Browsing by Author "Ünlü, M"

Now showing 1 - 5 of 5
  • No Thumbnail Available
    Item
    Effects of Efflux Pump Inhibitors and Antileishmanial Drug Combinations on Leishmania tropica and Leishmania infantum Isolates
    Özel, Y; Çavus, I; Tunali, V; Aksoy, T; Ünlü, M; Özbilgin, A
    Drug resistance, one of the most important public health problems facing humanity, necessitates new strategies and approaches in the development of antileishmanial agents. Although developments regarding efflux pump inhibitors (EPIs) and other candidate agents are promising, the search continues to increase the duration of use and efficacy of existing antileishmanials. The aim of this study was to investigate the antileishmanial effects of three EPIs, namely reserpine, berberine and verapamil. The antileishmanial activities of EPIs, pentostam and miltefosine against Leishmania tropica and Leishmania infantum strains were determined by broth microdilution method. Minimum parasiticidal concentration (MPC) values were determined by inverted microscope and IC50 values were determined by MTT viability assay method. The effects of EPIs with determined antileishmanial activities on miltefosine and pentostam were investigated by checkerboard method. The MPC values of antileishmanial drugs miltefosine and pentostam for L.tropica and L.infantum were determined as 64 and 196 pg/mL at 24 and 48 hours, respectively. The MPC values of EPIs reserpine and berberine were determined as 314 and 64 pg/mL for the same incubation times and for verapamil, they were determined as 80 pg/mL at 24 hours and 40 pg/mL at 48 hours. Among anti-leishmanials, the IC50 values of miltefosine were calculated as 4.91/3.47 and 4.05/2.91 pg/mL for L.tropica and L.infantum at 24 and 48 hours, respectively and that of pentostam were calculated as 34.58/59.86 and 18.48/40.63 pg/mL at the same incubation times, respectively.The IC50 values of EPIs, reserpine, berberine, and verapamil were calculated as 74.05/50.61, 7.27/6.1, and 12.52/4.53 pg/mL for L.tropica at 24/48 hours, respectively and 64.52/51.72, 8.21/8.01, and 11.59/7.69 pg/mL for L.infantum. When miltefosine was combined with reserpine, berberine or verapamil, synergistic interactions were observed at 24 and 48 hours of incubation. When pentostam was combined with reserpine, partial synergy was observed at 24 hours and synergy was observed at 48 hours. When pentostam was combined with berberine or verapamil, synergistic interactions were observed at both incubation conditions. Synergy results were found to be the same in both L.tropica and L.infantum strains. In recent years, the speed of research on the discovery of new antimicrobials has significantly decreased and it has become necessary to investigate new molecules that can affect resistance mechanisms. It is thought that EPIs may be a promising approach that can increase the clinical performance of antileishmanial agents and reduce the level of side effects in the fight against drug resistance.
  • No Thumbnail Available
    Item
    Comparison of Conventional Methods with Molecular Methods in the Diagnosis of Trichomonas vaginalis and Investigation of Metronidazole Resistance
    Özel, Y; Çavus, I; Usta, A; Ünlü, GV; Özbilgin, A; Ünlü, M
    Trichomoniasis is a sexually transmitted parasitic infection caused by Trichomonas vaginalis. In the diagnosis of trichomoniasis, direct microscopy (DM) is preferred, which is a cheap and fast method, although it has low sensitivity. Culture methods, which are accepted as the gold standard, can only be applied in certain centers due to the need for experienced personnel and the ability to get results within 2-7 days, despite their high sensitivity. In this study, it was aimed to compare conventional microscopic and culture methods used in the routine diagnosis of T.vaginalis with polymerase chain reaction (PCR) method and to investigate ntr4 and/or ntr6 gene polymorphism in the nitroreductase gene region, which are thought to be associated with metronidazole resistance in T.vaginalis strains isolated from clinical specimens. Vaginal swab specimens were collected from the posterior fornix of the vagina with two sterile ecuvion sticks during the gynecological examinations of 200 patients who applied to the Balikesir University Health Practice and Research Hospital, Obstetrics and Gynecology Polyclinic between March 2019 and August 2021. The first swab sample was used for direct microscopic examination, Giemsa staining and conventional PCR analysis, while the second swab specimen was taken into trypti- case-yeast-extract-maltose (TYM) medium for T.vaginalis culture and followed for eight days at 37 degrees C. All specimens were screened for the presence of T.vaginalis using primers specific to the beta-tubulin (btub1) gene region and clinical isolates grown in TYM medium were examined for metronidazole resistance using primers specific for the nitroreductase gene region by using conventional PCR. Drug resistance test was also performed for the isolates in which polymorphism associated with metronidazole resistance was detected. Eight (4%) of 200 patient specimens were found positive by both culture/staining and PCR methods. The mean age of the patients included in the study was 39.9, while the mean age of the patients with positive T.vaginalis was 41.8. The most common clinical findings in the patients were foul-smelling vaginal discharge (36%), groin pain (21%), vaginal itching (19%), and burning sensation during urination (18%). In three out of eight T.vaginalis strains isolated from clinical samples, the presence of polymorphism in the ntr6 gene, which is thought to be associated with metronidazole resistance, was demonstrated by PCR. It was observed that three isolates with ntr6 gene polymorphism were phe notypically resistant to metronidazole (MLK= 390 mu M). In this study, the fact that three of eight clinical isolates that were resistant to metronidazole by the broth microdilution method and as well as showing ntr6 gene polymorphism supported the thesis that there might be a close relationship between metro- nidazole resistance and ntr6 gene polymorphism. As a result, the use of culture and molecular methods in the diagnosis of T.vaginalis, in addition to the microscopy method, may contribute to a more accurate laboratory diagnosis of the agent, to detect metronidazole resistance molecularly and phenotypically, to determine metronidazole resistance rates in our country and to update treatment protocols within the framework of these data.
  • No Thumbnail Available
    Item
    Henoch-Schonlein purpura, post-streptococcal glomerulonephritis and acute rheumatic carditis after Group A β-haemolytic streptococcal infection
    Çamlar, SA; Soylu, A; Akil, I; Ünlü, M; Coskun, S; Ertan, P; Kavukçu, S
    Besides association with acute rheumatic fever (ARF) and acute glomerulonephritis (APSGN), in up to 40% of cases, Group A beta-haemolytic streptococcal (GABHS) infections are also implicated as a trigger for Henoch-Schonlein purpura (HSP). A 7-year-old girl with GABHS throat infection who developed HSP, APSGN and rheumatic carditis is reported. She presented with palpable purpura and arthritis in both ankles and later developed carditis characterised by mitral/aortic regurgitation and glomerulonephritis characterised by mixed nephritic/nephrotic syndrome. She had a raised anti-streptolysin titre (ASOT), blood urea nitrogen and creatinine and hypocomplementaemia (C-3), and renal biopsy demonstrated endocapillary and extracapillary proliferative glomerulonephritis with crescents. Immunofluorescence microscopy demonstrated a full house' of immunoglobulin and complement, viz. IgA+2, IgG+3, IgM+2, C(3)c+1, Clq+2 with predominantly IgG deposition. One week earlier, her 4-year-old sister had presented to another hospital with HSP complicated by microscopic haematuria, nephrotic-range proteinuria and gastro-intestinal involvement, and with raised ASOT and low C-3 levels. Although HSP has been associated with either ARF or APSGN, this is the first case of a child with HSP, ARF and APSGN in combination.
  • No Thumbnail Available
    Item
    Prevalence of testicular microlithiasis in an asymptomatic population
    Serter, S; Gümüs, B; Ünlü, M; Tunçyürek, Ö; Tarhan, S; Ayyildiz, V; Pabuscu, Y
    Objective. Testicular microlithiasis is a rare, usually asymptomatic, finding of the testes associated with various genetic anomalies and infertility. It is also widely believed that testicular microlithiasis is strongly associated with testicular tumor. The aim of this prospective study was to determine the true prevalence of testicular microlithiasis in an asymptomatic population by means of ultrasound screening. Material and methods. Healthy male volunteers (17-42 years old) were recruited from the annual Army Reserve Officer Training Corps training camp at Manisa, Turkey. A screening genitourinary history was obtained and a physical examination and screening scrotal ultrasound scan were performed. All men diagnosed with testicular microlithiasis underwent complete clinical evaluations, physical examinations and determination of tumor markers. Results. Fifty-three men with testicular microlithiasis were identified from the 2179 ultrasound scans, giving a prevalence of testicular microlithiasis of 2.4% in this asymptomatic population. The age (mean +/- SD) of subjects with testicular microlithiasis was 23.9 +/- 4.2 years (range 20-31 years). Conclusion. Our results suggest that there is no significant association between TM and testicular cancer, although it is difficult to rule out such an association without further studies with a longer follow-up period.
  • No Thumbnail Available
    Item
    Investigation of the Efficacy of Cinnamaldehyde, Cannabidiol and Eravacycline in a Malaria Model
    Özel, Y; Çavus, I; Ünlü, M; Özbilgin, A
    In this study, it was aimed to investigate the antimalarial activity of cinnamaldehyde (CIN) and can- nabidiol (CBD) which have shown various biological activities such as potent antimicrobial activity and eravacycline (ERA), a new generation tetracycline derivative, in an in vivo malaria model. The cytotoxic activities of the active substances were determined by the MTT method against L929 mouse fibroblasts and their antimalarial activity were determined by the four-day test in an in vivo mouse model. In this study, five groups were formed: the CIN group, the CBD group, the ERA group, the chloroquine group (CQ) and the untreated group (TAG). 2.5 x 107 parasites/mL of P.berghei-infected erythrocyte suspension was administered IP to all mice. The determined doses of active substances were given to the mice by oral gavage in accordance with the four-day test and the parasitemia status in the mice was controlled for 21 days with smear preparations made from the blood taken from the tail end of the mice. The IC50 values, which express the cytotoxic activity values of the active substances were determined as 27.55 mu g/mL, 16.40 mu M and 48.82 mu g/mL for CIN, CBD and ERA, respectively. The mean parasitemia rate in untreated mice was 33% on day nine and all mice died on day 11. On the ninth day, when compared with the TAG group, no parasites were observed in the CIN group, while the average parasitemia was 0.08% in the CBD group and 17.8% in the ERA group. Compared to the mice in the TAG group, the life expectancy of the other groups was prolonged by eight days in the CIN group, 12 days in the CBD group and eight days in the ERA group. It has been determined that all three active subtances tested in this study suppressed the development of Plasmodium parasites in an in vivo mouse model and prolonged the life span of the mice. It is thought that the strong antimalarial activity of CIN and CBD shown in the study and the possible positive effect of ERA on the clinical course can be improved by combining them with the existing and potential antimalarial molecules.