Synthesis of 1,3-diaryl-spiro[azetidine-2,3′-indoline]-2′,4-diones via the Staudinger reaction: cis- or trans-diastereoselectivity with different addition modes

A new synthetic approach for realizing biologically relevant bis-aryl spiro[azetidine-2,3′-indoline]-2′,4-diones was developed based on Staudinger ketene–imine cycloaddition through the one-pot reaction of substituted acetic acids and Schiff bases in the presence of oxalyl chloride and an organic base. A series of [azetidine-2,3′-indoline]-2′,4-diones were synthesized using this method. For comparison, the same compounds were obtained using a known technique, where ketene is generated from pre-synthesized acyl chloride. It was shown that the use of oxalyl chloride for ketene generation in the one-pot reaction at room temperature allows for the reversal of the diastereoselectivity of spiro-lactam formation, unlike previously described procedures.

Two experimental techniques of the ketene–imine Staudinger reaction allowed different diastereomers of spiro-indolinone-β-lactams to be obtained.     

Water Splitting on Multifaceted SrTiO3 Nanocrystals: Calculations of Raman Vibrational Spectrum

Various photocatalysts are being currently studied with the aim of increasing the photocatalytic efficiency of water splitting for production of hydrogen as a fuel and oxygen as a medical gas. A noticeable increase of hydrogen production was found recently experimentally on the anisotropic faces (facets) of strontium titanate (SrTiO₃, STO) nanoparticles. In order to identify optimal sites for water splitting, the first principles calculations of the Raman vibrational spectrum of the bulk and stepped (facet) surface of a thin STO film with adsorbed water derivatives were performed. According to our calculations, the Raman spectrum of a stepped STO surface differs from the bulk spectrum, which agrees with the experimental data. The characteristic vibrational frequencies for the chemisorption of water derivatives on the surface were identified. Moreover, it is also possible to distinguish between differently adsorbed hydrogen atoms of a split water molecule. Our approach helps to select the most efficient (size and shape) perovskite nanoparticles for efficient hydrogen/oxygen photocatalytic production.     

Hot Sliding Wear of 88 wt.% TiB–Ti Composite from SHS Produced Powders

Titanium alloys and composites are of great interest for a wide variety of industrial applications; however, most of them suffer from poor tribological performance, especially at elevated temperatures. In this study, spark plasma sintering was utilized to produce a fully dense and thermodynamically stable TiB–Ti composite with a high content of ceramic phase (88 wt.%) from self-propagating high temperature synthesized (SHS) powders of commercially available Ti and B. Microstructural examination, thermodynamic assessments, and XRD analysis revealed the in situ formation of titanium borides with a relatively broad grain size distribution and elongated shapes of different aspect ratio. The composite exhibits a considerable hardness of 1550 HV30 combined with a good indentation fracture toughness of 8.2 MPa·m^1/2. Dry sliding wear tests were performed at room and elevated temperature (800 °C) under 5 and 20 N sliding loads with the sliding speed of 0.1 m·s⁻¹ and the sliding distance of 1000 m. A considerable decline in the coefficient of friction and wear rate was demonstrated at elevated temperature sliding. Apart from the protective nature of generated tribo-oxide layer, the development of lubricious boric acid on the surface of the composite was wholly responsible for this phenomenon. A high load bearing capacity of tribo-layer was demonstrated at 800 °C test.     

Morpho-regulation of ectodermal organs: integument pathology and phenotypic variations in K14-Noggin engineered mice through modulation of bone morphogenic protein pathway

Ectodermal organs are composed of keratinocytes organized in different ways during induction, morphogenesis, differentiation, and regenerative stages. We hypothesize that an imbalance of fundamental signaling pathways should affect multiple ectodermal organs in a spatio-temporal-dependent manner. We produced a K14-Noggin transgenic mouse to modulate bone morphogenic protein (BMP) activity and test the extent of this hypothesis. We observed thickened skin epidermis, increased hair density, altered hair types, faster anagen re-entry, and formation of compound vibrissa follicles. The eyelid opening was smaller and ectopic cilia formed at the expense of Meibomian glands. In the distal limb, there were agenesis and hyperpigmentation of claws, interdigital webbing, reduced footpads, and trans-differentiation of sweat glands into hairs. The size of external genitalia increased in both sexes, but they remained fertile. We conclude that modulation of BMP activity can affect the number of ectodermal organs by acting during induction stages, influence the size and shape by acting during morphogenesis stages, change phenotypes by acting during differentiation stages, and facilitate new growth by acting during regeneration stages. Therefore during organogenesis, BMP antagonists can produce a spectrum of phenotypes in a stage-dependent manner by adjusting the level of BMP activity. The distinction between phenotypic variations and pathological changes is discussed.     

Urothelial cancer in patients with Endemic Balkan Nephropathy (EN) after renal transplantation

GOAL: Analysis of the incidence of urothelial cancer and outcome of treatment in patients with Endemic Balkan Nephropathy (EN) after renal transplantation. METHODS: From January 1985 until October 2006, 550 kidney transplantations (389 cadaveric) and 5 combined kidney and pancreas transplantations were performed in University Hospital Center Rijeka. In only 6 (1.1%) of 555 transplant recipients, EN was diagnosed as the original kidney disease, based on medical history, clinical findings, and laboratory results, but without pathohistologic verification. All patients with EN received the first renal transplant from a cadaver. Patients' mean age at transplantation was 50.3 +/-15.9 yrs, five patients (83.3%) were male. The incidence of malignant tumors in all 555 transplant recipients was analyzed, with an emphasis on the incidence of urothelial cancer and outcome of treatment in the group of patients with EN. RESULTS: During posttransplant follow-up period, malignancy was diagnosed in 27 (4.9%) out of 555 transplant recipients. Skin cancer was diagnosed in 7 patients (1.3%), followed by cancer of the urinary tract in 6 patients (1.1%) and breast cancer in 3 patients (0.5%). In 3 of 6 patients with EN, urothelial cancer was diagnosed, resulting in the death in two patients. In the third patient, urothelial cancer showed a high affinity for recurrence, and besides the strong reduction of immunosuppressive therapy, repeated surgical treatment was needed. CONCLUSIONS: Patients with EN show a high incidence of urothelial cancer after renal transplantation. A thorough nephro-urological evaluation is needed before transplantation, and a careful follow-up is required afterward to ensure an early diagnosis of malignancy. Preventive nephroureterectomy is recommended.     

The history of kidney transplantation at Susak hospital

Kidney transplantation is the most efficient method of renal replacement therapy. Development of kidney transplantation occurred in the second part of the 20th century. At Susak hospital, the first experimental surgical acts on animal models started in 1996. The first kidney transplantation from living related donor at Susak hospital was performed on January 31, 1971. One year later, first transplantation from cadaveric donor was performed. In the last 40 years, development of transplantation medicine in Rijeka and Croatia was successful and Rijeka has become one of the top transplantation centers in Croatia today. Since 2007, Department of Urology has become Referral Center for Kidney Transplantation of the Croatian Ministry of Health and Social Welfare.     

A novel method for assessing in vitro oncology drug combinations using growth rates

We propose a new method that allows screening oncology drug combinations using data from in vitro studies to select agents that have the promise of showing a synergistic effect in vivo. In contrast to known approaches that define combination effects either on the concentration scale or on the percent inhibition scale, we use the growth rate of treated cells as a primary indicator of treatment activity. The developed method is based on a novel statistical model that describes the growth of cancer cells that are subject to treatment with a combination of compounds. The model assumes a multicompartment cell population with transition rates between compartments modeled according to biochemical reaction properties, and cells in each compartment growing according to exponential law. This translates to a linear system of ordinary differential equations, whose solution is accurately approximated by a closed-form expression using rapid equilibrium assumptions. Special cases of the aforementioned model represent situations when the combination effect is absent or when the considered drugs act as the same compound. Assuming the normal distribution for the growth rate measurement error, we describe a formal statistical testing procedure to distinguish between different mechanisms of action for the considered compounds, and to test if a significant combination effect is being observed.     

A Novel Method for Assessing in Vitro Oncology Drug Combinations Using Growth Rates

We propose a new method that allows screening oncology drug combinations using data from in vitro studies to select agents that have the promise of showing a synergistic effect in vivo. In contrast to known approaches that define combination effects either on the concentration scale or on the percent inhibition scale, we use the growth rate of treated cells as a primary indicator of treatment activity. The developed method is based on a novel statistical model that describes the growth of cancer cells that are subject to treatment with a combination of compounds. The model assumes a multicompartment cell population with transition rates between compartments modeled according to biochemical reaction properties, and cells in each compartment growing according to exponential law. This translates to a linear system of ordinary differential equations, whose solution is accurately approximated by a closed-form expression using rapid equilibrium assumptions. Special cases of the aforementioned model represent situations when the combination effect is absent or when the considered drugs act as the same compound. Assuming the normal distribution for the growth rate measurement error, we describe a formal statistical testing procedure to distinguish between different mechanisms of action for the considered compounds, and to test if a significant combination effect is being observed.