HDAC specificity and kinase off-targeting by purine-benzohydroxamate anti-hematological tumor agents.

A series of hybrid inhibitors, combining pharmacophores of known kinase inhibitors bearing anilino-purines (ruxolitinib, ibrutinib) and benzohydroxamate HDAC inhibitors (nexturastat A), were generated in the present study. The compounds have been synthesized and tested against solid and hematological tumor cell lines. Compounds 4d-f were the most promising in cytotoxicity assays (IC ≤ 50 nM) vs.

Testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys: A 6 year experience from a Swiss multi-center network.

Testicular tissue cryopreservation is the only option of fertility preservation in prepubertal boys. While it is considered experimental, since procedures to obtain mature spermatozoa from prepubertal testicular tissue are still under development, testicular tissue cryopreservation programs have emerged worldwide. Our aim was to study the feasibility and safety of a program of testicular tissue cryopreservation in prepubertal and adolescent boys facing gonadotoxic treatment in three University hospitals in Switzerland.

Drug/Lead Compound Hydroxymethylation as a Simple Approach to Enhance Pharmacodynamic and Pharmacokinetic Properties.

Hydroxymethylation is a simple chemical reaction, in which the introduction of the hydroxymethyl group can lead to physical-chemical property changes and offer several therapeutic advantages, contributing to the improved biological activity of drugs. There are many examples in the literature of the pharmaceutical, pharmacokinetic, and pharmacodynamic benefits, which the hydroxymethyl group can confer to drugs, prodrugs, drug metabolites, and other therapeutic compounds. It is worth noting that this group can enhance the drug's interaction with the active site, and it can be employed as an intermediary in synthesizing other therapeutic agents.

Conformational flexibility determines the Nf2/merlin tumor suppressor functions.

The Neurofibromatosis type 2 gene encodes the Nf2/merlin tumor suppressor protein that is responsible for the regulation of cell proliferation. Once activated, Nf2/merlin modulates adhesive signaling pathways and thereby inhibits cell growth. Nf2/merlin controls oncogenic gene expression by modulating the Hippo pathway.

Design of Novel Phosphopantetheine Adenylyltransferase Inhibitors: A Potential New Approach to Tackle Mycobacterium tuberculosis.

Background: Tuberculosis (TB) has been a challenging disease worldwide, especially for the neglected poor populations. Presently, there are approximately 2 billion people infected with TB worldwide and 10 million people in the world fell ill with active TB, leading to 1.5 million deaths.

Use and Effectiveness of Sperm Cryopreservation for Adolescents and Young Adults: A 37-Year Bicentric Experience.

Sperm cryopreservation (SCP) should be offered to every adolescent before gonadotoxic treatment, but experience in this age range is still relatively limited. The goal of this study is to assess how to optimize this procedure. One hundred thirty-three patients between 12 and 20 years old, who underwent SCP between 1980 and 2017, were included.

A distinct talin2 structure directs isoform specificity in cell adhesion.

Integrin receptors regulate normal cellular processes such as signaling, cell migration, adhesion to the extracellular matrix, and leukocyte function. Talin recruitment to the membrane is necessary for its binding to and activation of integrin. Vertebrates have two highly conserved talin homologs that differ in their expression patterns.

Cell adhesion in cancer: Beyond the migration of single cells.

Homeostasis in healthy tissues strongly relies on cell-to-cell adhesion and cell-to-extracellular matrix interactions. For instance, normal epithelial cells maintain tissue structure by adhering to each other and to the extracellular matrix. The proteins that mediate these distinct interactions are collectively called cell adhesion molecules and are divided into four major groups: cadherins, integrins, selectins, and immunoglobulins.

[Preimplantation genetic testing: legal and ethical aspects in clinical practice].

In Switzerland, since modifications of the law regulating reproductive medicine introduced the 1rst of September 2017, preimplantation genetic testing (PGT) has been legalised. Infertile couples undergoing in vitro fertilization (IVF) can benefit from this technology by detecting which embryos are aneuploid (ie abnormal number of chromosomes, PGT-A). This is performed in order to transfer euploid embryos (normal number of chromosomes) and to optimise success, though data are limited.

Clomiphene citrate effect on testosterone level and semen parameters in 18 infertile men with low testosterone level and normal/low gonadotropines level.

Objective: To determine the effect of a 3-month course of clomiphene citrate (CC) on plasma testosterone (T) level and on semen parameters in 18 infertile men with low T level and normal or low gonadotropines level.

Study Design: A retrospective study was conducted by reviewing the medical records of men referred to a university fertility medicine unit for infertility management between January 2010 and March 2015. Men treated with CC for at least 3 months were included if they presented with: RESULTS: 18 patients met the inclusion criteria.

Ten-year single-centre experience in fertility preservation of 459 patients suffering from acute leukaemia.

Acute leukaemia is a life-threatening disease that needs treatment without delay. Fertility preservation is recommended, but often not possible because of the necessity to start treatment as soon as possible. The present study is a retrospective single-centre analysis of 459 patients diagnosed with acute leukaemia between 2002 and 2012.

[Assisted reproductive technology : strategies of elective single embryo transfer].

The development of assisted reproductive technology (ART) has led to the birth of nearly 6 million children since the first IVF baby in 1978. For many years, it was routine practice to transfer multiple embryos in order to obtain the highest pregnancy rates. This strategy has induced a dramatic increase in multiple pregnancies and the associated complications for the mother and the child.

Convergent QSAR studies on a series of NK₃ receptor antagonists for schizophrenia treatment.

The dopamine hypothesis states that decreased dopaminergic neurotransmission reduces schizophrenia symptoms. Neurokinin-3 receptor (NK3) antagonists reduce dopamine release and have shown positive effects in pre-clinical and clinical trials. We employed 2D and 3D-QSAR analysis on a series of 40 non-peptide NK3 antagonists.

Effect of embryo culture media on birthweight and length in singleton term infants after IVF-ICSI.

Questions Under Study: To investigate if two distinct, commercially available embryo culture media have a different effect on birthweight and length of singleton term infants conceived after IVF-ICSI.

Methods: University hospital based cohort study. Between 1 January 2000 and 31 December 2004, patients conceiving through IVF-ICSI at the University Hospital, Lausanne have been allocated to two distinct embryo culture media.

Medicinal Chemistry of New Compounds to Treat Tuberculosis.

Tuberculosis (TB), a 19th century disease, is still present in the beginning of the Third Millennium. It has been considered pandemic, since around two billion people are infected with M. tuberculosis.

Uranium deposition in bones of Wistar rats associated with skeleton development.

Sixty female Wistar rats were submitted to a daily intake of ration doped with uranium from weaning to adulthood. Uranium in bone was quantified by the SSNTD (solid state nuclear track detection) technique, and bone mineral density (BMD) analysis performed. Uranium concentration as a function of age exhibited a sharp rise during the first week of the experiment and a drastic drop of 70% in the following weeks.

[Fertility preservation and cancer in the male].

Improvement in cancer treatments resulted in an increased number of men surviving cancer. Quality of life has become an important issue in these patients. Anti cancer treatments might have transient or definitive harmful effects on male fertility.

Fertility preservation in cancer patients. Review of the French speaking part of Switzerland and recommendations for different situations.

Due to constant progress in oncology, survival rates of patients (children and adults) with cancer are increasing. Consequently, the reproductive future of young cancer patients needs to be addressed carefully. Fertility preservation techniques are available and issues such as the time available for fertility treatments, patients' age, presence of a partner and patients' personal wishes have to be considered.

Nitric oxide: state of the art in drug design.

Since the great discovery of Furchgott, Ignarro and Murad in the late 90's, nitric oxide (NO) is considered one of the most versatile endogenous molecules, which is involved in important signaling biochemistry pathways of the human body. Thus, it is directly related to pathological processes and its over- or low-production is able to cause damage in systems that are involved. By using certain functional groups present in molecules that already have potential therapeutic value, hybrid compounds, by means of inclusion of NO-donors (e.

Uranium content and dose assessment for sediment and soil samples from the estuarine system of Santos and Sao Vicente, SP, Brazil.

In this work, the uranium (U) content in sediment and soil samples collected near the Santos and São Vicente estuaries was determined using the fission track registration technique (SSNTD). The sediment and soil samples after oven-dried and pulverised were prepared in the solution form. About 10 microl of this solution was deposited on a plastic detector and irradiated at the IPEN-IEA-R1 (3.

Hatching: how to select the clinical indications.

Currently, most fertility centers around the world use assisted hatching (AH) techniques to help embryo release out of the zona pellucida (ZP) and thus increase the implantation rate. For the last 13 years, several retrospective and prospective studies, assessing AH in different clinical indications, have given disparate results, making the selection of patients or embryos in need of this treatment complex. The most relevant conclusion obtained so far is that AH has a beneficial effect in women with repeated failures of embryo implantation.

Number of transferred embryos: how to reduce multiple pregnancies.

Because the diagnostic tools for predicting whether an early cleavage stage embryo can lead to a viable pregnancy are still elusive, transfer of more than one embryo remains quite common. However, the only way to reduce multiple pregnancies, considered as the main adverse effect of assisted reproductive technology, is to transfer a single embryo. In countries such as Switzerland and Germany, the law allows cryopreservation only at the 2-pronuclear stage.

A European multicentre prospective randomized study to assess the use of assisted hatching with a diode laser and the benefit of an immunosuppressive/antibiotic treatment in different patient populations.

Background: Assisted hatching (AH) techniques, designed for facilitating the embryo escape out of the zona pellucida (ZP) have been used in IVF centres since 1992. The initial indications for AH were patient's age, ZP thickness, high basal FSH and repeated IVF failures. Several retrospective and prospective studies assessing AH in these indications have given disparate results.