Analysis of the steroidogenic acute regulatory protein (StAR) gene in Japanese patients with congenital lipoid adrenal hyperplasia

Genomic DNA from 19 Japanese patients with congenital lipoid adrenal hyperplasia (lipoid CAH) representing 16 different families was examined to identify the genetic alterations of steroidogenic acute regulatory protein (StAR). Ten of 19 patients had a 46,XX karyotype and nine had a 46,XY karyotype. Six of the 46,XX patients have experienced spontaneous pubertal changes including breast development and irregular menstruation whereas none of the 46,XY subjects displayed pubertal changes. Eight different mutations were identified. Sixteen patients were either homozygotes or compound heterozygotes for the Q258X mutation. The seven other mutations identified were 189delG, 246insG, 564del13bp, 838delA, Q212X, A218V and M225T. The 189delG, 246insG, 546del13bp and Q212X mutants encode truncated proteins. COS-1 cells transfected with expression vectors encoding cDNAs for the mutant StAR proteins which affect the C-terminus, 838delA, A218V and Q258X, exhibited no steroidogenesis enhancing activity. However, the M225T mutant retained some steroidogenic activity. The patient with the M225T mutation had late onset of this disorder and some capacity to secrete testosterone in response to hCG. These findings suggest: (i) that the Q258X mutation can be used as a genetic marker for the screening of Japanese for lipoid CAH, (ii) that the C-terminus of StAR plays an important role in the protein's activity and (iii) that there are differences in the extent of functional impairment of the testis and ovaries in lipoid CAH.      

Expression of superoxide dismutase and xanthine oxidase in myometrium, fetal membranes and placenta during normal human pregnancy and parturition

Superoxide, an agent which attenuates the half-life of nitric oxide, is metabolized and synthesized by superoxide dismutase (SOD) and xanthine oxidase, respectively. Over the last few years much work has focused on the role of nitric oxide in human parturition. The aim of this study was to determine whether the onset of human parturition is associated with a change in the expression of copper/zinc superoxide dismutase (Cu/Zn SOD), manganese superoxide dismutase (Mn SOD) or xanthine oxidase within the uterus. Samples of myometrium, placenta, decidua and fetal membranes were obtained from women before and after the onset of labour at term. Immunocytochemistry was used to localize Cu/Zn SOD, Mn SOD and xanthine oxidase and measure SOD enzyme activity. Cu/Zn and Mn SOD-like immunoreactivity was detected in syncytiotrophoblast cells, villous stromal cells and endothelial cells of blood vessels in the placenta. In the myometrium Cu/Zn and Mn SOD were localized to myocytes and endothelial cells and to some vascular smooth muscle cells. In the fetal membranes we observed staining for Cu/Zn SOD and Mn SOD in the amnion, chorion, extravillous trophoblast and decidua. There was no difference in SOD enzyme activity or staining intensity for SOD between different cell types before and during labour. Xanthine oxidase immunoreactivity was identified in each of the tissues examined and again there was no difference in immunostaining in tissues obtained from women delivered before or after the onset of labour. These results show that the pregnant uterus is capable of both synthesizing and degrading superoxide and suggest that superoxide dismutase and xanthine oxidase may play a role in the maintenance of uterine quiescence during pregnancy, but not in the initiation of parturition.      

Enhancement of motility by treating spermatozoa with an antioxidant solution (Sperm-Fit) following ejaculation

Oxygen radical generation is known to be detrimental to sperm function, especially motility, through the lipid peroxidation of the membranes. Generation of reactive oxygen species can be induced by leukocyte contamination, sperm centrifugation and the presence of abnormal spermatozoa with excess residual cytoplasm. This study aims to evaluate the effect on sperm motility of incubation in an antioxidant-containing solution, during liquefaction and centrifugation. Thirty semen samples were each divided into two equal parts: one mixed with Tyrode's solution, the other with a salt solution containing antioxidants (Sperm- Fit; Ellios Bio-Media, Paris, France). All the procedures were identical in the two groups. The ratio of leukocytes to spermatozoa was significantly correlated with the motility after liquefaction and after a 24 h incubation in routine in-vitro fertilization (IVF) medium and with the number of motile spermatozoa recovered after Percoll preparation. Moreover, when this ratio was > or = 0.2, all motility parameters were lowered. Incubation with Sperm-Fit allowed a higher percentage of motility after Percoll preparation when the ratio was > or = 0.2 (48 +/- 5% versus 41 +/- 6% for Sperm-Fit and Tyrode's solution respectively; P < 0.05) and a greater number of motile spermatozoa recovered after Percoll preparation, whatever the ratio (3.2 +/- 1.0 x 10(6) versus 2.4 +/- 0.7 x 10(6) for Sperm-Fit and Tyrode's solution respectively when ratio > or = 0.2; 18.1 +/- 3.4 x 10(6) versus 14.4 +/- 2.9 x 10(6) for Sperm-Fit and Tyrode's solution respectively when ratio < 0.2; P < 0.05). These results show that incubation with antioxidants during liquefaction and centrifugation increases recovery of motile spermatozoa.      

Efficacy and tolerability of estraderm MX, a new estradiol matrix patch

Objectives: To assess the efficacy and tolerability of a new matrix patch delivering 0.05 mg estradiol per day (Estraderm MX 50) in postmenopausal women with moderate to severe postmenopausal symptoms. Methods: A multicenter, double-blin, randomized, between-patient, placebo controlled trial in 109 postmenopausal women was carried out. Patches were applied twice weekly for 12 weeks. Patients were assessed at 4, 8 and 12 weeks of treatment. The primary efficacy variable was change from baseline in mean number of moderate to severe hot flushes (including night sweats) per 24 h during the last 2 weeks of treatment. Other variables included Kupperman Index, local and systemic tolerability. Plasma concentrations of estradiol (E2), estrone (E1) and estrone sulfate (E1S) were determined before and after treatment. Results: Estraderm MX was significantly superior to placebo (P < 0.001) in reducing mean number of moderate to severe hot flushes (including night sweats) per 24 h after 4, 8 and 12 weeks of treatment. The estimate of treatment group differences after 12 weeks was 4.2 hot flushes (95% confidence interval: 2.6–5.5). Estraderm MX also significantly reduced Kupperman Index at all time points compared to placebo (P < 0.001). Estraderm MX induced increases in mean E2, E1 and E1S plasma levels as expected (E2: baseline 2.7 pg/ml, 12 weeks 38.9 pg/ml; E1: baseline 18.8 pg/ml, 12 weeks 41.6 pg/ml; E1S: baseline 235.6 pg/ml, 12 weeks 765.1 pg/ml). Overall rates of adverse experiences were similar for Estraderm MX and placebo. The number of patients reporting skin irritation was low and similar in both groups. Conclusions: Estraderm MX 50, a new matrix patch, offers an effective and well tolerated dosage form for transdermal delivery of 0.05 mg E2 per day.     

LRRK2 variation and Parkinson's disease in African Americans

The global impact of LRRK2 mutations is yet to be realized with a lack of studies in specific ethnic groups, including those of Asian and African descent. Herein, we investigated the frequency of common LRRK2 variants by complete exon sequencing in a series of publicly available African American Parkinson's disease patients. Our study identified three novel synonymous exonic variants and 13 known coding variations; however, there did not appear to be any frequent (>5%) pathogenic mutations. Given the ethnic‐specific LRRK2 variation previously identified in PD further studies in under‐represented populations are warranted. © 2010 Movement Disorder Society.     

Oculocutaneous albinism

Oculocutaneous albinism represents a group of inherited skin disorders characterized by a generalized reduction of cutaneous, ocular and pilar pigmentation from the time of birth. Oculocutaneous albinism types 1 and 2 are the most common, but several other types have been described. A defect in the melanin synthesis pathway, resulting in reduced formation of melanin, is responsible for oculocutaneous albinism. Aetiology, clinical manifestations, diagnosis and management are discussed.     

Pulsatile masses surrounding vascular prostheses: real-time US color flow imaging

A prospective evaluation of color flow mapping and real-time ultrasound was performed to determine if pseudoaneurysms could be distinguished from other causes of masses surrounding vascular grafts of the lower extremities. Twelve palpable pulsatile masses were imaged. Diagnoses were confirmed at angiography (n = 11), computed tomography (n = 7), aspiration biopsy (n = 5), and operative intervention (n = 6). A swirling pattern of blood flow was seen in six of seven cases of pseudoaneurysm. Lack of flow signals was noted in four of the five collections representing hematoma (n = 2) or infection (n = 2). The seventh case was later shown to be an infected, thrombosed pseudoaneurysm. The single false-positive diagnosis was made early in the series when the flow signals detected were due to transmitted arterial pulsations. The authors conclude that color Doppler flow imaging is useful in the differential diagnosis of pulsatile masses associated with prosthetic grafts. Prosthetic graft pseudoaneurysms have a specific appearance of swirling blood flow arising from a wide neck and are distinguishable from traumatic or iatrogenic pseudoaneurysms of the native vascular tree.     

Segmental dilatation of the small bowel: report of three cases and literature review

Segmental dilatation of the small bowel is a rare congenital abnormality that occurs mainly in children and produces significant nonspecific symptoms. The authors reviewed 33 cases reported in the literature and present three new cases in which the lesion was demonstrated on radiographs obtained before laparotomy. These cases showed the spectrum of symptoms and characteristic radiologic features of this condition in both plain abdominal radiographs and barium studies. Plain radiographs of the abdomen may show an isolated loop of bowel containing an air-fluid level. The characteristic finding in barium studies of the small bowel is a localized dilatation of the small bowel lumen with afferent and efferent loops. In the absence of a complication or coexistent cause of obstruction, the transit time of contrast medium through the small bowel is not delayed. The radiologic examination is useful in diagnosis, and the condition is cured with surgery.