Retroperitoneal laparoscopic resection of adrenal tumor in pregnant woman with cushing's syndrome.

Cushing's syndrome (CS) during pregnancy is rare. It causes the clinical disorder by overproduction of cortisol. Hypercortisolemia in pregnancy can lead to severe complications, both for the mother and the fetus, including spontaneous abortion, perinatal death, prematurity, maternal hypertension, heart failure, diabetes and opportunistic infections. The most common cause of hypercortisolemia in pregnancy is a cortisol-secreting adrenal tumor. Herein we present a 31 year-old female patient, at 20 weeks' gestation, with CS secondary to a left adrenal tumor. A brief review of reported similar cases is included.

Evaluation of renal excretion and pharmacokinetics of furosemide in rats after acute exposure to high altitude at 4300 m.

With studies indicative of altered renal excretion under high altitude-induced hypobaric hypoxia, the consideration of better therapeutic approaches has long been the aim of research on the management of high altitude related illness. The pharmacokinetics of drugs such as furosemide might be altered under hypoxic conditions, making it essential to establish different dose-regimens to maintain therapeutic efficacy or to avoid toxic side effects at high altitude. Simultaneously, drug-drug interactions (DDIs) mediated by OAT1 occur at high altitude, severely affecting furosemide pharmacokinetics. This study investigated the influence of acute exposure to high altitude at 4300 m on the renal excretion of furosemide in rats. Significant changes in physiological parameters and kidney histopathology were found after acute high altitude exposure. Compared with low altitude, the pharmacokinetics of furosemide and the expression level of OAT1 in kidney were significantly changed after rapid ascent to high altitude. Additionally, the down-regulated OAT1 expression further sustained the potential mechanism for the decreased renal excretion of furosemide, resulting in extended residence of the drug in the human body. The elevation of AUC, Cmax , MRT, t1/2 of furosemide, and decreased CL at high altitude further reinforced the current findings. Moreover, the absorption of furosemide was markedly increased and renal excretion significantly declined after co-administration of captopril, resulting in local drug interaction at high altitude. In conclusion, acute exposure to high altitude may significantly affect the renal excretion of furosemide and the pharmacokinetic parameters of furosemide were altered after co-administration of captopril, which may then impact the conventional therapeutic dosage.

[Effect of hypoxia on expression of multidrug resistance protein 2 and its regulation mechanism].

Drug efflux transporters plays a key role in pharmacokinetics parameters changes. In recent years, in addition to P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), MRP2 has become an advanced research hotspot. Several signaling pathways andtranscription factors have been reported to be involved in regulation of MRP2 expression in hypoxic microenvironment of tumor, such as peroxisome proliferators-activated receptors (PPARα), nuclear factor κB (NF-κB), pregnane X receptor (PXR), farnesoid X receptor (FXR), constitutive androstane receptor (CAR) and microRNA. But it is not fully understood how MRP2 is regulated under hypoxia. MRP2 is one of the most important efflux transporter proteins. Many drugs or inhibitors have been shown to be its substrate. In the hypoxic environment, changes in expression of MRP2 can significantly affect drug's pharmacokinetics (absorption, distribution, metabolism, excretion). Simultaneously, the regulation of MRP2 expression under hypoxic might involve several signal pathways and many genes, which constitute an integral gene regulatory networks.

[Changes of P-gp expression in rats' small intestine and effects on uptake of levofloxacin after acute exposure to hypoxia].

The drug transporter play a key role in the absorption of drugs. Investigation of the changes of drug transporters in response to hypoxia will provide insight into the mechanism of drug absorption. In this study we investigated the mRNA and protein expression of the transporter P-gp after acute hypoxia, and evaluated the effects of P-gp changes on absorption of levofloxacin in the intestine. The relative expression of m RNA and protein were reduced by 50.80% and 71.30%(P < 0.05). In the single-pass intestinal perfusion model, the intestinal wall permeability was increased by 56.16%, 226.00%, 77.74% and 141.00% in the time intervals at 30-60 min, 60-90 min, 90-120 min and 120-150 min although P-gp expression was decreased(P < 0.05). These results suggest that hypoxia may decrease the expression of P-gp in the intestine to reduce the excretion of levofloxacin and increase the absorption.

Effects of almond intake on oxidative stress parameters: A systematic review and meta-analysis of clinical trials.

BACKGROUND AND AIMS: Several randomized controlled trials (RCTs) have shown that almonds can improve oxidative stress indices, but the results are controversial. Therefore, the goal of this research was to carry out a systematic review and meta-analysis of all RCTs that evaluated the effect of almonds on selected oxidative stress indices. METHODS: A systematic search was conducted up to April 2022 on PubMed, Scopus, Web of Science, and Google Scholar. We have selected the studies that investigated the effects of almonds on malondialdehyde (MDA), and oxidized low-density lipoprotein (Ox-LDL) levels in adults. Data were pooled by using the random-effects model. The risk of bias in individual studies was assessed using the Cochrane Collaboration risk of bias tool. RESULTS: Seven RCTs involving 424 participants were analyzed. The results indicated that almond intake led to a significant decrease in MDA levels (WMD: - 6.63 nmol/ml; 95 % CI: - 8.72 to - 4.54; P < 0.001). However, no significant effect was observed on Ox-LDL (Hedges' g: - 0.12; 95 % CI: - 0.34 to 0.10; P = 0.28). Sensitivity analysis showed that overall estimates were not affected by the elimination of any study. We did not observe any evidence regarding publication bias. CONCLUSION: The present meta-analysis suggests that almond intake can improve MDA levels and might play a beneficial role in the reinforcement of the antioxidant defense system and amelioration of oxidative stress in adults. There is a need for more studies with larger groups to better estimate this effect.

Increased NUSAP1 expression is associated with lymph node metastasis and survival prognosis in bladder urothelial carcinoma.

The main route of metastasis of bladder urothelial carcinoma is through lymph nodes; however, its exact mechanism remains unclear. In this study, we found an association of nucleolar and spindle associated protein 1 (NUSAP1) expression with BUC tissues along with lymph node metastasis and the survival prognosis. A total of 178 pathological specimens following radical bladder cancer resection were obtained. NUSAP1 expression was analyzed by immunohistochemistry. We evaluated the correlation between clinicopathological characteristics and NUSAP1 expression. Logistic regression was used to determine the independent variables that influenced lymph node metastasis. Uni- and multi-factorial Cox regression methods were used to determine the prognostic value of NUSAP1 expression in urothelial carcinoma of the bladder. High expression of NUSAP1 in BUC was not significantly related to the patient's gender, age, or tumor number (p > 0.05), however was significantly associated with pathological grade, tumor diameter, pathological stage, and lymph node metastasis (p < 0.05). Lymph node metastasis was significantly correlated with pathological stage, pathological grade, tumor number, tumor diameter, and NUSAP1 expression (p < 0.05); only NUSAP1 expression was an independent predictor of lymph node metastasis in BUC (OR:1.786, 95% CI 1.229-2.596, p = 0.002). In addition, high NUSAP1 expression was an independent prognostic predictor for BUC. In BUC, NUSAP1 showed high expression and was significantly associated with lymph node metastasis, pathological stage, pathological grade, and tumor diameter. NUSAP1 was an independent predictor of lymph node metastasis and prognosis in BUC; higher expression indicated poorer prognosis of BUC patients.

Exosome-Derived miRNAs as Potential Biomarkers for Prostate Bone Metastasis.

Purpose: The purpose of this study was to identify the potential exosome-derived microRNAs (miRNAs) related to prostate cancer (Pca) bone metastasis. Methods: Two datasets were collected. One dataset was from the authors' institute, for which two groups of 10 patients each were designed: in the first one, the patients had early-stage localised Pca without bone metastasis, and in the other, the patients presented with Pca with bone metastasis. Then, the miRNA expression profiles of the blood exosomes were obtained and analysed. The other dataset was a public dataset of the miRNA expression transcriptome (GSE26964), which was downloaded from Gene Expression Omnibus (GEO). The results of both datasets were jointly analysed and the most bone-metastatic-related differentially expressed miRNAs (diff-miRNAs) were identified and further validated. Finally, a series of bioinformatics analyses were performed and the relationship between target genes of the diff-miRNAs and the pathogenesis and progression of bone metastasis of Pca were studied. Results: From the authors' dataset, in all, 313 diff-miRNAs were identified, of which 205 were up-regulated while 108 were down-regulated. From the GSE26964 dataset, 107 diff-miRNAs were found, of which 44 were up-regulated and 63 were down-regulated. Taking the intersection of the results of both datasets, four diff-miRNAs were identified: hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613. In all, 94 target genes of the four diff-miRNAs were predicted. After considering the intersection of the results from the GSE32269 dataset, we obtained 25 target genes. Although either positive or negative correlations were found among the diff-miRNAs with some of the target genes, there is a lack of evidence on how such correlations regulate the development and promotion of Pca bone metastasis. Conclusion: Hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613 are potential biomarkers for Pca bone metastasis.

microRNA-145-5p inhibits prostate cancer bone metastatic by modulating the epithelial-mesenchymal transition.

Objective: To investigate the effects of miRNA-145-5p on the tumor development and progression of prostate cancer (Pca) bone metastasis. Methods: Levels of miRNA-145-5p were assessed by real-time quantitative PCR in PC3 (bone metastatic Pca cells), 22RV1 (non-metastatic Pca cells), RWPE-1 (non-cancerous prostate epithelial cells) and Pca tissues collected from patients with and without bone metastases. The impact of miRNA-145-5p on cell proliferation was tested by CCK8 assay, colony formation assay and flow cytometric cell cycle analysis. Effects on invasion and migration of PC3 cells were determined by Transwell and wound healing assays. Western blotting, enzyme-linked immunosorbent assay, and flow cytometry apoptosis analyses were also performed to assess roles in metastasis. Results: Levels of miRNA-145-5p were decreased in Pca bone metastases and miRNA-145-5p inhibited cell proliferation, migration and invasion. miRNA-145-5p inhibited the expression of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) and transforming growth factor-ß (TGF-ß) in PC3 cells. miR-145-5p increased the expression of the epithelial marker E-cadherin and reduced the expression of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9). It was found that miRNA-145-5p mediated the epithelial-mesenchymal transition (EMT) and induced apoptosis. Conclusions: miRNA-145-5p negatively regulated the EMT, inhibited Pca bone metastasis and promoted apoptosis in Pca bone metastasis. Mimicry of miRNA-145-5p action raises the possibility of a novel target for treating Pca with bone metastases.

Adrenocorticotropic Hormone-Independent Cushing Syndrome with Right Adrenal Adenoma and HIV Infection: A Case Report.

BACKGROUND: Adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome (CS) with right adrenal adenoma combined with HIV infection has rarely been reported. CASE PRESENTATION: A 39-year-old Chinese male patient with HIV infection was admitted to our hospital due to increased blood pressure in the previous 2 years and weight gain in the previous 6 months. Endocrinological examinations showed that blood cortisol (8 a.m.) was 22.23 µg/dl, the level of ACTH (8 a.m.) was less than 1pg/ml and twenty-four-hour urinary cortisol was 1429 µg/24h. ACTH-independent CS was diagnosed based on low ACTH levels (<1.00 pg/ml), a lack of cortisol circadian rhythms, and unsuppressed cortisol levels by dexamethasone. The ultrasonography and multislice spiral computed tomography scan revealed a right adrenal mass. Due to the HIV status of the patient, we measured the count of CD4+ T helper cells. Laparoscopic right adrenal resection was performed after the CD4+ T helper cell count was > 200 cells/µl. Subsequent immunohistochemical staining confirmed right adrenal adenoma. RESULTS: The postoperative recovery was good, and wound healing was possible. After surgical treatment, endocrinological examinations indicated that the level of ACTH increased and the levels of serum cortisol and twenty-four-hour urinary cortisol decreased, which indicated that CS was controlled. CD4/CD8 was 0.47 at reexamination, and the patient's immunity was improved. CONCLUSION: Due to the potential side effects of steroid drugs, clinicians should use these medications with caution and closely monitor the development of adrenal deficiency.

Successful endoscopic surgery for emphysematous pyelonephritis in a non-diabetic patient with autosomal dominant polycystic kidney disease: A case report.

BACKGROUND: Emphysema pyelonephritis (EPN) is a very dangerous type of urinary tract infection. It is a lethal disease that develops rapidly and causes the patient to deteriorate rapidly, and it can easily lead to systemic infections and even sepsis. The incidence is extremely low, and it is prevalent in patients with diabetes. We here report a case of EPN in a non-diabetic patient with autosomal dominant polycystic kidney disease (ADPKD). We share the diagnosis and treatment procedure for this extremely rare condition to make this disease easier to identify and address early. CASE SUMMARY: A 47-year-old woman presented to the emergency department of our hospital with a high fever and left back pain lasting 4 d. She had a history of autosomal dominant polycystic kidney and polycystic liver. She was diagnosed with left type I EPN and her vital signs deteriorated so quickly that she underwent an emergency operation in which a D-J tube was inserted into her left ureter on the second day after admission. Two months later, she underwent a second-stage flexible ureteroscopy and lithotripsy. Despite postoperative sepsis, she finally recovered after active symptomatic support treatment and effective anti-infective treatment. CONCLUSION: Although EPN is more likely to occur in diabetic patients, for non-diabetic patients with ADPKD and upper urinary tract obstruction, the disease also causes rapid deterioration. Early and accurate diagnosis and timely removal of the obstruction by invasive means may be able to save the damaged kidney and the patient's life.

Pharmacokinetic changes of norfloxacin based on expression of MRP2 after acute exposure to high altitude at 4300m.

BACKGROUND: This study was to investigate the influence of physiological changes and the expression of MRP2 efflux transporter on the pharmacokinetics of norfloxacin after acute exposure to high altitude 4300m. METHODS AND RESULTS: The rats were randomly divided into high altitude group and plain group. Blood gas and biochemical analysis showed that the physiological parameters significantly changed at high altitude. The mRNA and protein expression of MRP2 in high altitude group were higher than plain group in rat small intestine and kidney, while was reduced in rat liver. The AUC, Ka and Cmax of norfloxacin were significantly reduced in high altitude group (p<0.05). However, the MRT, CL, t1/2 and Vd were significantly increased (p<0.05). CONCLUSIONS: These results indicate that physiological indicators and expression levels of drug transporters MRP2 are changed in responded to high altitude, to severely affect norfloxacin pharmacokinetics. These changes may provide basis and new ideas to adjust the dosage and administration, so as to promote rational drug use in the high altitude.

[Effect of hypoxia on expressions of MDR1 and MRP2 in rats].

OBJECTIVE: To study the changes in the physiological parameters and gene expression of two drug efflux transporters MDR1 and MRP2 in the small intestine, liver and kidney of rats exposed to acute hypoxia. METHODS: Eighteen Wistar rats were randomly divided into control group, hypoxia for 24 h group and hypoxia for 72 h group. Blood samples were obtained from the abdominal aorta of the rats after the exposure for analyzing the physiological indexes. The mRNA expressions of MDR1 and MRP2 were determined using Real-Time PCR, and their protein expressions were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: The physiological parameters of the rats in hypoxia group were significantly changed compared with those in the control group. The expressions of MDR1 and MRP2 mRNA and proteins in the small intestine, liver and kidney were significantly increased in rats with hypoxic exposure than in the control rats (P<0.05 or 0.01). As the hypoxic exposure prolonged, the two transporters showed different patterns of variation in different tissues. CONCLUSION: Acute hypoxia affects the physiological parameters and expression levels of MDR1 and MRP2, thus causing changes in the metabolism of the substrates of the transporters. These changes may play an important role in the pharmacokinetics of drugs at a high altitude.