Cardioprotective effects of fetal kidney-derived mesenchymal stem cells on doxorubicin-induced cardiotoxicity in rats

Cardiotoxicity is one of the most common side effects of doxorubicin (DOX), a chemotherapy drug used in the treatment of many carcinomas. In recent years, stem-cell therapies have been successfully used to prevent cardiotoxicity. This study investigated the efficacy of intraperitoneally administered fetal kidney-derived mesenchymal stem cells (FKD-MSCs) in preventing DOX-induced cardiotoxicity in rats. For this purpose, thirty rats were randomly divided into three groups: control, DOX and mesenchymal stem cell (MSC) groups. Adriamycin was injected as a single dose via the tail vein in the DOX and MSC groups in order to induce cardiotoxicity. FKD-MSC was applied to the MSC group by the intraperitoneal route after cardiotoxicity had been established. Then the rats were euthanized, and routine histological procedures were performed on their hearts. H&E and Masson’s stains were used for histopathology. Cardiac Troponin-T and I (cTnT, cTnI), Caspase-3 and BCL-XL antibodies were used for immunohistochemistry. Vacuoles, edema, degeneration and necrosis were observed histopathologically mostly in the DOX group. Lesions in the control and MSC groups were less severe. Fibrosis in the control and MSC groups was milder. cTnT and cTnI immunopositive staining was most commonly seen in the control group, followed by the MSC group. Immunohistochemical staining by Caspase-3 and BCL-XL showed that their expressions in the MSC group were statistically similar to those in the control group. Accordingly, it was concluded that the intraperitoneal application of MSC had a positive effect on histopathological findings, fibrosis, immunohistochemistry, especially apoptosis, neovascularization, and anti-apoptotic development, whereas troponin levels were not found to be therapeutic.

Fetal Renal Volume and Fetal Renal Artery Doppler in Normal and Intrauterine Growth Restricted Fetuses

Background: Human fetal kidney undergoes constant changes throughout the pregnancy to attain final maturity in terms of structural and functional aspect. Approximately one million nephrons are seen on either side at birth in term fetuses. Many factors both maternal and fetal affect nephrogenesis viz. maternal malnutrition, maternal hyperglycemia, Intrauterine Growth Restriction (IUGR), vitamin A deficiency, and fetal exposure to some drugs. The aim of this study was to evaluate changes in the fetal renal artery Doppler parameter and fetal kidney volume measured by 3D ultrasound system with (VOCAL) method in normally grown and growth restricted fetuses after 26 weeks of gestation. Methods: This prospective study include 60 pregnant women divided in to two groups, first one (A) contains 30 pregnant women with intrauterine growth restricted fetuses, and the second one (B) contains 30 pregnant women with normally grown fetuses. Results: There was insignificant differences between two groups as regard gestational age by date but gestational age by US there was significant decrease in group A. There were insignificant differences between two groups as regard length of kidney either right or left. There was significant decrease in kidney width right and left side in group A versus group B. There was significant decrease in kidney depth right and left side in group A versus group B. There was significant decrease in kidney volume right and left side in group A versus group B. There was significant decrease in combined kidney volume in group A versus group B. There was significant increase in renal artery PI, RI in group A versus group B. Conclusions: Fetal hypoxemia which occurs in growth restricted fetuses leads to reduction in the percentage of the cardiac output reaching the kidneys which was reflected on Doppler as increase in the renal artery pulsatility index causing reduced renal perfusion. This reduction in the renal perfusion was responsible for impaired nephrogenesis and thus decreased kidney volume in growth restricted fetuses as compared to normal fetuses.

Possible Relevance of Soluble Luteinizing Hormone Receptor during Development and Adulthood in Boys and Men

Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are agonists for the luteinizing hormone receptor (LHCGR) which regulates male reproductive function. LHCGR may be released into body fluids. We wish to determine whether soluble LHCGR is a marker for gonadal function. Cross-sectional, longitudinal, and intervention studies on 195 healthy boys and men and 396 men with infertility, anorchia, or Klinefelter Syndrome (KS) were used to correlate LHCGR measured in serum, seminal fluid, urine, and hepatic/renal artery and vein with gonadal function. LHCGR was determined in fluids from in vitro and in vivo models of human testicular tissue and cell lines, xenograft mouse models, and human fetal kidney and adrenal glands. Western blot showed LHCGR fragments in serum and gonadal tissue of similar size using three different antibodies. The LHCGR-ELISA had no species cross-reactivity or unspecific reaction in mouse serum even after human xenografting. Instead, sLHCGR was released into the media after the culture of a human fetal kidney and adrenal glands. Serum sLHCGR decreased markedly during puberty in healthy boys (p = 0.0001). In healthy men, serum sLHCGR was inversely associated with the Inhibin B/FSH ratio (β −0.004, p = 0.027). In infertile men, seminal fluid sLHCGR was inversely associated with serum FSH (β 0.006, p = 0.009), sperm concentration (β −3.5, p = 0.003) and total sperm count (β −3.2, p = 0.007). The injection of hCG lowered sLHCGR in serum and urine of healthy men (p < 0.01). In conclusion, sLHCGR is released into body-fluids and linked with pubertal development and gonadal function. Circulating sLHCGR in anorchid men suggests that sLHCGR in serum may originate from and possibly exert actions in non-gonadal tissues. (ClinicalTrials: NTC01411527, NCT01304927, NCT03418896).

Outcomes of intrauterine interventions for the treatment in fetal urinary tract obstructions

Introduction: The leading cause of chronic renal failure in newborns, which occurs soon after birth is obstructive uropathies. Objectives: To prove the effectiveness of nephroamniotic shunting based on the evaluation of perinatal outcomes of this procedure, as well as a comparative analysis of the use of the stent manufactured by "Cook" (Ireland), 3.0 Fr/100 mm and the stent “SDE–MED”, 3.0 Fr/50 mm with the original shape of pigtails. Methods: After checking the safety of the stent “SDE-MED”, 3.0 Fr/50 mm developed by FGBU Mother and Child Care Research Institute with the original shape of pigtails in an animal experiment, the stent was used in clinical practice for intrauterine shunting in cases of unilateral or bilateral hydronephrosis of grade III to IV and posterior urethral valve disorder. In the final part of the study, a comparison of the outcomes of nephroamniotic shunting using two different stents was made. Results: The “SDE–MED” 3.0 Fr/50 mm stent provided more effective fixation in the fetal kidney cavity system in comparison to the stent manufactured by “Cook” (Ireland) 3.0 Fr/100 mm. Conclusion: Intrauterine shunting surgery of the upper urinary tract is a pathogenetically justified method of treating urinary tract obstructions and can be used to correct all types of fetal renal obstructions.

Determination of Gestational Age by Fetal Kidney Length Measurement after the 20th Week in Healthy Women with Uncomplicated Pregnancy in Tertiary Care Centre

Introduction: Various organs are measured to estimate the gestational age of fetus. Sonographically derived parameters used to date pregnancy include Crown rump length, Biparietal diameter, Head circumference, Femoral length and Abdominal circumference. Fetal kidney length, transcerebellar diameter and placental thickness are emerging as new parameters and are claiming to be more accurate in certain situations. In Nepalese context fetal kidney length has not been studied yet so this study was done to fill this need. Methodology: Obstetric sonography was performed in 108 pregnant women with uncomplicated pregnancy to evaluate the efficacy of FKL as a measure to calculate the predicted gestational age. Gestational age ranged from 20 weeks to term. Only patient with known LMP, previous history of normal menstrual cycle and without any exclusion criteria were included in the study. Results: The study showed mean fetal kidney length at 20-24, 25-29, 30- 34 and 35-37 weeks gestation as 22.5±0.5, 26.9±0.7, 32.32±0.7 and 36.3±0.6 respectively. Overall in combined second and third trimester , fetal kidney length showed strong linear correlation with gestation age with highest significant Pearson correlation coefficient of 0.989 as compared to other parameters (BPD=0.986, HC=0.976, AC=0.971, FL=0.984). Conclusion: Fetal kidney showed strongest linear correlation with clinical gestational age and it also demonstrated positive correlation with biparietal diameter, head circumference, abdominal circumference and femur length. Therefore fetal kidney length can be used as a reliable parameter for determination of gestational age.

Correlation between Fetal Renal Blood Flow and Fetal Kidney Volume in Normal and Growth Restricted Fetuses

Background: Some trials have shown decreased weight of fetal kidney in cases of reduced neonatal weight and infants with growth-restriction at birth. In infants with growth-restriction due to poor nutrition, most of the fetal blood supply is directed to vital organs such as fetal heart and brain that leads to deprivation of remaining organs from its nutrients, such as kidney. This work aimed to assess whether the size of fetal kidney in cases of normal and restricted fetal growth patterns after 28 weeks could be affected by reduced fetal renal blood supply or not. Methods: This case-control trial included 60 patients who were divided into two groups: Each group composed of 30 patients; Study group: fetuses with IUGR and control group: fetuses with normal growth pattern. Results: There was no significance between both study groups as regard to age, weight, BMI, and gravidity. No significance between the studied groups regarding the clinical findings, gestational age, diabetes, HTN, congenital fetal anomalies, and previous C.S. A high significance was present among both groups as regard to measurements of renal artery Doppler. A correlation of statistical significance was noted as regard Doppler indices and kidney volume in the study group. Conclusions: The elevated pulsatility index of the renal artery of fetus in fetuses with IUGR showed -ve correlation with the volume of the fetal kidney, resulting in reduced nephron-genesis and perfusion. Restrictions in intrauterine growth are believed to be associated with a significant reduction in renal volume compared to the normal growth of fetuses. The Doppler of renal artery also reveals significant differences among study groups.