having disrupted expression of marker genes osteocalcin and dentin sialophosphoprotein. The formation of, initiation of mineralization within, and rupture of matrix vesicles in Alpl^?/? dentin matrix was not affected. Osteopontin (OPN), an inhibitor of mineralization that contributes to the skeletal pathology in Alpl^?/? mice, was present in the generally unmineralized Alpl^?/? mantle dentin at ruptured mineralizing matrix vesicles, as detected by immunohistochemistry and by immunogold labeling. However, ablating the OPN‐encoding Spp1 gene in Alpl^?/? mice was insufficient to rescue the dentin mineralization defect. Administration of bioengineered mineral‐targeting human TNAP (ENB‐0040) to Alpl^?/? mice corrected defective dentin mineralization in the molar roots. These studies reveal that TNAP participates in root dentin formation and confirm that reduction of PP_i during dentinogenesis is necessary for odontoblast differentiation, dentin matrix secretion, and mineralization. Furthermore, these results elucidate developmental mechanisms underlying dentin pathology in HPP patients, and begin to explain the reported variability in the dentin/pulp complex pathology in these patients. © 2013 American Society for Bone and Mineral Research