Effect of rutin on retinal VEGF,TNF-α, aldose reductase,and total antioxidant capacity in diabetic rats: molecular mechanism and ocular pharmacokinetics

International Ophthalmology - The current study was conducted to explore the potential of rutin in preventing sight-threatening diabetic retinopathy. Wistar albino rats (either sex) weighing...     

Intralenticular changes in eyes with mature senile cataract on modified posterior segment optical coherence tomography

Purpose:To study the morphological changes within mature senile cataracts on modified posterior segment optical coherence tomography (OCT).Methods:A cross-sectional observational study recruiting patients of mature cataracts admitted for elective cataract surgery in tertiary eye care. A modified OCT imaging of the lens was done and lenticular findings were noted by a single observer. Corresponding slit-lamp biomicroscopic findings and intraoperative experiences were also noted by a second observer and respective surgeons.Results:Forty-four eyes of 44 patients were included. The mean age of patients was 65 ± 5.7 years. The intralenticular findings were uniform in groups of eyes, and they were characterized into three stages. First was a stage of early lamellar separation where small intralenticular clefts were noted superficially. Second was the stage of established lamellar separation where crescentic fluid clefts appeared interspersed between the lens fibers, and the depth increased as a function of severity. Both these stages did not show any distinct slit-lamp or intraoperative findings. A third stage of liquefaction identified as extensive lamellar separation with subcapsular fluid pockets. This was also reflected in slit-lamp biomicroscopy, showing the hydrated cortex with intraoperative challenges. Two cases showed peculiar changes, one of a hyperreflective subcapsular sheath and another of superficial nuclear lamellar separation.Conclusion:Mature cataracts may also show graded progression, which could be delineated on lenticular OCT. This could be of immense help in pre-operative planning and optimal management of these high-risk cases.     

Comparative pharmacodynamics of keliximab and clenoliximab in transgenic mice bearing human CD4

Keliximab and clenoliximab are monkey/human chimeric CD4 monoclonal antibodies (mAbs) of the IgG1 and IgG4 isotypes, respectively. The pharmacokinetics (PK) and pharmacodynamics (PD) of these mAbs were evaluated in transgenic mice bearing human CD4 molecules on their T cells after a single i.v. administration at three dose levels (5-125 mg/kg). The PK of keliximab and clenoliximab were similar, dose-dependent, and adequately described by a two-compartment model with saturable elimination from both compartments. The enumeration of circulating CD4(+) T cells and density of CD4 on their surface were determined as the PD effects. An indirect response model was proposed to characterize the PD effects. With the increase in mAb dose, the maximum intensity (R(max)) of PD effects was increased, and the time to reach R(max) shifted to later times. At all three dose levels, keliximab caused a relatively rapid decline in the number of circulating CD4(+) T cells, which then recovered gradually. In contrast, clenoliximab at the lowest dose (5 mg/kg) did not produce a significant effect on CD4(+) T cell counts compared with the placebo group. At high doses, clenoliximab caused a significant decrease in the number of CD4(+) T cells. Keliximab appeared to be more potent and efficient in depleting CD4(+) T cells. Both mAbs produced similar down-modulation of CD4 at corresponding dose levels. The findings of this study are consistent with the results of a recent clinical trial that emphasize the importance of this transgenic mouse model for evaluating PK/PD to support clinical development of anti-human CD4 mAbs.     

Successful renal transplantation in a family with a novel mutation in COL4A3 gene and autosomal recessive Alport syndrome

Alport syndrome (AS) is an inherited disorder of basement membranes caused by mutations affecting specific proteins of the type IV collagen family, presenting with nephropathy and extrarenal manifestations such as sensorineural deafness and ocular anomalies. Ten percentage to 15% of the patients with AS have autosomal recessive (ARAS) due to mutation in either COL4A3 or COL4A4 gene. We report a novel mutation in the COL4A3 gene in an Indian family with ARAS. The above‐mentioned genetic anomaly was a missense variation in exon 26 of the COL4A3 gene (chr2:228137797G>A; c.1891G>A) that resulted in the amino acid substitution of Arginine for Glycine at codon 631 (p.Gly631Arg) that was present in the heterozygous state in the asymptomatic parents and homozygous state in the male offspring who presented with early‐onset end‐stage renal disease, lenticonus and hearing loss. The patient (male offspring) underwent successful renal transplantation with his mother as a donor.     

Ultra‐short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients

We conducted an adaptive design single‐center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra‐short‐term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)‐nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R?). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12‐week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first‐line DAA therapy; and two after retreatment with second‐line DAA). At a median follow‐up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4‐day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%‐20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R ? transplants.     

Absent left common carotid artery in a right aortic arch: Separate origins of left internal and external carotid arteries from brachiocephalic artery

We present a case of cyanotic congenital heart disease with left common carotid artery agenesis in the setting of the right aortic arch highlighting the potential implications in management.     

Ruptured sinus of valsalva presenting late following repair of tetralogy of fallot

Rupture of sinus of valsalva following repair of tetralogy of fallot (TOF) is very rare. It should be suspected as a cause of recurrent or prolonged pleural effusion and congestive cardiac failure in patients who have undergone repair of TOF. We report one such patient.