Sperm from fertile men (donors who attend the IVI Murcia clinic) will be included in this arm.

Sperm from patients (subfertile men, i.e. men who possess one altered spermiogram parameter, according to the WHO 2010 guidelines) will be included in this arm.

Male Infertility

This study will include: fertile and subfertile men (who will provide the semen samples) and women donors (who will provide the follicular fluid samples).

The sperm will be capacitated in the presence and absence of follicular fluid (FF). In a first set of experiments, the FF will be supplemented with L-Arginine and the NOS inhibitor L-NAME. In another set of experiments the same supplementations to the capacitation medium will be examined, but without using FF.
Changes in NOS expression, protein nitrosylation, PKA activity, tyrosine phosphorylation and tyrosine nitration in sperm will be determined.

Control (fertile semen donors)

Patients (subfertile men)

IVI Murcia

Relationship Between Nitric Oxide (NO) in Follicular Fluid and Sperm Fertilization Ability

Upon collection and after oocyte removal, the follicular fluid samples will be centrifuged to remove cellular debris. An aliquot will be further centrifuged in tubes with 10 kDa filters to remove proteins. This alliquot will then be used to determine NO concentration with the help of a commercially available measurement system. NO is rapidly oxidized into two stable ions, namely nitrite and nitrate, which can be assayed by using ions selective electrodes. A software will then be used to calculate the initial concentration of Nitric Oxide (micromolar).

The IPD will not be shared at any point during this study. To preserve participant's anonymity, the biological samples (semen and follicular fluid) that will be collected will be identified with a code which will be different from the Number of Clinical History of the donors/patients.

Universidad de Murcia

Harvard School of Public Health

European Commission

Semen and FF samples will be obtained from donors and patients by masturbation after 2-7 days of sexual abstinence and they will be analyzed according to WHO guidelines (2010). FF samples will be obtained during the oocyte pick up procedure. After oocyte removal, the FF will be centrifuged for 10 min at 2000g and stored at -20°C until evaluation. NO concentration will be determined in the FF samples with the help of ion selective electrodes.
Sperm will be capacitated in the presence and absence of FF. In a first set of experiments, the FF will be supplemented with L-Arginine and the NOS inhibitor L-NAME. In another set of experiments the same supplementations to the capacitation medium will be examined, but without using FF.
Changes in NOS expression, protein nitrosylation, PKA activity, tyrosine phosphorylation and tyrosine nitration in sperm will be determined. The same treatment will be performed on all semen samples regardless of whether they come from patients or donors.

stereotactic brain surgery of human stem cells (OK99)

Idiopathic Parkinson Disease

MRI-guided stereotactic intraputaminal cell implantation into PD patients was performed.
For target locations, measurements were made using CT-scan images fused with previous MR images. Bilateral parasagittal incisions and corresponding 14 mm burr holes were made in preparation for cell suspension injections.
To ensure complete cell suspension delivery, injections were carried out slowly for 2 min with reciprocal withdrawal of the delivery needle to avoid both damage to stem cells and brain tissue, as well as to avert reflux or bubble formation.
After surgery, patients were kept in a conventional post-operative care unit for 1 h. The day following surgery, MR images were obtained to confirm correct placement of cell suspensions. All patients were discharged 24 h after surgery.

Human Stem Cells

Procurement was performed according to NIH Guidelines

Hospital Angeles del Pedregal

Parkinsonian Brain Repair Using Human Stem Cells

Human OK99 Allogeneic Stem Cell Transplantation for Patients With Severe Parkinson's Disease

Celavie Bioscences, LLC

Patients not responding to high- dose zidovudine and valganciclovir alone may be treated with botezomib plus high- dose zidovudine and valganciclovir

Single agent sirolimus for patients where targeted oncolytic virotherapy seems suboptimal

EPOCH chemotherapy with rituximab may be utilized to rescue such patients, with the intent of stabilizing suchpatients

Rituximab with liposomal doxorubicin (R-Dox) followed by consolidation or lmaintenancel therapy with dose escalating interferon-alpha

Lymphoproliferative Disorder

HHV-8

Malignancy

Etoposide 50 mg/m2 /day continuous intravenous infusion (CIVI) over 24 hours x 4 days (days 1-4) of 21 day cycle. A maximum of 6 cycles of R-EPOCH-R will be administered except in exceptional circumstances.

Etoposide

Ages 18 and over: Initial dose of 7.5 million units subcutaneous, three times weekly x 14 days; subsequent dosesincrease dose as tolerated each 14 days to a maximum of 45 million units subcutaneous three times weekly; Ages 12-17: Initial dose of 5 million units/m2 subcutaneous, three times weekly x 14 days Subsequent doses: Increase dose as tolerated each 14 days to a maximum of 30 million units/m2 subcutaneous, three times weekly

Interferon-alpha

Rituximab 375 mg/m2 IV day 1, shall be administered prior to Doxil injection. When combined with EPOCH chemotherapy, Rituximab will be given on days 1 and 5.

Rituximab

Cycle 1: Zidovudine 600 mg PO QID x 7-21 days in outpatient setting;600 mg PO q6hours x 7-21 (Intravenous zidovudine 300 mg q 6 hours may be substituted) days for inpatients; Cycle 2 and beyond: 600 mg PO QID x 7 days in outpatient setting; 600 mg PO q 6 hours x 7 days (300 mg q 6 hours may be substituted)

Zidovudine

21 day cycle; 20 mg/m2 Liposomal Doxorubicin given on day 1 and shall be administered after completion of Rituximab infusion from 2 to 6 cycles.

Liposomal Doxorubicin

1.3 mg/m2 IV days 1, 4, 8, and 11. Cycle length is 21 days.

Bortezomib

Cycle 1: Valganciclovir 900 mg PO BID x 7-21 days in outpatient setting; 900 mg PO q 12 hours x 7-21 days for inpatients; Cycle 2 and beyond: 900 mg PO BID x 7 days for outpatients; 900 mg PO q 12 hours x 7 days (Intravenous ganciclovir 5 mg/kg may be substituted) for inpatients

Valganciclovir

10 mg/m2 /day CIVI over 24 hours x 4 days (days 1-4) of 21 day cycle.

Doxorubicin

0.4 mg/m2 /day CIVI over 24 hours x 4 days (days 1-4) of 21 day cycle.

Vincristine

Cyclophosphamide: if CD4 < 100 cells/mm3, 187 mg/m2 IV (Day 5) if CD4 greater than or equal to 100 cells/mm3, 375 mg/m2 IV (Day 5) of 21 day cycle.

Cyclophosphamide

Filgrastim 300 micrograms subcutaneous daily beginning day 6 until absolute neutrophil count recovery 5000 cells/mm3 (Pegfilgrastim may be substituted with PI approval, at the recommended dose of one 6mg syringe)

Filgrastim (G-CSF)

Prednisone 60 mg/m2/day PO x 5 days (days 1-5)of 21 day cycle.

Prednisone

Maximum daily dose of 40 mg given as a single agent on 21 day cycle.

Sirolimus

Observation Only

National Institutes of Health Clinical Center, 9000 Rockville Pike

Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity

Targeted Oncolytic Virotherapy and Natural History Study of KSHV-Associated Multicentric Castleman's Disease With Laboratory and Clinical Correlates of Disease Activity

Preliminarily assess the feasibility of risk-stratifying patients according to disease parameters associated with MCD

To study in a preliminary fashion the therapeutic efficacy and toxicity of several rationally designed therapeutic approaches to KSHV-MCD aimed at KSHV cytoreductive therapy, or therapy aimed at suppressing KSHV-induced pathogenic mechanisms:-High-dose zidovudine combined with valganciclovir (HDAZT+VGCV)-Bortezomib in combination with (HDAZT+VGCV)-Sirolimus-Rituximab in combination with liposomal doxorubicin followed by Interferon- or high-dose AZT with valganciclovir-EPOCH-R (rituximab combined with oral prednisone and infusional etoposide, vincristine, and doxorubicin followed by bolus cyclophosphamide, prednisone and rituximab)

Preliminarily assess additional rationally designed treatments for MCD aimed at KSHV reductive therapy

percentage of patients alive until study closure

the length of time during and after the treatment that patients live with the disease but it does not get worse

infertility/tyrosine

Relationship Between Nitric Oxide (NO) in Follicular Fluid and Sperm Fertilization Ability

Parkinsonian Brain Repair Using Human Stem Cells

Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity

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