Benefits and risks of immediately sequential bilateral cataract surgery: a literature review

Immediately sequential bilateral cataract surgery (ISBCS) is a highly contended issue in ophthalmology, mainly due to the risk of bilateral endophthalmitis and financial penalties that many ophthalmologists face when performing simultaneous cataract surgeries. The purpose of this review is to understand the current status of the knowledge of ISBCS, mainly its benefits and risks and how they compare with the standard of care, delayed sequential bilateral cataract surgery. Evidence, although limited, increasingly supports ISBCS for providing faster rehabilitation, improved visual outcomes, and cost and time savings. Evidence does not support the fear of bilateral endophthalmitis resulting from the simultaneous procedure. However, stronger and greater evidence is needed before ISBCSs can be considered the standard of care. Where ISBCS can potentially create the most beneficial impact is in public eye health programmes in developing countries, but this has not yet been explored.     

Reducing Ventral Tegmental Dopamine D2 Receptor Expression Selectively Boosts Incentive Motivation

Altered mesolimbic dopamine signaling has been widely implicated in addictive behavior. For the most part, this work has focused on dopamine within the striatum, but there is emerging evidence for a role of the auto-inhibitory, somatodendritic dopamine D2 receptor (D2R) in the ventral tegmental area (VTA) in addiction. Thus, decreased midbrain D2R expression has been implicated in addiction in humans. Moreover, knockout of the gene encoding the D2R receptor (Drd2) in dopamine neurons has been shown to enhance the locomotor response to cocaine in mice. Therefore, we here tested the hypothesis that decreasing D2R expression in the VTA of adult rats, using shRNA knockdown, promotes addiction-like behavior in rats responding for cocaine or palatable food. Rats with decreased VTA D2R expression showed markedly increased motivation for both sucrose and cocaine under a progressive ratio schedule of reinforcement, but the acquisition or maintenance of cocaine self-administration were not affected. They also displayed enhanced cocaine-induced locomotor activity, but no change in basal locomotion. This robust increase in incentive motivation was behaviorally specific, as we did not observe any differences in fixed ratio responding, extinction responding, reinstatement or conditioned suppression of cocaine, and sucrose seeking. We conclude that VTA D2R knockdown results in increased incentive motivation, but does not directly promote other aspects of addiction-like behavior.     

Pharmacokinetics of ramipril in the elderly

Ramipril (HOE 498) is a pro-drug of which the main metabolite (HOE 498 diacid or ramiprilat) is a potent angiotensin converting enzyme inhibitor. Thirteen healthy white volunteers (5 females and 8 males, ages 65 to 76 years) participated in a study to investigate the pharmacokinetics of HOE 498 in the elderly. After administration of 10 mg of HOE 498, sequential urine and serum specimens were obtained for assay of HOE 498 and metabolites (HOE 498-glucuronide, diacid, diacid-glucuronide, diketopiperazine and diketopiperazine acid). Side effects, clinical chemistry and hematology were monitored. HOE 498 reached peak concentrations of 62.4 +/- 23.3 ng/ml in serum after 0.7 +/- 0.3 hours. Serum levels decreased with an apparent half-life of 0.9 +/- 0.4 hours. The diacid was rapidly formed in serum, reaching peak concentrations of 40.6 +/- 14.0 ng/ml after 2.0 +/- 0.6 hours and declining with a half-life of 2.2 +/- 0.5 hours. A prolonged terminal phase of serum concentration versus time curve was observed at concentrations less than 1 ng/ml. The mean recovery of HOE 498 and metabolites in urine, up to 26 hours after administration, was 35 +/- 14% of the dose. The apparent half-lives, calculated from urine parameters, for HOE 498 and the diacid were 2.6 +/- 0.9 and 4.0 +/- 1.1 hours, respectively. The mean peak concentration and half-life of HOE 498 in serum are slightly higher in the elderly than in younger volunteers. Complete urinary collection was not possible, but urinary recovery did not seem different from younger volunteers.     

Leptin expression in offspring is programmed by nutrition in pregnancy

Birth weight is a determinant of blood leptin concentrations in adults. Since nutrition during pregnancy can affect birth weight, the hypothesis that feed intake during pregnancy alters leptin expression in progeny was examined. Leptin mRNA was measured in subcutaneous adipose tissue and leptin protein was measuredin blood plasma from 59 day old female pigs whose mothers were fed at the same restricted rate except that half were permitted to consume 35% more feed during the second quarter of pregnancy. Leptin mRNA abundance in adipose tissue (P=0.015) and plasma leptin concentration (P=0.01) were higher in progeny from mothers provided with more feed. Body weight at birth was negatively correlated with the abundance of leptin mRNA in subcutaneous fat at 59 days of age (P=0.01). This study shows for the first time that maternal nutrition during pregnancy programs postnatal leptin expression in offspring.     

Inflammatory, abscess-forming foreign body reaction mimics a thrombus formation on an atrial septal defect closure device: A commented case report.

We are presenting a case of floating left and right atrial formations on an atrial septal defect occluder system (23mm StarFLEX)-Occluder) initially supposed to be thrombotic appositions in a 57-year-old man. The closure was performed on the background of left hemispheric stroke and atrial septal aneurysm (ASA) with patent foramen ovale (PFO). The suspect structures were detected in the 6-month follow-up by transesophageal echocardiography (TEE). The patient underwent a successful surgical explantation of the closure device and closure of the patent foramen ovale (PFO) using a pericardial patch. The pathological evaluation of the biatrial device associated appositions revealed hytrophic heart muscle tissue with perifocal scarring and purulent abscess-forming, granulating and foam-cell including inflammatory foreign body reaction instead of the expected thrombus formation.     

A PKR-like eukaryotic initiation factor 2alpha kinase from zebrafish contains Z-DNA binding domains instead of dsRNA binding domains

The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is induced as part of the IFN response in mammals and acts to shut down protein synthesis by the phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha). In fish, a PKR-like kinase activity has been detected, but the enzyme responsible has eluded characterization. Here, we describe a PKR-like kinase from zebrafish. Phylogenetic analysis shows that the C-terminal kinase domain is more closely related to the kinase domain of PKR than to any of the other three known eIF2alpha kinases. Surprisingly, instead of the two dsRNA binding domains found at the N terminus of PKR, there are two Zalpha domains. Zalpha domains specifically bind dsDNA and RNA in the left-handed Z conformation, often with high affinity. They have been found previously in two other IFN-inducible proteins, the dsRNA editing enzyme, ADAR1, and Z-DNA binding protein 1 (ZBP1), as well as in the poxvirus virulence factor, E3L. This previously undescribed kinase, designated PKZ (protein kinase containing Z-DNA binding domains), is transcribed constitutively at low levels and is highly induced after injection of poly(inosinic)-poly(cytidylic) acid, which simulates viral infection. Binding of Z-DNA by the Zalpha domain of PKZ was demonstrated by circular dichroism. PKZ inhibits translation in transfected cells; site-directed mutagenesis indicates that this inhibition depends on its catalytic activity. Identification of a gene combining Zalpha domains with a PKR-like kinase domain strengthens the hypothesis that the ability to bind left-handed nucleic acid plays a role in the host response to viruses.     

The distribution of HBV, HCV and HGV among livers with fulminant hepatic failure of different aetiology

Background/Aims: The aim of the study was to assess the impact factor of HCV and HGV in fulminant hepatic failure.Methods: The 5′-untranslated regions of HCV RNA and HGV RNA and a segment of the core antigen sequence of HBV were amplified after extracting the nucleic acids from snap-frozen tissue aliquots from explanted livers of 26 consecutive patients undergoing orthotopic liver transplantation for fulminant hepatic failure preoperatively diagnosed as either autoimmune (n=2), HAV/HBV (n=8), toxic (n=4) or aetiologically unknown (n=12).Results: HCV RNA was detected in five of 26 (19.2%) livers with fulminant hepatic failure. All five HCV RNA-positive livers belonged to the group of non-toxic, non-autoimmune liver failure (n=20), three of them were found in the group of liver failure with unknown aetiology (n=12) and two in the group of HBV-associated liver failure (n=7), making an HCV incidence of 25%, 25%, and 28.6%, in the different groups, respectively. HGV RNA was detected in 10 of 17 (58.8%) explants and in all four groups of fulminant hepatic failure as defined preoperatively. HBV DNA was identified in six livers of 26 patients (23.1%) with fulminant hepatic failure. Neither HCV RNA nor HBV DNA was detected in the livers of patients with toxic or autoimmune fulminant hepatic failure.Conclusions: These results indicate that HBV and HCV, but not HGV, play an aetiologic role in fulminant hepatic failure. HCV-positive cases were concentrated either in the group of otherwise unexplained fulminant hepatic failure or in the group of HBV fulminant hepatic failure. HGV-positive cases, on the other hand, were found within all four preoperatively defined groups, indicating a role as cofactor rather than as single aetiologic agent.     

The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients

OBJECTIVE Several in-vitro studies have suggested that the biological actions of IGF-I can be modified by the presence of specific IGF binding proteins. In man, the 24-hour serum levels of IGF-I and IGFBP-3 remain constant, but short-term changes in the IGF-l/IGFBP-3 ratio have been described following GH administration. Serum levels of IGF-I and IGFBP-3 decrease with age in normal adults and are elevated In active acromegaly due to excessive GH secretion. However, the Individual ratios between serum levels of IGF-I and IGFBP-3 in acromegalic and healthy adults have not been described previously. METHODS AND MATERIALS We studied this ratio In 198 healthy adults and In 56 acromegalic patients, grouped according to their serum GH levels (group I GH < 2mLU/l II GH 2–10mLU/l; III GH > 10mLU/l). In all subjects a single blood sample was drawn for IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and GH measurements by specific RIAs. In 38 of the patients a 24-hour urinary collection was performed for GH determination. RESULTS In healthy adults serum levels of IGF-I and IGFBP-3 decreased with Increasing age (r =?0.52 and r=?0.34, respectively, P< 0.0001). In addition, the molar IGF-l/IGFBP-3 ratio declined with increasing age (r =?0.44, P – 0.0001). In patients with acromegaly and high serum GH levels (group III), circulating IGF-I was increased 7–97 standard deviations (SDS) and IGFBP-3 was increased 4.20 SOS (P < 0.0001). Serum levels of IGF-II were normal in all three groups (588 ± 240μ/l) whereas IGFBP-1 and IGFBP-2 levels were low and IGFBP-2 levels decreased significantly with increasing serum GH levels (P < 0.0001). The molar IGF-l/IGFBP-3 ratio in the acromegalic patients was significantly higher than in the controls (P < 0.0001) and correlated significantly with urinary GH excretion (r = 0.67, P < 0.0001) as well as with serum GH levels (r = 0.73, P < 0.0001). CONCLUSION We demonstrated a decreasing molar IGF-l/IGFBP-3 ratio with increasing age in healthy adults and an increased ratio between serum IGF-I and IGFBP-3 levels in acromegalic patients. As IGF-II is normal and IGFBP-1 and IGFBP-2 are inversely correlated to the serum GH levels In the acromegalic patients, we speculate that the molar ratio between IGF-I and IGFBP-3 reflects free (biologically active) IGF-I and Is dependent on GH levels.