In Vitro and In Vivo Scalp Retention and Penetration of 99mTc-Minoxidil Solution.

The present study assessed the effect of retention on ex vivo skin and in vivo scalp penetration of radiolabeled minoxidil formulations (5% w/v). Minoxidil was radiolabeled with technetium (99mTc) with an efficiency of 99.1% using 0.2% stannous chloride as reducing agent at pH 6 and incubation temperature of 40 °C. Three different 99mTc-minoxidil formulations were prepared using aqueous ethanolic solution as vehicle. Formulation A contains 99mTc-minoxidil dissolved in vehicle, formulation B contains 10% propylene glycol (PG) and formulation C contains 10% hydroxypropyl cellulose (HPC), in addition. Results showed that addition of HPC resulted in enhanced viscosity (400 mPa.s) and significantly higher ex vivo retention (p < 0.05) and permeation (0.75±0.12%, 8 h). PG does not improve the permeation and the results (0.44±0.05%, 8 h) were not significantly different from vehicle alone (0.40±0.05%, 8 h). The results of the in vivo human scalp studies corroborated with the ex vivo results and addition of hydroxypropyl cellulose (HPH) showed significantly higher (p < 0.05) scalp retention. Post 8 h application, scalp penetration in group treated with formulation C was nearly 2.8-fold and 2.2-fold higher than those treated with formulation A and B, respectively. Further, absence of minoxidil in systemic circulation during study duration indicates safety. In conclusion, our results showed that increasing contact time of minoxidil with scalp by modifying viscosity results in reduced frequency of application and improved efficacy.

Quality Indicators for Evaluating Errors in the Preanalytical Phase.

Objective The aim of this study was to study the incidence of preanalytical errors in the clinical chemistry laboratory attached to a tertiary care hospital. Design and Methods The study was conducted in a clinical chemistry laboratory using the samples and forms received for analysis. Five hundred random samples were analyzed using a predefined set of quality indicators (QIs) over a period of 3 months. The incidence of each preanalytical error was described as a percentage of the total samples analyzed in the study. Statistical Analysis Individual QIs were assigned values as 0 and 1 and were used to assess each sample; 0 if the error was present, and 1 if absent. The incidence of each preanalytical error was described as a percentage of the total samples analyzed in the study. Result Out of the 500 samples observed, 138 samples were error free, while 21 samples had the maximum number of errors, that is, 6. The error committed most often was the omission of provisional diagnosis being mentioned on the requisition form. No preanalytical error was observed for QIs: selecting the appropriate blood collection vial or storage of sample. Conclusion This study confirms that error rate in the preanalytical phase is high and vastly ignored. Errors committed here may be overlooked, given the large number of samples received in the clinical laboratory of a tertiary center. To reduce these errors, the laboratory should provide training to all workers involved in the preanalytical phase. Daily or weekly QI scores should be recorded to assess and rectify shortcomings, thereby improving patient care.

Evaluation of Placental VEGFA mRNA Expression in Preeclampsia: A Case Control Study.

OBJECTIVE: The aim of our case-control study was to determine expression of VEGFA mRNA in placentae of preeclamsia (PE) versus uncomplicated pregnancy to further clarify its differential expression in pregnancy hypertensive disorders. STUDY DESIGN: The PE group was subdivided into severe and non-severe; those with or without HELLP syndrome and placental VEGFA characteristics were compared for these cohorts. Additionally, the neonatal and maternal outcomes were recorded. The quantification of placental VEGFA was done using quantitative real-time PCR and results were expressed as fold change. RESULTS: Out of 42 PE cases, 23 (55%) were non-severe and 19 cases (45%) were severe PE. Out of 19 severe PE patients, 8 (42%) were HELLP syndrome (complete HELLP) and remaining 11 (58%) were non-HELLP severe PE. Compared to controls, the true fold change in PE, HELLP, non-HELLP, severe PE, non-severe PE was - 2.186, - 13.333, - 6.698, - 8.950 and 1.466, respectively. CONCLUSIONS: Our results showed a lowered VEGFA expression in PE placentae compared to uncomplicated controls. The finding of initial increase of VEGFA in non-severe PE and subsequent marked lowering in HELLP strengthens the existing hypothesis of decompensated VEGF being a major role player in PE.

In vivo, Extract from Withania somnifera Root Ameliorates Arthritis via Regulation of Key Immune Mediators of Inflammation in Experimental Model of Arthritis.

BACKGROUND: Rheumatoid Arthritis (RA) is a devastating disease characterized by continual addition of leukocytes and T cells within the articular cavity causing inflammation and cartilage destruction. Withania somnifera is one of the most precious medicinal herbs, reported to have antioxidant, anti-inflammatory, and immunomodulatory properties. OBJECTIVE: The purpose of this study was to evaluate anti-inflammatory activity of aqueous extract of Withania somnifera roots (WSAq) in Collagen Induced Arthritic (CIA) rats. METHODS: To achieve this, we assessed the level of inflammatory cytokines such as Tumor Necrosis Factor (TNF)-α, IL-1ß, IL-6 and IL-10 in CIA rats. Further, transcription factor, oxidative stress parameters and CD+8 expressions were also analyzed in CIA rats. RESULTS: Arthritic rats showed a greater increase in the levels of pro inflammatory cytokines such as TNF-α, IL-1ß, IL-6, transcription factor NF-κB and a decrease in IL-10 concentration than controls rats. Oral administration of WSAq at a dose of 300mg/kg.wt. (WSAq300) appreciably attenuated the production of these pro inflammatory cytokines. This anti-inflammatory activity of WSAq300 might be partly mediated through an increase in the secretion of IL-10 and inhibition of NF-κB activity. Further, arthritic rats also show increased oxidative stress as compared to control rats. This increased oxidative stress in the arthritic rats appears to be the outcome of both an activated pro-oxidant and a poor antioxidant defense system. Treatment with WSAq300 strongly ameliorates all these ROS parameters significantly to near normal. Additional, metalloproteinase MMP-8 levels were also measured and found to be increased in CIA rats, which after treatment with WSAq300 came down to near normal. CONCLUSION: From the above results, it can be concluded that the use of WSAq300 may be a valuable supplement which can improve human arthritis.

Alteration in cognitive behaviour, brain antioxidant enzyme activity and their gene expression in F1 generation mice, following Cd exposure during the late gestation period: modulation by quercetin.

We investigated whether in-utero Cd(II) chloride exposure of the dams between 14th to 21st day of gestation affects memory and learning, oxidative stress, antioxidant enzyme activity and their gene expression in brain of the pups in their adulthood. In the Morris water maze, cadmium (Cd) exposure impaired spatial memory which was reversed following co-treatment with quercetin (100 mg/kg). In the passive avoidance paradigm, retention memory was adversely affected but was significantly reversed by co treatment with quercetin (25, 50, 100 mg/kg). The malondialdehyde and catalase (CAT) levels and glutathione-S-transferase (GST) activity were increased significantly in Cd-treated group, but were reversed by quercetin (all doses). The gene expression for CAT and GST in brain tissue of Cd treated animals also increased many folds as compared to the control, and this effect was decreased on co-treatment with quercetin (all doses), thus matching with the respective enzyme activities. Quercetin (25 mg/kg) when co-treated with Cd caused a decrease in GST activity compared to control, which points towards a complex interplay with oxidative free radicals and promoters and transcription factors. Thus, Cd exposure during late gestation causes impaired spatial and retention memory in the next generation which may be due to alteration of activity as well as gene expression of the antioxidant enzymes, CAT and GST. Quercetin may offer some protection of memory impairment probably by modulating these effects.

Pregnancy-Associated Plasma Protein A Levels in Late First Trimester Pregnancies with Small-for-Gestational Age Neonates: A Prospective Case-Control Study.

OBJECTIVE: We aimed to investigate the association of pregnancy associated plasma protein A (PAPP-A) levels in late first trimester with small for gestational age (SGA) neonates and adverse pregnancy outcomes in a low-income setting. METHODS: The inclusion criteria were late first trimester (11-13 + 6 weeks) women with singleton and non-anomalous pregnancy. Enrolled participants were sampled for PAPP-A and prospectively followed up for delivery outcome and antenatal complications. A multiple of median (MoM) was calculated and statistically compared between groups. RESULTS: Out of total 284 subjects, 14.54% delivered SGA babies and formed cases (Group A), 66.5% delivered appropriate for gestational age (AGA) neonates with uneventful antenatal period (controls, Group B), and 19.3% were AGA group with adverse pregnancy complications (Group C). The late first trimester median PAPP-A MoM was significantly lower (0.61) in Group A compared to Group B (1.47). Using receiver operating characteristic (ROC) curve for PAPP-A MoM, optimal cutoff value was found at 0.45 MoM, with positive predictive value of 56.2%, specificity of 92.6% and sensitivity of 45%. The median interquartile range (IQR) of PAPP-A MoM value in Group C in comparison with Group B was significantly lower except for abruption. At PAPP-A MoM cutoff value <1, <0.8, <0.6 and <0.4, the odds ratio for adverse pregnancy outcome was 8.30, 7.29, 10.97 and 10.60, respectively, indicating an inverse relationship. CONCLUSION: With 0.45 MoM cutoff of PAPP-A, the detection rate, specificity and positive predictive value for SGA were 45, 92.6 and 56.2%, respectively. As PAPP-A MoM values decreased, the odds ratio of having adverse pregnancy outcomes increased.

Idiopathic Fetal Growth Restriction: Repercussion of Modulation in Oxidative Stress.

Oxidative stress has been proposed as one of the causes involved in idiopathic fetal growth restriction (IFGR). However, the exact relationship between oxidative stress and IFGR is not understood. This study aimed at understanding the role of oxidative stress and antioxidant status in IFGR materno-fetal dyads and matched controls. 75 materno-fetal dyads with IFGR were enrolled with equal number of normal low risk controls. Malondialdehyde (MDA) levels were measured as marker of oxidative stress, while paraoxonase-1 (PON1) activity and total antioxidant capacity (TAC) of serum were measured as markers of antioxidant status. MDA levels were increased in both maternal and cord blood of IFGR neonates as compared to controls (p < 0.001). TAC of serum were found to be decreased in IFGR (both maternal and cord blood) as compared to controls (p < 0.001; p < 0.05, respectively). PON1 activity was found to be decreased in the IFGR mothers while it was found increased in IFGR cord blood (p < 0.01; p < 0.001)). IFGR is a state of increased oxidative stress. Decreased PON1 enzymatic activity in mothers is also associated with IFGR.