Nano-purification of raw semen minimises oxidative stress with improvement in post-thaw quality of buffalo spermatozoa

The study consisted of application of anti-ubiquitin antibodies (Abs)-coated iron oxide-nanoparticles (IONPs) for minimisation of oxidative stress to contemporary live spermatozoa from the raw semen. Round-shaped IONPs (12.09 ± 0.91 nm) after two-stage functionalisation (silanisation and pegylation) were conjugated with Abs. Four aliquots from each of the 24 ejaculates (4 buffalo bulls) formed Control (Group I) and treatment (II, III and IV) groups; each containing 150 ± 25 million dead/damaged spermatozoa. IONPs-Abs complex were added at ratio of 1:1 (0.5 µg/ml), 1:2 (1.0 µg/ml) and 1:4 (2.0 µg/ml), respectively, in Groups II, III and IV. The semen quality parameters showed improvement at lag-stage (post-nano-purification before processing for cryopreservation). The mean post-thaw motility (%) in Group IV was found to be greater (p < .05) than Group I. Moreover, the overall DNA integrity (%) at post-thaw stage was improved in the nano-purified semen samples. The value of malondialdehyde was greater (p < .001) in Group I than Groups II, III and IV. The mean total antioxidant capacity and superoxide dismutase (U/mg protein) activity values in Group IV was greater (p < .05) than Group I. The study results show that IONPs conjugated with anti-ubiquitin Abs at 2.0 µg/ml can be an effective dose for depletion of dead/damaged spermatozoa from buffalo ejaculates to minimise oxidative stress.     

Clinical, anatomic, and electrophysiologic evaluation following intravitreal bevacizumab for macular edema in retinal vein occlusion

PURPOSE: To investigate clinical, anatomic, and electrophysiologic response after single intravitreal injection of bevacizumab for macular edema attributable to retinal vein occlusion. DESIGN: Prospective nonrandomized, interventional case series. METHODS: Twenty-one patients with macular edema attributable to vein occlusion received intravitreal injection of bevacizumab 1.25 mg. Nine patients had central retinal vein occlusion (CRVO), and 12 patients had branch retinal vein occlusion (BRVO). Complete ophthalmic examination including optical coherence tomography (OCT) was done at baseline and follow-up visits. Fifteen patients underwent fluorescein angiography at baseline. Selected patients underwent electroretinography (ERG) and visual evoked potential (VEP) at baseline and follow-up. Follow-up was for 12 weeks. RESULTS: At baseline, mean visual acuity was 20/381 (median, 20/400) and showed improvement to mean 20/135 (median, 20/60) after one month, (P = .001). At 12 weeks, mean visual acuity was 20/178 (median, 20/80) (P = .001). The mean central retinal thickness (CRT) was 647.81 microm (median, 609.00 microm) at baseline and decreased to mean 293.43 microm (median, 222.00 microm) at one month (P = .001). At 12 weeks, mean CRT was 320.90 mum (median, 280.00 microm) (P = .001). ERG and VEP showed no worsening of the waveforms. There was no significant difference in the visual outcome between the BRVO and CRVO groups. CONCLUSION: Intravitreal injection of bevacizumab appears to result in significant short-term improvement of visual acuity and macular edema secondary to vein occlusion. The present report confirms the previous studies. No ocular toxicity or adverse effects were observed. However, prospective, randomized, controlled long-term studies are required with an adequate number of patients.     

Neonatal Purpura Fulminans Due to Methicillin Resistant Staphylococcus aureus

Abstract: Neonatal purpura fulminans is rare and may be inherited or acquired. It may ultimately lead to multiorgan failure and death. Purpura fulminans in a premature neonate resulting from Staphylococcus aureus septicemia is illustrated. Unfortunately, the baby succumbed to septicemia.     

Neonatal brain: color Doppler imaging. Part I. Technique and vascular anatomy

Color Doppler imaging (CDI) can demonstrate the relative direction and velocity of blood flow in color, superimposed on a conventional gray-scale ultrasound image that depicts stationary tissue. Twenty-five infants were studied with portable CDI in the coronal, sagittal, and axial planes. Bilateral antegrade flow was noted in the anterior, middle, and posterior cerebral arteries in all patients. Multiplanar CDI can image flow in the circle of Willis and its tributaries and branches.     

Population Pharmacokinetic Modeling of the Enterohepatic Recirculation of Fimasartan in Rats,Dogs, and Humans

Enterohepatic recirculation (EHC) can greatly enhance plasma drug exposures and therapeutic effects. This study aimed to develop a population pharmacokinetic model that can simultaneously characterize the extent and time-course of EHC in three species using fimasartan, a novel angiotensin II receptor blocker, as a model drug. All fimasartan plasma concentration profiles in 32 rats (intravenous doses, 0.3–3 mg/kg; oral doses, 1–10 mg/kg), 34 dogs (intravenous doses, 0.3–1 mg/kg; oral doses, 1–10 mg/kg), and 42 healthy volunteers (single or multiple oral doses, 20–480 mg) were determined via liquid chromatography-tandem mass spectrometry (LC-MS/MS) and simultaneously modeled in S-ADAPT. The proposed model quantitatively characterized EHC in three species after oral and intravenous dosing. The median (range) fraction of drug undergoing recirculation was 76.3% (64.9–88.7%) in rats, 33.3% (24.0–45.9%) in dogs, and 65.6% (56.5–72.0%) in humans. In the presence compared with the absence of EHC, the area under the curve in plasma was predicted to be 4.22-fold (2.85–8.85) as high in rats, 1.50-fold (1.32–1.85) in dogs, and 2.91-fold (2.30–3.57) in humans. The modeled oral bioavailability in rats (median (range), 38.7% (20.0–59.8%)) and dogs (median, 7.13% to 15.4%, depending on the formulation) matched the non-compartmental estimates well. In humans, the predicted oral bioavailability was 25.1% (15.1–43.9%) under fasting and 18.2% (12.2–31.0%) under fed conditions. The allometrically scaled area under the curve predicted from rats was 420 ng ⋅ h/mL for 60 mg fimasartan compared with 424 ± 63 ng ⋅ h/mL observed in humans. The developed population pharmacokinetic model can be utilized to characterize the impact of EHC on plasma drug exposure in animals and humans.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-015-9764-2) contains supplementary material, which is available to authorized users.KEY WORDS: animal to human scaling, enterohepatic recirculation, fimasartan, population pharmacokinetics, S-ADAPT     

Aminoacidopathies: A review of 3 years experience of investigations in a Kuwait hospital

Summary We present a summary of the results of quantitative amino acid analysis in 800 subjects over a three-year period in Al-Sabah Hospital, Kuwait. Thirty-five patients with aminoacidopathy were identified, all but two of whom were the offspring of first-degree consanguineous marriages: nine cases of phenylketonuria, one benign hyperphenylalaninaemia, seven non-ketotic hyperglycinaemia, five tyrosinaemia, five homocystinuria, four citrullinaemia, two cystinuria, one hyperprolinaemia, and one maple syrup urine disease. The clinical and biochemical findings in these cases are described.     

Structural basis for substrate discrimination by E. coli repair enzyme,AlkB

E. coli AlkB, a repair enzyme of the dioxygenase family, catalyses the removal of mutagenic methylated nucleotides from the genome. Known for substrate promiscuity, AlkB''s catalytic mechanism and conformational changes accompanying substrate binding have been extensively dissected. However, the structural parameters of various substrates governing their recognition by AlkB still remain elusive. In this work, through solution-state vibrational spectra of methylated substrates bound to AlkB in combination with computational analysis, we show that the recognition specificity is dictated by the protonation states of the substrates. Specificity is conferred predominantly through hydrogen bonding and cation–π interactions. Furthermore, we report on the interaction of AlkB with normal, unmodified nucleotides, wherein the presence of an exocyclic amino group serves as an essential criterion for the initial process of substrate recognition. Taken together, these results provide a rationale for structural determinants of substrate specificity as well as mode of lesion discrimination employed by AlkB.

Positive charge on methylated nucleotides is a prime criterion for substrate recognition by E. coli AlkB.