Evaluation of a (99m) Tc-labelled meso-bisphenylporphyrin as a tumour image agent.

Porphyrins are excellent agents for photodynamic treatment of various types of cancer and also good metal chelators that form highly stable metallo-complexes with different radionuclides. Therefore, radiolabelled porphyrins could also be potentially used as tumour imaging agents. In this context, the aim of this work was the radiolabelling of meso-bis[3,4-bis(carboxymethyleneoxy)phenyl]porphyrin, 2CPP, with Technetium-99 m ((99m) Tc) and the evaluation of its radiochemical and biological properties in vitro and in vivo. The labelling procedure was optimized resulting in an efficiency of 92.52 ± 0.48%. The complex (99m) TC-2CPP remained stable for more than 4 h. The biodistribution showed that (99m) Tc-2CPP is eliminated by gastrointestinal and urinary pathways. The tumour/muscle ratio increases over time, being 3.33 ± 1.22 and 3.55 ± 1.29 in WiDr-bearing tumours mice and in H1299-bearing tumours mice, respectively, 6 h post-injection, showing the tumour specificity of the (99m) Tc-2CPP complex. The favourable tumour/muscle ratio of (99m) Tc-2CPP shows that this complex could potentially be used as tumour imaging agent. Moreover, it could be used to follow the progression or regression of tumours before, during and after the radiotherapy, chemotherapy and photodynamic therapy.

Urothelial bladder cancer with cardiac metastasis: Literature review and case report.

INTRODUCTION AND IMPORTANCE: Urothelial bladder cancer can infrequently result in cardiac metastasis, and be usually diagnosed in severe clinical conditions. We report a urothelial bladder cancer with cardiac metastasis and perform a literature review of published cases of transitional cell carcinoma (TCC) of the bladder with cardiac metastasis from 1934 to 2023 published in Pubmed. CASE PRESENTATION: 42-year-old woman with urinnary bladder TCC, underwent radical cystectomy, developing cardiac metastasis after 25 months, cardiac surgery for partial removal of the lesion and using pembrolizumab with the highest reported survival to date. CLINICAL DISCUSSION: After analysis of 20 case reports in the world among our case, men are more affected, tobacco exposure was the most prevalent risk factor, baseline T3 staging was the most common, and right ventricular and myocardium metastases are more prevalent. The most common symptoms were respiratory failure, changes in cardiac auscultation, and loss of weight. Six patients had cardiac tamponade, and the mean of drained fluid was 1040 ml. Immunohistochemical markers, such as CK7 and Calretinin, were decisive in elucidating the diagnosis. The average time between diagnosis of TCC and cardiac metastasis was 48.69 months, and the survival time after diagnosis of cardiac metastasis was 60.69 days. CONCLUSION: Bladder TCC with cardiac metastasis is rare and with a low survival rate after the diagnosis. Patients with more advanced stages of TCC deserve diagnostic suspicion of cardiac metastasis if they progress with previously unreported respiratory and cardiac symptoms.

Cytotoxicity of ascorbic acid in a human colorectal adenocarcinoma cell line (WiDr): in vitro and in vivo studies.

Vitamin C, available in its reduced form (ascorbic acid; AA) and in its oxidized form (dehydroascorbic acid; DHA), may act in physiological conditions as an antioxidant or pro-oxidant. The aim of this study is to evaluate the cytotoxic effects of pharmacological doses of AA in a human colorectal adenocarcinoma cell line (WiDr) in vitro, through spectrophotometry, clonogenic assays and flow cytometry, and in vivo with xenotransplanted Balb/c nu/nu mice. The results show that the reduced form of vitamin C induces an anti-proliferative and cytotoxic effect in adenocarcinoma colorectal cells under study. The results obtained in vivo after treatment with AA showed a large reduction in the rate of tumor growth. Such understanding can guide decisions about which colorectal cancer patients might potentially benefit from vitamin C pharmacologic therapy.

Decompressive hemicraniectomy for acute ischemic stroke: A neurosurgical view in a pandemic COVID-19 time highlights of literature.

Background and purpose: The novel coronavirus, SARS-CoV-2, which was identified after the outbreak in Wuhan, China, in December 2019, has kept the whole world in tenterhooks due to its severe life-threatening nature of the infection. The World Health Organization (WHO) declared coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 a pandemic in 2020, an unprecedented challenge, having a high contagious life-threatening condition with unprecedented impacts for worldwide societies and health care systems. Neurologic symptoms related to SARS-CoV-2 have been described recently in the literature, and acute cerebrovascular disease is one of the most serious complications. The occurrence of large-vessel occlusion in young patients with COVID-19 infection has been exceedingly rare. In this article, we describe the profile of patients undergoing decompressive craniectomy for the treatment of intracranial hypertension by stroke associated with COVID-19 published so far. A narrative review of the central issue in focus was designed: decompressive craniectomy in a pandemic time.

The role of vitamins in cancer: a review.

Vitamins are essential nutrients for human metabolism, playing an important role as coenzymes or enzymes in many vital processes for the normal functioning of the body. In recent years, it has become apparent that vitamins are crucial in health and human disease, due to several studies that studied this relationship. Currently, it is known that vitamins can have an important role in the prevention and treatment of cancer, but until now no conclusive results were obtained. In this review, we will present the work and more relevant conclusions obtained in recent years of investigation about the relationship between vitamins and cancer, namely vitamin A, vitamin B complex, vitamin C, vitamin D, vitamin E, and vitamin K.

Microalgae starch: A promising raw material for the bioethanol production.

Ethanol is currently the most successful biofuel and can be produced from microalgal biomass (third-generation). Ethanol from microalgal biomass has advantages because it does not use arable land and reduces environmental impacts through the sequestration of CO2 from the atmosphere. In this way, micro and macroalgal starch, which is structurally similar to that from higher plants can be considered a promise raw material for the production of bioethanol. Thus, strategies can be used to intensify the carbohydrate concentration in the microalgal biomass enabling the production of third-generation bioethanol. The microalgae biomass can be destined to biorefineries so that the residual biomass generated from the extraction processes is used for the production of high value-added products. Therefore, the process will have an impact on reducing the production costs and the generation of waste. In this context, this review aims to bring concepts and perspectives on the production of third-generation bioethanol, demonstrating the microalgal biomass potential as a carbon source to produce bioethanol and supply part of the world energy demand. The main factors that influence the microalgal cultivation and fermentation process, as well as the processes of transformation of biomass into the easily fermentable substrate are also discussed.

Synergistic interaction between a PDE5 inhibitor (sildenafil) and a new adenosine A2A receptor agonist (LASSBio-1359) improves pulmonary hypertension in rats.

INTRODUCTION: Pulmonary hypertension (PH) is characterized by enhanced pulmonary vascular resistance, which causes right ventricle (RV) pressure overload and results in right sided heart failure and death. This work investigated the effectiveness of a combined therapy with PDE5 inhibitor (PDE5i) and a new adenosine A2A receptor (A2AR) agonist in mitigating monocrotaline (MCT) induced PH in rats. METHODS: An in vitro isobolographic analysis was performed to identify possible synergistic relaxation effect between sildenafil and LASSBio 1359 in rat pulmonary arteries (PAs). In the in vivo experiments, PH was induced in male Wistar rats by a single intraperitoneal injection of 60 mg/kg MCT. Rats were divided into the following groups: control (saline injection only), MCT + vehicle, MCT + sildenafil, MCT + LASSBio 1359 and MCT + combination of sildenafil and LASSBio 1359. Fourteen days after the MCT injection, rats were treated daily with oral administration of the regimen therapies or vehicle for 14 days. Cardiopulmonary system function and structure were evaluated by echocardiography. RV systolic pressure and PA endothelial function were measured. RESULTS: Isobolographic analysis showed a synergistic interaction between sildenafil and LASSBio 1359 in rat PAs. Combined therapy with sildenafil and LASSBio 1359 but not monotreatment with low dosages of either sildenafil or LASSBio 1359 ameliorated all of PH related abnormalities in cardiopulmonary function and structure in MCT challenged rats. CONCLUSIONS: The combination of sildenafil and LASSBio 1359 has a synergistic interaction, suggesting that combined use of these pharmacological targets may be an alternative to improve quality of life and outcomes for PH patients.

Dexmedetomidine prolongs spinal anaesthesia induced by levobupivacaine 0.5% in guinea-pigs.

Alpha-2 adrenoceptor agonists have been used in association with local anaesthetic to increase the duration of spinal anaesthesia. Intrathecal administration of clonidine prolonged motor blockade induced by local anaesthetic. Since the affinity of dexmedetomidine (DEX) to alpha-2 adrenoceptors is eight-times greater than clonidine, it is expected that DEX could be advantageous in clinical anaesthesia. We investigated the duration of motor nerve block induced by spinal injection of 0.5% levobupivacaine (LVB) associated with intrathecal or intraperitoneal administration of DEX. Seventy-two guinea-pigs were randomly divided in 12 groups, which were all treated with intrathecal injection of 50 microL of LVB. DEX was injected intrathecally with LVB in 6 groups or injected intraperitoneally after LVB in another 6 groups. Intrathecal DEX (0.1, 0.2 and 0.4 microg) increased the LVB-induced motor anaesthesia from 48 (41-66) min to 84.5 (52-91) min (P < 0.05), 101.5 (83-115) min (P < 0.05) and 105 (97-114) min (P < 0.05), respectively. Similarly, intraperitoneal DEX (20 and 40 microg kg(-1)) increased the motor blockade from 48.5 (33-59) min to 88 (71-114) min (P < 0.05) and 114.5 (103-156) min (P < 0.05), respectively. Pre-treatment with yohimbine reduced the duration of motor block from 101.5 (83-115) to 76.5 (68-86) min (P < 0.05) or from 114.5 (103-156) to 90 (83-93) min (P < 0.05) when DEX was administered by the intrathecal or intraperitoneal routes. Motor block induced by spinal injection of LVB was prolonged by intrathecal and systemic administration of DEX, which was partially dependent on activation of alpha-2 adrenoceptors.

Novel agonist of adenosine receptor induces relaxation of corpus cavernosum in guinea pigs: an in vitro and in vivo study.

OBJECTIVE: To test the relaxation effect of a new adenosine receptor agonist N-acylhydrazone derivative, 3,4-dimethoxyphenyl-N-methyl-benzoylhydrazide (LASSBio-1359), on in vitro and in vivo preparation of corpus cavernosum (CC), and its interaction with type-5 phosphodiesterase enzyme inhibitor, sildenafil. METHODS: For in vitro study, an increasing concentration of LASSBio-1359 was added in the solution at the plateau isometric tension recording of isolated guinea pig CC induced by phenylephrine (30 µM). Concentration-response curve was repeated in the presence of A2A receptor antagonist, ZM 241385 (10 µM). Sildenafil-induced CC relaxing effect was compared with that of LASSBio-1359. Isobolographic analysis was performed to identify possible synergistic interaction between LASSBio-1359 and sildenafil. For in vivo study, blood pressure response in the CC of guinea pig was measured after administration of LASSBio-1359 (10 mg/kg intravenously) or sildenafil (10 mg/kg intravenously). RESULTS: LASSBio-1359 caused relaxation of phenylephrine-induced contraction of isolated CC in a concentration-dependent manner (IC50 = 10.1 ± 1.8 µM), which was shifted to the right in the presence of ZM 241385 (IC50 = 27.1 ± 1.4 µM; P <.05). Isobolographic analysis showed synergistic interaction between LASSBio-1359 and sildenafil. As sildenafil, LASSBio-1359 increased blood pressure oscillation in the CC confirming its systemic efficacy. CONCLUSION: CC relaxing effects induced by the adenosine A2A receptor agonist, LASSBio-1359, demonstrated in vitro and in vivo experimental protocols, represent a promise therapeutic option for the treatment of erectile dysfunction. Synergistic interaction of LASSBio-1359 with sildenafil suggests a combined use to reach a higher population of patients with erectile dysfunction.

Interaction of morphine with a new alpha2-adrenoceptor agonist in mice.

UNLABELLED: Finding new chemicals or adjuvants with analgesic effects in the central nervous system is clinically relevant due to the limited number of drugs with these properties. Here, we present PT-31, which is chemically related to 3-benzyl-imidazolidine, with an analgesic profile that results from alpha(2)-adrenoceptor activation. Intraperitoneal administration of PT-31 dose-dependently produced antinociception in the hot plate test, and interacted synergistically with morphine. This effect was completely reversed by yohimbine, a non-selective antagonist of alpha(2)-adrenoceptors, and by BRL 44408, a selective alpha(2A)-adrenoceptor antagonist. The combination of morphine and PT-31 produced greater antinociceptive activity than either alone, and isobolographic analysis revealed a synergistic interaction between these compounds. Docking results confirm the high affinity of the PT-31 ligand at the alpha(2A)-adrenoceptor. PERSPECTIVE: This study introduces a new analgesic compound (PT-31) that acts via alpha(2A)-adrenoceptor activation. A significant increase in analgesia was observed when co-administered with morphine. PT-31 is an interesting new substance for pain therapy.

Evaluation of the NNECDSG Score in a Brazilian public hospital.

OBJECTIVE: To compare the observed incidence of mediastinitis and strokes versus the expected incidence according to the NNECDSG score (Northern New England Cardiovascular Disease Study Group) in a population submitted to coronary artery bypass graft surgery. METHODS: A retrospective consultation was made of medical records of all patients submitted to isolated CABG from January 1st, 2000 to December 31st, 2004, at the Cardiac Surgery Service of the Triângulo Mineiro Federal University (UFTM). Data regarding the incidences of observed mediastinitis and strokes and those estimated by the NNECDSG score were submitted to the Kolmogorov-Smirnov normality test. A comparison was achieved using the paired Student t test, with the level of significance determined as p=0.05. RESULTS: A group of 230 patients were analyzed, including 144 (62.60%) men and 86 (37.39%) women. Sixty-one (26.52%) presented with diabetes, 30 (13.04%) with chronic obstructive pulmonary disease (COPD) and 23 (10%) had peripheral vascular disease (PVD). Emergency surgery occurred in 34 (14.78 %) cases. In 37 (16.08%) patients an ejection fraction (EF) of less than 40% was identified. Mediastinitis occurred in 12 (5.21%) patients and despite the greater general incidence in the sample studied, no statistical significance was found. Strokes occurred in 12 patients (5.21%) and in spite of the higher mean percentage incidence of observed strokes for all scores, a level of statistical significance was not found. CONCLUSIONS: Although the incidences of mediastinitis and strokes were greater in the population studied, these values showed no statistical significance, confirming the score recommended by the NNECDSG as a safe and efficient method for predicting postoperative mediastinitis and strokes in patients submitted to myocardial revascularization surgery in the UFTM.

Avaliação do Escore NNECDSG em um hospital público brasileiro / Evaluation of the NNECDSG Score in a Brazilian public hospital

OBJETIVO: Comparar as incidências observadas de mediastinite e acidente vascular cerebral (AVC) versus as incidências esperadas pelo escore NNECDSG (Northern New England Cardiovascular Disease Study Group), em população submetida à cirurgia de revascularização do miocárdio. MÉTODO: Foram analisados, retrospectivamente, os prontuários de todos os pacientes submetidos à CRVM isolada, no período de 1/1/2000 a 31/12/2004, no Serviço de Cirurgia Cardíaca da Universidade Federal do Triângulo Mineiro (UFTM). Foi aplicado o escore proposto pelo NNECDSG e calculadas as incidências esperadas de mediastinite e AVC para cada paciente. Os dados de incidência observados e a incidência estimada pelo escore do NNECDSG foram submetidos ao teste de normalidade de Kolmogorov-Smirnov. A comparação foi realizada pelo teste t-Student pareado. O nível de significância foi de alfa=0,05. RESULTADOS: Foram analisados 230 pacientes, sendo 144 (62,60 por cento) homens e 86 (37,39 por cento) mulheres. Sessenta e um (26,52 por cento) doentes apresentavam diabetes, 30 (13,04 por cento), doença pulmonar obstrutiva crônica (DPOC) e 23 (10 por cento), doença vascular periférica (DVP). Cirurgia de urgência aconteceu em 34 (14,78 por cento) casos. Trinta e sete (16,08 por cento) pacientes tinham uma fração de ejeção (FE) menor que 40 por cento. Mediastinite ocorreu em 12 (5,21 por cento) pacientes. Apesar da incidência geral de mediastinite ter sido maior nesta amostra, não houve significância estatística. AVC ocorreu em 12 (5,21 por cento) pacientes. Apesar da incidência percentual média de AVC observada ter sido maior, não atingiu nível de significância estatística. CONCLUSÃO: Apesar das incidências de mediastinite e AVC terem sido maiores na população estudada, estes valores não atingiram significância estatística, sendo o escore preconizado pela NNECDSG um método seguro e eficaz na predição de mediastinite e AVC pós-operatórios nos pacientes submetidos à CRVM na UFTM.

OBJECTIVE: To compare the observed incidence of mediastinitis and strokes versus the expected incidence according to the NNECDSG score (Northern New England Cardiovascular Disease Study Group) in a population submitted to coronary artery bypass graft surgery. METHODS:A retrospective consultation was made of medical records of all patients submitted to isolated CABG from January 1st, 2000 to December 31st, 2004, at the Cardiac Surgery Service of the Triângulo Mineiro Federal University (UFTM). Data regarding the incidences of observed mediastinitis and strokes and those estimated by the NNECDSG score were submitted to the Kolmogorov-Smirnov normality test. A comparison was achieved using the paired Student t test, with the level of significance determined as p=0.05. RESULTS:A group of 230 patients were analyzed, including 144 (62.60 percent) men and 86 (37.39 percent) women. Sixty-one (26.52 percent) presented with diabetes, 30 (13.04 percent) with chronic obstructive pulmonary disease (COPD) and 23 (10 percent) had peripheral vascular disease (PVD). Emergency surgery occurred in 34 (14.78 percent) cases. In 37 (16.08 percent) patients an ejection fraction (EF) of less than 40 percent was identified. Mediastinitis occurred in 12 (5.21 percent) patients and despite the greater general incidence in the sample studied, no statistical significance was found. Strokes occurred in 12 patients (5.21 percent) and in spite of the higher mean percentage incidence of observed strokes for all scores, a level of statistical significance was not found. CONCLUSIONS: Although the incidences of mediastinitis and strokes were greater in the population studied, these values showed no statistical significance, confirming the score recommended by the NNECDSG as a safe and efficient method for predicting postoperative mediastinitis and strokes in patients submitted to myocardial revascularization surgery in the UFTM.