PD-1 /PD-L1 checkpoint in hematological malignancies.

Programmed cell death protein 1 (PD-1), is a cell surface receptor with an important role in down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. PD-1/PDL1 axis represents a checkpoint to control immune responses and it is often used as a mechanism of immune escaping by cancers and infectious diseases. Many data demonstrate its important role in solid tumors and report emerging evidences in lymphoproliferative disorders. In this review, we summarized the available data on the role of PD-1/PD-L1 checkpoint in lymphoproliferative diseases and the therapeutics use of monoclonal blocking antibodies.

Protective Isolation for Patients with Haematological Malignancies: A Pilot Study Investigating Patients' Distress and Use of Time.

Background: Patients with haematological malignancies are often hospitalized in protective isolation until full neutrophil recovery in order to prevent infections. This descriptive pilot study evaluate the level of isolation-related distress and the use of free time in a sample of Italian onco-haematological patients who were hospitalized in protective isolation. Materials and Methods: Participants were 18 patients hospitalized in hematologic ward to receive induction therapy (n=12) or autologous stem cell transplant (n=6). They completed a self-report questionnaire before discharge. Results: Participants reported a moderate level of isolation-related distress, anxiety, and boredom: the more the anxiety and the boredom, the more the distress (r=.77; P<.001), (r=.79; P<.001), respectively. The activities performed during isolation were: watching TV (72.2%), reading (55.6%), thinking (33.3%), surfing in Internet or using PC (33.3%), and playing games or making cross-words (16.7%). Participants who reported pessimistic thinking had higher isolation-related distress (P=.004) as well as anxiety (P<.001) and boredom (P=.001). Conclusion: Haematology Units should support isolated patients in spending their time in recreational activities, allowing more contacts with immediate relatives and friends, providing free TV and Wi-Fi connection inside the room. In addition, patients should have to keep themselves physically active. Isolation-related distress could also be reduced by providing psychological support.

Preparation, characterization and in vitro antimicrobial activity of ampicillin-loaded polyethylcyanoacrylate nanoparticles.

In this paper, the experimental conditions for preparing ampicillin-loaded polyethylcyanoacrylate (PECA) nanoparticles are described. The effects of drug concentration and surfactant type in the polymerization medium on the particle size distribution and loading capacity were studied. The results of these studies show that only the type of surfactant has an impact on the nanoparticle dimensions. The release rate of ampicillin from PECA nanoparticles at pH 7.4 (extracellular value pH) performed either with and without esterases, show that the drug release is considerably increased in the presence of these exzymes. The results of drug release study at pH 1.1 (simulated gastric juice) are very interesting. This study has evidenced that the 70% of ampicillin is released quickly, while the remaining fraction is firmly incorporated in nanoparticles. The released ampicillin is quickly degraded in acid medium while the entrapped fraction is protected from acid degradation and afterwards, when nanoparticles reach the small intestine, can be readily released in the presence of esterases. This result could be exploited for the oral administration of the ampicillin-PECA system. Finally, studies of antimicrobial activity of prepared systems evidenced that ampicillin-loaded PECA nanoparticles exhibit an activity equal or higher than the free drug.

Swellable microparticles containing Suprofen: evaluation of in vitro release and photochemical behaviour.

Suprofen, an anti-inflammatory drug was incorporated in polymer networks based on biocompatible macromolecules, such as alpha,beta-polyasparthydrazide (PAHy) and alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) crosslinked by glutaraldehyde or gamma-rays, respectively. Swelling tests carried out in aqueous media showed that pH value affects the swelling degree of the prepared hydrogels. In vitro release tests were performed in simulated gastrointestinal fluids (pH 1/6.8) using the pH variation method and in phosphate-buffered saline, pH 7.4. Experimental data indicated that Suprofen was released in a sustained way both from PAHy and PHEA microparticles. Further, incorporation of Suprofen in PAHy and PHEA networks provided a significant reduction of the drug photosensitizing activity, as evidenced by in vitro hemolysis tests.

A hydrogel based on a polyaspartamide: characterization and evaluation of in-vivo biocompatibility and drug release in the rat.

This paper deals with the characterization of a new microparticulate hydrogel obtained by gamma irradiation of alpha, beta-poly[N-(2-hydroxyethyl)-DL-aspartamide] (PHEA). When enzymatic digestion of PHEA hydrogel was evaluated using various concentrations of pepsin and alpha-chymotrypsin no degradation occurred within 24 h. In-vivo studies showed that this new material is biocompatible after oral administration to rats. PHEA hydrogel was also studied as a system for delivery of diflunisal, an anti-inflammatory drug. In-vitro release studies in simulated gastrointestinal juice (pH 1 or 6.8) showed that most of the drug was released at pH 6.8. In-vivo studies indicated that diflunisal-loaded PHEA microparticles significantly improved the gastric tolerance and oral bioavailability of the drug in comparison with free diflunisal. These results suggest the potential application of PHEA hydrogel as a new delivery system for the oral administration of anti-inflammatory drugs.

Tuberculous meningoencephalitis in a patient with hairy cell leukemia in complete remission.

Tuberculous meningoencephalitis is a rare disease associated with high morbidity and mortality. We report a patient with hairy cell leukemia in complete remission who, after a single cycle of chemotherapy with cladribine, presented fever and neurological deficits. Laboratory diagnosis of tuberculous meningoencephalitis was made by polymerase chain reaction testing for Mycobacterium tuberculosis in cerebrospinal fluid. Despite the prompt institution of antitubercular-therapy, patient's general condition did not improve and he died. Mycobacterial infection should be considered in patients with intra-cranial lesions, affected by hematological malignancies and persistent immunosuppression.