Impulse oscillometry assessment of respiratory function in pediatric patients with a history of COVID-19.

OBJECTIVE: While coronavirus disease 2019 (COVID-19) is generally considered to exhibit a less severe clinical course in children than in adults, studies have demonstrated that respiratory symptoms can endure for more than 3 months following infection in at least one-third of pediatric cases. The present study evaluates the respiratory functions of children aged 3-15 years within 3-6 months of their recovery from COVID-19 using impulse oscillometry (IOS) and compares them with the values of healthy children. METHODS: Included in this prospective cross-sectional study were 63 patients (patient group) aged 3-15 years who contracted COVID-19 between December 2021 and May 2022, as well as 57 healthy children as a control group, matched for age and sex. The demographic, clinical, and laboratory data of the patients were recorded, and respiratory function was assessed based on airway resistance (zR5, zR20, R5-20) and reactance (zX5, zX20, reactance area [AX], resonant frequency [Fres]) using an IOS device. RESULTS: There were no significant differences in the age, weight, height, and body weight z score values of the two groups (p > .05). While the zR5 and R5-20 levels of the patient group were higher (p = .008 and p < .001, respectively) than those of the controls, the zR20, AX, and Fres values did not differ significantly between the groups (p > .05). The parameters indicating the reactance, including zX5 and zX20, were significantly lower in the patient group than in the control group (p = .028 and p < .001, respectively). CONCLUSION: Total and peripheral airway resistances were found to be elevated in children who had recovered from COVID-19 in the preceding 3-6 months.

Effect of fullerenol C60 on lung and renal tissue in lower extremity ischemia­reperfusion injury in sevoflurane­treated rats.

The aim of the present study was to examine the effect of fullerenol C60 on lung and kidney tissue in sevoflurane­treated rats with lower extremity ischemia­reperfusion (IR) injury. A total of 30 Wistar albino rats weighing 225­275 g were used and were equally divided into five groups (n=6/group): i) Sham; ii) IR; iii) IR­fullerenol C60 (IR­FUL); iv) IR­sevoflurane; and v) IR­fullerenol C60­sevoflurane (IR­FUL­SEVO). Fullerenol C60 was administered intraperitoneally prior to lower extremity IR induction and sevoflurane was administered during the IR injury. Subsequently, lung and kidney histopathological examinations, and serum biochemical analyses were performed. Lung tissue showed markedly increased congestion and neutrophil infiltration in the IR group compared with in the sham group, and notable decreases in congestion and neutrophil infiltration were observed in the treatment groups compared with in the IR group. In the histopathological evaluation of the kidney samples, vacuolization, loss of brush border in tubular epithelial cells, tubular epithelial loss and varying degrees of tubular damage were observed in all groups that underwent IR. There was a significant increase in the mean renal tubule injury score in all IR groups compared with that in the sham group. In addition, the mean kidney injury score was significantly lower in the IR­FUL and IR­FUL­SEVO groups than that in the IR group. It was observed that the expression levels of tumor necrosis factor­α, interleukin 1ß and intercellular adhesion molecule 1 in the lung and kidney tissues were increased following IR, and were decreased in the groups treated with fullerenol C60 and sevoflurane. Notably, it was determined that the reduction in cytokine expression was greatest in the IR­FUL group. When the oxidant status parameters in the lungs and kidneys were examined, thiobarbituric acid reactive substances levels, and catalase and glutathione S­transferase enzyme activities were significantly different in the groups receiving sevoflurane or fullerenol C60 treatment compared with those in the IR group. The present study demonstrated the protective effects of fullerenol C60 on the lung and kidney tissues of rats under sevoflurane anesthesia after establishment of lower extremity IR. The results of the present study showed that fullerenol C60 can reduce oxidative and histopathological damage in the lungs and kidneys following IR of the lower extremities.

Protective effects of hydrogen rich saline solution in rats with experimental myocardial ischemia reperfusion injury.

Aim: The aim of our study is to show whether the administration of hydrogen-rich saline solution (HRSS) intraperitoneally before left main coronary artery (LAD) ischemia protects the myocardium against ischemia-reperfusion (IR) injury. Materials and methods: After ethics committee approval, 24 Wistar Albino rats were divided into 4 groups, 6 rats in each group. For experimental IR, myocardial ischemia was performed by LAD ligation. Left thoracotomy was performed without ischemia in the Control group (Group C). Left thoracotomy was performed without myocardial ischemia to the rats in the HRSS group, and HRSS was given intraperitoneally (ip) at a rate of 10 ml/kg throughout the procedure. In the MIR-HRSS group, a single dose of 10 ml/kg HRSS was administered 5 min before reperfusion. Histopathological and biochemical parameters were compared in myocardial tissue samples taken at the end of the reperfusion period. Results: When the groups were compared among themselves in terms of TOS and TAS levels, there was a significant difference between the groups (p = 0.006, p = 0.002). The severity of cardiomyocyte degeneration was significantly greater in MIR group than that in the control and HRSS groups (p = 0.002 and p = 0.001, respectively), as well as severity score of cardiomyocyte degeneration was higher in MIR-HRSS group compared with HRSS group (p = 0.035). Conclusion: Our study shows that HRSS is protective in IR injury, with the application of HRSS 5 min before reperfusion, interstitial edema severity, subendocardial haemorrhage are reduced, and oxidant status parameters are increased, while antioxidant status parameters are decreased. We believe that when it is supported by other studies, the protective effects of HRSS on IR damage will be shown in detail and its indications will be expanded.

Beyond the Skin: Reduced Lung Function Associated With Atopic Dermatitis in Infants.

BACKGROUND: Very few studies have examined lung function parameters using tidal breath analysis (TBA) in atopic dermatitis (AD) with its high potential for progression to asthma. OBJECTIVE: To measure lung functions using TBA in infants with AD and in healthy controls (HCs), and to investigate the effects of disease severity, food sensitivity, and history of recurrent wheezing on TBA parameters in infants with AD. METHODS: Two hundred thirty infants were included in this prospective cross-sectional study, including an AD group (n = 150) and an HC group (n = 80). Food sensitivity was assessed by means of food-specific IgE or the skin prick test. The severity of the disease was evaluated using the SCORing Atopic Dermatitis. Lung function was assessed using TBA. RESULTS: The following TBA parameters were significantly lower in the AD group than in the HC group (P < .05): time to peak tidal expiratory flow, exhaled volume to peak tidal expiratory flow, ratio of time to peak tidal expiratory flow to expiratory time, ratio of exhaled volume to peak tidal expiratory flow to total expiratory volume, expiratory flow when 25% of tidal volume remains in the lungs, respiratory rate, and minute ventilation. No difference was observed in the AD group when TBA parameters were compared according to disease severity, food sensitivity, and history of recurrent wheezing (P > .05). The receiver-operating characteristic curve demonstrated by the ratio of time to peak tidal expiratory flow to expiratory time yielded an area under the curve of 0.826 (CI, 0.772-0.879), with a cutoff value of 31.65 or higher in differentiating AD, with a sensitivity of 78.7% and a specificity of 77.5%. CONCLUSIONS: TBA curves can be a useful tool for demonstrating expiratory airway obstruction in AD and for providing objective information for the clinician. Bronchial obstruction was detected in young children with AD irrespective of the severity of the disease, food sensitivity, and history of recurrent wheezing.

Does maternal fermented dairy products consumption protect against cow's milk protein allergy in toddlers?

BACKGROUND: Cow's milk protein allergy (CMPA) is the most common immunoglobulin E-mediated food allergy in childhood. OBJECTIVE: To investigate the potential impact on the disease of the frequency, amount, and diversity of maternal consumption of fermented dairy products (FDP) during pregnancy and lactation in children with immunoglobulin E-mediated CMPA. METHODS: One hundred sixty toddlers (80 with physician-diagnosed CMPA and 80 healthy controls) and their mothers participated in this case-control study. The data were collected using a structured questionnaire and were compared between the 2 groups. RESULTS: The most commonly consumed FDP were cheese, yogurt, and tarhana. The amounts of maternal yogurt, tarhana, and kefir consumed during pregnancy (P < .001, P < .001, and P = .04, respectively) in addition to yogurt and tarhana consumption during lactation (P < .001 and P = .001, respectively) were lower in toddlers with CMPA. The frequency of maternal consumption of yogurt, cheese, and tarhana during lactation (P = .001, P = .003, and P = .02, respectively) and the diversity of FDP were also lower in toddlers with CMPA (P = .001). At multivariate logistic regression analysis, maternal weight gain during pregnancy (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.04-1.18; P = .001), maternal age (OR, 1.20; 95% CI, 1.09-1.31; P < .001), and gestational age at birth (OR, 1.23; 95% CI, 1.03-1.48; P = .02) increased the odds of the baby having CMPA. The diversity of FDP consumed during lactation was protective against CMPA (OR, 0.439; 95% CI, 0.272-0.711; P = .001). CONCLUSION: Weekly maternal consumption of FDP was low during pregnancy and lactation in toddlers with CMPA. Although the diversity of FDP consumed during lactation may reduce the risk of CMPA, this effect was not observed during pregnancy.

The impact of adenoid hypertrophy on pulmonary functions measured using impulse oscillometry in preschool-age children.

PURPOSE: To assess pulmonary impedance [resistance (zR5, zR20, R5-20, Fres, and AX) and reactance (zX5 and zX20)] using impulse oscillometry (IOS) in children with adenoid hypertrophy (AH) and its association with the degree of AH, and to evaluate subsequent changes in pulmonary function 3 months after adenoidectomy. METHODS: This prospective cross-sectional study was conducted with 170 preschool-age children [110 with AH and 60 sex- and age-matched healthy controls (HCs)]. Pulmonary function was analyzed using IOS at baseline (1st visit) in all participants and 3 months after adenoidectomy (2nd visit) in patients who underwent the operation. RESULTS: The IOS parameters of zR5, zR20, R5-20, Fres, and AX were higher, but zX20 was lower, in children with AH compared to the HCs (p < 0.05 for all). The parameters of zR5, Fres, and AX were higher in children with grade IV AH than in those with grade I (p < 0.001). zR5, zR20, R5-20, Fres, and AX decreased, but zX20 increased, after adenoidectomy (2nd visit) compared to baseline (1st visit) (p < 0.05). Post-adenoidectomy (2nd visit) zR5, AX, Fres values were higher in children with AH compared to baseline values in the HCs (1st visit) (p < 0.05). The area under the ROC curve (AUC) value for estimating adenoidectomy was 0.741 for zX20 (CI 0.648-0.834, p < 0.001) with a cut-off value of  ≤ -3.21, sensitivity of 68.8%, and specificity of 70%. CONCLUSION: This study shows that IOS is a useful method for demonstrating subclinical bronchial obstruction in preschool-age children with AH with greater pulmonary impedance (resistance and reactance). Pulmonary impedance decreased 3 months after adenoidectomy, but remained higher than in the HCs. The IOS parameter of X20 may be predictive of adenoidectomy. This study evaluated the pulmonary functions of children with adenoid hypertrophy (AH) using impulse oscillometry (IOS) and the association with the scale of AH. Pulmonary functions were analyzed using IOS. The main IOS parameters include resistances (zR5 and zR20), reactance (zX5 and zX20), R5-20 (resistance at 5 Hz minus resistance at 20 Hz), resonant frequency (Fres), and AX. Fres is the point at which reactance is zero and is measured in Hz (1/s). The Reactance Area (AX - "Goldman Triangle") represents the integrated low-frequency respiratory reactance magnitude between 5 Hz and Fres. Faster frequencies of R (~ 20 Hz) reflect larger airways, regarded as resistance around the central airways. Lower frequencies of R (~ 5 Hz) providing information around the entire (small and large) airways. Peripheral (small) airway resistance is defined by R5-20. IOS parameters of zR5, zX20, Fres, and AX differed among AH grades I-IV and compared to the HCs (p < 0.001 for all).

Effects of Dexmedetomidine Administered Through Different Routes on Kidney Tissue in Rats with Spinal Cord Ischaemia-Reperfusion Injury.

Background: Ischaemia-reperfusion (IR) injury, which can be encountered during surgical procedures involving the abdominal aorta, is a complex process that affects distant organs, such as the heart, liver, kidney, and lungs, as well as the lower extremities. In this study, we aimed to contribute to the limited literature by investigating the protective effect of dexmedetomidine, which was administered through different routes, on kidney tissue in rats with spinal cord IR injury. Methods: A total of 30 rats were randomly divided into five groups: control (C group), IR (IR group), IR-intraperitoneal dexmedetomidine (IRIPD group), IR-intrathecal dexmedetomidine (IRITD group), and IR-intravenous dexmedetomidine (IRIVD group). The spinal cord IR model was established. Dexmedetomidine was administered at doses of 100 µg/kg intraperitoneally, 3 µg/kg intrathecally, and 9 µg/kg intravenously. Histopathologic parameters in kidney tissue samples taken at the end of the reperfusion period and biochemical parameters in serum were evaluated. Results: When examined histopathologically, tubular dilatation was found to be significantly reduced in the IRIVD, IRITD, and IRIPD groups compared with the IR group (p = 0.012, all). Vascular vacuolization and hypertrophy were significantly decreased in the IRIVD, IRITD, and IRIPD groups compared with the IR group (p = 0.006, all). Tubular cell degeneration and necrosis were significantly reduced in the IRIVD, IRITD, and IRIPD groups compared with the IR group (p = 0.008, p = 0.08, and p = 0.030, respectively). Lymphocyte infiltration was significantly decreased in the IRIVD and IRITD groups compared with the IR group (p = 0.006 and p = 0.06, respectively). Conclusion: It was observed that dexmedetomidine administered by different routes improved the damage caused by IR in kidney histopathology. We think that the renoprotective effects of dexmedetomidine administered intravenously and intrathecally before IR in rats are greater.

Spectroscopic and molecular modeling methods to investigate the interaction between psycho-stimulant modafinil and calf thymus DNA using ethidium bromide as a fluorescence probe.

Interaction type of modafinil with calf thymus DNA (ct-DNA) was examined systematically using ethidium bromide (EB) as a fluorescence probe by fluorescence spectroscopy, UV-Vis spectroscopy, viscosity and molecular docking method. The fluorescence quenching mechanism of ct-DNA-EB by modafinil can be combination of static and dynamic quenching. Results of UV-Vis absorption, competitive binding with Hoechst 33258, ionic strength effect studies, viscosity measurements were confirmed that the interaction type of modafinil with ct-DNA was intercalation. According to docking studies R-modafinil showed better interaction with ct-DNA which is consistent with known pharmacological properties of modafinil. The calculated thermodynamic parameters, enthalpy and entropy change, suggested that the driven forces are hydrogen bonding or van der Walls forces. Results of the docking studies were compatible with the experimental results and confirmed the hydrogen bond formation between modafinil and ct-DNA.

Molecular docking and inhibition profiles of some antibiotics on lactoperoxidase enzyme purified from bovine milk.

Antibiotics are generally used for human and veterinary applications to preserve and to control microbial diseases. Milk has a biologically significant enzyme known as lactoperoxidase (LPO) that is a member of peroxidase family. In metabolism, LPO has ability to catalyze the transformation of thiocyanate (SCN-) to hypothiocyanite (OSCN-) that is an antibacterial agent and the reaction occurs with hydrogen peroxide. In this work, LPO inhibition effects of some antibiotics including cefazolin, oxytetracycline, flunixin meglumine, cefuroxime, tylosin, vancomycin, chloramphenicol and lincomycin were tested. Among the antibiotics cefazolin was indicated the strongest inhibitory efficacy. The half maximal inhibitory concentration (IC50) and the inhibition constant (Ki) values of cefazolin were found as 8.19 and 34.66 µM, respectively. It was shown competitive inhibition. 5-Methyl-1,3,4-thiadiazol-2-yl moiety activity plays a key role in the inhibition mechanism of cefazolin.Communicated by Ramaswamy H. Sarma.

Some sulfonamides as aldose reductase inhibitors: therapeutic approach in diabetes.

In this study, aldose reductase (AR) was purified from sheep kidney using chromatographic methods and examined the interactions between some sulfonamides and the enzyme. According to results, sulfonamides display effective inhibitor features for sheep kidney AR with IC50 values in the range of 37.27-87.65 µM and Kis in the range of 25.72 ± 6.45 to 73.56 ± 17.49 µM. The sulfonamides displayed different inhibition mechanisms. It was found that studied all compounds displayed non-competitive inhibition type except for 5-chlorothiophene-2-sulfonamide (1). It showed competitive inhibition. Among these compounds, 2,5-dichlorothiophene-3-sulfonamide compound (2) was showed the most potent AR inhibitor (Ki: 25.72 ± 6.45). These compounds may be useful in the treatment of diabetic complications.

Inhibition effects of selected thiophene-2-sulfonamides on lactoperoxidase.

Lactoperoxidase (LPO, E.C.1.11.1.7) is a natural antibacterial agent which is secreted from salivary, mammary, and other mucosal glands. It is one of the crucial enzymes in biological systems, so protection of LPO activity is extremely important for the immune system. Within the scope of this study; in vitro effects of some thiophene-2-sulfonamide derivatives (1a-7a) on bovine milk LPO enzymatic activity were investigated. LPO was purified from the Sepharose-4B-L-tyrosine-5-amino-2-methylbenzenesulfonamide column prepared using affinity chromatography technique with a yield of 169.66 EU/mg specific activity in 452.44 times. As a result, 5-(2-thienylthio) thiophene-2-sulfonamide demonstrated the strongest inhibition impact among these compounds. This molecule has shown a competitive inhibition and it was determined that the IC50 value was 3.4 nM and the Ki value was 2 ± 0.6 nM.

Evaluation of some thiophene-based sulfonamides as potent inhibitors of carbonic anhydrase I and II isoenzymes isolated from human erythrocytes by kinetic and molecular modelling studies.

BACKGROUND: Thiophene(s) are an important group in therapeutic applications, and sulfonamides are the most important class of carbonic anhydrase (CA) inhibitors. In this study, inhibition effects of some thiophene-based sulfonamides on human erythrocytes carbonic anhydrase I and II isoenzymes (hCA-I and hCA-II) were investigated. Thiophene-based sulfonamides used in this study showed potent inhibition effect on both isoenzymes at very small concentrations. MATERIALS AND METHODS: We report on the purification of the carbonic anhydrase I and II isoenzymes (hCA-I and hCA-II) using affinity chromatography method. The inhibition effect of the thiophene-based sulfonamides was determined by IC50 and Ki parameters. A molecular docking study was performed for each molecule. RESULTS: Thiophene-based sulfonamides showed IC50 values of in the range of 69 nM to 70 µM against hCA-I, 23.4 nM to 1.405 µM against hCA-II. Ki values were in the range of 66.49 ± 17.15 nM to 234.99 ± 15.44 µM against hCA-I, 74.88 ± 20.65 nM to 38.04 ± 12.97 µM against hCA-II. Thiophene-based sulfonamides studied in this research showed noncompetitive inhibitory properties on both isoenzymes. To elucidate the mechanism of inhibition, a molecular docking study was performed for molecules 1 and 4 exhibiting a strong inhibitory effect on hCA-I and hCA-II. The compounds inhibit the enzymes by interacting out of catalytic active site. The sulfonamide and thiophene moiety played a significant role in the inhibition of the enzymes. CONCLUSION: We hope that this study will contribute to the design of novel thiophene-based sulfonamide derived therapeutic agents that may be carbonic anhydrase inhibitors in inhibitor design studies.

Lactoperoxidase, an antimicrobial enzyme, is inhibited by some indazoles.

Lactoperoxidase (LPO) has bactericidal and bacteriostatic activity on various microorganisms and it creates a natural antimicrobial defense system. So, LPO is one of the essential enzyme in biological systems and the protection of the LPO activity is extremely important for the immune system. Because of these features, the protection of the activity of the LPO has vital importance for the health of the organisms. Also, LPO is used in various sectors from cosmetics industry to agriculture industry due to its broad antimicrobial properties. Therefore, the identification of inhibitors and activators of the LPO is becoming increasingly important. In present study we aimed to investigate the inhibitory effects of some indazoles [1H-indazole (1a), 4-Bromo-1H-indazole (2a), 6-Bromo-1H-indazole (3a), 7-Bromo-1H-indazole (4a), 4-chloro-1H-indazole (5a), 6-chloro-1H-indazole (6a), 7-chloro-1H-indazole (7a), 4-fluoro-1H-indazole (8a), 6-fluoro-1H-indazole (9a), 7-fluoro-1H-indazole (10a)] on bovine milk LPO. Indazole derivatives are heterocyclic organic molecules with a wide range of biological activity. For this aim, bovine milk LPO was purified using Sepharose-4B-l-tyrosine-5-amino-2-methyl benzenesulfonamide affinity chromatography method. Then, the potential inhibitory effects of indazoles on LPO activity were investigated. Ki values were calculated for each indazole molecule. Ki values were ranging from 4.10 to 252.78 µM for 1a to10a. All of the indazole molecules we studied showed strong inhibitory effect on LPO activity. Also we determined inhibition types of the indazoles to clarify the mechanisms of inhibition.

In vitro effects of standard antioxidants on lactoperoxidase enzyme-A molecular docking approach.

Lactoperoxidase (LPO), an antioxidant enzyme, is a natural antimicrobial system that eliminates the harmful effects of microorganisms in milk. It has a wide range of applications and is also preferred in cosmetic and clinical applications, as well as used in foods. The use of antioxidants is well recognized in the food and feed industries to improve the shelf life of products. This study aimed to determine the in vitro inhibition effects of Trolox, α-tocopherol, butylated hydroxyanisole, butylated hydroxytoluene, and propyl gallate, which are commonly used as antioxidants in food and pharmaceutical products. For this purpose, LPO was first purified in a single step using sepharose-4B-l-tyrosine-sulfanilamide affinity gel chromatography. Also, some inhibition parameters, including half-maximal inhibitory concentration (IC50 ), Ki values, and inhibition types, were calculated for each antioxidant molecule. The IC50 values of these molecules, which exhibited competitive inhibition, varied between 377.7 and 3397.8 nM. Molecular docking studies were also performed for all compounds. According to the binding scores, α-tocopherol was shown to exhibit the most effective inhibitor property (IC50 : 377.7 nM and Ki : 635.8 ± 16.8 nM) among the standard antioxidants used in this study. Inhibiting the LPO activity by standard antioxidants results in the weakening of the immune system during lactation, which is important for metabolism.

Lactoperoxidase inhibition of some natural phenolic compounds: Kinetics and molecular docking studies.

The inhibition effects of some phenolic compounds from natural products such as taxifolin, resveratrol, olivetol, cynarine, and phloretin on bovine milk lactoperoxidase (LPO) enzyme were examined. For this aim, LPO was purified by the affinity chromatography technique with a yield of 77.68% in 421.32 times. The kinetic value, Ki , was calculated from the equations obtained from drawn graphs. In order to discover inhibition mechanism of phenolic compounds, induced fit docking process was performed on the LPO receptors. The binding affinity of the compounds was calculated and at the best-scored ligand-receptor complex, residues responsible for enzyme inhibition were detected. As a result, this molecule demonstrated the potential inhibitory effect on LPO. According to the results of kinetic study. It has shown a noncompetitive inhibition effect, Phloretin's Ki value was determined by 48.89 ± 14.22 nM. PRACTICAL APPLICATIONS: There are natural antimicrobial systems, such as the lactoperoxidase (E.C.1.11.1.7; LPO) system, which eliminates the harmful effects of microorganisms in milk. The chemical reactions in this system are catalyzed by the LPO. In the dairy industry, the LPO system is considered critical for the preservation of pasteurized milk, yogurt, raw milk, and cheese. The system is used for improvement the protection condition of milk at high temperatures.

The inhibition effects of some sulfonamides on human serum paraoxonase-1 (hPON1).

BACKGROUND: Paraoxonase 1 (PON1) is an antiatherogenic and organophosphate hydrolyzer enzyme. It has important roles including protecting low density lipoprotein (LDL) against oxidation and the detoxification of highly toxic substances. Reducing the levels of this enzyme in patients with diabetes mellitus, cardiovascular diseases, hyperthyroidism, and chronic renal failure is a major risk. METHODS: Here, we report on the purification of the human serum PON1 using simple methods and determine the interactions between some sulfonamides and the enzyme. RESULTS: We found that some sulfonamides exhibit potential inhibitor properties for the human serum PON1 with IC50 values in the range of 24.10-201.45 µM and Ki values in the range of 4.41 ± 0.52-150.23 ± 20.73 µM. The sulfonamides showed different inhibition mechanisms. We determined that sulfonamides 1, 2, 4, 5, 8, and 9 showed a non-competitive inhibition effect whereas sulfonamides 3, 6 and 7 showed competitive inhibition. CONCLUSION: Use of drugs containing the sulfonamides molecule groups with crucial biological activity would be very dangerous in some cases.

Investigation of the effects of some sulfonamides on acetylcholinesterase and carbonic anhydrase enzymes.

Human carbonic anhydrase I and II isoenzymes (hCA I and II) and acetylcholinesterase (AChE) are important metabolic enzymes that are closely associated with various physiological and pathological processes. In this study, we investigated the inhibition effects of some sulfonamides on hCA I, hCA II, and AChE enzymes. Both hCA isoenzymes were purified by Sepharose-4B-L-Tyrosine-5-amino-2-methylbenzenesulfonamide affinity column chromatography with 1393.44 and 1223.09-folds, respectively. Also, some inhibition parameters including IC50 and Ki values were determined. Sulfonamide compounds showed IC 50 values of in the range of 55.14 to 562.62 nM against hCA I, 55.99 to 261.96 nM against hCA II, and 98.65 to 283.31 nM against AChE. Ki values were in the range of 23.40 ± 9.10 to 365.35 ± 24.42 nM against hCA I, 45.87 ± 5.04 to 230.08 ± 92.23 nM against hCA II, and 16.00 ± 45.53 to 157.00 ± 4.02 nM against AChE. As a result, sulfonamides had potent inhibition effects on these enzymes. Therefore, we believe that these results may contribute to the development of new drugs particularly in the treatment of some disorders.

Assessment of the inhibitory effects and molecular docking of some sulfonamides on human serum paraoxonase 1.

Paraoxonase-1 (PON1) is an organophosphate hydrolyzer and antiatherogenic enzyme. Due to the PON1's crucial functions, inhibitors and activators of PON1 must be known for pharmacological applications. In this study, we investigated the in vitro effects of some sulfonamides compounds on human serum PON1 (hPON1). For this aim, we purified the hPON1 from human serum with high specific activity by using simple chromatographic methods, and after the purification processes, we investigated in vitro interactions between the enzyme and some sulfonamides (2-amino-5-methyl-1,3-benzenedisulfonamide, 2-chloro-4-sülfamoilaniline, 4-amino-3-methylbenzenesulfanilamide, sulfisoxazole, sulfisomidine, and 5-amino-2-methylbenzenesulfonamide). IC50 , Ki values, and inhibition types were calculated for each sulfonamide. 2-amino-5-methyl-1,3-benzenedisulfonamide and 2-chloro-4-sülfamoilaniline exhibited noncompetitive inhibition effect, whereas 4-amino-3-methylbenzenesulfanilamide, sulfisoxazole, and sulfisomidine exhibited mixed type inhibition. On the other hand, 5-amino-2-methylbenzenesulfonamide showed competitive inhibition and so molecular docking studies were performed for this compound in order to assess the probable binding mechanism into the active site of hPON1.

The inhibition effects of some natural products on lactoperoxidase purified from bovine milk.

In this study, inhibition profiles of some natural products, which are digoxin, L-Dopa, dopamine, isoliquiritigenin, and 1,1,2,2-tetrakis(p-hydroxyphenyl)ethane (Tetrakis), were investigated against bovine lactoperoxidase (LPO) enzyme. Digoxin, L-Dopa, and dopamine are active ingredients of some drugs, which have important functions in our body, especially in cases of heart failure. Isoliquiritigenin and tetrakis are types of natural phenolic compounds, which play an important role in cancer prevention and treatment. LPO enzyme was purified from bovine milk using sepharose-4B-l-tyrosine sulfonamide affinity column chromatography. LPO is responsible for the nonimmune biological defense system and has antibacterial activity so selection of these active substances is important. The inhibition studies are performed with the ABTS substrate. Bovine LPO enzyme was effectively inhibited by phenolic molecules. Ki values of these natural products were found as 0.20 ± 0.09, 0.22 ± 0.17, 0.49 ± 0.11, 0.49 ± 0.27, and 1.20 ± 0.25 µM, respectively. Tetrakis and digoxin exhibited noncompetitive inhibition, and other molecules showed competitive inhibition.