IGF-I and NGFβ enhance in vitro progressive motility and vitality of human spermatozoa

Purpose

Progressive motility (PM) and vitality are positively associated with fertilization ability of spermatozoa. Here, the effects of IGF-I and NGFβ on PM and vitality of human spermatozoa were investigated.

Methods

Forty-three volunteers gave semen samples after 2-3 days of sexual abstinence. Each sample was processed with density gradient centrifugation and sperm washing. The pellet was divided into 3 aliquots. An aliquot containing one million of progressively motile spermatozoa was incubated for an hour (37°C) in standard culture medium (control group), and two aliquots with the same number of progressively motile spermatozoa were incubated in medium supplemented with IGF-I or NGFβ. Two concentrations of IGF-I (100 ng/ml and 1000 ng/ml) and NGFβ (0,5 ng/ml and 5 ng/ml) were tested.

Results

Both growth factors significantly increased PM and vitality in comparison with control either at the low or the high concentration. IGF-I seemed to be more effective than NGFβ. The effects did not seem to be dose dependent with the exception of the effect of IGF-I on vitality.

Conclusions

The enhancement of PM and vitality of human spermatozoa by IGF-I and NGFβ opens new ways for the improvement of sperm processing. Further research is needed to determine the most effective concentrations.

     

Out-of-office blood pressure in children and adolescents: disparate findings by using home or ambulatory monitoring

BACKGROUND: The validity of home blood pressure (HBP) measurements in children has not been evaluated, although in clinical practice such measurements are being used. This study compares HBP, with clinic (CBP) and daytime ambulatory blood pressure (ABP) in children and adolescents. METHODS: Fifty-five children and adolescents aged 6 to 18 years were evaluated with CBP (three visits), HBP (6 days), and daytime ABP. Mean age was 12.3 +/- 2.9 (SD) years, 33 boys. According to the Task Force CBP criteria, 26 were hypertensives, 6 had high-normal BP (hypertensive group), and 23 were normotensives (normotensive group). RESULTS: In the hypertensive group, CBP was 130.8 +/- 7.6/72.5 +/- 8.1 mm Hg (systolic/diastolic), HBP 118.9 +/- 6.3/73.7 +/- 6.7, and ABP 130.8 +/- 8.1/75.5 +/- 8.3. In the normotensive group, CBP was 112.8 +/- 8/63.1 +/- 6.3, HBP 106.7 +/- 8.4/67.2 +/- 5.2, and ABP 123.9 +/- 7.2/72 +/- 4.3. Strong correlations (P < .001) were observed between CBP-HBP (r = 0.73/0.57, systolic/diastolic), CBP-ABP (r = 0.59/0.49), and HBP-ABP (r = 0.72/0.66). In normotensive subjects, ABP was higher than both CBP and HBP for systolic and diastolic BP (P < .001). Furthermore, systolic HBP was lower than CBP (P < .01), whereas the opposite was true for diastolic BP (P < .05). In hypertensive subjects systolic HBP was lower than both CBP and ABP (P < .001), whereas CBP did not differ from ABP. For diastolic BP no differences were found among measurement methods. CONCLUSIONS: These data suggest that, in contrast to adults in whom HBP is close to the levels of daytime ABP, in children and adolescents HBP appears to be significantly lower than daytime ABP. Until more data become available, caution is needed in the interpretation of HBP in children and adolescents.     

Peritonitis in children with automated peritoneal dialysis: a single-center study of a 10-year experience

Peritoneal dialysis (PD) constitutes the preferred dialysis modality for children requiring renal replacement therapy with peritonitis being one of the most common complications of PD. This study was performed to evaluate the epidemiology, microbiology, and outcomes of PD-associated peritonitis in Greek children for a 10-year period. A total of 27 patients (16 males) with a mean age 121.8?±?57.2 months were retrospective analyzed. Patients were on PD therapy for a mean duration of 45.2?±?26.1 months. We found 23 episodes of PD-associated peritonitis occurred in 9 out of 27 patients (0.23 episodes/patient-year), with four patients experienced two or more peritonitis episodes. Gram-positive bacteria were responsible for 15 (65.2%) peritonitis episodes, with Staphylococcus aureus being the predominant specie isolated in 30.4% of cases. A total of seven episodes of exit-site infections (ESIs) were identified in five patients (0.069 episodes/patient-year) with the most common bacteria isolated being S. aureus (57.4%). Initial antibiotic treatment included intraperitoneal vancomycin plus ceftazidime in the majority of cases (82.6%). At the end of study, 12 (44.4%) patients remained on PD, 11 (41.8%) underwent renal transplantation, 2 (7.4%) shifted to hemodialysis and unfortunately, two patients (7.4%) died. Conclusively, our study revealed a noticeable low peritonitis and ESIs rate as compared to international data and represents the first evaluation of the characteristics and outcomes of peritonitis in the Greek pediatric PD population.     

Translation efficiency of EBNA1 encoded by lymphocryptoviruses influences endogenous presentation of CD8+ T cell epitopes

Lymphocryptoviruses (LCV) that infect humans and Old World primates display a significant degree of genetic identity. These viruses use B lymphocytes as primary host cells to establish a long-term latent infection and express highly homologous latent viral proteins. Of particular interest is the expression of the EBV-encoded nuclear antigen-1 (EBNA1), which plays a crucial role in maintaining the viral genome in B cells. Using human and Old World primate homologues of EBNA1, we show that the internal repeat sequences differentially influence their in vitro translation efficiency. Although the glycine-alanine repeat domain of human LCV (EBV) EBNA1 inhibits its self-synthesis, the repeat domains within the simian LCV homologues of EBNA1 do not inhibit self-synthesis. As a consequence, simian LCV EBNA1-expressing cells are more efficiently recognized by virus-specific CTL when compared to human EBV EBNA1, even though both proteins are highly stable in B cells. Interestingly, we also show that similar to human EBNA1, CD8+ T cell epitopes from simian LCV EBNA1 are predominantly derived from newly synthesized protein rather than the long-lived pool of stable protein. These observations provide additional evidence that supports the theory that immune recognition of EBNA1 can occur without compromising the biological maintenance function of this protein.     

Efficacy and safety of a low monthly dose of intravenous iron sucrose in peritoneal dialysis patients

Purpose

Scientific data regarding intravenous iron supplementation in peritoneal dialysis (PD) patients are scarce. In attempting to administer the minimum monthly IV iron dose that could improve erythropoiesis, we wanted to assess the safety and efficacy of monthly maintenance intravenous administration of 100 mg iron sucrose in PD patients.

Methods

In a 9-month prospective study, all clinically stable PD patients received intravenously 200 mg of iron sucrose as a loading dose, followed by monthly doses of 100 mg for five consecutive months. Levels of hemoglobin (Hb), ferritin, transferrin saturation (TSAT), reticulocyte hemoglobin content (CHr) and C-reactive protein (CRP) were measured before each administration and 3 months after the last iron infusion. Also, doses of concurrent erythropoietin administration were recorded.

Results

Eighteen patients were eligible for the study. Mean levels of Hb and ferritin increased significantly (from 10.0 to 10.9 mg/dL, p?=?0.01 and from 143 to 260 ng/mL, p?=?0.005), as well as the increase in TSAT levels approached borderline significance (from 26.2 to 33.1%, p?=?0.07). During the 6 months of iron administration, the erythropoietin dose was reduced in five patients and discontinued in one. During the 3 months following the last iron infusion, three of them again raised the erythropoietin dose to previous levels. None of the patients experienced any side effects related to IV iron administration.

Conclusions

A monthly maintenance intravenous dose of 100 mg iron sucrose may be a practical, effective, and safe in the short term, treatment of anemia in PD patients resulting in improved hemoglobin levels, iron indices, and erythropoietin response.

     

Assessment of highly angiogenic and disseminated in the peripheral blood disease in breast cancer patients predicts for resistance to adjuvant chemotherapy and early relapse

The assessment of tumor molecular features in combination with the detection of occult malignant cells may provide important clinical information, beyond the standard staging of breast cancer. Using a nested RT-PCR technique, we assessed prospectively the presence of cytokeratin-19 (CK19) mRNA positive cells in the blood of 100 operated patients with breast cancer before the initiation of adjuvant chemotherapy and local radiotherapy. Tissue samples were prospectively collected and analyzed for estrogen (ER) and progesterone (PgR) receptor, c-erbB-2 overexpression, mutant-p53 and bcl-2 protein accumulation, proliferation index and microvessel density (MVD). CK-19 mRNA-positive cells were detected in the peripheral blood of 33% of patients. Simultaneous display of high intratumoral MVD and of CK-19 mRNA-positive cells, which characterized highly angiogenic and disseminated in the peripheral blood (HAD) disease was noted in 25% of patients. Detection of CK-19 positive cells was significantly associated with increased MVD (p = 0.002). In univariate analysis (median follow-up 30 months) CK19 mRNA detection and MVD were the most significant factors related to a short relapse-free survival (RFS), (p < 0.0001). In multivariate analysis, CK19 positivity, high MVD and c-erbB-2 overexpression were the only significant and independent variables associated with relapse (p = 0.0005, 0.03 and 0.04, respectively). Patients with HAD had an expected relapse rate close to 70% vs. <5% in the remaining patients irrespectively of the used chemotherapy regimen. The simultaneous presence of high MVD and CK19-positive cells in the blood of patients with early breast is linked with poor prognosis, which cannot be improved with standard chemotherapy regimens.     

Decrease of CD4<Superscript>+</Superscript> and B-Lymphocyte Populations Is Not Associated with Severe Infectious Complications in Children with Acute Lymphoblastic Leukemia during Maintenance

The suppression of lymphopoiesis and immune competence during the maintenance phase in children with acute lymphoblastic leukemia (ALL) and the occurrence of infectious complications remain an unexplored area. In this study we assessed lymphocyte subpopulation disturbances during maintenance for childhood ALL along with the incidence, type, and severity of infections that occur during that period in the absence of neutropenia. Twenty-eight children (13 boys, 15 girls) with ALL aged 3-14 years (median 7 years) and treated according to the ALL-BFM 90/95 protocol were studied during maintenance for ALL. Complete white blood cell (WBC) counts and peripheral blood lymphocyte (PBL) analyses were performed. Major lymphocyte subsets (CD19+, CD3+CD4+, CD3-CD8+, CD3-CD16+CD56+, CD45RA-, CD45RO+) and markers of T-cell activation (CD25, CD38, CD69, HLA-DR) were analyzed with flow cytometry. Serum immunoglobulin G (IgG), IgA, and IgM levels were measured by a nephelometric assay. All infectious episodes during the study period were recorded in detail. Additionally, 41 age-matched immunocompetent children were used as controls. Absolute WBC counts (median, 3627/microL) and PBL counts (median, 1206/microL) were significantly below the age-adjusted control values (7400/microL and 2673/microL, respectively; P < .0001). B-lymphocyte, total CD4+, and memory CD4+ (CD4+CD45RO+) subsets were also significantly decreased (33/microL versus 377/microL [P < .0001], 531/microL versus 1045/microL [P < .01], and 80/microL versus 299/microL [P < .001], respectively). Significantly lower immunoglobulin levels were found in all patients. Twenty-two of the 28 patients presented with 74 episodes of a variety o minor infections (mostly respiratory viral [39], skin [7], and gastrointestinal [3]), none demanding prolonged hospital treat ment. Our findings demonstrate a profound immunosuppression throughout maintenance therapy in children with ALL tha has no major clinical impact in terms of increased incidence or severity of systemic infections.     

Transcranial Doppler versus transthoracic echocardiography for the detection of patent foramen ovale in patients with cryptogenic cerebral ischemia: A systematic review and diagnostic test accuracy meta‐analysis

Schwannomatosis is a genetic disorder characterized by the occurrence of multiple peripheral schwannomas. Segmental schwannomatosis is diagnosed when schwannomas are restricted to 1 extremity and is thought to be caused by genetic mosaicism. We studied 5 patients with segmental schwannomatosis through microstructural magnetic resonance neurography and mutation analysis of NF2, SMARCB1, and LZTR1. In 4 of 5 patients, subtle fascicular nerve lesions were detected in clinically unaffected extremities. Two patients exhibited LZTR1 germline mutations. This appears contrary to a simple concept of genetic mosaicism and suggests more complex and heterogeneous mechanisms underlying the phenotype of segmental schwannomatosis than previously thought. Ann Neurol 2016;80:625–628