Human sperm express a functional androgen receptor: effects on PI3K/AKT pathway

BACKGROUND: Results from mice lacking the androgen receptor (AR) showed that it is critical for the proper development and function of the testes. The aim of this study was to investigate whether a functional AR is present in human sperm. METHODS: The expression of AR and its effects on sperm were evaluated by RT-PCR, Western Blot, Immunocytochemistry, PI3Kinase and DNA laddering assays. RESULTS: We showed in human sperm that AR is located at the head region. Dihydrotestosterone (DHT), in a dose-dependent manner, leads to the rapid phosphorylation of the AR on tyrosine, serine and threonine residues and this effect was reduced by the AR antagonist hydroxyflutamide (OH-Flut). The effects of AR were evaluated on the phosphoinositide-3 kinase/protein kinase B (PI3K/AKT) pathway. Specifically, 0.1 and 1 nM DHT stimulated PI3K activity, whereas 10 nM DHT decreased PI3K activity and levels of p-AKT S473 and p-AKT T308, p-BCL2, and enhanced phosphatase and tensin homologue (PTEN) phosphorylation. In addition, 10 nM DHT was able to induce the cleavage of caspases 8, 9 and 3 and cause DNA laddering, and these effects were reversed either by casodex or OHFlut. By using wortmannin, a specific PI3K inhibitor, the cleavage of caspase 3 was reproduced, confirming that in sperm the PI3K/AKT pathway is involved in caspase activation. CONCLUSIONS: Human sperm express a functional AR that have the ability to modulate the PI3K/AKT pathway, on the basis of androgen concentration.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Congestive Heart Failure: A Case of Protein Misfolding

This article describes an interesting case of a patient presenting with congestive heart failure found to have restrictive cardiomyopathy with initial laboratory evaluation showing hypogammaglobuminemia without a monoclonal band on serum and urine electrophoresis. This case highlights the clinically significant cardiac manifestation caused by protein misfolding, a defect in protein homeostasis. In addition, the utility of a relatively newer laboratory test, serum free light chains as well as the importance of clinical and pathophysiologic correlation is also discussed. We present a relatively uncommon cause of heart disease, cardiac amyloidosis in a patient with a systemic plasma cell dyscrasia, and multiple myeloma.     

IgG Against Dengue Virus in Healthy Blood Donors,Zanzibar, Tanzania

We conducted a seroprevalence survey among 500 healthy adult donors at Zanzibar National Blood Transfusion Services. Dengue virus IgG seroprevalence was 50.6% and independently associated with age and urban residence. These data will aid in building a surveillance, preparedness, and response plan for dengue virus infections in the Zanzibar Archipelago.Key words: dengue, seroprevalence, Zanzibar, viruses, vector-borne infections     

Validation of the Italian version of Parkinson’s Disease-Cognitive Rating Scale (PD-CRS)

Cognitive impairment (CI) is a frequent feature associated with both early and advanced stages of Parkinson’s disease (PD). An evaluation of cognitive functions is relevant to identify those parkinsonians at risk of developing dementia. In the present study, the Italian version of Parkinson’s Disease-Cognitive Rating Scale (PD-CRS) assessing fronto-subcortical and cortical cognitive functions in PD was validated in 387 parkinsonians and was used to test the empirical validity of the item 1.1 (cognitive impairment) of the Italian version of MDS-UPDRS as screening tool for CI in PD. PD-CRS was free from floor and ceiling effect. The mean PD-CRS score was 76.1 (mean cortical score, 24.5 ± 4.6; mean subcortical score, 51.5 ± 17.5). The internal consistency was satisfactory (α = 0.89); corrected item-total correlation was 0.570 (naming) to 0.696 (working memory). The correlation between PD-CRS and part I–IV of MDS-UPDRS was weak. The low agreement between classification of PD sample into patients with mild cognitive impairment (PD-MCI), dementia (PD-D) and normal cognition (PD-NC) according to scores of item 1.1 and classification according to cutoff scores of PD-CRS for PD-MCI, PD-D and PD-NC indicated a poor empirical validity of item 1.1 of MDS-UPDRS as cognitive screening tool for CI in PD (Κ = 0.114; weighted Κ = 0.17; SE of Κ = 0.038; 95 % confidence interval from 0.040 to 0.1895). The Italian version of PD-CRS is an easy, consistent and valid tool for assessment of the cognitive cortical and subcortical impairments in PD.     

A 20-year long term experience of the Italian Diamond-Blackfan Anaemia Registry: RPS and RPL genes,different faces of the same disease?

Diamond–Blackfan anaemia (DBA) is a rare and heterogeneous disease characterised by hypoplastic anaemia, congenital anomalies and a predisposition for malignancies. The aim of this paper is to report the findings from the Italian DBA Registry, and to discuss the Registry’s future challenges in tackling this disease. Our 20-year long work allowed the connection of 50 Italian Association of Paediatric Haematology and Oncology (AIEOP) centres and the recruitment of 283 cases. Almost all patients have been characterised at a molecular level (96%, 271/283), finding a causative mutation in 68% (184/271). We confirm the importance of determination of erythrocyte adenosine deaminase activity (eADA) and of ribosomal RNA assay in the diagnostic pipeline and characterisation of a remission state. Patients with mutations in large ribosomal subunit protein (RPL) genes had a significant correlation with the incidence of malformations, higher eADA levels and more severe outcomes, compared to patients with mutations in small ribosomal subunit protein (RPS) genes. Furthermore, as a consequence of our findings, particularly the incidence of malignancies and the high percentage of patients aged >18 years, we stress the importance of collaboration with adult clinicians to guarantee regular multi-specialist follow-up. In conclusion, this study highlights the importance of national registries to increase our understanding and improve management of this complex disease.     

Self-assessed neurological disturbances after surgical removal of impacted lower third molar: a pragmatic prospective study on 423 surgical extractions in 247 consecutive patients

Clinical Oral Investigations - The aim of this study was to assess the combined role of current radiographic risk indicators and patient age in predicting lower lip sensitivity disturbances after...     

Influence of Age and Type of Underlying Disease on Complications Related to Home Enteral Nutrition

Background: No data about the influence of age and underlying diseases on home enteral nutrition (HEN)–related complications are reported in the literature. Herein, we retrospectively investigated this issue by analyzing HEN‐related complications in a cohort of consecutive patients grouped according to the underlying disease and age. Material and Methods: We reviewed the medical records of 101 patients referring to our team in 2007–2010 to obtain patients’ demographic data, age, nutrition status, duration of HEN treatment, and type of HEN‐related complications. They were divided in cancer and neurologic patients and subgrouped on the basis of their age. HEN‐related complications were expressed as complication rates. Results: Patients with neurological diseases suffered a significantly higher number of complications as compared with cancer patients (P = .04). Age did not significantly influence complication rates. The mechanical complications were the most frequent. The majority of HEN‐related complications were resolved at home. Conclusion: Our data strongly suggest that HEN‐related complications are influenced by underlying diseases and not by age. In neurologic patients, dementia, loss of autonomy, and the different therapies administered by PEG probably play an important role in increasing the number of HEN‐related complications as compared with cancer patients. The most frequent complications can be managed at home, reducing the costs of hospitalizations and discomfort for the patient.