Evaluation and correlation of placental vasculature by three-dimensional power Doppler ultrasonography with umbilical Doppler in normal and IUGR pregnancies

Background: In recent years there have been significant developments in the use of 3D Power Doppler (3DPD) imaging and quantitative 3DPD histogram analysis to estimate both placental volume and intraplacental vasculature. This study is to evaluate the distribution and variation of placental vascular indices according to gestational age and placental volume and position. Co relate the umbilical Doppler indices with placental vascular indices.Methods: From September 2016 to October 2017, three-dimensional (3D)-power Doppler ultrasound was performed in 200 singalton pregnancies from 20 to 40 weeks of gestation. Using the same pre-established settings for all patients, power Doppler was applied to the placenta and placental volume was obtained by the rotational technique (VOCAL). The 3D-power histogram was used to determine the placental vascular indices: vascularization index (VI), flow index (FI) and vascularization-flow index (VFI). Umbilical Doppler was measured on the free loop of umbilical cord. The placental vascular indices were then plotted against gestational age placental volume, position and umbilical Doppler SD ratio, PI and RI. These values were evaluated in IUGR fetus.Results: Analysis of the results showed that the placental vascular indices estimated by 3D-power Doppler ultrasonography presented constant distribution throughout gestation despite the significant increase in placental volume. Placental position at fundal region shows higher value of VI, FI, and VFI. Placental position with relation to VI, FI, and VFI shows statistically significant with p value <0.01. Placental vascular indices VI, FI and VFI when corelated with systolic/ diastolic ratio, pulsatility index and resistive resistance index of umbilical artery shows poor negative correlation, only VI and FI shows statistically significant with SD ratio as p value is <0.01and <0.04. VFI did not show statistically significant as p value is 0.10(NS). With pulsatility index p value is statistically significant is less than<0.01 with vascular indices. Resistive index p value is statistically significant is less than <0.01 for VI and VFI but not significant with FI as p value is 0.06.Conclusions: Doppler ultrasound assists in the evaluation of placental vascularization in normal and IUGR pregnancies, may play an important role in future research on fetoplacental insufficiency

Renal Cystic Disease Proteins Play Critical Roles in the Organization of the Olfactory Epithelium

It was reported that some proteins known to cause renal cystic disease (NPHP6; BBS1, and BBS4) also localize to the olfactory epithelium (OE), and that mutations in these proteins can cause anosmia in addition to renal cystic disease. We demonstrate here that a number of other proteins associated with renal cystic diseases – polycystin 1 and 2 (PC1, PC2), and Meckel-Gruber syndrome 1 and 3 (MKS1, MKS3) – localize to the murine OE. PC1, PC2, MKS1 and MKS3 are all detected in the OE by RT-PCR. We find that MKS3 localizes specifically to dendritic knobs of olfactory sensory neurons (OSNs), while PC1 localizes to both dendritic knobs and cilia of mature OSNs. In mice carrying mutations in MKS1, the expression of the olfactory adenylate cyclase (AC3) is substantially reduced. Moreover, in rats with renal cystic disease caused by a mutation in MKS3, the laminar organization of the OE is perturbed and there is a reduced expression of components of the odor transduction cascade (Golf, AC3) and α-acetylated tubulin. Furthermore, we show with electron microscopy that cilia in MKS3 mutant animals do not manifest the proper microtubule architecture. Both MKS1 and MKS3 mutant animals show no obvious alterations in odor receptor expression. These data show that multiple renal cystic proteins localize to the OE, where we speculate that they work together to regulate aspects of the development, maintenance or physiological activities of cilia

Pregnancy outcome in renal transplant recipients: Indian scenario

Background: Pregnancy in renal transplant recipient is a high risk pregnancy, associated with increased risk of graft rejection and other complications. Many pregnancies have been reported, still there is limited data on optimal counseling and clinical management of these patients. Objectives: To study maternal and fetal outcomes in renal transplant recipients. Material and methods: Study design: This is a retrospective observational study conducted at tertiary health center in Ahmedabad, from 2004 to 2014. Sample size: There were 3016 renal transplant recipients out of which 2507 were males and 509 were females. Among 509 females, 211 recipients were in reproductive age group (20–40 years) who were included in the study. Out of 211 recipients, 113 (53.5%) had complete family, 46 (21.8%) did not tried for pregnancy, 33 (15.63%) were lost to follow up, 16 (7.58%) patients conceived and 3 (1.41%) were infertile. Method: Maternal and fetal outcomes were studied and patients were followed up till 2 years of postpartum. Exclusion criteria: Unmarried, divorcee and widow patients were excluded. Results: There were 16 patients who had conceived, out of which 8 patients had abortions, 6 patients had full term deliveries and 2 patients had preterm delivery. Two patients developed newly diagnosed gestational hypertension from 20 weeks of gestation. One patient had graft rejection 2 months post abortion and one had cholestasis of pregnancy from 7 months of gestation. On follow up, one patient expired 1 year after abortion due to tuberculosis meningitis and one patient (10 months post abortion) is on intermittent hemodialysis since 3 months, after 1.5 years of renal transplant. Conclusion: These patients are at risks for developing many complications during pregnancy, out of which graft rejection is most grievous one. However, with proper peritransplant and periconceptional counseling regarding optimal time for pregnancy, these patients can have good pregnancy outcome

Polycystin-1 C-terminal Cleavage Is Modulated by Polycystin-2 Expression*

Autosomal dominant polycystic kidney disease is caused by mutations in the genes encoding polycystin-1 (PC-1) and polycystin-2 (PC-2). PC-1 cleavage releases its cytoplasmic C-terminal tail (CTT), which enters the nucleus. To determine whether PC-1 CTT cleavage is influenced by PC-2, a quantitative cleavage assay was utilized, in which the DNA binding and activation domains of Gal4 and VP16, respectively, were appended to PC-1 downstream of its CTT domain (PKDgalvp). Cells cotransfected with the resultant PKDgalvp fusion protein and PC-2 showed an increase in luciferase activity and in CTT expression, indicating that the C-terminal tail of PC-1 is cleaved and enters the nucleus. To assess whether CTT cleavage depends upon Ca2+ signaling, cells transfected with PKDgalvp alone or together with PC-2 were incubated with several agents that alter intracellular Ca2+ concentrations. PC-2 enhancement of luciferase activity was not altered by any of these treatments. Using a series of PC-2 C-terminal truncated mutations, we identified a portion of the PC-2 protein that is required to stimulate PC-1 CTT accumulation. These data demonstrate that release of the CTT from PC-1 is influenced and stabilized by PC-2. This effect is independent of Ca2+ but is regulated by sequences contained within the PC-2 C-terminal tail, suggesting a mechanism through which PC-1 and PC-2 may modulate a novel signaling pathway