To assess ovulation in infertile women using urinary luteinizing hormone surge kits versus transvaginal ultrasonography

Background: The study was conducted to evaluate the efficacy of urinary LH surge kits and TVS to detect ovulation in induced cycles and to compare the ovulation rates by both methods.Methods: Prospective experimental randomized control trial on 72 women with an ovulatory infertility aged 18-35 years, fulfilling the inclusion criteria were given letrozole for ovulation induction. All were randomly divided in two groups. Group 1 woman were asked to check ovulation by urinary LH surge kits and group 2 women were called for follicle monitoring by TVS.Results: Letrozole has no negative effect on endometrium; induced cycle has larger diameter of follicle (median: 22 mm). In induced cycle ovulation occurs later compared to normal cycle (D-16) and half of the women had a BMI more than the recommended WHO criteria (average was 25.28 kg/m2). Number of letrozole cycles (p=0.2642), dose requirement (p=0.0812) and pregnancy rates (10.26% versus 18.19%) were comparable in both groups.Conclusions: TVS is objective, accurate and thus standard modality for ovulation detection. LH surge kit is subjective, having more chances of error but can be used as a good alternative in certain settings like woman of remote area, woman having fear of invasive modality and COVID era woman who are afraid to visit hospital repeatedly.

DO VKORC1 AND CYP2C9 MUTATIONS LEAD TO WARFARIN RESISTANCE?

The objective of this study was to determine the influence of VKORC1 and CYP2C9 polymorphisms on warfarin resistant patients. Warfarin resistance is described as the inability to prolong the prothrombin time or raise the INR up to the 2 therapeutic range when the drug is given at typically doses. Polymorphisms may play a role as some VKORC1 and CYP2C9 variant alleles are known to be associated with these circumstances. 28 patients who were taking warfarin more than 15 mg/day and had INR values below 2.1 and had thromboembolic events while using warfarin were enrolled in this study. Heterozygote mutation in the VKORC1 gene was identified in 15 of 28 patients. Seven patients had heterozygote mutation of the CYP2C9 gene, and that may correspond to the ultrarapid metabolism of warfarin. VKORC1 and CYP2C9 polymorphism contribute to the difference in dose requirement amongst the patients, but other additional possible factors may play a role in different races. We suggest that medicians may use this tests before starting warfarin therapy and shape the treatment course according to this results.

Circadian Variation in the Median Effective Dose of Epidural Ropivacaine for Labor Analgesia

Background: Labor pain perception has been demonstrated to exhibit a circadian rhythm with lower pain scores during the day compared with the night. This study aimed to determine and compare the median effective dose (ED50) of ropivacaine in parturients having epidural labor analgesia during the day vs. during the night.Methods: The study group consisted of 60 nulliparous healthy parturients who were assigned to one of two groups according to the time they requested labor analgesia: Day Group (7:01 am to 7:00 pm) and Night Group (7:01 pm to 7:00 am). A bolus of.15% ropivacaine was administered epidurally and effective analgesia was defined as the attainment of a visual analog scale (VAS) pain score ≤ 10 mm within 30 min. The dose of ropivacaine for the first parturient in each group was 18 mg. The dose for each subsequent parturient was varied with increments or decrements of 3 mg based on the response of the previous subject. The ED50 was calculated using up-down sequential analysis. Probit regression was used to estimate the relative mean potency of ropivacaine between groups.Results: The ED50 (mean [95% CI]) of ropivacaine was lower in the Day Group (17.9 [16.5–19.4] mg) than in the Night Group (20.9 [19.2–22.7] mg) (P = 0.003). The estimate of relative potency for ropivacaine for the Night Group vs. the Day Group was 0.85 (95% CI:0.56–0.98).Conclusions: Under the conditions of this study, the dose requirement for epidural ropivacaine for labor analgesia was ~ 15% greater during the night than during the day.Clinical Trials Registration: Chinese Clinical Trial Registry (No.: ChiCTR1900025269. http://www.chictr.org.cn/showprojen.aspx?proj=36993).

SURFACE MODIFIED NANOSTRUCTURED LIPID CARRIER FOR IMPROVED OCULAR DELIVERY: IN VITRO AND EX-VIVO STUDY

Nano structured lipid carrier (NLC) is a new generation Nano particulate system that offers several advantages over polymeric nanoparticles. However, NLC possesses less muco-adhesiveness in the eye due to its anionic nature. Therefore, the present study aimed to modify the surface of NLC with cationic compounds to improve corneal permeability. The objective of the present study was to prepare and optimize Dexamethasone NLC, surface modification of NLC with carboxymethyl chitosan, and comparative evaluation of both with the marketed formulation. A combined melt emulsification and ultrasonication method was used to prepare NLC. The optimized NLC formulations shown particle size (64±2.3 nm), polydispersity in Dexamethasone (0.270±0.008), zeta potential (-12±3.42 mV), and entrapment efficiency (96.66±0.41%). Carboxymethyl chitosan modified dexamethasone loaded NLC showed particle size (260.73±4.66 nm) and dexamethasone (10.8±6.0 mV). It exhibited sustained drug release than NLC and marketed eye drop. In the ex vivo study, surface modified NLC had a permeability coefficient of 228.88 cm h-1, which is 2.60-and 1.61-times greater than eye drop and NLC, respectively. Surface-modified NLC has shown comparatively sustained release with plain NLC and commercial eye drops. The surface-modified form can adhere firmly with mucin and shown improved trans corneal permeability. Therefore, CNLC would be the potential nanocarrier for dexamethasone to minimize dose requirement and overcome systemic adverse events.

A comparative study of induction of labour with intravaginal misoprostol and intracervical dinoprostone gel and its fetomaternal outcome in a tertiary care hospital

The objective of the present study was to compare the two most commonly used agents for induction of labor-vaginal misoprostol and intracervical dinoprostone gel in terms of the incidence of cardiotocography (CTG) abnormalities and its correlation with fetal distress and fetomaternal outcome.This is prospective case-control study conducted in department of obstetrics and gynecology, C. U. Shah Medical College and Hospital, Surendranagar over a period of 15 months. 112 women requiring induction were randomly assigned to two groups of 56 each, Group M received vaginal misoprostol and Group D received intracervical dinoprostone E2 gel. 56 women with spontaneous labor served as control group. Groups were compared in terms of the incidence of suspicious or pathological CTG tracings, fetal distress, induction to vaginal delivery time, vaginal delivery rates, dose requirements, rate of emergency cesarean.Misoprostol was associated with shorter induction to delivery time (9.54 hours) than dinoprostone gel (13.54 hours), higher vaginal delivery rates (80.35% versus 62.5%), higher delivery rates (73.9%) with single dose itself unlike Group D, where 47.22% required more than one dose. Incidence of suspicious CTG was higher in group M (15.68%) versus 10.25% in Group D. Incidence of pathological CTG was also highest in Group M (7.8%) followed by Group D (2.56%) and Group C (7.8%). Dinoprostone gel lead to failed induction in 25% women, and hence higher caesarean rates.While misoprostol is a better agent for induction when compared with dinoprostone E2 gel in terms of induction-delivery time, higher vaginal delivery rates, less dose requirement, it is associated with greater incidence of non-reassuring/pathological CTG. There was justified improvement in perinatal outcome due to preparedness beforehand with use of CTG.

CYP3A-status is associated with blood concentration and dose-requirement of tacrolimus in heart transplant recipients

High inter-individual variability in tacrolimus clearance is attributed to genetic polymorphisms of CYP3A enzymes. However, due to CYP3A phenoconversion induced by non-genetic factors, continuous changes in tacrolimus-metabolizing capacity entail frequent dose-refinement for optimal immunosuppression. In heart transplant recipients, the contribution of patients’ CYP3A-status (CYP3A5 genotype and CYP3A4 expression) to tacrolimus blood concentration and dose-requirement was evaluated in the early and late post-operative period. In low CYP3A4 expressers carrying CYP3A5*3/*3, the dose-corrected tacrolimus level was significantly higher than in normal CYP3A4 expressers or in those with CYP3A5*1. Modification of the initial tacrolimus dose was required for all patients: dose reduction by 20% for low CYP3A4 expressers, a 40% increase for normal expressers and a 2.4-fold increase for CYP3A5*1 carriers. The perioperative high-dose corticosteroid therapy was assumed to ameliorate the low initial tacrolimus-metabolizing capacity during the first month. The fluctuation of CYP3A4 expression and tacrolimus blood concentration (C0/D) was found to be associated with tapering and cessation of corticosteroid in CYP3A5 non-expressers, but not in those carrying CYP3A5*1. Although monitoring of tacrolimus blood concentration cannot be omitted, assaying recipients’ CYP3A-status can guide optimization of the initial tacrolimus dose, and can facilitate personalized tacrolimus therapy during steroid withdrawal in the late post-operative period.

Retrospective Evaluation on the Use of a New Polysaccharide Complex in Managing Paediatric Type 1 Diabetes with Metabolic Syndrome (MetS)

Background: Children and adolescents affected by type 1 diabetes have an increased risk of being overweight or obese and of suffering from cardiometabolic symptoms. Aims: To retrospectively evaluate the effects of a new complex of polysaccharide macromolecules, Policaptil Gel Retard® (PGR), on auxological and metabolic parameters, glycaemic variability and control parameters in paediatric patients with type 1 diabetes and metabolic syndrome (MetS). Patients and Methods: Data for 27 paediatric patients with a diagnosis of type 1 diabetes in conjunction with obesity and MetS of at least 5 years’ standing were collected and retrospectively studied. Of these, 16 (median age 12.9, range 9.5–15.8 years) had been adjunctively treated with PGR and 11 (median age 12.6, range 9.4–15.6 years) had not been treated with PGR. Auxological, metabolic and glycaemic control and variability parameters and insulin dosing were compared after 6 months in the two groups. Results: PGR significantly reduced BMI standard deviation score (SDS) (p < 0.005), waist SDS (p < 0.005), HbA1c (p < 0.05) and daily mean insulin dose requirement (p < 0.005). A significant improvement was also observed in the metabolic and glycaemic variability parameters of mean daily blood glucose (BG) levels (p < 0.005), SD of daily BG levels (p < 0.0001), mean coefficient of variation (p < 0.05), LBGI (p < 0.0001), HBGI (p < 0.0001), J-index (p < 0.005), total cholesterol (p < 0.005), HDL-cholesterol (p < 0.005) and LDL-cholesterol (p < 0.005) and triglycerides (p < 0.05). Conclusions: PGR produces a good auxological and metabolic response in obese patients with MetS who are affected by type 1 diabetes. It led to a significant reduction in BMI SDS, waist SDS and an improvement in glucose control and variability as well as in other MetS parameters. The use of polysaccharide compounds, especially if associated with appropriate dietary changes, may help achieve treatment targets in type 1 diabetes and reduce the risk that patients develop metabolic syndrome.

Use of priming principle in the induction dose requirement of propofol and its hemodynamic stability- A cross sectional study

In anesthesia propofol induction is administered at a dose of 2mg/kg as a single bolus and when given at this dose the commonest problem faced by the anesthetist is the sudden drop in the blood pressure, as the hypotensive effect of propofol is proportional to the dose and rate of administration.To study the effect of auto co-induction (priming principle) in the requirement of induction dose of propofol and the resulting hemodynamic parameters. A prospective randomized double blinded study was conducted for a period of one year in the department of anesthesia at a government medical college hospital in TamilNadu. A total of 60 patients were selected for our study and were randomly allocated into two groups of 30 each. Group A is the study group (priming) and group B is the control group (non-priming group). In the priming group, three minutes after premedication the co induction agent was administered (25% of the calculated dose of propofol) and two minutes later the patient received propofol at a rate of 30mg/10 sec until loss of vocalization was achieved. The hemodynamic parameters along with the total dose requirement of propofol and BIS values were monitored at regular intervals after induction.The mean total dose of propofol required among the priming group patients was 78.2 mg compared to the total dose requirement in the non-priming group which was 92.5 mg and the mean difference was found to be statistically significant. A statistically significant fall in the heart rate and blood pressure was observed at 1 min and 3 mins after induction in non priming group compared to priming group. By applying priming principle the induction dose of propofol was reduced by 14.25% with a good hemodynamic stability.

Intranasal Neuropeptide Y as a Potential Therapeutic for Depressive Behavior in the Rodent Single Prolonged Stress Model in Females

The susceptibility to stress-elicited disorders is markedly influenced by sex. Women are twice as likely as men to develop posttraumatic stress disorder (PTSD), depression, anxiety disorders, and social impairments following exposure to traumatic stress. However, most of the studies in animal models examining putative therapeutics for stress-triggered impairments, including single prolonged stress (SPS), were performed predominantly with males. Previous studies in males demonstrated that intranasal neuropeptide Y (NPY) can provide therapeutic relief of many SPS-triggered behaviors, but is ineffective in females at the same dose. Thus, females may need a higher dose of exogenous NPY to attain a therapeutically significant concentration since the overwhelming majority of studies found that NPY levels in females in many brain regions are lower than in male rodents. Here, we examined SPS as an appropriate model to elicit many PTSD-associated symptoms in females and whether intranasal NPY at higher doses than with males is able to alter the development of SPS-triggered behavioral impairments. Sprague-Dawley female rats were exposed to SPS only, or in a separate cohort after SPS stressors were immediately infused intranasally with one of several doses of NPY, starting with 600 μg/rat—four times the dose effective in males. In the third cohort of animals, females were infused intranasally with either 600 μg NPY, omarigliptin [a dipeptidyl peptidase IV (DPP4) inhibitor], or both right after the SPS stressors. After 19 days they were tested on several behavioral tests. SPS elicited significant depressive/despair like behavior on the forced swim test (FST), anxiety behavior on the elevated plus maze (EPM), as well as impaired social interaction. On the FST, there was a dose-response effect of intranasal NPY, with 1,200 μg, but not 600 μg, preventing the development of the SPS-elicited depressive-like behavior. The omarigliptin and 600 μg NPY combined treatment, but neither alone, was also sufficient at preventing depressive-like behavior on the FST. The results demonstrate that: (1) SPS elicits several behavioral manifestations of PTSD in females; (2) early intervention with a high dose of intranasal NPY has therapeutic potential also for females; and (3) NPY cleavage by DPP4 may play a role in the higher dose requirement for females.