Cooperative chemoenzymatic and biocatalytic cascades to access chiral sulfur compounds bearing C(sp)-S stereocentres.

Biocatalysis has been widely employed for the generation of carbon-carbon/heteroatom stereocentres, yet its application in chiral C(sp)-S bond construction is rare and limited to enzymatic kinetic resolutions. Herein, we describe the enantioselective construction of chiral C(sp)-S bonds through ene-reductase biocatalyzed conjugate reduction of prochiral vinyl sulfides. A series of cooperative sequential/concurrent chemoenzymatic and biocatalytic cascades have been developed to access a broad range of chiral sulfides, including valuable β-hydroxysulfides bearing two adjacent C(sp)-S and C(sp)-O stereocentres, in a stereoconvergent manner with good to excellent yields (up to 96%) and enantioselectivities (up to >99% ee).

Clinical Outcomes and Prognostic Factors in Patients With Penile Carcinoma: A Sub-Analysis From Meet-URO 23 (I-RARE) Registry Study.

Introduction: Penile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors.

The prognostic Value of Thyroid Hormone Levels in Immunotherapy-Treated Patients With Metastatic Urothelial Carcinoma.

Introduction: A low fT3/fT4 ratio has been associated with a poorer prognosis in patients treated for different solid malignancies. However, the prognostic role of baseline thyroid function in patients with metastatic urothelial carcinoma (mUC) has not yet been established.

Patients And Methods: We analyzed 72 consecutive immunotherapy-treated patients with mUC from a single institution.

Nivolumab drug holiday in patients treated for metastatic renal cell carcinoma: A real-world, single-centre experience.

Introduction: Immunotherapy with nivolumab (a monoclonal antibody that targets the programmed cell death protein 1, PD1) has become the standard treatment for patients with metastatic renal cell carcinoma (mRCC) after progression to single-agent tyrosine kinase inhibitors. However, the optimal duration of immunotherapy in this setting has not yet been established.

Patients And Methods: We retrospectively reviewed all patients treated with nivolumab at our institution from January 2014 to December 2021 and identified those who discontinued treatment for reasons other than disease progression (PD).

Acanthamoeba proteases contribute to macrophage activation through PAR , but not PAR.

Aim: Acanthamoeba infections are characterized by an intense localized innate immune response associated with an influx of macrophages. Acanthamoeba protease production is known to affect virulence. Herein, the ability of Acanthamoeba trophozoite proteases, of either the laboratory Neff strain or a recently isolated clinical strain, to stimulate IL-12 and IL-6 and to activate protease-activated receptors, PAR and PAR expressed on murine macrophages, was investigated.

Free-Living Amoebae Keratitis.

Purpose: To describe the diagnostic and clinical features and treatment results in 43 consecutive patients with microbiologically proven free-living amoebae (FLA) keratitis.

Methods: In this hospital-based, prospective case series, corneal scrapings from 43 patients with presumed amoebic keratitis were plated on nonnutrient agar. Amoebic isolates were identified morphologically and by the polymerase chain reaction.

Acanthamoeba Activates Macrophages Predominantly through Toll-Like Receptor 4- and MyD88-Dependent Mechanisms To Induce Interleukin-12 (IL-12) and IL-6.

is a ubiquitous free-living amoeba with a worldwide distribution that can occasionally infect humans, causing particularly severe infections in immunocompromised individuals. Dissecting the immunology of infections has been considered problematic due to the very low incidence of disease, despite the high exposure rates. While macrophages are acknowledged as playing a significant role in infections, little is known about how this facultative parasite influences macrophage activity.

Acanthamoeba castellanii Genotype T4 Stimulates the Production of Interleukin-10 as Well as Proinflammatory Cytokines in THP-1 Cells, Human Peripheral Blood Mononuclear Cells, and Human Monocyte-Derived Macrophages.

Free-living amoebae of the genus Acanthamoeba can cause severe and chronic infections in humans, mainly localized in immune privileged sites, such as the brain and the eye. Monocytes/macrophages are thought to be involved in Acanthamoeba infections, but little is known about how these facultative parasites influence their functions. The aim of this work was to investigate the effects of Acanthamoeba on human monocytes/macrophages during the early phase of infection.

Characterization of the spoilage lactic acid bacteria in "sliced vacuum-packed cooked ham".

The lactic acid bacteria are involved with food fermentation and in such cases with food spoilage. Considering the need to reduce the lactic acid bacteria growth in meat products, the aim of this work was to enumerated and investigated the lactic acid bacteria present on sliced vacuum-packed cooked ham stored at 4 °C and 8 °C for 45 days by phenotypic and molecular techniques. The quantification showed that the lactic acid bacteria were present from the first day with mean count of 1.

Evaluation of the presence of microorganisms in solid-organ preservation solution.

Objective: To assess the presence of microorganism contamination in the preservation solution for transplant organs (kidney/pancreas).

Method: Between August 2007 and March 2008, 136 samples of preservation solution were studied prior to graft implantation. Variables related to the donor and to the presence of microorganisms in the preservation solution of organs were evaluated, after which the contamination was evaluated in relation to the "recipient culture" variable.

In vitro activity of Acanthamoeba castellanii on human platelets and erythrocytes.

The effect of Acanthamoeba on human platelets and erythrocytes has not been fully elucidated. This paper reports that cell-free supernatants prepared from A. castellanii can activate human platelets, causing both a significant increase in the cytosolic free-calcium concentration and platelet aggregation.

Acanthamoeba castellanii promotion of in vitro survival and transmission of coxsackie b3 viruses.

This work was undertaken to determine whether Acanthamoeba could play a role in the survival and transmission of coxsackieviruses and focused on in vitro interactions between Acanthamoeba castellanii and coxsackie B3 viruses (CVB-3). Residual virus titer evaluations and immunofluorescence experiments revealed a remarkable CVB-3 adsorption on amoeba surfaces and accumulation inside cells. The survival of viruses was independent of the dynamics of amoeba replication and encystment.

In vitro acanthamoebicidal activity of a killer monoclonal antibody and a synthetic peptide.

Objectives: To evaluate the in vitro microbicidal activity against Acanthamoeba castellanii of a murine monoclonal anti-idiotypic antibody (KTmAb) and a synthetic killer mimotope (KP), which mimic a yeast killer toxin (KT) characterized by a wide spectrum of antimicrobial activity through interaction with specific cell wall receptors, mainly constituted by beta-glucans.

Methods: Amoebicidal activity was investigated after incubation of trophozoites under different experimental conditions with laminarinase, KTmAb, KP and a scrambled decapeptide (SP). To confirm the specific interaction of KP with beta-glucans, the experiments were also carried out in the presence of laminarin (beta1-3-glucan) or pustulan (beta1-6-glucan); both glucan molecules were co-incubated with KP or SP.

In vitro evaluation of the effectiveness of the macrolide rokitamycin and chlorpromazine against Acanthamoeba castellanii.

The present study demonstrates the in vitro effectiveness of the macrolide rokitamycin and the phenothiazine compound chlorpromazine against Acanthamoeba castellanii. Growth curve evaluations revealed that both drugs inhibit trophozoite growth in dose- and time-dependent ways. The effects of both drugs when they were used at the MICs at which 100% of isolates are inhibited were amoebistatic, but at higher doses they were amoebicidal as well as cysticidal.

Synthesis, anti-mycobacterial, anti-trichomonas and anti-candida in vitro activities of 2-substituted-6,7-difluoro-3-methylquinoxaline 1,4-dioxides.

A new series of 23 6,7-difluoro-3-methyl-2-phenylthio/phenylsulfonyl/phenylsulfinyl/benzylamino/phenylamino-quinoxaline 1,4-dioxides variously substituted in the phenyl moiety, was synthesized and submitted to in vitro evaluation for anti-mycobacterial, anti-trichomonas, anti-candida, anti-mycoplasma and antibacterial activities. In anti-mycobacterial assays, several compounds resulted active (MIC90 = 2.0-4.

ADP and other metabolites released from Acanthamoeba castellanii lead to human monocytic cell death through apoptosis and stimulate the secretion of proinflammatory cytokines.

Monocytes/macrophages are thought to be involved in Acanthamoeba infections. The aim of this work was to study whether soluble metabolites (ADP and other compounds) released by Acanthamoeba castellanii trophozoites could induce morphological and biochemical changes in human monocytic cells in vitro. We demonstrate here that ADP constitutively released in the medium by A.

Catabolism of exogenous deoxyinosine in cultured epithelial amniotic cells.

Uptake and catabolism of purine nucleosides have been commonly considered as means to salvage the purine ring for nucleic acid synthesis, usually neglecting the destiny of the pentose moiety. With the aim to ascertain if deoxyribose derived from exogenous DNA can be utilised as a carbon and energy source, we studied the catabolism of exogenous deoxyinosine in a cell line derived from human amnion epithelium (WISH). Intact WISH cells catabolise deoxyinosine by conversion into hypoxanthine.

By releasing ADP, Acanthamoeba castellanii causes an increase in the cytosolic free calcium concentration and apoptosis in wish cells.

The role played by soluble molecules that may participate in acanthamoebal cytopathogenicity has yet to be fully characterized. We demonstrate here that Acanthamoeba castellanii trophozoites constitutively release ADP in the medium. Cell-free supernatants prepared from A.

[Human fibrin glue in the treatment of residual parenchymal surface after total pericystectomy for hepatic echinococcus].

The aim of this study was to evaluate the presumed efficacy of fibrin sealant in limiting bleeding and biliary leakage from liver residual surface after total pericystectomy for hydatid disease. Forty-five patients (group A) who underwent total pericystectomy in our Institution from 1986 to 1995 and liver residual surface treated with conventional techniques and fibrin sealant for control of haemorrhage and bile leakage were selected. A control group (B) was carefully selected, matching the main characteristics of patients in group A: it consisted of 44 patients, who underwent total pericystectomy from 1981 to 1993 and in which fibrin sealant was not used.

Deoxyadenosine metabolism in a human colon-carcinoma cell line (LoVo) in relation to its cytotoxic effect in combination with deoxycoformycin.

We have assessed the intracellular metabolism of 2'-deoxyadenosine in a human colon-carcinoma cell line (LoVo), both in the absence and in the presence of deoxycoformycin, the powerful inhibitor of adenosine deaminase. The combination of 2'-deoxyadenosine and deoxycoformycin has been reported to inhibit the growth of LoVo cells in culture. In this paper we demonstrate that the observed toxic effect is strictly dependent on cell density.

Acanthamoeba castellanii metabolites increase the intracellular calcium level and cause cytotoxicity in wish cells.

Previous studies have shown that trophozoites of the pathogenic free-living amoeba Acanthamoeba castellanii rapidly lyse a variety of cells in vitro. However, the role played by cytolitic molecules that may participate in Acanthamoebal cytopathogenicity has yet to be completely elucidated. The aim of this work was to study whether soluble molecules released by A.

[Stomach cancer in the elderly patient].

Gastric cancer is a typical disease of old age, in fact about one half of the patients affect by it are aged over 65. Elderly patients imply a problematical choice of surgical treatment due to the general and specific risk and to life expectancy. In order to evaluate the specific features of gastric cancer in aged people and to share their experience in choosing the surgical treatment, a series of 50 patients with gastric cancer selected on the age > or = 75 years and observed from 1970 to 1993, was reviewed by the authors.

Kinetic changes of alpha B crystallin expression in neoplastic cells and syngeneic rat fibroblasts at various subculture stages.

Alpha B crystallin, a structural at variable levels, in many extraocular tissues where it plays a protective role in stress conditions. In fact, heat or toxic shocks, as well as pathological states, increase alpha B crystallin levels in many cell types. Here we show that alpha B crystallin expression is also modulated in subcultures of rat fibroblasts and Galliera sarcoma cells.