Evaluation of Oxidative Stress and Endothelial Dysfunction in COVID-19 Patients.

Background and Objectives: Heat shock proteins (HSPs) are stress proteins. The endogenous nitric oxide (NO) synthase inhibitor asymmetric dimethyl arginine (ADMA) is a mediator of endothelial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes endothelial dysfunction and coagulopathy through severe inflammation and oxidative stress. Using these markers, we analyzed the prognostic value of serum ADMA and HSP-90 levels for early prediction of severe coronavirus disease (COVID-19) patients. Materials and Methods: A total of 76 COVID-19 patients and 35 healthy control subjects were included in this case-control study. COVID-19 patients were divided into two groups: mild and severe. Results: Serum ADMA and HSP-90 levels were significantly higher in the COVID-19 patients compared to the control subjects (p < 0.001). Additionally, serum ADMA and HSP-90 levels were determined to be higher in a statistically significant way in severe COVID-19 compared to mild COVID-19 (p < 0.001). Univariable logistic regression analysis revealed that ADMA and HSP-90, respectively, were independent predictors of severe disease in COVID-19 patients (ADMA (OR = 1.099, 95% CI = 1.048-1.152, p < 0.001) and HSP-90 (OR = 5.296, 95% CI = 1.719-16.316, p = 0.004)). When the cut-off value for ADMA was determined as 208.94 for the prediction of the severity of COVID-19 patients, the sensitivity was 72.9% and the specificity was 100% (AUC = 0.938, 95%CI = 0.858-0.981, p < 0.001). When the cut-off value for HSP-90 was determined as 12.68 for the prediction of the severity of COVID-19 patients, the sensitivity was 88.1% and the specificity was 100% (AUC = 0.975, 95% CI= 0.910-0.997, p < 0.001). Conclusions: Increased levels of Heat shock proteins-90 (HSP-90) and ADMA were positively correlated with increased endothelial damage in COVID-19 patients, suggesting that treatments focused on preventing and improving endothelial dysfunction could significantly improve the outcomes and reduce the mortality rate of COVID-19. ADMA and HSP-90 might be simple, useful, and prognostic biomarkers that can be utilized to predict patients who are at high risk of severe disease due to COVID-19.

Diagnostic Value of Galectin-3 in Exacerbations of Chronic Obstructive Pulmonary Disease.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by acute exacerbations. Systemic inflammation and oxidative stress play an important role in the pathogenesis of COPD. Exacerbations in COPD reduce the quality of life and are associated with rapid disease progression. Galectin-3 is a beta-galactoside-binding lectin of approximately 30 kDa with pro-inflammatory and pro-fibrotic properties. This study aims to analyze the efficacy of serum galectin-3 in predicting exacerbations in COPD patients. Materials and Methods: Baseline demographic and clinical characteristics of all patients were recorded and blood samples were collected. A total of 58 consecutive COPD patients, including 28 patients (19 male and 9 female) with stable COPD and 30 patients (23 male and 7 female) with acute exacerbation of COPD (AECOPD), were included in the study. Results: Serum galectin-3 levels were significantly higher in the AECOPD group compared to the stable COPD group. A logistic regression analysis revealed that increased galectin-3 levels and disease duration were independent predictors of COPD exacerbation (OR = 5.322, 95% CI: 1.178-24.052, p = 0.03; and OR = 1.297, 95% CI: 1.028-1.635, p = 0.028; respectively). Conclusions: The results of our study demonstrated that Galectin-3 was a strong and independent predictor of exacerbations in COPD patients.

The effects of disease severity and comorbidity on oxidative stress biomarkers in obstructive sleep apnea.

PURPOSE: Ischemia-modified albumin (IMA), total oxidant status (TOS), and total antioxidant status (TAS) are biomarkers used to evaluate oxidative stress status in various diseases including obstructive sleep apnea (OSA). In this study, we investigated the effects of disease severity and comorbidity on IMA, TOS and TAS levels in OSA. METHODS: Patients with severe OSA (no-comorbidity, one comorbidity, and multiple comorbidities) and mild-moderate OSA (no-comorbidity, one and multiple comorbidities), and healthy controls were included in the study. Polysomnography was applied to all cases and blood samples were taken from each participant at the same time of day. ELISA was used to measure IMA levels in serum samples and colorimetric commercial kits were used to perform TOS and TAS analyses. In addition, routine biochemical analyses were performed on all serum samples. RESULTS: A total of 74 patients and 14 healthy controls were enrolled. There was no statistically significant difference between the disease groups according to gender, smoking status, age, body mass index (BMI), HDL, T3, T4, TSH, and B12 (p > 0.05). As the severity of OSA and comorbidities increased, IMA, TOS, apnea-hypopnea index (AHI), desaturation index (T90), cholesterol, LDL, triglyceride, AST, and CRP values increased significantly (p < 0.05). On the other hand, TAS, minimum desaturation, and mean desaturation values decreased significantly (p < 0.05). CONCLUSIONS: We concluded that IMA, TOS, and TAS levels may indicate OSA-related oxidative stress, but as the severity of OSA increases and with the presence of comorbidity, IMA and TOS levels may increase and TAS levels decrease. These findings suggest that disease severity and presence/absence of comorbidity should be considered in studies on OSA.

Efficacy of serum apelin and galectin-3 as potential predictors of mortality in severe COVID-19 patients.

Apelin is a cardioprotective biomarker while galectin-3 is a pro-inflammatory and profibrotic biomarker. Endothelial dysfunction, hyperinflammation, and pulmonary fibrosis are key mechanisms that contribute to the development of adverse outcomes in Coronavirus disease 2019 (COVID-19) infection. This study aims to analyze the prognostic value of serum apelin and galectin-3 levels to early predict patients at high risk of mortality in patients hospitalized for severe COVID-19 pneumonia. The study included 78 severe COVID-19 patients and 40 healthy controls. The COVID-19 patients were divided into two groups, survivors and nonsurvivors, according to their in-hospital mortality status. Basic demographic and clinical data of all patients were collected, and blood samples were taken before treatment. In our study, serum apelin levels were determined to be significantly lower in both nonsurvivor and survivor COVID-19 patients compared to the control subjects (for both groups, p < 0.001). However, serum apelin levels were similar in survivor and nonsurvivor COVID-19 patients (p > 0.05). Serum galectin-3 levels were determined to be higher in a statistically significant way in nonsurvivors compared to survivors and controls (for both groups; p < 0.001). Additionally, serum galectin-3 levels were significantly higher in the survivor patients compared to the control subjects (p < 0.001). Positive correlations were observed between galectin-3 and age, ferritin, CK-MB and NT-proBNP variables (r = 0.32, p = 0.004; r = 0.24, p = 0.04; r = 0.24, p = 0.03; and r = 0.33, p = 0.003, respectively) while a negative correlation was observed between galectin-3 and albumin (r = -0.31, p = 0.006). Multiple logistic regression analysis revealed that galectin-3 was an independent predictor of mortality in COVID-19 patients (odds ratio [OR] = 2.272, 95% confidence interval [CI] = 1.106-4.667; p = 0.025). When the threshold value for galectin-3 was regarded as 2.8 ng/ml, it was discovered to predict mortality with 80% sensitivity and 57% specificity (area under the curve = 0.738, 95% CI = 0.611-0.866, p = 0.002). Galectin-3 might be a simple, useful, and prognostic biomarker that can be utilized to predict patients who are at high risk of mortality in severe COVID-19 patients.

Carbonic Anhydrase IX as a Marker of Disease Severity in Obstructive Sleep Apnea.

Background and Objectives: Carbonic anhydrase (CA) enzymes are a family of metalloenzymes that contain a zinc ion in their active sites. CA enzymes have been implied in important situations such as CO2 transport, pH regulation, and oncogenesis. CA-IX is a transmembrane glycoprotein and stimulates the expression of hypoxia-inducible factor-1 (HIF-1) CA-IX. This study aimed to determine serum CA-IX levels in OSA patients in whom intermittent hypoxia is important and to investigate the relationship between serum CA-IX levels and disease severity. Materials and Methods: The study included 88 people who applied to Malatya Turgut Özal University Training and Research Hospital Sleep Disorders Center without a history of respiratory disease, malignancy, and smoking. Patients were divided into three groups: control (AHI < 5, n = 31), mild−moderate OSA (AHI = 5−30, n = 27) and severe OSA (AHI > 30, n = 30). The analysis of the data included in the research was carried out with the SPSS (IBM Statistics 25, NY, USA). The Shapiro−Wilk Test was used to check whether the data included in the study had a normal distribution. Comparisons were made with ANOVA in multivariate groups and the t-test in bivariate groups. ANCOVA was applied to determine the effect of the CA-IX parameter for OSA by controlling the effect of independent variables. The differentiation in CA-IX and OSA groups was analyzed regardless of BMI, age, gender, and laboratory variables. ROC analysis was applied to determine the parameter cut-off point. Sensitivity, specificity, and cut-off were calculated, and the area under the curve (AUC) value was calculated. Results: Serum CA-IX levels were 126.3 ± 24.5 pg/mL in the control group, 184.6 ± 59.1 pg/mL in the mild−moderate OSA group, and 332.0 ± 39.7 pg/mL in the severe OSA group. Serum CA-IX levels were found to be higher in the severe OSA group compared to the mild−moderate OSA group and control group and higher in the mild−moderate OSA group compared to the control group (p < 0.001, p < 0.001, p < 0.001, respectively). In addition, a negative correlation between CA-IX and minimum SaO2 and mean SaO2 (r = −0.371, p = 0.004; r = −0.319, p = 0.017, respectively). A positive correlation between CA-IX and desaturation index (CT90) was found (r = 0.369, p = 0.005). A positive correlation was found between CA-IX and CRP (r = 0.340, p = 0.010). When evaluated by ROC curve analysis, the area under the curve (AUC) value was determined as 0.940 (95% CI 0.322−0.557; p < 0.001). When the cut-off value for CA-IX was taken as 254.5 pg/mL, it was found to have 96.7% sensitivity and 94.8% specificity in demonstrating severe OSA. Conclusions: Our study found that serum CA-IX value was higher in OSA patients than in control patients, and this elevation was associated with hypoxemia and inflammation. CA-IX value can be a fast, precise, and useful biomarker to predict OSA.

Using artificial intelligence to improve the diagnostic efficiency of pulmonologists in differentiating COVID-19 pneumonia from community-acquired pneumonia.

Coronavirus disease 2019 (COVID-19) has quickly turned into a global health problem. Computed tomography (CT) findings of COVID-19 pneumonia and community-acquired pneumonia (CAP) may be similar. Artificial intelligence (AI) is a popular topic among medical imaging techniques and has caused significant developments in diagnostic techniques. This retrospective study aims to analyze the contribution of AI to the diagnostic performance of pulmonologists in distinguishing COVID-19 pneumonia from CAP using CT scans. A deep learning-based AI model was created to be utilized in the detection of COVID-19, which extracted visual data from volumetric CT scans. The final data set covered a total of 2496 scans (887 patients), which included 1428 (57.2%) from the COVID-19 group and 1068 (42.8%) from the CAP group. CT slices were classified into training, validation, and test datasets in an 8:1:1. The independent test data set was analyzed by comparing the performance of four pulmonologists in differentiating COVID-19 pneumonia both with and without the help of the AI. The accuracy, sensitivity, and specificity values of the proposed AI model for determining COVID-19 in the independent test data set were 93.2%, 85.8%, and 99.3%, respectively, with the area under the receiver operating characteristic curve of 0.984. With the assistance of the AI, the pulmonologists accomplished a higher mean accuracy (88.9% vs. 79.9%, p < 0.001), sensitivity (79.1% vs. 70%, p < 0.001), and specificity (96.5% vs. 87.5%, p < 0.001). AI support significantly increases the diagnostic efficiency of pulmonologists in the diagnosis of COVID-19 via CT. Studies in the future should focus on real-time applications of AI to fight the COVID-19 infection.

Genotoxicity evaluation of a new phthalazine substituted ß-lactam derivative in human lymphocytes.

The aim of present study, to evaluate the genotoxic potential of 1-(4-(3,3-dimethyl-1,6-dioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2b] phthalazine-13yl)phenyl)-2-phenylazetidine-3-yl-acetate which was synthesised assuming that it may be a pharmaceutical raw material and found to inhibit human carbonic anhydrase I, II isozymes. To determine the genotoxic potential of this phthalazine substituted ß-lactam compound, chromosomal aberration (CA) and micronucleus (MN) tests were implemented in human peripheral blood lymphocytes. In these tests, lymphocyte cultures were treated with four concentrations (30, 15, 7.5, 3.75 µg/mL) of test compound and simultaneously with negative control (sterile distilled water), solvent control (DMSO) positive control (MMC). According to our results, CA frequencies were significantly increased in two high applied concentrations (30, 15 µg/mL) compared with negative and solvent control. MN frequencies were significantly increased in three applied concentrations (30, 15, 7.5 µg/mL) except lowest concentration (3.75 µg/mL) compared with solvent control. Mitotic indices were also affected by treatment with test compound. The obtained results provide evidence to demonstrate that new phthalazine substituted ß-lactam derivative can exert genotoxic and cytotoxic effects in peripheral human lymphocytes especially at high concentrations.

EFFECTS OF HYDROXYCHLOROQUINE PLUS FAVIPIRAVIR TREATMENT ON THE CLINICAL COURSE AND BIOMARKERS IN HOSPITALIZED COVID-19 PATIENTS WITH PNEUMONIA.

Background: The novel coronavirus disease 2019 (COVID-19) has a broad spectrum of clinical manifestations, the most common serious clinical manifestation of the coronavirus infection being pneumonia. Unfortunately, the optimal treatment approach is still uncertain. However, many studies have been conducted on the effectiveness of several medications in the treatment of COVID-19 infection. The aim of this study was to evaluate the effectiveness of the hydroxychloroquine (HCQ) + favipiravir (FAV) treatment regimen and HCQ alone by comparing the patient's clinical response and laboratory results on the fifth day of treatment in patients hospitalized due to COVID-19 infection. Patients and methods: This retrospective cohort study was conducted in Malatya Training and Research Hospital between March 2020 and July 2020. The study included 69 patients with confirmed COVID-19 with pneumonia. The patients were divided into 2 groups, those receiving HCQ alone and those receiving the HCQ + FAV combination. Results: A total of 69 patients were included in the study, and the mean age was 60.09±15.56 years. A statistically significant decrease was observed in C-reactive protein (CRP) levels, at the end of the fifth day, in patients who received HCQ + FAV treatment (p=0.002), whereas there was no decrease in CRP levels in patients who received HCQ treatment alone. In addition, an increase in lymphocyte count and a better fever response was observed at the end of the fifth day in patients who received HCQ + FAV (p=0.008). However, there was no statistical difference between both treatment regimens in terms of hospital stay and treatment results (p=0.008, p=0.744, p=0.517). Conclusion: Although the combination of HCQ + FAV treatment was observed to be effective on CRP levels and fever response in patients with COVID-19 pneumonia, there was no difference in terms of hospital stay and discharge.

MTU-COVNet: A hybrid methodology for diagnosing the COVID-19 pneumonia with optimized features from multi-net.

PURPOSE: The aim of this study was to establish and evaluate a fully automatic deep learning system for the diagnosis of COVID-19 using thoracic computed tomography (CT). MATERIALS AND METHODS: In this retrospective study, a novel hybrid model (MTU-COVNet) was developed to extract visual features from volumetric thoracic CT scans for the detection of COVID-19. The collected dataset consisted of 3210 CT scans from 953 patients. Of the total 3210 scans in the final dataset, 1327 (41%) were obtained from the COVID-19 group, 929 (29%) from the CAP group, and 954 (30%) from the Normal CT group. Diagnostic performance was assessed with the area under the receiver operating characteristic (ROC) curve, sensitivity, and specificity. RESULTS: The proposed approach with the optimized features from concatenated layers reached an overall accuracy of 97.7% for the CT-MTU dataset. The rest of the total performance metrics, such as; specificity, sensitivity, precision, F1 score, and Matthew Correlation Coefficient were 98.8%, 97.6%, 97.8%, 97.7%, and 96.5%, respectively. This model showed high diagnostic performance in detecting COVID-19 pneumonia (specificity: 98.0% and sensitivity: 98.2%) and CAP (specificity: 99.1% and sensitivity: 97.1%). The areas under the ROC curves for COVID-19 and CAP were 0.997 and 0.996, respectively. CONCLUSION: A deep learning-based AI system built on the CT imaging can detect COVID-19 pneumonia with high diagnostic efficiency and distinguish it from CAP and normal CT. AI applications can have beneficial effects in the fight against COVID-19.

Evaluation of erectile dysfunction in patients with asthma.

OBJECTIVES: The aim of the current study was to investigate Erectile dysfunction (ED) in asthma patients without comorbidity and the relationship between the level of asthma control and ED. METHODS: Forty male patients aged 24-50 years with controlled-to-uncontrolled asthma and 20 healthy volunteers were included in this study. The International Index of Erectile Function Questionnaire (IIEF) for ED was used. RESULTS: Evaluation of the IIEF scores for ED showed that 23 (57.5%) of the asthma patients and 4 (20.0%) of the controls had various degrees of ED, and the difference was statistically significant. In total, 25% of asthma patients had mild ED, 22.5% moderate ED, and 10% severe ED. Severe, moderate and mild ED was more frequent in the asthma group. Of the 23 patients who had various degrees of ED, 13 were in the uncontrolled asthma group. While all asthma patients with severe ED were in the uncontrolled asthma group, of the 9 asthma patients with moderate ED, 6 were in the uncontrolled asthma group, 2 were in the partially controlled asthma group and one was in the controlled asthma group. Additionally, of the 10 asthma patients with mild ED, 3 were in the uncontrolled asthma group, 2 were in the partially controlled asthma group and 5 were in the controlled asthma group. CONCLUSION: The current study showed that ED is frequent and more severe in asthma patients than controls with same age. A highly negative correlation was found between ED degree and asthma control severity.

Investigation of SARS-CoV-2 RNA in milk produced by women with COVID-19 and follow-up of their infants: A preliminary study.

OBJECTIVES: Studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily transmitted from person to person via airborne droplets. It is unclear whether it can be shed into human milk and transmitted to a child via breastfeeding. We investigated the presence of SARS-CoV-2 RNA in human milk samples of 15 mothers with coronavirus disease 19 (COVID-19) and in the throat swab samples of their infants. METHODS: This is a prospective observational study in which breast milk samples were collected from 15 mothers with COVID-19. The presence of SARS-CoV-2 RNA in the whole human milk samples of the patients was investigated using RT-qPCR. All of the infants underwent a clinical follow-up during their 14-day isolation and their throat swab samples were tested for SARS-CoV-2 RNA. RESULTS: Of 15 mothers with COVID-19, SARS-CoV-2 RNA was detected in milk samples from 4 mothers. The throat swab samples from these mothers' infants were found to be positive for SARS-CoV-2 RNA. Three of the four mothers were breastfeeding. In addition, during the 14-day isolation, all but three of the mothers breastfed their infants. Of the 12 breastfed infants, while the test for SARS-CoV-2 RNA in throat swab samples was negative in 6 of the infants, the other 6 infants, who had mild COVID-19 symptoms, tested positive for SARS-CoV-2 RNA. Clinical outcomes of all mothers and infants were uneventful. CONCLUSION: To our knowledge, this is the first case series with the largest number of cases with SARS-CoV-2 RNA positivity in human milk samples of mothers with COVID-19. However, we believe that the benefits of breastfeeding may outweigh the risk of SARS-CoV-2 infection in infants.

Peripheral Blood Smear Findings of COVID-19 Patients Provide Information about the Severity of the Disease and the Duration of Hospital Stay.

BACKGROUND: Data about the morphological changes in peripheral blood smears during COVID-19 infection and their clinical severity association are limited. We aimed to examine the characteristics of the cells detected in the pathological rate and/or appearance and whether these findings are related to the clinical course by evaluating the peripheral blood smear at the time of diagnosis in COVID-19 patients. METHODS: Clinical features, laboratory data, peripheral blood smear of fifty patients diagnosed with COVID-19 by PCR was evaluated at diagnosis. Peripheral smear samples of the patients were compared with the age and sex-matched 30 healthy controls. Pictures were taken from the patient's peripheral blood smear. Patients were divided into two groups. Mild and severe stage patient groups were compared in terms of laboratory data and peripheral smear findings. The relationship between the laboratory values of all patients and the duration of hospitalization was analyzed. RESULTS: The number of segmented neutrophils and eosinophils were low, pseudo-Pelger-Huet, pseudo-Pelger-Huet/mature lymphocyte ratio, atypical lymphocytes, monocytes with vacuoles, bands, and pyknotic neutrophils rates were higher in the peripheral blood smear of the patient group (p <0.05). Increased pseudo-Pelger-Huet anomaly, pseudo-Pelger Huet/mature lymphocyte ratio, a decreased number of mature lymphocytes, and eosinophils in peripheral blood smear were observed in the severe stage patients (p <0.05). A negative correlation was observed between hospitalization duration and mature lymphocyte and monocytes with vacuoles rates (p <0.05). CONCLUSION: A peripheral blood smear is an inexpensive, easily performed, and rapid test. Increased Pseudo-Pelger-Huet anomaly/mature lymphocyte rate suggests a severe stage disease, while high initial mature lymphocyte and monocytes with vacuoles rates at the time of diagnosis may be an indicator of shortened duration of hospitalization.

Synthesis of new series of thiazol-(2(3H)-ylideneamino)benzenesulfonamide derivatives as carbonic anhydrase inhibitors.

Human carbonic anhydrase I and II isoenzymes (hCA I and II) are important metabolic enzymes. In this study, a new series of thiazol-(2(3H)-ylideneamino)benzenesulfonamide derivatives were synthesized and also some inhibition parameters including IC50 (hydratese) and inhibition constant values (Ki , esterase) were determined. All studied compounds exhibited potent inhibition against these enzymes. They inhibited carbonic anhydrases (CAs) with the IC50 values of 113 to 395.8 nM (Ki = 77.38-319.59 nM) for hCA I and 91.9 to 516 nM (Ki = 62.79-425.89 nM) for hCA II. Among the compounds, 5c was found to be the most active one (Ki : 77.38 nM) for hCA I and 5g was found for hCA II with the value of 62.79 nM.

The effects of home oxygen therapy on energy metabolism in patients with COPD.

Background: COPD is preventable and treatable and is characterized by completely nonreversible airflow obstruction. In this study, we aimed to investigate the effect of long-term oxygen therapy on patients with stage 4 COPD who were followed up and treated at the polyclinic or clinic service. We evaluated the effects of oxygen therapy on energy metabolism and physical activity in patients with COPD. Methods: Nineteen patients with COPD (16 male/3 female), treated with oxygen therapy for the first time, were included in this study. Analysis of arterial blood gases and pulmonary function test was performed. Metabolic Holter device (SenseWear® Armband) was placed pre- and post-oxygen therapy on the patients' arm for at least 3 days. This device captures Holter data in a digitized electronic system, and the daily average value was calculated from the data. Results: Post-oxygen treatment showed a significant increase in energy expenditure by patients with COPD (pretreatment, 1,497±596 joule; posttreatment, 2,977±5,985 joule; P=0.044). Moreover, number of steps during walking (pretreatment, 2,056±256; posttreatment, 2,120±195; P=0.03), resting (pretreatment, 6.36±3.31 hours; posttreatment, 3.47±2.19 hours; P<0.03), and sleeping (pretreatment, 4.23±2.13 hours; posttreatment, 2.33±1.42 hours; P<0.00) showed significant differences. Increased daily energy expenditure in patients with respiratory failure was detected with long-term oxygen therapy. In addition, the immobility of patients decreased and duration of physical activity increased in patients with COPD. Conclusion: In this study, positive effects of long-term oxygen therapy have been demonstrated with respect to energy metabolism and physical activity of patients with COPD. Thus, we recommend that medication adherence and long-term oxygen therapy should begin early in patients with COPD.

SYNTHESIS AND EVALUATION OF NEW PHTHALAZINE SUBSTITUTED ß-LACTAM DERIVATIVES AS CARBONIC ANHYDRASE INHIBITORS.

A new series of phthalazine substituted ß-lactam derivatives were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase (hCA I and II) were evaluated. 2H-Indazolo[2,1-b]phthala- zine-trione derivative was prepared with 4-nitrobenzaldehyde, dimedone, and phthalhydrazide in the presence of TFA in DMF, and the nitro group was reduced to 13-(4-aminophenyl)-3,3-dimethyl-3,4-dihydro- 2H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione with SnCl2 · 2H2O. The reduced compound was re- acted with different aromatic aldehydes, and phthalazine substituted imines were synthesized. The imine compounds undergo (2+2) cycloaddition reactions with ketenes to produce 2H-indazolo[2,1-b]phthala-zine-trione substituted ß-lactam derivatives. The ß-lactam compounds were tested as inhibitors of the CA isoenzyme activity. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. 1-(4-(3,3-dimethyl- 1,6,1 1-trioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2-b]phthalazin-13- yl)phenyl)-2-oxo-4-p-tolylazetidin-3-yl acetate (IC50 = 6.97 µM for hCA I and 8.48 µM for hCA II) had the most inhibitory effect.

Pulmonary embolism as the initial presentation of testicular carcinoma.

Objective. The risk of pulmonary embolism is well recognized as showing an increase in oncological patients. We report a case presenting with pulmonary embolism initially, which was then diagnosed with testicular cancer. Clinical Presentation and Intervention. A 25-year-old man was admitted to the emergency department with a complaint of dyspnoea. Thoracic tomography, lung ventilation/perfusion scintigraphy, and an increased D-dimer level revealed pulmonary embolism. For the aetiology of pulmonary embolism, a left orchiectomy was performed and the patient was diagnosed with a germinal cell tumour of the testicle. Conclusion. In this paper, we present a patient for whom pulmonary embolism was the initial presentation, and a germinal cell tumour was diagnosed later during the search for the aetiology.