Yes / The synthesis and characterization of three aromatic oligoamides, constructed from the same pyridyl carboxamide core but incorporating distinct end groups of acetyl (Ac) 1, tert-butyloxycarbonyl (Boc) 2 and amine 3 is reported. Single crystal X-ray diffraction analysis of 1-3 and a dimethylsulfoxide (DMSO) solvate of 2 (2-DMSO), has identified the presence of a range of intra- and intermolecular interactions including N-H⋯N, N-H⋯O=C and N-H⋯O=S(CH3)2 hydrogen-bonding interactions, C-H⋯π interactions and off-set, face-to-face stacking π-π interactions that support the variety of slipped stack, herringbone and cofacial crystal packing arrangements observed in 1-3. Additionally, the cytotoxicity of this series of aromatic oligoamides was assessed against two human ovarian (A2780 and A2780cisR), two human breast (MCF-7 and MDA-MB-231) cancerous cell lines and one non-malignant human epithelial cell line (PNT-2), to investigate the influence of the terminal functionality of these aromatic oligoamides on their biological activity. The chemosensitivity results highlight that modification of the terminal group from Ac to Boc in 1 and 2 leads to a 3-fold increase in antiproliferative activity against the cisplatin-sensitive ovarian carcinoma cell line, A2780. The presence of the amine termini in 3 gave the only member of the series to display activity against the cisplatin-resistance ovarian carcinoma cell line, A2780cisR. Compound 2 is the lead candidate of this series, displaying high selectivity towards A2780 cancer cells when compared to non-malignant PNT-2 cells, with a selectivity index value >4.2. Importantly, this compound is more selective towards A2780 (cf. PNT-2) than the clinical platinum drugs oxaliplatin by > 2.6-fold and carboplatin by > 1.6-fold. / University of Bradford Development Fund; University of Birmingham - Birmingham Fellowship; UKRI Future Leaders Fellowship (MR/T041315/1); UKRI Future Leaders Fellowship (MR/S035486/2)

Submitted by Valquíria Barbieri (kikibarbi@hotmail.com) on 2018-04-18T20:05:35Z No. of bitstreams: 1 DISS_2015_Aurélio Abdias Sampaio Ferreira.pdf: 588938 bytes, checksum: b0dd84c74c6dea32ca2dada05d4e04ea (MD5) / Approved for entry into archive by Jordan (jordanbiblio@gmail.com) on 2018-04-27T17:28:39Z (GMT) No. of bitstreams: 1 DISS_2015_Aurélio Abdias Sampaio Ferreira.pdf: 588938 bytes, checksum: b0dd84c74c6dea32ca2dada05d4e04ea (MD5) / Made available in DSpace on 2018-04-27T17:28:39Z (GMT). No. of bitstreams: 1 DISS_2015_Aurélio Abdias Sampaio Ferreira.pdf: 588938 bytes, checksum: b0dd84c74c6dea32ca2dada05d4e04ea (MD5) Previous issue date: 2015-08-13 / Investigar a resposta metabólica e inflamatória de pacientes submetidos à intervenção cirúrgica por câncer de mama que receberam cuidados tradicionais ou um protocolo multimodalde cuidados perioperatórios (protocolo ACERTO). Métodos: Estudo prospectivo com 18 pacientes operadas por câncer de mama e randomizadas para dois tipos de cuidados perioperatórios: 1) bebida contendo maltodextrina 12,5%, 06 horas(400 ml) e 02 horas (200 ml) antes da anestesia, nenhuma hidratação venosa no pós-operatório (PO), realimentação em até 12h no PO (grupo ACERTO,n= 09) ou 2) jejum completo de 6-8 horas, hidratação venosa no PO imediato, realimentação no 1º dia de PO (grupo controle, n= 09). Foram coletadas amostras de sangue na indução, com 10h e 24h de PO para dosagem deglicose, insulina, albumina e proteína C-reativa (PCR). Avaliou-se a sensibilidade a insulina pela equação de Quicki e o índice inflamatório foi calculado pela razão PCR/albumina. Os dados foram comparados entre os grupos por ANOVA de medidas repetidas. Resultados: Houve aumento da glicemia (p< 0,001), da insulinemia (p=0,002), e redução da sensibilidade insulínica (p=0,007) nos 02 grupos, sem diferença entre eles. Na indução anestésica a dosagem de PCR (4.1±1.9 vs. 2.6±1.3 mg/L; p=0,049) e o índice inflamatório (p=0,046) foram menores no grupo ACERTO. Comparando a evolução em cada grupo houve queda significativa albumina sérica apenas no grupo controle (de 4.1±0.3para 3.7±0.3 g/dl; p<0.05). Na evolução pós-operatória, a dosagem de albumina no grupo controle foi significantemente menor em relação ao ACERTO (p=0,023). Conclusão: O uso do protocolo multimodal ACERTO não modifica a resposta metabólica, mas diminui a resposta inflamatória de fase aguda em cirurgia de câncer de mama. / To investigate the metabolic and inflammatory response in patients submitted to breast cancer surgery receiving either traditional or a multimodal protocol of perioperative care (Acerto protocol). Methods: A prospective study including 18 patients submitted to breast cancer surgical procedures and randomized to receive two types of perioperative care: 1) a drink containing 12% maltodextrine 6h (400 ml) and 2h (200 ml) before anesthesia, no postoperative intravenous hydration, refeeding up to 12h after surgery (Acerto group, n=9) or 2) 6-8h preoperative fasting, intravenous hydration during immediate postoperative period, and refeeding on PO day 1 (Control group, n=9). Blood samples were collected at anesthetic induction, and at 10h and 24h postoperatively for glucose, insulin, albumin, C-reactive protein (PCR) assays. The insulin sensitivity was assessed by Quicki equation and the inflammatory index by the PCR/albumin ratio. Data were compared by repeated measures ANOVA. Results: We found a significant increase of serum glucose (p<0.001), insulin ((p=0.002), and a reduction of insulin sensitivity (p=0.007) in the two groups without difference between them. At induction of anesthesia PCR levels (4.1±1.9 vs. 2.6±1.3 mg/L; p=0,049) and the inflammatory index (p=0,046) were significant lesser in the Acerto group. During evolution there was a significant fall of serum albumin only in control group (from 4.1±0.3 to 3.7±0.3 g/dl; p<0.05). Albumin values were significantly lesser in controls than in the Acerto patients (p=0.023) during the postoperative phase. Conclusion: The use of the Acerto multimodal protocol of perioperative care do not modify the metabolic response but reduces the acute phase inflammatory response in breast cancer surgery.

Tikslas: įvertinti moterų po radikalios modifikuotos mastektomijos bei krūties onkoplastinės operacijos gyvenimo kokybę. Tyrimo metodika. Tyrime dalyvavo trys grupės moterų. Pirmajai grupei priskirtos moterys, kurioms atlikta onkoplastinė krūties operacija KMUK, Chirurgijos klinikoje. Antrąją grupę sudarė moterys, kurioms atlikta radikali modifikuota mastektomija, Kauno medicinos universiteto klinikų (KMUK) filiale, Onkologijos ligoninėje. Kontrolinę grupę sudarė moterys, kurios nesirgo krūties vėžiu ir buvo atsitiktinai atrinktos iš apsilankiusių profilaktiškai pasitikrinti krūtis KMUK. Pirmos ir antros grupės moterys apklaustos praėjus trims metams po operacijos. Rezultatai. Tyrimo metu nustatyta, kad bendra sveikatos būklė blogiausia moterų po onkoplastinės operacijos (68,49 (19,02) balo). Nesirgusių moterų bendra sveikatos būklė geriausia. Jos surinko 30,63 (19,97) balo. Fizinė sveikata buvo blogesnė moterų, kurios nesirgo krūties vėžiu lyginant su tomis, kurioms atlikta mastektomija ir onkoplastinė krūties operacija. Socialinė funkcija blogesnė „sveikų“ moterų (87,32 (27,74) balo). Onkoplastinės grupės moterų socialinė funkcija prastesnė (78,79 (27,72)balo) nei grupės, kurioms atlikta radikali modifikuota mastektomija (69,75 (34,3) balo). Nuovargis didžiausias buvo moterų, kurioms atlikta radikali modifikuota mastektomija (41,15 (28,38) balo). Moterys, kurios nesirgo krūties vėžiu mažiausiai skundėsi nuovargiu (38,65 (18,7) balo) (p=0,018). Seksualinės funkcijos... [toliau žr. visą tekstą] / The objective. To assess women quality of life after radical modified mastectomy and oncoplastical operation for breast. Method of research. Three groups of women attended in the research. First group composed of women, who were after oncoplastical operation for breast in the KMUK, surgery department. Second group composed of women, who were after radical modified mastectomy in the KMUK branch, oncology hospital. The pilot group composed of women, who weren’t ill breast canser and selected casually from women who came to check profilactic their breast in the KMUK. Women were asked two years after operation from first and second group. Results. The research found out, that general state of health was worest thous women, who were after oncoplastical operation (68,49 (19,02)). Women, who were healthy, their general condition was best. They polled 30,63 (19,97) of points. Physical health was wors thous women, who weren’t ill breast cancer neither thous, who were after mastectomy or after breast oncoplastical operation. Social function was worse for “healthy” women (87,32 (27,74)). Social function of oncoplastical group of women was worse (78,79 (27,72)), neither group of radical modified mastectomy (69,75 (34,3)). The fatigue of mastectomy group was the worst (41,15 (28,38)). Women, who weren’t ill breast cancer felt fatigue the least (38,65 (18,7)) (p=0,018). Sexual function was the best thous women, who were in the group of oncoplasty (36 (31,43)). Sexual satisfaction of... [to full text]