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Overcoming drug-resistance is a big challenge to improve the survival of patients with epithelial ovarian cancer (EOC). In this study, we investigated the effect of chloroquine (CQ) and its combination with cisplatin (CDDP) in drug-resistant EOC cells. Tubacin in vivo We used the three EOC cell lines CDDP-resistant A2780-CP20, RMG-1 cells, and CDDP-sensitive A2780 cells. The CQ-CDDP combination significantly decreased cell proliferation and increased apoptosis in all cell lines. The combination induced expression of γH2AX, a DNA damage marker protein, and induced G2/M cell cycle arrest. Although the CQ-CDDP combination decreased protein expression of ATM and ATR, phosphorylation of ATM was increased and expression of p21WAF1/CIP1 was also increased in CQ-CDDP-treated cells. Knockdown of p21WAF1/CIP1 by shRNA reduced the expression of γH2AX and phosphorylated ATM and inhibited caspase-3 activity but induced ATM protein expression. Knockdown of p21WAF1/CIP1 partly inhibited CQ-CDDP-induced G2/M arrest, demonstrating that knockdown of p21WAF1/CIP1 overcame the cytotoxic effect of the CQ-CDDP combination. Ectopic expression of p21WAF1/CIP1 in CDDP-treated ATG5-shRNA/A2780-CP20 cells increased expression of γH2AX and caspase-3 activity, demonstrating increased DNA damage and cell death. The inhibition of autophagy by ATG5-shRNA demonstrated similar results upon CDDP treatment, except p21WAF1/CIP1 expression. In an in vivo efficacy study, the CQ-CDDP combination significantly decreased tumor weight and increased expression of γH2AX and p21WAF1/CIP1 in A2780-CP20 orthotopic xenografts and a drug-resistant patient-derived xenograft model of EOC compared with controls. These results demonstrated that CQ increases cytotoxicity in combination with CDDP by inducing lethal DNA damage by induction of p21WAF1/CIP1 expression and autophagy inhibition in CDDP-resistant EOC.BACKGROUND Repetition disorder can be used as an important criterion for aphasia classification, and damaged arcuate fasciculus in the dominate hemisphere has been reported to be closely related to repetition disorder, but the underlying neurological mechanism remains unclear. MATERIAL AND METHODS Fifteen stroke patients with poststroke aphasia and 9 healthy controls were included in the study. The value of fractional anisotropy (FA) in the dominate arcuate fasciculus in stroke patients and healthy controls were measured using DTI. We also assessed their repetition dysfunction with the Aphasia Battery of Chinese (ABC) assessment and calculated the correlation between the FA values in the dominate arcuate fasciculus and ABC scores of word repetition and sentence repetition. RESULTS There was a moderate correlation between the total score of repetition evaluation and the FA value of injured arcuate fasciculus in the dominant hemisphere (r=0.551, P=0.033). We found no correlation between the score of word repetition and the FA value of injured arcuate fasciculus in the dominant hemisphere (r=0.330, P=0.230), but there was a strong correlation between the score of sentence repetition and the FA value of injured arcuate fasciculus in the dominant hemisphere (r=0.795, P≤0.001). CONCLUSIONS We found that unintegrated left arcuate fasciculus might be related to the repetition dysfunction after stroke, especially sentence repetition deficit, which suggests that sentence repetition evaluation could be used to indicate the integrity of the arcuate fasciculus in the dominant hemisphere after stroke.BACKGROUND Duodenal trauma usually consists of retroperitoneal lesions. Its management can be complicated by the location of the injury and difficulty in making an early diagnosis. Duodenal injuries are divided into blunt and penetrating trauma, and the possible results are hematoma, laceration, and devascularization. Duodenal lesions due to blunt trauma are usually accompanied by lesions of nearby organs. We present a rare case of a single duodenal laceration due to blunt abdominal trauma caused by a horse kick, along with a literature review. CASE REPORT A 13-year-old boy presented to our emergency department after being kicked by a horse in his abdomen. He was stable and complained of abdominal pain without any other specifications. Computed tomography imaging revealed a retropneumoperitoneum and free fluid in the abdominal cavity. The patient was taken for an emergency laparotomy, which showed a single duodenal laceration of the second and third portions of the duodenum. The laceration was repaired with a double-layer closure using monofilament 3-0 polypropylene suture. The patient recovered from his injuries and was well at his last follow-up. CONCLUSIONS This case highlights the possible outcomes of an innocent blunt trauma and the importance of early diagnosis for the best outcome of a duodenal laceration. It also identifies the dissociation between the patient's clinical presentation and his significant intra-abdominal injury.
Calcium channel blockers (CCBs) are commonly used agents in the treatment of hypertension as part of monotherapy or combination therapy. Peripheral edema is the most common side effect that requires discontinuation or replacement of treatment. Some studies in the literature have shown that long-acting dihydropyridine type CCBs lead chylous ascites in peritoneal dialysis patients. However, amlodipine-associated serous ascites cases are not available in the literature.
In this case report, we describe a rare case of amlodipine induced massive ascites in a 30-year-old male with renal transplantation.
We aimed to create awareness that pharmacologic causes should be considered in cases of ascites of unknown aetiology.
We aimed to create awareness that pharmacologic causes should be considered in cases of ascites of unknown aetiology.
Sirolimus (Rapamune) is an important immunosuppressive drug in kidney transplant patients. The usual maintenance dose of Sirolimus in these patients is 2 to 5 mg/d and its optimal maintenance trough level is 5 to 10 ng/mL. The required Sirolimus doses may differ markedly from patient to patient. It is because of high inter and intrapatient variability in its pharmacokinetics. link2 There have been no studies in Iran on the correlation of Sirolimus blood level and its target dose. This study has been done to show the target dose of Sirolimus in kidney transplanted patients in Isfahan.
This is a longitudinal cross-sectional study conducted from June 2018 to September 2019. The study population included all kidney transplanted patients treated with Sirolimus in a nephrology private clinic. Inclusion criteria were age (equal or more than 18 years old) and the existence of complete data in the patient's file. The participants were excluded if there were not at least two Sirolimus levels in the patient's file. Demogranian kidney transplant recipients needed lower daily doses of Sirolimus (1.2 mg/d) to achieve the desired whole blood level. Further studies are recommended to confirm it.
Atherosclerosis is associated with increased intima- media thickness (IMT) and vascular calcification (VC) in maintenance hemodialysis (MHD) patients. Fetuin-A is a serum protein, which inhibits vascular calcification. The aim of this study was to investigate the association between fetuin-A and VC, in a group of MHD patients.
One hundred and forty-three MHD patients were included and followed for 3 years. link3 Blood samples were studied for calcification and inflammation markers and fetuin-A was checked 3 times at the start, middle and the end of the study. We used common carotid doppler sonography for assessment of indices of VC, which were performed at baseline and at the end of the study. Vascular calcification was defined as a common carotid intima media thickness ≥ 0.8 mm on either side or the existence of any plaque or stenosis ≥ 50% on either side.
From 143 patients (mean age 57.5 ± 15.9, 60.1% male), 104 patients (75.4%) had VC at baseline. The mean age and the prevalence of DM were significantly hiients with VC. We didn't find any correlation between the level of fetuin-A and VC. It seems that the traditional risk factors of VC, including age and diabetes mellitus are the main predictors of VC in MHD patients.
L-Carnitine is a cardioprotective agent which balances metabolism by promoting mitochondrial β-oxidation and facilitating transportation of long chain fatty acids into the mitochondrial matrix. It has been shown that L-Carnitine level in plasma and tissue is lower in hemodialysis patients and they may lose the benefits of this substance. The aim of this trial was to evaluate the effects of L-Carnitine supplementation on cardiorespiratory Function in hemodialysis patients through ergospirometry.
The current study was conducted on 46 chronic hemodialysis patients. The patients were divided into two groups. In both groups ergospirometry parameters (VE Max, VO2-Max and VCO2 Max, AT, VE/VCO2 Slope) were recorded for a 3-month period of time. During this period, one group received L-Carnitine at doses of 2 g/d orally and the other group received only placebo. After three months, all of the mentioned parameters reevaluated and statistical analysis was done.
Only CRP value was different between two group and in placebo group increased significantly after 3 months (P < .05). No significant difference was detected in Cardio-respiratory factors. In terms of ergospirometry, PET-CO2 was the only parameter which was significantly increased in the treatment group but decreased in placebo group (P < .05).
Significant differences between our groups showed that L-Carnitine could help hemodialysis patients with cardiopulmonary problems to suffer lower rate of inflammation and poor life quality as shown at least in comparison of the two factors including CRP and PETCO2 at rest.
Significant differences between our groups showed that L-Carnitine could help hemodialysis patients with cardiopulmonary problems to suffer lower rate of inflammation and poor life quality as shown at least in comparison of the two factors including CRP and PETCO2 at rest.
To avoid temporary hemodialysis, urgent initiated PD (UIPD) has been designed. In these patients, PD is initiated within 3 days after PD catheter placement. In this study, we evaluated the outcomes of UIPD in end-stage renal disease patients compared with the conventional start of PD.
This is a single-center observational study, comparing outcomes of UIPD to conventional initiation of PD. All patients diagnosed with ESRD from March 2013 to February 2019 and were willing for CAPD were recruited. In UIPD group treatment was initiated at day 2 of catheter insertion with a dialysate volume of 1000 mL per dwell for 2 hours gradually increased to 2000 mL per dwell volume by 8 to 10 days.
During the study period, 98 patients were started on peritoneal dialysis in our hospital 35 UIPD, 63 conventional PD. The mean age was 60.81 ± 13.04 years. 67% of patients were males with diabetes mellitus (32%) being the most common cause of CKD. Among the patients in UIPD, the mean age was 58.49 ± 16.1 years, while as in conventional group mean age was 62.10 ± 10.9 years. The Median follow-up time was 381 days. Technique survival was seen in 95 patients (96.9%). There was no difference in technique failure between UIPD vs conventional group. Total complications in our study occurred in 16 patients out of 98 patients during this period. There was no significant difference in the complication rates between the UIPD group and the conventional group.
Our study showed that catheter patency, technique survival, and catheter-related complications were comparable between UIPD and conventional start peritoneal dialysis.
Our study showed that catheter patency, technique survival, and catheter-related complications were comparable between UIPD and conventional start peritoneal dialysis.
Homepage: https://www.selleckchem.com/products/Tubacin.html
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