Abdurrahman Aksoy

Efficacy of tigecycline/colistin combination in a pneumonia model caused by extensively drug-resistant Acinetobacter baumannii

Due to increasing drug resistance, available antimicrobial options are limited in the treatment of Acinetobacter baumannii infections. Particularly in cases caused by extensively drug-resistant (XDR) A. baumannii, combination regimens must also be taken into consideration. In this study, the efficacies of tigecycline, colistin and tigecycline/colistin combination on bacterial counts in lung tissue were investigated in a rat pneumonia model. One A. baumannii strain resistant to all antimicrobial agents except tigecycline and colistin was selected for the study. In vivo studies revealed a >3 log reduction in bacterial counts in the tigecycline, colistin and combination groups at 24 h and 48 h compared with the control group. No significant differences were determined between colistin, tigecycline and combination groups (P>0.05). On the other hand, differences between treatment groups and the control group were statistically significant (P=0.01). A greater reduction in bacterial counts was observed at 48 h compared with 24 h in the tigecycline group than in the colistin group (P=0.038 and P=0.139, respectively); the most significant decrease between 24 h and 48 h was observed in the combination group (P=0.014). Despite detection of in vitro synergistic activity in this study, no statistically significant differences were found between colistin, tigecycline and combination treatments in terms of efficacy on bacterial counts in lung tissue. In the treatment of infections with a high mortality rate such as pneumonia caused by XDR A. baumannii, combining tigecycline with colistin during the first 48 h and continuing treatment with one of these agents seems a rational approach.

Therapeutic role of curcumin in oxidative DNA damage caused by formaldehyde

Formaldehyde is a common environmental contaminant that causes oxidative DNA damage in cells by increasing the production of reactive oxygen species. The aim of this study was to investigate the amount of 8‐hydroxy‐deoxyguanosine (8‐OhdG), tumor protein 53(TP53), beta‐amyloid[Aß(1‐42), Aß (1‐40)], total antioxidant capacity (TAC) and malondialdehyde (MDA) and the therapeutic role of curcumin in rat cells with oxidative DNA damage caused by formaldehyde. Method: The control group was given physiological saline for 15 days (ip) and the second group was given 37% formaldehyde (ip) at a dose of 9 mg/kg group every other day. The third group was given 9 mg/kg formaldehyde (ip) every other day and treated therapeutically with 100 mg/kg curcumin every day by gavage. At the end of the trial period, urine, blood, and brain tissue was collected from the rats. Results: The levels of MDA in sera were increased and the TAC, TP53, and Aß (1−40) levels were reduced in the formaldehyde‐treated group with respect to the control group (p<0.005). After treatment with curcumin, the levels of sera MDA were significantly reduced, the TAC, TP53, and Aß (1‐40) levels were significantly increased (P < 0.05). The levels of whole brain Aß (1‐42) and 8‐OhdG were increased in the formaldehyde‐treated group and reduced after treatment with curcumin (P < 0.05). Urinary 8‐OhdG excretion increased in the formaldehyde‐treated group (P < 0.05) and decreased after treatment with curcumin (P > 0.05).

Subacute oral toxicity of combinations of selected synthetic pyrethroids, piperonyl butoxide, and tetramethrin in rats

In this study, 70 Wistar rats were randomly divided into seven equal groups (six experimental and one control), which consisted of animals belonging to both sexes. Different combinations of insecticides were administered daily to the experimental groups (group 1: cypermethrin + piperonyl butoxide (PBO); group 2: alphacypermethrin + PBO; group 3: deltamethrin + PBO; group 4: cypermethrin + PBO + tetramethrin; group 5: alphacypermethrin + PBO + tetramethrin; and group 6: deltamethrin + PBO + tetramethrin) for 28 days. During the study period, mortality and serious clinical findings were not observed in any animal. However, feed consumptions decreased in groups 1 and 3 (p < 0.05). Red blood cells, white blood cells, and hemoglobin levels, especially in cypermethrin and alphacypermethrin groups (groups 1, 2, and 4), were found to be higher than the control group (p < 0.05). Furthermore, biochemical changes related to liver, kidney functions, and protein metabolism occurred in males of almost all the groups. Relative liver and kidney weights of the male animals increased in the cypermethrin and alphacypermethrin groups (p < 0.05). The most common finding observed during the histopathological examination of all the experimental groups was centrilobular degeneration in the liver. It was concluded that although clinical symptoms were not observed, synthetic pyrethroid, synergist, and knockdown agent combinations might cause serious abnormalities when administered in certain doses in mammalians.

Repeated-dose 14-day dermal toxicity of different combinations of some synthetic pyrethroid insecticides, piperonyl butoxide, and tetramethrin in rats

The aim of this study was to evaluate the repeated-dose 14-day dermal toxicity of different combinations of some synthetic pyrethroid insecticides, piperonyl butoxide, and tetramethrin in rats. A total of 70 adult Wistar rats were randomly divided into 7 (6 experimental and 1 control) groups. Different combinations of insecticides were dermally applied to the rats in the experimental groups for 14 days. Clinical observations were performed daily; hematologic and biochemical parameters were also determined. Gross necropsy and histopathologic examinations were performed systematically, and organ weights were recorded. Although the administered doses of the insecticides were relatively lower than their acute dermal toxicity values, a high mortality rate (27 of 60 experimental animals, 45%) was observed. Furthermore, the insecticide combinations caused decreased body weights and feed consumptions, increased organ weights, and hematologic, biochemical, and common histopathologic changes. As a result, the findings showed that although pyrethroids are considered to be of low acute toxicity, they become more toxic when combined with piperonyl butoxide or tetramethrin in certain doses.

Human brain mercury levels related to exposure to amalgam fillings

The safety of dental amalgam as the primary material in dental restoration treatments has been debated since its introduction. It is widely accepted that amalgam restorations continuously release elemental mercury (Hg) vapor, which is inhaled and absorbed by the body and distributed to tissues, including the brain. The aim of the present study was to investigate whether the presence of amalgam fillings is correlated with brain Hg level. The Hg levels in the parietal lobes of the brains of 32 cadavers were analyzed with an atomic absorption spectrometer with the mercury hydride system. A total of 32 brain samples were tested; of these, 10 were from cadavers with amalgam fillings, while 22 of them were amalgam free. Hg was detected in 60.0% (6 of 10) of the samples in the amalgam group and in 36.3% (8 of 22) in the amalgam-free group. The average Hg level of the amalgam group was 0.97 ± 0.83 µg/g (minimum: 0.3 µg/g and maximum: 2.34 µg/g), and in the amalgam-free group, it was 1.06 ± 0.57 µg/g (minimum: 0.17 µg/g and maximum: 1.76 µg/g). The results of the present study showed no correlation between the presence of amalgam fillings and brain Hg level.

Examination of caspase-dependent apoptotic and necrotic changes in rat kidney exposed to different doses of permethrin

Abstract We investigated dose-related pathological alterations and apoptosis in rat kidney tissue exposed to permethrin. Histopathological findings, apoptotic cell death and urinary 3-phenoxybenzoic acid concentrations (3-PBA) were evaluated. Different doses of permethrin were administered to animals by oro-gastric gavage. A dose-dependent increase of urine 3-PBA concentration was observed in all the permethrin-treated groups. SDS-PAGE separated 30–45 kD and 100–220 kD protein bands in all experimental groups. Histopathologically, degenerative changes were observed in the epithelial lining of the S1, S2, and S3 segments of the renal proximal tubules. Apoptotic cells were seen in the inner stripe of the outer medulla in Group I, and both the cortex and medulla in Groups II and III. Immunohistochemical staining of caspase 3 and caspase 9 also was observed in the same areas. Our results suggest that damage to regions of the proximal tubules is dose-related, and caspase-9-dependent, mitochondria-related apoptotic cell death could play an important role in permethrin-induced nephrotoxicity. We also observed morphologically necrotic cells. We concluded that both necrosis and apoptosis are produced by permethrin.

Do the monomers release from the composite resins after artificial aging

The aim of this study is to measure the effect of thermal cycling on the amount of monomer released from three different composite materials by HPLC analysis method.

Does systemic clarithromycin therapy have an inhibitory effect on tympanosclerosis? An experimental animal study

OBJECTIVE To demonstrate the inhibitory effects of clarithromycin on in vitro tympanosclerosis. METHOD Twenty-eight rats were divided into three groups: a clarithromycin group, a non-clarithromycin group and a negative control group. Those in the first two groups were injected with Streptococcus pneumoniae following a myringotomy, and tympanosclerosis was experimentally induced. Oral clarithromycin therapy was administered in the clarithromycin group. The other groups received no medical treatment. RESULTS All eardrums in the clarithromycin and non-clarithromycin groups developed myringosclerosis, but there was only one eardrum, in the clarithromycin group, with very severe myringosclerosis. In the clarithromycin group, 11 ears showed no inflammation and there were no ears with severe inflammation. In the non-clarithromycin group, there were 11 ears with severe inflammation. The mean eardrum thickness in the clarithromycin group was 20.93 µm and in the non-clarithromycin group it was 42.71 µm. CONCLUSION Acute otitis media and myringotomies induced tympanosclerosis, but clarithromycin reduced the severity of tympanosclerosis.

3-nitrotyrosine levels in dichlorvos-induced neurotoxicity.

Summary The aim of this study was to evaluate dichlorvos toxicity in terms of nitro-oxidative stress by determining 3-nitrotyrosine (3-NT) levels in the fore, mid, and hindbrain regions in acutely exposed rats. Male Sprague- Dawley rats were randomly allocated to three groups of eight. Group 1 was administered a single intraperitoneal dichlorvos dose of 1.8 mg kg-1 (0.1xLD50) and group 2 a dose of 9 mg kg-1 (0.5xLD50). The control group received 0.5 mL saline solution via the same route. 3-NT and tyrosine (TYR) levels were measured using high performance liquid chromatography with a photodiode array detector (HPLC-PDA) and expressed as a ratio of 3-NT to TYR. The 3-NT/1000 TYR ratios increased significantly in the fore-, mid- and hindbrains of the exposed groups compared to control (p<0.01). In the forebrain, the increase was also significant between the treated groups. Our study has confirmed that acute exposure to dichlorvos leads to nitro-oxidative stress in the brain and that 3-NT may play a role in the mechanism of dichlorvos neurotoxicity. Sažetak Cilj je ovog ispitivanja bio ocijeniti neurotoksičnost diklorvosa kroz nitrooksidativni stres mjerenjem razina 3-nitrotirozina (3-NT) u prednjem, središnjem i stražnjem režnju mozga akutno izloženih mužjaka štakora Sprague-Dawley, koji su u tu svrhu nasumce bili podijeljeni u tri skupine po osam životinja. Skupina 1 primila je jednokratnu intraperitonealnu dozu diklorvosa od 1,8 mg kg-1 (0,1xLD50), a skupina 2 dozu od 9 mg kg-1 (0,5xLD50). Kontrolna je skupina primila 0,5 mL fiziološke otopine, također intraperitonealno. Razine 3-NT-a i tirozina (TIR) izmjerene su tekućinskim kromatografom visoke djelotvornosti s detektorom s nizom dioda (HPLC-PDA) te su izražene kao omjer 3-NT:TIR. Omjeri 3-NT/1000 TIR značajno su se povećali u svim režnjevima izloženih skupina (1 i 2) u odnosu na kontrolnu skupinu (p<0,01). Povećanje je također bilo značajno u prednjem režnju skupine 2 u odnosu na skupinu 1, ali nije bilo značajne razlike između izloženih skupina u ostalim režnjevima. Naše je istraživanje potvrdilo da akutna izloženost diklorvosu dovodi do nitrooksidativnog stresa u mozgu te da 3-NT sudjeluje u mehanizmu neurotoksičnosti diklorvosa.

d‐phenothrin‐induced oxidative DNA damage in rat liver and kidney determined by HPLC‐ECD/DAD

The objective of this study was to assess the risk of genotoxicity of d‐phenothrin by measuring the oxidative stress it causes in rat liver and kidney. The level of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodG)/106 2′‐deoxyguanosine (dG) was measured by using high performance liquid chromatography (HPLC) with a diode array (DAD) and an electrochemical detector (ECD). Sixty male Wistar albino rats were randomly divided into five experimental groups and one control group of 10 rats/group. d‐phenothrin was administered intraperitoneally (IP) to the five experimental groups at 25 mg/kg (Group I), 50 mg/kg (Group II), 66.7 mg/kg (Group III), 100 mg/kg (Group IV), and 200 mg/kg (Group V) for 14 consecutive days, and the control group received only the vehicle, dimethyl sulfoxide (DMSO). DNA from samples frozen in liquid nitrogen was isolated with a DNA isolation kit. Following digestion with nuclease P1 and alkaline phosphatase (ALP), hydrolyzed DNA was subjected to HPLC. The dG and 8‐oxodG levels were analyzed with a DAD and ECD, respectively. In the experimental groups, the mean 8‐oxodG/106 dG levels were 48.15 ± 7.43, 68.92 ± 20.66, 82.07 ± 14.15, 85.08 ± 28.50, and 89.14 ± 21.73 in livers and 39.06 ± 7.63, 59.69 ± 14.22, 61.13 ± 17.46, 65.13 ± 23.40, and 72.66 ± 19.04 in kidneys of Groups I, II, III, IV, and V, respectively. The mean 8‐oxodG/106 dG levels in the control groups were 44.96 ± 12.66 for the liver and 39.07 ± 4.80 for the kidney. A statistically significant (p < 0.05), dose‐dependent increase in oxidative DNA damage was observed in both organs of animals exposed to d‐phenothrin when compared to controls. Furthermore, the liver showed a significantly higher level of oxidative DNA damage than the kidney (p < 0.01). In conclusion, d‐phenothrin administered to rats intraperitoneally for 14 consecutive days generated free radical species in a dose‐dependent manner and caused oxidative DNA damage in the liver and kidney.