A novel action of insulin sensitizing drug as a potential promotor of preovulatory follicles, ovulation rate and prolificacy in sheep.

The effect of the insulin-sensitizing drug metformin on preovulatory follicle (POF) number, ovulation rate, fetal rate and prolificacy was studied in forty-six cyclic Malpura ewes. After estrus synchronization, the ewes were equally divided into two groups (n = 23). The treatment group (MET) received a daily oral dose of metformin at a rate of 500 mg/animal for approximately 12 weeks, spanning five estrous cycles, as against untreated control (CON). All the ewes were bred to proven rams at the end of treatment. Ovarian ultrasound scans were performed at each estrus and day 9 of each cycle to assess the number and diameter of POFs and corpora lutea (CL), respectively. A comprehensive assessment of circulating hormones including, estradiol, progesterone, androstenedione, and insulin as well as metabolic indicators such as glucose, and lipid profile parameters was performed. At the end of treatment on the day of estrus (E5D0), the treatment showed a stimulatory effect on follicular development with a 53.2% (P < 0.001) increase in the number of POFs. It also increased the ovulation rate by 67.4% (P < 0.01), with a higher proportion (χ2df1 = 10.7, P < 0.001) of ewes in the MET group having multiple ovulations compared to the CON group (82.6 vs. 30.4%). With 1.48 ± 0.12 prolificacy rate in MET ewes, the proportion of ewes giving birth to multiple lambs was 2.9-fold higher than in the CON group. Plasma estradiol, insulin, glucose, total cholesterol, and LDL-cholesterol concentrations were lower (P < 0.05) in the MET ewes than in the CON. The results of the present study indicate that metformin can increase the number of POF, ovulation rate, fetal rate and prolificacy in ewes, while reducing the plasma estradiol, insulin, glucose and cholesterol in MET ewes.

Dietary n-3 PUFA augments pre-ovulatory follicle turnover and prolificacy in well-fed ewes.

The present study evaluated the effect of dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) on preovulatory follicle (POF) turnover, prolificacy, and endocrine and metabolic milieu in Malpura sheep. Fifty cyclic ewes with 3-3.5 body condition scores on a five-point scale were allocated equally to two groups (n = 25) following estrus synchronization and were supplemented with 0.6 mL/kg body weight of n-3 PUFA-rich fish oil (FO) or palm oil (PO) as control, for 60 d following an acclimatization period of 7 d. All ewes were mated with sexually active rams at the end of the supplementation period. On ultrasonographic ovarian scanning at the last fourth estrus, the mean number of POFs was 77.8% greater (P < 0.01) in FO ewes than in the PO ewes. The proportion of ewes with multiple ovulations two months after the beginning of supplementation was 56% in the FO group as compared to 8% in the PO group. The number of fetuses was 46% higher (P < 0.01) in the FO than in the PO ewes at d 45 of gestation. At lambing, the twinning percent in the FO ewes was three times greater than in the PO ewes (27.3 vs. 9.1%). Plasma cholesterol, estradiol, and insulin concentrations were lower (P < 0.01) in ewes fed with FO than those offered PO group at the end of the feeding period. It was concluded that the dietary supplementation of n-3 PUFA-rich FO in well-fed Malpura ewes improved the number of follicles and ovulation rate which led to an increased prolificacy, accompanied by a reduction of plasma cholesterols, estradiol, and insulin.

Inflammatory optic disc neovascularisation managed with oral steroids/immunosuppressants and intravitreal ranibizumab.

Inflammatory optic disc neovascularisation (NVD) has been treated with periocular or systemic steroids, immunosuppressants, panretinal photocoagulation and bevacizumab. However, the role of intravitreal ranibizumab in inflammatory NVD has not been explored in the peer-reviewed indexed literature. In case 1, NVD and associated subhyaloid haemorrhage showed rapid and dramatic regression after intravitreal ranibizumab. Recurrence was noted 8 weeks after injection which was managed by oral steroids. In case 2, intravitreal ranibizumab led to partial resolution of NVD. The addition of steroids, azathioprine and panretinal photocoagulation led to further fibrosis of the neovascularisation. Ranibizumab may be an important adjunct to anti-inflammatory therapy in the management of inflammatory NVD.

Delayed onset of congenital hereditary endothelial dystrophy due to compound heterozygous SLC4A11 mutations.

BACKGROUND: Congenital hereditary endothelial dystrophy (CHED) is an autosomal recessive disorder characterized by bilateral, symmetrical, noninflammatory corneal clouding (edema) present at birth or shortly thereafter. This study reports on an unusual delayed presentation of CHED with compound heterozygous SLC4A11 mutations. MATERIALS AND METHODS: A 45-year-old female, presenting with bilateral decreased vision since childhood that deteriorated in the last 5 years, was evaluated to rule out trauma, viral illness, chemical injury, glaucoma, and corneal endothelial dystrophies. Tear sample was sent for herpes simplex viral (HSV) antigen testing. Genomic DNA from peripheral blood was screened for mutations in all exons of SLC4A11 by direct sequencing. Full-thickness penetrating keratoplasty was done and corneal button was sent for histopathological examination. RESULTS: Slit-lamp findings revealed bilateral diffuse corneal edema and left eye spheroidal degeneration with scarring. Increased corneal thickness (762 µm and 854 µm in the right and left eyes, respectively), normal intraocular pressure (12 mmHg and 16 mmHg in the right and left eyes, respectively), inconclusive confocal scan, and specular microscopy, near normal tear film parameters, were the other clinical features. HSV-polymerase chain reaction was negative. Histopathological examination revealed markedly thickened Descemet's membrane with subepithelial spheroidal degeneration. SLC4A11 screening showed a novel variant p.Ser415Asn, reported mutation p.Cys386Arg and two polymorphisms, all in the heterozygous state and not identified in 100 controls. CONCLUSIONS: The study shows, for the first time, compound heterozygous SLC4A11 mutations impair protein function leading to delayed onset of the disease.

Association of ZEB1 and TCF4 rs613872 changes with late onset Fuchs endothelial corneal dystrophy in patients from northern India.

PURPOSE: Fuchs endothelial corneal dystrophy (FECD) results in loss of vision associated with progressive corneal edema and loss of corneal transparency. The aim of the study was to evaluate changes in ZEB1, COL8A2, SLC4A11, and TCF4 rs613872 and correlate them with clinical findings. METHODS: Eighty-two patients with clinically diagnosed FECD and 143 controls were recruited during the period 2007-2012. Clinical details, pedigree information up to three generations, and 5 ml of blood samples were collected. Histopathological and transmission electron microscopy studies were performed on host corneal buttons from patients who underwent keratoplasty. Genomic DNA from blood was processed for PCR amplification followed by direct sequencing to screen genetic changes in the candidate genes. The pathogenic nature of the genetic variants was assessed using Sorting Intolerant From Tolerant (SIFT) and MutationTaster. RESULTS: The mean age at the onset of symptoms was 59.14±1.41years, the male to female ratio was 1:1.5, and the mean specular count (endothelial cell density) was 1629±93.62 cells/mm(2) with a mean central corneal thickness (CCT) of 617.30±15.73 µm. ZEB1 showed a novel variant IVS2+276 C/T in 14% of the cases, a novel nonsense p.Leu947stop mutation in one patient, two novel missense mutations (p.Glu733Lys, p.Ala818Val) in one patient each, and one novel synonymous variation (p.Ser234Ser) in two patients. Reported mutation p.Gln840Pro and five polymorphisms were also identified. The TCF4 single nucleotide polymorphism (SNP) rs613872 was significantly higher in patients with FECD. CONCLUSIONS: This is the first report of genetic variations in ZEB1 and TCF4 SNP rs613872 in patients with FECD from northern India that suggests a possible role in disease pathogenesis and the regulation of endothelial cell density.