An evaluation of the protective effect of esomeprazole in an experimental model of renal ischemia–reperfusion

Purpose

The ischemia and subsequent reperfusion (IR) which occurs in partial nephrectomy used in the treatment of renal tumors causes loss of parenchyma in the damaged kidney. The aim of this study is to evaluate, both biochemically and histologically, the efficacy of esomeprazole in an ischemia–reperfusion model in rat kidneys.

Methods

The rats were randomized into three groups of seven animals each, referred to as the sham, control, and PPI groups. In the sham group, only a laparotomy was performed. In the control group, following laparotomy the left renal artery was dissected and tied for 30-min ischemia. In the PPI group, a vascular route to the tail vein was opened, and 10 mg/kg esomeprazole was administered. After 1 h, the same procedures described for the control group were performed. All the animals were killed 24 h after the procedure. Biochemical analyses were applied for evaluation of oxidant and antioxidant agents in the blood and left kidney of each subject (oxidative markers: malondialdehyde, myeloperoxidase; antioxidant marker: superoxide dismutase). In the histological examination of the kidney tissues stained with hematoxylin–eosin, the TUNEL method was applied in the evaluation of apoptosis.

Results

No statistically significant biochemical difference was determined in the blood and tissue samples. In the histological and apoptosis evaluations, a statistically significant difference was determined between the sham, control, and PPI groups. The median (IQR) values of the TUNEL-positive cells were counted as 1.50 (4) in the sham group, 11.50 (12) in the control group, and 6.00 (9) in the PPI group (p < 0.001).

Conclusions

A protective effect of esomeprazole was confirmed in renal ischemia–reperfusion damage created in an experimental rat model.

     

Treatment outcomes of patients with cervical cancer with complete metabolic responses after definitive chemoradiotherapy

Purpose

We sought to evaluate failure patterns and prognostic factors predictive of recurrences and survival in cervical cancer patients who are treated with definitive chemoradiotherapy (ChRT), who have a subsequent complete metabolic response (CMR) with ¹⁸?F-fluorodeoxyglucose positron-emission tomography (FDG-PET) after treatment.

Methods

The records of 152 cervical cancer patients who were treated with definitive chemoradiotherapy were evaluated. All patients underwent pre-treatment positron emission tomography (PET-CT), and post-treatment PET-CT was performed within a median of 3.9 months (range, 3.0–9.8 months) after the completion of ChRT. The prognoses of partial response/progressive disease (PR/PD) cases (30 patients, 18 %) and CMR cases (122 patients, %82) were evaluated. Univariate and multivariate analysis effecting the treatment outcome was performed in CMR cases.

Results

The median follow-ups for all patients and surviving patients were 28.7 (range, 3.3–78.7 months) and 33.2 months (range, 6.23–78.7 months), respectively. Four-year overall survival (OS) rate was significantly better in patients with CMR compared to patients with PR/PD (66.9 % vs. 12.4 %, p?<?0.001, respectively). Patients with PR/PD had higher maximum standardized uptake value (SUV_max) of primary cervical tumor (26.4?±?10.1 vs. 15.9?±?6.3; p?<?0.001) and larger tumor (6.4 cm?±?2.3 cm vs. 5.0 cm?±?1.4 cm; p?<?0.001) compared to patients with CMR. Of the 122 patients with post-treatment CMRs, 25 (21 %) developed local, locoregional, or distant failure. In univariate analysis, tumor size ≥ 5 cm, ‘International Federation of Obstetricians and Gynecologists’ (FIGO) stage?≥?IIB, and pelvic and/or para-aortic lymph node metastasis were predictive of both overall survival (OS) and disease-free survival (DFS), while histology was predictive of only OS. In multivariate analysis, tumor size, stage and lymph node metastasis were predictive of OS and DFS.

Conclusion

Although CMR is associated with better outcomes, relapses remain problematic, especially in patients with bulky tumors (≥ 5 cm), extensive stage (≥ IIB) or pelvic and/or para-aortic lymph node metastasis. These findings could support the need for more aggressive treatment or adjuvant chemotherapy regimens.     

Echocardiographic Diagnosis and Transcatheter Occlusion of Pulmonary Arteriovenous Fistula in Cyanotic Newborn

Pulmonary arteriovenous malformation (PAVM) is a rare cause of cyanosis in newborn. A 12‐day‐old male newborn (2.8 kg) was referred to our hospital with the complaints of cyanosis and respiratory distress. On two‐dimensional echocardiography, the right pulmonary artery (PA) appeared larger than left PA and the left atrium, left ventricle were dilated. The right heart chambers were in normal limits. A color flow Doppler echocardiogram revealed a turbulent flow due to a PAVM originating from medium branch of right PA, and continuous wave Doppler showed continuous flow pattern. Agitated saline injection resulted in the delayed appearance of the contrast in the left‐side chambers three to four heart cycles after appearance in the right‐side chambers; the study was considered positive and indicative of an intrapulmonary shunt. Selective angiography of the right PA confirmed the diagnosis of a large solitary PAVM in the right middle lobe with a feeding artery. Amplatzer vascular plug I, which is designed to close abnormal vascular structures, was chosen to close the PAVM. The deployment of device performed safely and the oxygen saturation of baby increased to 95% immediately after deployment. Heart failure and respiratory distress also resolved after the procedure.     

Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of d-galactose-induced aging mice

Context: Morus nigra L. (Moraceae) has various uses in traditional medicine. However, the effect of M. nigra on cognitive impairment has not been investigated yet.

Objective: The objective of this study is to determine the phenolic acid content and DNA damage protection potential of M. nigra leaf extract and to investigate the extract effect on cognitive impairment and oxidative stress in aging mice.

Materials and methods: Phenolic acid content was determined by quantitative chromatographic analysis. DNA damage protection potential was evaluated on pBR322 plasmid DNA. Thirty-two Balb-C mice were randomly divided into four groups (control, d-galactose, d-galactose?+?M. nigra 50, and d-galactose?+?M. nigra 100). Mice were administered d-galactose (100?mg/kg, subcutaneous) and M. nigra (50 or 100?mg/kg, orally) daily for 8 weeks. Behavioral responses were evaluated with Morris water maze. Activities of antioxidant enzymes and levels of malondialdehyde (MDA) were assayed in serum, brain, and liver.

Results: In extract, vanillic (632.093?μg/g) and chlorogenic acids (555.0?μg/g) were determined. The extract between 0.02 and 0.05?mg/mL effectively protected all DNA bands against the hazardous effect of UV and H₂O₂. Morus nigra significantly improved learning dysfunctions (p <?0.01), increased memory retention (p?<?0.01), reduced MDA levels (p?<?0.05), and elevated SOD, GPx, and CAT activities (p?<?0.05) compared with the d-galactose group.

Discussion and conclusion: These results show that M. nigra has the potential in improving cognitive deficits in mice and that M. nigra may be useful to suppress aging, partially due to its scavenging activity of free radicals and high antioxidant capacity.     

On demand use of anakinra for attacks of familial Mediterranean fever (FMF)

Clinical Rheumatology - To evaluate the efficacy of on-demand use of anakinra in patients with crFMF. The Gazi FMF cohort was established in the year 2010, and from that date, 689 patients with FMF...     

The impact of platelet membrane glycoprotein Ib alpha and Ia/IIa polymorphisms on the risk of thrombosis in the antiphospholipid syndrome

Background

Pathogenesis of thrombus formation in antiphospholipid syndrome (APS) is not clear. Platelet membrane glycoprotein (GP) receptors play important roles in development of thrombosis.

Objectives

We investigated the association between development of thrombosis in APS and polymorphisms of GPIb alpha variable number of tandem repeats (VNTR), Kozak, and GPIa C807T.Patients/MethodsSixty patients with APS (30 with proven thrombosis and 30 without thrombosis) and 63 controls were included. Presence of GPIa C807T polymorphism was determined with real-time PCR and GPIb alpha Kozak and VNTR polymorphisms by conventional PCR.

Results

Frequency of C807T TT genotype was significantly higher in APS with thrombosis than APS without thrombosis (p = 0.023) and also in APS with multiple thrombi compared to APS without thrombi (p = 0.023). Frequency of Kozak TC genotype was higher in APS with arterial thrombosis compared to APS with venous thrombosis, controls, and APS without thrombosis (p = 0.03, p = 0.0007, and p = 0.0024 respectively). D allele frequency and D allele carrier state for VNTR were significantly less in APS than controls (p = 0.0018 and p = 0.0046 respectively).

Conclusions

C807T TT genotype may confer a risk for thrombosis and Kozak TC genotype for arterial thrombosis. D allele of VNTR may protect from APS. No patients with C807T TT or Kozak TC genotypes carried the protective DD genotype of VNTR. These polymorphisms may increase risk for both arterial and venous thrombosis. The utility of prophylaxis with anti-platelet drugs in at least a subgroup of APS patients should be investigated with clinical trials.