Isocyanide-based synthesis of spirorhodanine-cyclopentadiene and spirorhodanine-iminobutenolide conjugates from Winterfeldt's zwitterions and 5-ylidene rhodanines.

An ultrasonic-assisted isocyanide-based protocol to access a series of functionalized spirorhodanine-cyclopentadiene and spirorhodanine-iminobutenolide conjugates from alkyl isocyanides and dialkyl acetylenedicarboxylates in the presence of 5-ylidene rhodanines in MeCN, is described. The reaction proceeds via interception of the reactive Winterfeldt's zwitterions by 5-ylidene rhodanine derivatives. The structures of the target compounds were confirmed by X-ray diffraction studies.

Misdiagnosis of a Cardiac Angiosarcoma During the COVID-19 Pandemic. / Diagnóstico Errôneo de Angiossarcoma Cardíaco na Era COVID-19.

The final months of 2019 saw the emergence of a new pandemic termed "COVID-19". Since then, this infection and its complications have been the priority of healthcare providers, with many symptoms attributed to its early and late presentations. Thus far, other diseases, even fatal situations, have been overlooked or misdiagnosed due to the attribution of patient symptoms to the presence of COVID-19 infection. We herein present a case of cardiac angiosarcoma in a young boy who had previously become infected with COVID-19 about two months earlier. Given the history of infection, the initial approach was post-COVID-19 myopericarditis management. However, the patient's condition worsened, necessitating reevaluation via multimodalities with higher precision. Ultimately, the patient was diagnosed with a cardiac tumor. This article seeks to underscore the significance of taking heed of other diseases and fatal conditions during the COVID-19 pandemic with an emphasis on avoiding misdiagnosing other diseases.

Os últimos meses de 2019 foram marcados pelo surgimento de uma nova pandemia, denominada "COVID-19". Desde então, essa infecção e suas complicações têm sido a prioridade de profissionais de saúde, com muitos sintomas atribuídos às suas apresentações precoces e tardias. Até o momento, outras doenças, mesmo em situações fatais, têm sido negligenciadas ou diagnosticadas incorretamente devido à atribuição dos sintomas do paciente à presença da infecção por COVID-19. Apresentamos aqui um caso de angiossarcoma cardíaco, em um menino que, cerca de 2 meses antes, havia sido infectado com COVID-19. Dado o histórico de infecção, a abordagem inicial foi o manejo da miopericardite pós-COVID-19. No entanto, o quadro do paciente piorou, exigindo reavaliação por multimodalidades com maior precisão. Por fim, o paciente foi diagnosticado com um tumor cardíaco. Este artigo procura enfatizar a importância da atenção a outras doenças e condições fatais na era COVID-19, com ênfase em evitar diagnósticos incorretos de outras doenças.

Diagnóstico Errôneo de Angiossarcoma Cardíaco na Era COVID-19 / Misdiagnosis of a Cardiac Angiosarcoma During the COVID-19 Pandemic

Resumo Os últimos meses de 2019 foram marcados pelo surgimento de uma nova pandemia, denominada "COVID-19". Desde então, essa infecção e suas complicações têm sido a prioridade de profissionais de saúde, com muitos sintomas atribuídos às suas apresentações precoces e tardias. Até o momento, outras doenças, mesmo em situações fatais, têm sido negligenciadas ou diagnosticadas incorretamente devido à atribuição dos sintomas do paciente à presença da infecção por COVID-19. Apresentamos aqui um caso de angiossarcoma cardíaco, em um menino que, cerca de 2 meses antes, havia sido infectado com COVID-19. Dado o histórico de infecção, a abordagem inicial foi o manejo da miopericardite pós-COVID-19. No entanto, o quadro do paciente piorou, exigindo reavaliação por multimodalidades com maior precisão. Por fim, o paciente foi diagnosticado com um tumor cardíaco. Este artigo procura enfatizar a importância da atenção a outras doenças e condições fatais na era COVID-19, com ênfase em evitar diagnósticos incorretos de outras doenças.

Abstract The final months of 2019 saw the emergence of a new pandemic termed "COVID-19". Since then, this infection and its complications have been the priority of healthcare providers, with many symptoms attributed to its early and late presentations. Thus far, other diseases, even fatal situations, have been overlooked or misdiagnosed due to the attribution of patient symptoms to the presence of COVID-19 infection. We herein present a case of cardiac angiosarcoma in a young boy who had previously become infected with COVID-19 about two months earlier. Given the history of infection, the initial approach was post-COVID-19 myopericarditis management. However, the patient's condition worsened, necessitating reevaluation via multimodalities with higher precision. Ultimately, the patient was diagnosed with a cardiac tumor. This article seeks to underscore the significance of taking heed of other diseases and fatal conditions during the COVID-19 pandemic with an emphasis on avoiding misdiagnosing other diseases.

A synthesis of functionalized 3-amino-1,2,4-triazoles from nitrile imines and guanidine derivatives.

A regioselective synthesis of trisubstituted 1,2,4-triazoles through reaction of nitrile imines with guanidine derivatives is described. These 1,3-dipolar cycloaddition reactions proceeded smoothly in moderate to good yields and excellent regioselectivity under ambient conditions. This method provides fast access to a range of functionalized 3-amino-1,2,4-triazoles.

Synthesis of thia- and thioxo-tetraazaspiro[4.4]nonenones from nitrile imines and arylidenethiohydantoins.

5-Arylidene-1-methyl-2-thiohydantoins undergo [3+2]-cycloaddition reaction with nitrile imines, generated in situ from hydrazonyl chlorides, at C=C and C=S dipolarophiles in the thiohydantoin moiety to afford thioxo-tetraazaspiro[4.4]nonenones and thia-tetraazaspiro[4.4]nonenones in moderate to good yields. The stereochemistry of these spiroheterocycles has been confirmed by X-ray diffraction studies.

A synthesis of N-(1H-pyrazol-5-yl)-1,3,4-thiadiazol-2(3H)-imines from nitrile imines and Erlenmeyer thioazlactones.

Erlenmeyer thioazlactones are reacted with hydrazonoyl chlorides in the presence of Et3N to afford functionalized N-(1H-pyrazol-5-yl)-1,3,4-thiadiazol-2(3H)-imines in excellent yields. This strategy is based on a domino double 1,3-dipolar cycloaddition reaction of nitrile imines to Erlenmeyer thioazlactones, followed by the elimination of carbon monoxide and phenylmethanthiol from the initially formed cycloadducts. This method provides fast access to a variety of structurally diverse N-(1H-pyrazol-5-yl)-1,3,4-thiadiazol-2(3H)-imines. The structure of a typical product was established by X-ray crystallography.

Retraction Note: Inhibition of hTERT Gene Expression by SilibininLoaded PLGA-PEG-Fe3O4 in T47D Breast Cancer Cell Line.

[This retracts the article DOI: 10.5681/bi.2013.005.].

NLRP3 Localizes to the Tubular Epithelium in Human Kidney and Correlates With Outcome in IgA Nephropathy.

Nod-like receptor pyrin domain-containing-3 (NLRP3) has been implicated in the pathogenesis of experimental renal injury, yet its characterization in human kidney disease remains largely unexplored. NLRP3 expression was evaluated in human kidney biopsies, primary renal tubular cells (HPTC) and correlated to disease outcomes in patients with IgA nephropathy (IgAN). NLRP3 localized to renal tubules in normal human kidney tissue and to mitochondria within HPTC by immunohistochemistry and immunofluorescence microscopy. Compared to control kidneys, NLRP3 gene expression was increased in biopsies of patients with IgAN. While NLRP3 expression in IgAN was detected in glomeruli, it remained largely confined to the tubular epithelial compartment. In vitro NLRP3 mRNA and protein expression were transiently induced in HPTC by TGF-ß1 but subsequently diminished over time as cells lost their epithelial phenotype in a process regulated by transcription and ubiquitin-mediated degradation. Consistent with the in vitro data, low NLRP3 mRNA expression in kidney biopsies was associated with a linear trend of higher risk of composite endpoint of doubling serum creatinine and end stage renal disease in patients with IgAN. Taken together, these data show that NLRP3 is primarily a kidney tubule-expressed protein that decreases in abundance in progressive IgAN.

Diagnostic Value and Effective Factors on Transbronchial Lung Biopsy Using Cup and Alligator Forceps.

BACKGROUND: Lung biopsy through the airways by using a flexible bronchoscope (transbronchial lung biopsy: TBLB) is a suitable method for obtaining tissue specimens. This study aimed at evaluating the factors influencing TBLB results in order to increase the diagnostic power of this method. MATERIALS AND METHODS: This was a prospective double blind observational study. We had a total of 44 patients with pulmonary lesions who underwent biopsy and 4 specimens were obtained from each patient. A total of 176 specimens were obtained from all patients. Biopsy specimens were taken using cup and alligator forceps alternatively. Characteristics of the obtained specimens including size, floatation, alveolarity, and bleeding were thoroughly studied. After sending to the pathologist, specimens were divided into 2 groups of diagnostic and non-diagnostic specimens. RESULTS: Of a total of 176 specimens, 37 (21%) were diagnostic and 139 (79%) were non-diagnostic. From 88 specimens obtained by the alligator forceps, 16 were diagnostic while from the same number of specimens taken by the cup forceps 21 had diagnostic value. However, this difference was not statistically significant (P>0.05). Of the small specimens (57 cases), 12 (21.1%) were diagnostic while among the 66 medium specimens, 12 (18.2%) and from the 53 large specimens, 13 (24.5%) were diagnostic. No statistically significant difference was detected in this respect (P>0.05). Among specimens floating on the surface of the liquid (48 cases), 6 (12.5%) had diagnostic value. Of the 12 specimens suspended in the liquid, 2 (16.7%) and among the 116 specimens precipitated at the bottom, 29 (25%) were diagnostic. These differences were not significant either (P>0.05). Of the 84 specimens with more than 20 alveoli, 31 (36.9%) were diagnostic. Among 26 specimens with less than 20 alveoli 5 (19.2%) were diagnostic. This correlation was statistically significant indicating that the higher the number of alveoli in the biopsy specimen, the greater the chance of being diagnostic. CONCLUSION: This study failed to find a significant correlation between the diagnostic power of TBLB and type of forceps, sample size or floatation of the specimen in the liquid. However, number of alveoli present in the tissue specimens was significantly correlated with its diagnostic value. Increasing the number of specimens to four can increase the chance of diagnosis.

Effects of propofol versus isoflurane on liver function after open thoracotomy.

BACKGROUND: Anesthetic agents and type of surgery may contribute to postoperative hepatic injury. Inhalational anesthetics have been associated with hepatic dysfunction after surgery, however, propofol is expected to have a lower potential for postoperative liver injury. This prospective double-blind randomized clinical study was planned to determine whether postoperative liver function differs after anesthesia with isoflurane and total intravenous anesthesia with propofol in patients undergoing a posterolateral thoracotomy. METHODS: Eighty-eight patients in American Society of Anesthesiologists physical status 1 or 2, aged 16-60 years, and scheduled for an elective posterolateral thoracotomy, were randomly assigned to an anesthetic protocol: propofol (n = 44) or isoflurane (n = 44). Induction of anesthesia was similar in both groups. Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, and γ-glutamyltransferase were measured before induction of anesthesia and on the first and third days after either propofol or isoflurane anesthesia. RESULTS: Mild changes in postoperative serum levels of liver enzymes were significant within each group but the differences between groups were not significant. CONCLUSIONS: Propofol and isoflurane anesthesia have a comparable minor effect on liver function after an elective posterolateral thoracotomy.

No association between simian virus 40 and diffuse malignant mesothelioma of the pleura in Iranian patients: a molecular and epidemiologic case-control study of 60 patients.

BACKGROUND: Diffuse malignant mesothelioma (DMM) is increasing in incidence on a worldwide basis and is linked to exposure to asbestos. Simian virus 40 (SV40), a DNA virus, was introduced inadvertently to human populations through contaminated polio vaccine during the years 1956-1963. It has been associated with various types of malignancy in animal experiments. There have been suggestions that SV40 might play a role in the pathogenesis of DMM. OBJECTIVE: To evaluate the association between SV40 and DMM in Iranian patients. METHOD: In a case-control study between the years 2007-2008, isolated DNA from 60 paraffin blocks of patients with DMM and 60 controls was assessed to detect three human polyomaviruses (JCV, BKV, and SV40) using three different sets of primers by multiplex nested PCR analysis. We related the patients with diffuse malignant mesothelioma to possible sites of exposure to asbestos. RESULTS: None of the DMMs nor any patient in the control group had SV40 genome on polymerase chain reaction (PCR). All of the cases were SV40 T antigen negative. CONCLUSION: This study suggests that DMM is independent of SV40 infection in Iran.

Inhibition of hTERT Gene Expression by Silibinin-Loaded PLGA-PEG-Fe3O4 in T47D Breast Cancer Cell Line.

Introduction : Nowadays, using drug delivery is an essential method to improve cancer therapy through decreasing drug toxicity and increasing efficiency of treatment. Silibinin (C25H22O10), a polyphenolic flavonoid which is isolated from the milk thistle plant, has various applications in cancer therapy but it has hydrophobic structure with low water solubility and bioavailability. To increase the effect of silibinin, silibinin-loaded PLGA-PEG-Fe3O4 was prepared to determine the inhibitory effect of this nanodrug on Telomerase gene expression. Methods : The rate of silibinin loaded into PLGA-PEG-Fe3O4 was measured. Then, the cytotoxic effect of silibinin-loaded PLGA-PEG-Fe3O4 was determined by Methyl Thiazol Tetrazolium (MTT) assay. After that, inhibition of Telomerase gene expression was indicated through Real-time PCR. Results : Data analysis from MTT assay showed that silibinin-loaded PLGA-PEG-Fe3O4 had dose dependent cytotoxic effect on T47D cell line. MTT assay showed no cytotoxic effect of free PLGA-PEG-Fe3O4 on T47D breast cancer cell line. Real Time PCR analysis showed that the level of telomerase gene expression more efficiently decreased with silibinin-loaded PLGA-PEG-Fe3O4 than with free silibinin alone. Conclusion : The present study indicates that this nanodrug causes down-regulation of Telomerase gene expression in cancer cells. Therefore, PLGA-PEG-Fe3O4 could be an appropriate carrier for hydrophobic agents such as silibinin to improve their action in cancer therapy.

Clonality of the immunoglobulin heavy chain genes in B cell non-hodgkin lymphoma using semi-nested PCR.

BACKGROUND: Identification of gene rearrangements and clonality analysis are important techniques for the diagnosis of malignant lymphoproliferative diseases. These methods have various sensitivities based on the type of primer used and method of determination of polymerase chain reaction (PCR) products. This study aimed at determining the clonality of B cell non-Hodgkin lymphoma in Iranian patients using PCR method and 2 primers of FR2 and FR3. MATERIALS AND METHODS: Paraffin embedded blocks of 67 patients with B cell lymphoma and 19 cases with lymphoid hyperplasia of the lymph nodes who presented to NRITLD, Masih Daneshvari Hospital were retrospectively reviewed. After extracting the genomic DNA using phenol and chloroform, clonal analysis was performed using semi-nested PCR by using two primers: FR2 and FR3. PCR products were determined using 2 techniques of heteroduplex analysis, polyacrylamide gel and silver staining and the conventional method of agarose gel and ethidium bromide staining. Appearance of 1 or 2 bands in the desired location were considered as a sign of clonality. RESULTS: Monoclonal gene rearrangement was observed in 62 out of 67 patients (92.5%) as one or two discrete bands appeared within 60-120 base pairs (bp) and 200-300 bp range. Of the mentioned patients, 53 cases (79.1%) had FR2 and 51 (76.1%) had FR3 rearrangement. Heteroduplex analysis along with silver nitrate staining detected 3 out of the remaining 5 cases of lymphoma to be monoclonal. These cases had been reported negative by the conventional technique. In total, 65 out of 67 patients (97%) showed monoclonal gene rearrangement using both the abovementioned techniques. All hyperplasia cases were polyclonal by this method. CONCLUSION: Our study showed that evaluation and detection of clonality using PCR, FR2 and FR3 primers along with heteroduplex analysis is a rapid sensitive technique for the diagnosis of malignant lymphomas.

Systemic lymphadenopathy as the initial presentation of malignant mesothelioma: a report of three cases.

Systemic lymph node metastasis is a rare event in malignant mesothelioma. It is even more exceptional when systemic lymph node metastasis is the initial clinical presentation. Review of literature discloses only four cases in which metastatic lymphadenopathy was the only symptom of malignant mesothelioma. We, herewith, report three cases where the initial diagnosis of malignant mesothelioma was made by biopsy of enlarged lymph nodes, which were the only clinical presentation. Immunohistochemistry played a pivotal role in elucidating the mesothelial origin of their unusual systemic lymph node metastasis.

Primary pulmonary plasmacytoma with diffuse alveolar consolidation: a case report.

Solitary extramedullary plasmacytomas are plasma cell tumors that tend to develop in mucosa-associated lymphoid tissues including the sinonasal or nasopharyngeal regions. Primary plasmacytoma of the lung is exceedingly rare and often presents as a solitary mass or nodule in mid-lung or hilar areas and diagnosed after resection. Herein, we report a case of primary pulmonary plasmacytoma that presented with diffuse alveolar consolidation and diagnosed by transbronchial lung biopsy.

Incidence of fever and bacteriemia following flexible fiberoptic bronchoscopy: a prospective study.

The latest American Heart Association (AHA) statement for preventing infectious endocarditis, has not recommended prophylactic antibiotic therapy prior to fiberoptic bronchoscopy (FB) except for patients with preexisting predisposing cardiac conditions. Our aim was to determine the incidence of bacteriemia and fever following FB in our experience and compare with those which have been mentioned in AHA guideline as well as other studies. Venous blood of 85 consecutive patients was evaluated for both aerobic and anaerobic cultures before (for detecting possible previous bacteriemia) and after FB. None of the patients were treated with antibiotics prior to the procedure. All the patients were examined during the first 24 hours after FB for detecting fever defined as temperature more than 38 °C. Positive hemocultures were noted in 7 (8.2 %) patients after FB examination. Coagulase negative Staphylococcus, coagulase positive Staphylococcus, beta haemolytic Streptococcus, Citrobacter freundii and Streptococcus viridans were found in 4, 1, 1 and 1 cultures of patients, respectively. By excluding 6 contaminated samples, the rate of bacteriemia reduced to 1 (1.1%) patient in whom the identical pathogen (Streptococcus viridans) was found both in bronchial lavage and venous blood culture. We also found fever in 9 (10.5 %) cases in the first 24 hours following the bronchoscopy. Our results were in consistent with AHA recommendations regarding prevention of infectious endocarditis as a practical gridline in patients who schedule for FB. Besides, transient fever following bronchoscopy is a common self-limited event which does not need medical intervention.

The diagnostic value of Ki-67 and repp86 in distinguishing between benign and malignant mesothelial proliferations.

CONTEXT: The differentiation of benign mesothelial proliferations from malignant mesotheliomas may be difficult, especially when evaluating small specimens from pleural biopsies. OBJECTIVE: To explore the potential value of 2 proliferative cell markers, Ki-67 and restrictedly expressed proliferation-associated protein 86 kDa (repp86), in distinguishing between malignant mesothelioma (MM) and benign reactive mesothelial hyperplasia (MH). DESIGN: Thirty-six cases of MM from 26 men and 10 women with a mean age of 62.9 years (range, 36-80 years) and 22 cases of benign reactive MH from 14 male and 8 female patients with a mean age of 51.5 years (range, 15- 88 years) were included in this study. The proliferative status of the lesions was assessed by immunohistochemistry using monoclonal antibodies to Ki-S2 (repp86) and Ki-S5 (Ki-67). The labeling indices were quantified. RESULTS: The mean labeling indexes for Ki-67 in MM and benign reactive MH were 24.6% (range, 1%-66%) and 6.23% (range, 0%-25%), respectively. The mean labeling indexes for repp86 in MM and benign reactive MH were 26.3% (range, 0%-50%) and 3.26% (range, 0%- 21%), respectively. The average proliferative cell count was significantly higher in MM compared with benign reactive MH (P < .001). Furthermore, both markers showed a significant correlation in their expression in MM and benign reactive MH (r = 77.5, P < .001). Sensitivities of 88% and 92% and specificities of 92% and 94% were obtained at a cutoff point of 9% for Ki-67 and repp86, respectively. CONCLUSIONS: Used in combination, Ki-67 and repp86 appear to be useful markers in differentiating MM from benign reactive MH.

Prognostic values of proliferative markers ki-67 and repp86 in breast cancer.

BACKGROUND: Breast cancer is the leading cause of carcinoma death in women. Proper treatment depends on the consideration of molecular biology status of tumor cells, which may determine the patient's treatment and prognosis. To determine the prognostic models for this disease, we evaluated the role of cell proliferation-related antigens including ki-67 (a nuclear antigen, expressed in G1, G2, and M phases of cell cycle) and repp86 (an 86-kDa nuclear protein expressed in S, G2, and M phases of cell cycle) for detection of biologic behavior of breast cancer. METHODS: We studied 60 women with grade I and II lymph node-negative and 27 with grade III lymph node-positive breast cancers. The mean follow-up periods for these two groups were 60 and 72 months, respectively. Tumor cell proliferation was measured by immunohistochemical methods with monoclonal antibodies directed against the nuclear antigens ki-67 and repp86. RESULTS: The ki-67, repp86 labeling indices (percentage of antibody-stained tumor cell nuclei) were not statistically different between the cases and controls of lymph node-negative patients (ki-67 with P = 0.33; repp86 with P = 0.40). The odds ratio (the mean chance of ki-67 labeling index > 10%, repp86 labeling index >10%) in patients with recurrence was 4 (CI = 0.2 - 76.5) for ki-67 and 3.6 (CI = 0.4 - 32.5) for repp86. Both indices were statistically different in lymph node-positive cases and controls (P < 0.0001). The odds ratio in patients with recurrence was 87 (CI = 4 - 18.71) for ki-67 and 71.5 (CI = 5.7 - 899.2) for repp86. CONCLUSION: The present study confirms the importance of cell proliferation as a determinant of biologic behavior of breast cancer. Measurement of ki-67 and repp86 labeling indices may be very helpful for physicians to detect high-risk patients and to adopt appropriate procedure such as adjuvant therapy.