Beck’s Tetrad? Adding POCUS To The Clinical Exam For Pericardial Tamponade Improves Diagnostic Accuracy In Obstructive Shock

Beck’s Tetrad? Adding POCUS To The Clinical Exam For Pericardial Tamponade Improves Diagnostic Accuracy In Obstructive Shock Cody Wiench, MD Providence Portland Medical Center – Portland, OR Additional Authors: Benjamin Pedroja, MD Introduction: Obstructive shock due to tamponade is an important, but rare, cause for sudden cardiovascular collapse. Accurate treatment requires prompt (and correct) diagnosis. Bedside echocardiogram can provide rapid and accurate diagnosis, however the physical exam can provide important clues to consider tamponade. In patients with conditions that predispose them to pericardial disease, such as SLE, one must have a high index of suspicion for tamponade when patients suddenly de-compensate. Case Presentation: A 27-year old woman with a history of SLE on chronic immunosuppression, pulmonary hypertension and chronic pain presents to the Emergency Department with subjective fevers to 40C, diaphoresis and sudden onset back pain. Vitals in the ED were impressive for heart rate of 106, blood pressure of 92/67, respiration rate of 10. Labs and imaging were unremarkable. Pt admitted to hospital for potential sepsis of unclear cause in an immunosuppressed patient and was started on vancomycin and piperacillin-tazobactam. On day 5 of hospitalization, a rapid response was called due to sudden onset of heart rate to 150, respiration rate to 24, blood pressures of 80s/50s and severe chest pain. Physical exam at that time was notable for muffled heart sounds and pulsus paradoxus. Bedside ultrasound demonstrated a large pericardial effusion resulting in cardiac tamponade. Emergent pericardial fluid drainage was preformed, draining 70 cc of fibrinous, bloody fluid. After procedure, the patient had rapid normalization of hemodynamics. Pericardial fluid analysis was performed, but nonspecific. It is thought that the effusion was secondary to SLE, and the patient was discharged to home in stable condition. Discussion: Cardiac involvement in SLE is thought to occur in more than 50% of SLE patients, however tamponade is much rarer with an estimated incidence of \u3c1% in a review series. Tamponade portends a poor prognosis in SLE patients. During acute cardiovascular collapse in SLE, one much have a rapid approach to evaluating for tamponade. Pulsus paradoxus is one of those maneuvers; in one prospective study, it was found in 2/3 of patients with tamponade. Unfortunately, patients presenting with the classical “Beck’s Triad” (hypotension, distended neck veins and distant heart sounds) is uncommon; in once study of ultrasound-confirmed tamponade, Beck’s Triad was present in 0% of patients. Fortunately, there are key findings on POCUS exam that, in conjunction with the physical exam, can lead to rapid and accurate diagnosis of tamponade, for instance the absence of a dilated IVC can exclude tamponade with 97% sensitivity.https://digitalcommons.psjhealth.org/ppmc_internal/1006/thumbnail.jp

Easily Prepared Chiral Scorpionates: Tris(2-oxazolinyl)boratoiridium(I) Compounds and Their Interactions with MeOTf

Optically active C3-symmetric monoanionic ligands are uncommon in organometallic chemistry. Here we describe the synthesis of readily prepared tris(4S-isopropyl-2-oxazolinyl)phenylborate [ToP] and fluxional, zwitterionic four- and five-coordinate iridium(I) compounds [Ir(ToP)(η4-C8H12)] (4) and [Ir(ToP)(CO)2] (5). The highly fluxional nature of 4 and5 makes structural assignment difficult, and the interaction between the iridium(I) center and the [ToP] ligand is established by solid-state and solution 15N NMR methods that permit the direct comparison between solution and solid-state structures. Although iridium cyclooctadiene 4 is a mixture of four- and five-coordinate species, the dicarbonyl 5 is only the five-coordinate isomer. The addition of electrophiles MeOTf and MeI provides the oxazoline N-methylated product rather than the iridium methyl oxidative addition product. N-Methylation was unequivocally proven by through-bond coupling observed in 1H−15N HMBC experiments

Cytotoxicity and Modes of Action of the Methanol Extracts of Six Cameroonian Medicinal Plants against Multidrug-Resistant Tumor Cells

Introduction. The present study aims at evaluating the cytotoxicity of twelve parts from six Cameroonian medicinal plants on sensitive and drug-resistant cancer cell lines. We also studied the mode of action of the most active plants, Gladiolus quartinianus, Vepris soyauxii, and Anonidium mannii. Methods. The cytotoxicity of the extracts was determined using a resazurin assay. Flow cytometry was used for cell-cycle analysis and detection of apoptosis, analysis of mitochondrial membrane potential (MMP), and measurement of reactive oxygen species (ROS). Results. At 40 g/mL, three extracts showed a growth of CCRF-CEM leukemia cells by less than 50%. This includes the extracts from G. quartinianus (GQW; 25.69%), Vepris soyauxii leaves (VSL; 29.82%), and Anonidium mannii leaves (AML; 31.58%). The lowest IC 50 values below 30 g/mL were obtained with GQW, AML and VSL against 7/9, 8/9, and 9/9 tested cancer cell lines, respectively. The lowest IC 50 values for each plant were 4.09 g/mL, and 9.14 g/mL (against U87MG.ΔEGFR cells), respectively, for VSL and AML and 10.57 g/mL (against CCRF-CEM cells) for GQW. GQW induced cell cycle arrest between G0/G1 and S phases, whilst VSL and AML induced arrest in G0/G1. All three extracts induced apoptosis in CCRF-CEM cells by loss of MMP, whilst AML also enhanced production of ROS. Conclusion. The three active plants may be a source for the development of new anticancer drugs

Cytotoxicity of Elaoephorbia drupifera and other Cameroonian medicinal plants against drug sensitive and multidrug resistant cancer cells

BACKGROUND: Multidrug resistance (MDR) is a major hurdle for cancer treatment worldwide and accounts for chemotherapy failure in over 90% of patients with metastatic cancer. Evidence of the cytotoxicity of Cameroonian plants against cancer cell lines including MDR phenotypes is been intensively and progressively provided. The present work was therefore designed to evaluate the cytotoxicity of the methanol extracts of twenty-two Cameroonian medicinal plants against sensitive and MDR cancer cell lines. METHODS: The methanol maceration was used to obtain the crude plant extracts whilst the cytotoxicity of the studied extracts was determined using a resazurin reduction assay. RESULTS: A preliminary assay on leukemia CCRF-CEM cells at 40 μg/mL shows that six of the twenty plant extract were able to enhance less than 50% of the growth proliferation of CCRF-CEM cells. These include Crinum zeylanicum (32.22%), Entada abyssinica (34.67%), Elaoephorbia drupifera (35.05%), Dioscorea bulbifera (45.88%), Eremomastax speciosa (46.07%) and Polistigma thonningii (45.11%). Among these six plants, E. drupifera showed the best activity with IC(50) values below or around 30 μg/mL against the nine tested cancer cell lines. The lowest IC(50) value of 8.40 μg/mL was recorded with the extract of E. drupifera against MDA-MB231 breast cancer cell line. The IC(50) values below 10 μg/mL were recorded with the extracts of E. drupifera against MDA-MB231 breast cancer cells, C. zeylanicum against HCT116 p53(+)/(+) and HCT116p53(-)/(-) colon cancer cells and E. abyssinica against HCT116 p53(+)/(+) cells. CONCLUSION: The results of the present study provide evidence of the cytotoxic potential of some Cameroonian medicinal plants and a baseline information for the potential use of Elaoephorbia drupifera in the treatment of sensitive and drug-resistant cancer cell lines

Anticancer Activities of Six Selected Natural Compounds of Some Cameroonian Medicinal Plants

BACKGROUND: Natural products are well recognized as sources of drugs in several human ailments. In the present work, we carried out a preliminary screening of six natural compounds, xanthone V(1) (1); 2-acetylfuro-1,4-naphthoquinone (2); physcion (3); bisvismiaquinone (4); vismiaquinone (5); 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone (6) against MiaPaCa-2 pancreatic and CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000. Compounds 1 and 2 were then tested in several other cancer cells and their possible mode of action were investigated. METHODOLOGY/FINDINGS: The tested compounds were previously isolated from the Cameroonian medicinal plants Vismia laurentii (1, 3, 4, 5 and 6) and Newbouldia laevis (2). The preliminary cytotoxicity results allowed the selection of xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, which were then tested on a panel of cancer cell lines. The study was also extended to the analysis of cell cycle distribution, apoptosis induction, caspase 3/7 activation and the anti-angiogenic properties of xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone. IC(50) values around or below 4 µg/ml were obtained on 64.29% and 78.57% of the tested cancer cell lines for xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, respectively. The most sensitive cell lines (IC(50)<1 µg/ml) were breast MCF-7 (to xanthone V(1)), cervix HeLa and Caski (to xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone), leukemia PF-382 and melanoma colo-38 (to 2-acetylfuro-1,4-naphthoquinone). The two compounds showed respectively, 65.8% and 59.6% inhibition of the growth of blood capillaries on the chorioallantoic membrane of quail eggs in the anti-angiogenic assay. Upon treatment with two fold IC(50) and after 72 h, the two compounds induced cell cycle arrest in S-phase, and also significant apoptosis in CCRF-CEM leukemia cells. Caspase 3/7 was activated by xanthone V(1). CONCLUSIONS/SIGNIFICANCE: The overall results of the present study provided evidence for the cytotoxicity of compounds xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, and bring supportive data for future investigations that will lead to their use in cancer therapy

Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function <it>in vivo</it>. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c.</p> <p>Methods</p> <p>In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth.</p> <p>Results</p> <p>These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival.</p> <p>Conclusions</p> <p>We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number can identify genes that are likely important for chemotherapy response. Our findings suggest a new approach to identify candidate genes that are critical for anti-tumor therapy.</p

Shikonin Directly Targets Mitochondria and Causes Mitochondrial Dysfunction in Cancer Cells

Chemotherapy is a mainstay of cancer treatment. Due to increased drug resistance and the severe side effects of currently used therapeutics, new candidate compounds are required for improvement of therapy success. Shikonin, a natural naphthoquinone, was used in traditional Chinese medicine for the treatment of different inflammatory diseases and recent studies revealed the anticancer activities of shikonin. We found that shikonin has strong cytotoxic effects on 15 cancer cell lines, including multidrug-resistant cell lines. Transcriptome-wide mRNA expression studies showed that shikonin induced genetic pathways regulating cell cycle, mitochondrial function, levels of reactive oxygen species, and cytoskeletal formation. Taking advantage of the inherent fluorescence of shikonin, we analyzed its uptake and distribution in live cells with high spatial and temporal resolution using flow cytometry and confocal microscopy. Shikonin was specifically accumulated in the mitochondria, and this accumulation was associated with a shikonin-dependent deregulation of cellular Ca2+ and ROS levels. This deregulation led to a breakdown of the mitochondrial membrane potential, dysfunction of microtubules, cell-cycle arrest, and ultimately induction of apoptosis. Seeing as both the metabolism and the structure of mitochondria show marked differences between cancer cells and normal cells, shikonin is a promising candidate for the next generation of chemotherapy

Cytotoxicity and modes of action of the methanol extracts of six Cameroonian medicinal plants against multidrug-resistant tumor cells

Introduction. The present study aims at evaluating the cytotoxicity of twelve parts from six Cameroonian medicinal plants on sensitive and drug-resistant cancer cell lines. We also studied the mode of action of the most active plants, Gladiolus quartinianus, Vepris soyauxii, and Anonidium mannii. Methods. The cytotoxicity of the extracts was determined using a resazurin assay. Flow cytometry was used for cell-cycle analysis and detection of apoptosis, analysis of mitochondrial membrane potential (MMP), and measurement of reactive oxygen species (ROS). Results. At 40 g/mL, three extracts showed a growth of CCRF-CEM leukemia cells by less than 50%. This includes the extracts from G. quartinianus (GQW; 25.69%), Vepris soyauxii leaves (VSL; 29.82%), and Anonidium mannii leaves (AML; 31.58%). The lowest IC50 values below 30 mu g/mL were obtained with GQW, AML and VSL against 7/9, 8/9, and 9/9 tested cancer cell lines, respectively. The lowest IC50 values for each plant were 4.09 mu g/mL, and 9.14 mu g/mL (against U87MG.DeltaEGFR cells), respectively, for VSL and AML and 10.57 mu g/mL (against CCRF-CEM cells) for GQW. GQW induced cell cycle arrest between G0/G1 and S phases, whilst VSL and AML induced arrest in G0/G1. All three extracts induced apoptosis in CCRF-CEM cells by loss of MMP, whilst AML also enhanced production of ROS. Conclusion. The three active plants may be a source for the development of new anticancer drugs