Comparison of infliximab with adalimumab in biologic-naïve patients with Crohn's disease: a single-center 13-year experience.

OBJECTIVE: Long-term comparison studies between infliximab (IFX) and adalimumab (ADA) with or without immunomodulator therapy are still needed in Crohn's disease (CD). In this study, we evaluated IFX and ADA for long-term clinical effectiveness and safety in CD patients who had not previously received a biologic treatment. PATIENTS AND METHODS: The data of adult CD patients were collected retrospectively between December 2007 and February 2021. We compared CD-related hospitalization, CD-related abdominal surgery, steroid use, and serious infections. RESULTS: Out of 224 CD patients, 101 started IFX first (median age: 38.12 years, 61.4% male), while 123 started ADA first (median age: 30.2 years, 64.2% male). The disease durations were 7.01 years and 6.91 years for IFX and ADA, respectively. There were no significant differences between the two groups with respect to age, gender, smoking, immunomodulator usage, and disease activity score at the onset of anti-TNF therapy (p>0.05). Overall, the median follow-up time was 2.36 and 1.86 years after starting anti-tumor necrosis factor-alpha (anti-TNF) therapy in the IFX and ADA groups, respectively. Steroid use (4.0% vs. 10.6%, p=0.109), hospitalization for CD (13.9% vs. 22.8%, p=0.127), abdominal surgery for CD (9.9% vs. 13.0%, p=0.608), and major infections (1.0% vs. 0.8%, p>0.999) did not differ significantly from one another. There were also no significant differences in the rates of these outcomes between concomitant immunomodulator therapy and monotherapy (p>0.05). CONCLUSIONS: In this study, we observed no significant differences in the long-term effectiveness and safety of IFX and ADA in biologic-naïve patients with CD.

Reproductive toxic effects and possible mechanisms of zonisamide in male rats.

Zonisamide (ZNS) is an anticonvulsant which is used to treat the symptoms of epilepsy. Although it is frequently used during reproductive ages, studies that investigated the effects of ZNS on reproductive system are limited. Therefore, we aimed to assess the effects of ZNS on male reproductive system by oral administration to rats in 25, 50, and 100 mg/kg doses for 28 days. After the exposure period, sperm concentration, motility, morphology, and DNA damage, as biomarkers of reproductive toxic effects, were determined, and histopathological examination of testis was performed. In addition, levels of the hormones that play a role in the regulation of reproductive functions, such as follicle-stimulating hormone, luteinizing hormone (LH), and testosterone were measured and the levels of oxidative stress biomarkers that take part in the reproductive pathologies such as catalase, superoxide dismutase, glutathione, and malondialdehyde, were determined. Reproductive toxic effects related to ZNS administration were shown by the significant decrease of sperm concentration and normal sperm morphology in ZNS groups. Additionally, pathological findings were observed in the testicular tissues of ZNS-administered groups dose dependently. In addition, serum LH and testosterone levels were significantly decreased in the ZNS groups. Decreased catalase activities and increased malondialdehyde levels in ZNS groups were evaluated as oxidative stress findings in the testis tissue. It could be expressed that ZNS administration induced dose-dependent reproductive toxic effects in rats, and pathological findings associated with the reproductive system could be the result of that hormonal changes and testicular oxidative stress, which in turn might be considered as possible mechanisms of male reproductive toxicity.

Assessment of trazodone-induced cardiotoxicity after repeated doses in rats.

Trazodone (TRZ) is an antidepressant drug commonly used in the treatment of depression, anxiety, and insomnia. Although some studies demonstrated the adverse effects of TRZ related to cardiovascular system, the conflicting results were observed in these studies. Therefore, we aimed to investigate the cardiac adverse effects of TRZ in rats at repeated doses in our study. In accordance with this purpose, TRZ was administered orally to rats at 5, 10, and 20 mg/kg doses for 28 days. Electrocardiogram records, serum aspartate aminotransferase (AST), lactate dehydrogenase, creatine kinase-myoglobin band, cardiac troponin-T (cTn-T) levels, DNA damage in cardiomyocytes, and histologic view of heart tissues were evaluated. In addition, glutathione (GSH) and malondialdehyde (MDA) levels were measured to determine the oxidative status of cardiac tissue after TRZ administration. Heart rate was decreased, PR interval was prolonged, and QRS and T amplitudes were decreased in 20 mg/kg TRZ-administered group compared to the control group. Serum AST and cTn-T levels were significantly increased in 10 and 20 mg/kg TRZ-administered rats with respect to control rats. DNA damage was significantly increased in these groups. Additionally, degenerative histopathologic findings were observed in TRZ-administered groups. Although there was no difference in MDA levels between groups, GSH levels were significantly decreased in 10 and 20 mg/kg TRZ-administered groups compared to the control group. Our results have shown that TRZ induced cardiotoxicity in rats dose-dependently. It is assumed that oxidative stress related to GSH depletion may be accompanied by these adverse effects.

Atomic structure and crystalline order of graphene-supported ir nanoparticle lattices.

We present the atomic structure of Ir nanoparticles with 1.5 nm diameter at half height and three layers average height grown on graphene/Ir(111). Using surface x-ray diffraction, we demonstrate that Ir nanoparticles on graphene/Ir(111) form a crystallographic superlattice with high perfection. The superlattice arrangement allows us to obtain detailed information on the atomic structure of the nanoparticles themselves, such as size, shape, internal layer stacking and strain. Our experiments disclose that the nanoparticles reside epitaxially on top of the graphene moiré structure on Ir(111), resulting in significant lateral compressive intraparticle strain. Normal incidence x-ray standing wave experiments deliver additional information on the particle formation induced restructuring of the graphene layer.