Totalsynthesis of Pentamycin

The polyene macrolide pentamycin, first isolated from Streptomyces penticus in 1958, displays impressive biological activities against various pathogens, including Trichomonas vaginalis or Candida albicans, and can be used clinically to treat vaginal candidiasis, trichomoniasis, and other mixed infections. Its powerful biological properties combined with its unique 3D structure have attracted considerable interest from the synthetic community. However, a total synthesis has remained elusive, mainly due to the notorious instability caused by the pentaene fragment. In this work, the first total synthesis of pentamycin was accomplished by a modular strategy in 25 steps (longest linear sequence) in an overall yield of 1.5%. The key step was a final Stille-type ring closure that circumvented any stability problems during the synthesis, which proved essential for the realization of this total synthesis. This linchpin insertion of a protective group free bis-vinyl iodide and a trienyl-bis-stannane concomitantly closed the macrocycle and installed the sensitive pentaene fragment in the very last step. Presumably, a linear hydrogen bonding network of the polyol substrate, enabled by the 1,3-syn polyol moiety between C1* and C13, facilitates ring closure. The total synthesis unequivocally confirms the full relative and absolute stereochemistry of this polyketide, including the previously uncertain hydroxyl bearing center at C14. Furthermore, it represents one of the first examples of an extended hydrogen bond network being designed as a conformational template for complex macrocyclization and documents the importance of conformational design in total synthesis of complex natural products

Analysis of intravaginal misoprostol 0.2 mg versus intracervical dinoprostone 0.5 mg doses for labor induction at term pregnancies

Objectives: Labor-induction methods are used in about 23% of labors. Most commonly, pharmacological methods are used to pre-induct the labor with dinoprostone — a PGE2 analog, and misoprostol — a PGE1 analog. The aim of this study was to evaluate two pharmacological methods of labor induction with the use of prostaglandins applied via an intravagi­nal insert containing misoprostol at a dose of 0.2 mg and intracervical gel containing dinoprostone at a dose of 0.5 mg. Material and methods: This retrospective study was conducted on a group of 50 adult patients qualified for the pre-induction of labor. Following data were recorded: the time from the drug administration to the beginning of regular contractile function, the time from administration to amniotic fluid rupture, the time from medicament administration to the vaginal labor or caesarean section, the duration of I, II and III stages of labor, the delivery method and in the event of caesarean section — the indications for surgery. Results: In comparison to dinoprostone, the misoprostol application was found to shorten the time from drug administration to amniotic fluid rupture by 14.1 hours, the time to the beginning of the first stage of labor by 11.7 hours and from the drug administration to the delivery by 17.3 hours (p-value < 0.05). The duration of the first stage of labor in the misoprostol group was shorter by 1.2 hours than in dinoprostone group (p-value < 0.05). Conclusions: Application of intravaginal insert with misoprostol at a dose of 0.2 mg appears to be a more effective method of labor induction in comparison to intracervical gel with dinoprostone at a dose of 0.5mg. Thorough analysis of these methods requires further studies

Indications for sexology consultation in women after surgical treatment due to breast cancer

Introduction and objectives. Surgical treatment due to brest cancer have an impact on women sexuality. There is a need for research about effective indications for sexology consultation in women after such treatment. The aim of this study is to determine the indications for sexology consultation in women after surgical treatment for breast cancer. Materials and method. We tested 42 women patients diagnosed with breast cancer who had undergone mastectomy 3 months before the study. 3 months after the surgery the women were surveyed using the Polish version of FSFI assessing sexual functioning in women. The result of PL-FSFI were compared with the control group. Results. It was found that the mean score of PL-FSFI in the study group 3 months after the surgery was 13.33 points (score range: 1.2–31.7; median 8.3 points) with a statistically significant difference in terms of areas: desire, arousal, lubrication and orgasm in favour of the control group. The total score of PL-FSFI was significantly lower in women after mastectomy than in women after breast-conserving surgery. It has been shown that sexually active women in whom the surgery concerned the right breast (on the side of the dominant hand) scored lower on the scale “sexual functioning” of QLQ-BR-23 than women with surgery of the left breast, with this difference being statistically significant. There was a statistically significant correlation between the baseline performance status on the Zubrod scale and the scales: desire, lubrication and satisfaction of PL-FSFI. Living in a small town proved to be statistically significant for predicting a lower risk of sexual dysfunction among the surveyed women. Conclusions. The women who underwent surgery due to breast cancer had a higher risk of sexual dysfunction compared to the general population. Higher risk of sexual dysfunction especially concerns women after mastectomy, those who underwent breast surgery on the side of the dominant hand, and those with a worse preoperative overall level of functioning of ≥ 1 point on the Zubrod scale. A lower risk of disorders was observed in women living in smaller towns. The above factors indicate the advisability for sexology consultation in women with breast cancer

Current management of cervical cancer in Poland : analysis of the questionnaire trial for the years 2002-2014 in relation to ASCO 2016 recommendations

OBJECTIVES:To assess the survival of patients with cervical cancer (CC). Since the recommendations concerning cervical cancer management adopted by Polish medical societies do not differ significantly from the ESGO or non-European guidelines, and the fact that evaluation of the system for CC treatment in Poland, as well as the mortality rate of Polish women with CC, which is 70% higher than the average for European Union (EU) countries, justifies the hypothesis that treatment of CC in Poland deviates from the Polish and international recommendations. This article puts forward the current management of cervical cancer in Poland and discusses it in the context of ASCO guidelines. MATERIAL AND METHODS:A survey retrospective multicenter analysis of the medical records of 1247 patients with cervical cancer who underwent treatment for disease and who had completed at least two years of follow-up. RESULTS:Although concurrent radiotherapy and chemotherapy is a standard treatment of FIGO IB to IVA cervical cancer patients in enhanced- and maximum-resources settings, in our analysis, we found that the percentage of women subjected to chemotherapy was lower than in countries where total survival rates were lower. CONCLUSION:Within the IA to II A cervical cancer patients studied group, the methods of treatment remained in line with ASCO guidelines for countries with the highest standard of care. Although concurrent radiotherapy and chemotherapy is a standard treatment of FIGO IB to IVA cervical cancer patients in enhanced- and maximum-resources settings, in our analysis, we found that the percentage of women subjected to chemotherapy was lower than in countries where total survival rates were lower. Our findings, together with the inconsistencies within the cervical cancer screening program, may be one of the explanations of poorer survival rate of women with cervical cancer in Poland

Stem Cells on Biomaterials for Synthetic Grafts to Promote Vascular Healing

This review is divided into two interconnected parts, namely a biological and a chemical one. The focus of the first part is on the biological background for constructing tissue-engineered vascular grafts to promote vascular healing. Various cell types, such as embryonic, mesenchymal and induced pluripotent stem cells, progenitor cells and endothelial- and smooth muscle cells will be discussed with respect to their specific markers. The in vitro and in vivo models and their potential to treat vascular diseases are also introduced. The chemical part focuses on strategies using either artificial or natural polymers for scaffold fabrication, including decellularized cardiovascular tissue. An overview will be given on scaffold fabrication including conventional methods and nanotechnologies. Special attention is given to 3D network formation via different chemical and physical cross-linking methods. In particular, electron beam treatment is introduced as a method to combine 3D network formation and surface modification. The review includes recently published scientific data and patents which have been registered within the last decade

Exosomes: A New Hope for Angiogenesis-Mediated Bone Regeneration

Bone is a metabolically dynamic structure that is generally remodeled throughout the lifetime of an individual but often causes problems with increasing age. A key player for bone development and homeostasis, but also under pathological conditions, is the bone vasculature. This complex system of arteries, veins, and capillaries forms distinct structures where each subset of endothelial cells has important functions. Starting with the basic process of angiogenesis and bonespecific blood vessel formation, coupled with initial bone formation, the importance of different vascular structures is highlighted with respect to how these structures are maintained or changed during homeostasis, aging, and pathological conditions. After exemplifying the current knowledge on bone vasculature, this review will move on to exosomes, a novel hotspot of scientific research. Exosomes will be introduced starting from their discovery via current isolation procedures and state-of-the-art characterization to their role in bone vascular development, homeostasis, and bone regeneration and repair while summarizing the underlying signal transduction pathways. With respect to their role in these processes, especially mesenchymal stem cell-derived extracellular vesicles are of interest, which leads to a discussion on patented applications and an update on ongoing clinical trials. Taken together, this review provides an overview of bone vasculature and bone regeneration, with a major focus on how exosomes influence this intricate system, as they might be useful for therapeutic purposes in the near future