New synthetic pathway leading to oxospirochlorins

In this work we propose a completely new approach for the synthesis of spirochlorin derivatives based on the use of an imino-keto intermediate formed in situ from 2-amino-5,10,15,20-tetraphenylporphyrins and inverse electron demand Diels–Alder (iEDDA) cycloaddition with 3,6-di-2-pyridyl-1,2,4,5-tetrazine. The mechanism of reaction was analyzed employing theoretical methods by comparing the difference in energy of Frontier Molecular Orbitals (FMO) for appropriate reagents. Ground-state molecular electrostatic (ESP) potential maps were employed as additional tools allowing explanation of the reactivity of substrates. The new class of spirochlorin compounds was fully characterized by means of mass spectrometry, IR, liquid and solid state NMR and X-ray crystallography. Correlation between molecular structure and optical properties for the obtained title compounds is discussed.

Oxospirochlorins – novel analogs of porphyrinoids were synthesized and characterized by various methods including X-ray, NMR spectroscopy and mass spectrometry.     

A case report of a patient with dermatomyositis as a prodromal sign of lung cancer

Dermatomyositis (DM) is a connective tissue disease characterized by specific inflammatory lesions in muscle biopsy. It is caused by vasculitis determined by humoral factors with subsequent inflammatory cell accumulation, mainly T CD4+ and B cells, which infiltrate myocytes leading to its vacuolization and degeneration (mainly in the skeletal muscles, rarely in the smooth muscles). The incidence of DM is estimated at 1-10 per million in adults and at 1-3.2 per million in children. The autoimmune mechanism of disease induction is not fully recognized. Several lines of evidence showed the link between DM and neoplastic disease. The first report of dermatomyositis associated with stomach cancer, by Stertz, comes from 1916. In the same time, Kankeleit reported DM associated with breast cancer. Presumably, it is the result of immune reaction against antigens common for muscle and neoplastic cells or some paraneoplastic syndrome underlying mechanism. The report presents the case of a 52-year-old woman with DM (diagnosed according to the Bohan and Peter criteria) and with coexistent squamous lung cancer in situ. The left upper lobectomy was performed. No complications in postoperative period were observed. During more than 2 years of follow-up after the surgery, the patient remained in good condition, without DM symptoms, or cancer relapse. Considering that DM may be associated with lung cancer; extensive diagnostic work-up to exclude neoplastic lesions should be performed. Patients aged 40 years or more should be particularly screened.     

Imbalance in serum soluble CD30/CD30L and CD40/CD40L systems are associated with ovarian tumors

The aim of the study was to examine the concentrations of the soluble receptors and their ligands of CD30/CD30L and CD40/CD40L systems in the serum of women with ovarian tumor and in the ovarian cyst fluid of women with Cystadenoma serosum. The study included 120 women with ovarian tumors. As a control, sera were obtained from 60 healthy female volunteers. Concentrations of the sCD30, sCD30L, sCD40 and sCD40L in the serum and the ovarian cyst fluid were measured by ELISA enzyme-linked immunosorbent assay. Concentrations of both sCD30 and sCD30L in serum of women with ovarian tumors were significantly higher than in control (p < 0.0001). The highest serum receptor and its ligand levels were observed in women with ovarian cancer (p < 0.0001). Moreover, results showed significantly increased levels of sCD40 and sCD40L serum in women with ovarian tumors, as compared to the control group (p < 0.0001). The highest concentration of sCD40 in the serum of women with ovarian cancer and sCD40L in serum of women with Teratoma maturum (p < 0.0001) were observed. Impaired apoptosis among women with ovarian tumors is associated with the impairments of soluble CD30/CD30L and CD40/CD40L systems. Measurement of studied parameter concentrations in serum of women with ovarian tumors has been suggested to be a potential tool in monitoring of inflammatory. Evaluation of sCD30, sCD30L and sCD40 might be an early diagnostic marker in patients with the ovarian cancer. Concentrations of the studied parameters in the ovarian cyst fluid higher than the serum values suggest local suppression of the immune response. However, the final evaluation of the importance of measurement of serum levels of them requires further investigation.     

Towards metabolically stable 5-HT7 receptor ligands: a study on 1-arylpiperazine derivatives and related isosters

Serotonin 7 (5-hydroxytryptamine7 or 5-HT₇) is the most recently identified serotonin receptor. It is involved in mood disorders and is studied as a target for antidepressants. Here, we report on the structural manipulation of the 5-HT₇ receptor ligand 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine (1a) aimed at obtaining 5-HT₇ receptor ligands endowed with good in vitro metabolic stability. A set of N-[3-methoxyphenyl)ethyl-substituted] 1-arylpiperazine, 4-arylpiperidine and 1-aryl-4-aminopiperidine was synthesized and tested in radioligand binding assays at human cloned 5-HT₇ and 5-HT_1A receptors. In vitro metabolic stability of the target compounds was assessed after incubation with rat hepatic S9 microsomal fraction. Among the new compounds, 1-(2-biphenyl)-4-[2-(3-methoxyphenyl)ethyl]piperazine (1d) and 4-(2-biphenyl)-1-[2-(3-methoxyphenyl)ethyl]piperidine (2d) showed a good compromise between affinity at 5-HT₇ receptor (K _i = 7.5 nM and 13 nM, respectively) and in vitro metabolic stability (26 and 65 % recovery of parent compound, respectively) but were poorly selective over 5-HT_1A receptor.     

Terapia celowana i transplantacja komórek krwiotwórczych szansą na wyleczenie chorych z ostrą białaczką szpikową

Acute myeloid leukemia (AML) is a heterogeneous disorder with a diverse prognosis. About 70% of AML patients may achieve complete remission after conventional chemotherapy, but long-term outcome remains unsatisfactory. The development of molecular biology resulted in a better understanding of AML pathogenesis as well as it allowed us the introduction of targeted therapy. However, most AML patients still require the allogeneic hematopoietic stem cell transplantation (alloHSCT) to be cured. The long-term results of alloHSCT for AML depend on a variety of factors including the age at transplant, the presence of well-defined risk factors and disease status at transplant. It seems that the combination of targeted therapy with conventional chemotherapy and subsequent alloHSCT may be a chance for curing a significant proportion of AML patients.     

Progressive-toric IOL design reduces residual astigmatism with increasing pupil size: a ray-tracing simulation based on corneal topography data

Population studies indicate that astigmatism decreases from the corneal center toward the periphery. A standard toric intraocular lens (IOL) with a constant cylinder power cannot correct uniformly across this gradient. We built an astigmatic eye model based on corneal topography data. A progressive-toric lens with gradually decreasing cylinder power was compared with an identically designed lens but featuring conventional astigmatism correction. Residual astigmatism did not differ significantly (P=0.06) at 3 mm, and the Strehl ratio was identical for both lenses (0.51 ±0.15, P=0.88). At 5 mm, the progressive IOL yielded significantly lower residual astigmatism by 0.10 D (P<0.001). The Strehl ratio was 0.30 ±0.08 with the progressive and 0.29 ±0.08 with the standard lens (P<0.001). At 3 mm, the optical performance was comparable for both IOLs. However, at 5 mm, the progressive-toric was more effective in correcting astigmatism, and it yielded reduced residual astigmatism compared to a standard toric lens.