5-Fluoro-Uracil and Low Molecular Weight Heparin in the Management of Proliferative Vitreo-retinopathy

Background

Proliferative vitreo-retinopathy (PVR) is the most common cause of failed repair of a primary rhegmatogenous retinal detachment (RRD). The success rates for the surgery of complicated RRD has doubled with improved vitreous techniques from 35–40% to approximately 65–75% at six months. However, despite these advances, recurrent vitreo-retinal traction leads to re-detachment in more than one-fourths of the initially successful cases. The use of adjunctive treatments to prevent cellular proliferation holds promise for the prevention of PVR or recurrences after surgery. One focus has been on the use of intra-vitreal antimetabolites to prevent the occurrence of PVR.

Methods

Thirty patients of complicated retinal detachment associated with PVR, C1 or more were managed by vitreo-retinal (VR) surgery with the addition of 250 μg / ml of 5-fluorouracil (5FU) and 1 IU / ml of low molecular weight heparin (LMWH) to the vitreous infusion. The patients were examined for any evidence of PVR till 180 days as also for any systemic or other ophthalmic complication.

Result

Out of the 30 cases in the study group, 25 (83.34%) cases had retinal settlement at the end of six weeks, which is similar to the outcomes of conventional VR surgery. There was no case of any serious complication.

Conclusion

The addition of LMWH and 5FU did not enhance the outcome of VR surgery.Key Words: Proliferative vitreo-retinopathy, Rhegmatogenons retinal detachment, 5-fluorouracil, Low molecular weight heparin     

A correlative study of gliomas usingIn vivo bromodeoxyuridine labeling index and computer-aided malignancy grading

An in vivo bromodeoxyuridine (BrdU) labeling index (LI) was estimated in 43 cases of astrocytic tumors and mixed gliomas by one hour intra-operative intravenous infusion at a dose of 200 mg/m2 and correlated with (a) histological grading using a computer aided malignancy classifier TESTAST-268; and (b) histological typing using WHO classification. The lowest BrdU LI was seen in pilocytic and gemistocytic astrocytomas followed by astrocytomas, anaplastic astrocytomas and glioblastoma multiforme in that order. Mixed oligoastrocytomas followed the pattern of their astrocytic counterparts. Tumors of similar histological type showed different BrdU LI values especially amongst astrocytomas and glioblastomas. A statistically significant difference in the BrdU LI was also noted between the higher TESTAST grades of astrocytomas (T III and IV) versus the lower TESTAST grades (T II). Unlike earlier reports in literature, in the present study the category of BrdU LI of <1 contained no case of anaplastic astrocytoma or glioblastoma multiforme (TESTAST grades III and IV). Likewise, the category of BrdU LI >5 contained only anaplastic astrocytoma and glioblastoma multiforme (TESTAST grades III and IV). Maximum spread of cases was seen in the BrdU LI category of 1-5, not only in terms of histological types but also TESTAST grades. Thus there appeared to be a positive trend of increasing BrdU LI values both with histological types and increasing TESTAST grades. Further, an interesting observation was that by using a combination of TESTAST grades and BrdU LI, the histologically homogenous glioblastoma group could be further subdivided into 4 categories which showed a trend towards prognostic correlation. Thus, this study though preliminary with number of cases being small in some groups, highlights the possible usefulness of combined histological typing, TESTAST grading and in vivo BrdU LI for prognostication of gliomas especially glioblastoma multiforme.     

Effect of dexamethasone on the expression of binding sites for high-density lipoproteins in cultured rat hepatocytes (Independence of the hormone effect on the intracellular cholesterol pool)

It is shown that glucocorticoids play a key regulatory role directed toward the maintenance of an optimal level of binding and internalization of HDL₃ in hepatocytes. Their stimulatory effect on the expression of HDL receptors proves to be independent of changes in the CH content in parenchymal cells. Translated fromByulleten' Eksperimentalnoi Biologii i Meditsiny, Vol. 117, N ^o 1, pp. 50–53, January, 1994     

Glucocorticoid-dependent regulation of the expression of high-density lipoprotein binding sites in rat hepatocytes

It is shown that dexamethasone increases the number of HDL binding sites in cultured hepatocytes bothin vivo andin vitro. The glucocorticoid acts in a dose-dependent and reversible manner within a wide range of concentrations, including physiological and subphysiological doses. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 1, pp. 47–50, January, 1994     

Vaccine-elicited Human T Cells Recognizing Conserved Protein Regions Inhibit HIV-1

Virus diversity and escape from immune responses are the biggest challenges to the development of an effective vaccine against HIV-1. We hypothesized that T-cell vaccines targeting the most conserved regions of the HIV-1 proteome, which are common to most variants and bear fitness costs when mutated, will generate effectors that efficiently recognize and kill virus-infected cells early enough after transmission to potentially impact on HIV-1 replication and will do so more efficiently than whole protein-based T-cell vaccines. Here, we describe the first-ever administration of conserved immunogen vaccines vectored using prime-boost regimens of DNA, simian adenovirus and modified vaccinia virus Ankara to uninfected UK volunteers. The vaccine induced high levels of effector T cells that recognized virus-infected autologous CD4⁺ cells and inhibited HIV-1 replication by up to 5.79 log₁₀. The virus inhibition was mediated by both Gag- and Pol- specific effector CD8⁺ T cells targeting epitopes that are typically subdominant in natural infection. These results provide proof of concept for using a vaccine to target T cells at conserved epitopes, showing that these T cells can control HIV-1 replication in vitro.     

Morphological alterations in endothelial cells from human aorta and umbilical vein induced by forskolin and phorbol 12-myristate 13-acetate: a synergistic action of adenylate cyclase and protein kinase C activators.

The morphological effects on human endothelial cells of phorbol 12-myristate 13-acetate (PMA) and of agents that increase intracellular cAMP concentration were studied. The adenylate cyclase activator forskolin (10 microM), the cyclic nucleotide phosphodiesterase inhibitor methylisobutylxanthine (100 microM), dibutyryl-cAMP (10 microM), histamine (10 microM), and PMA (0.1 microM) significantly altered the morphology of human aortic and umbilical vein endothelial cells in primary cultures. These effects reached a maximum 40-80 min after the effector addition and became negligible 30-60 min after its removal. PMA and forskolin were strongly synergistic in altering endothelial cell morphology. All the effects of cAMP-elevating compounds and of PMA were abolished completely by 1 microM colchicine. In explants taken from human adult or child aortas, forskolin and PMA produced alterations in endothelial morphology qualitatively identical to those observed in endothelial cell cultures. Endothelium in these preparations closely resembled that found in zones of expected altered hemodynamic stresses of human aorta. Our data suggest that the morphology of endothelium in vivo may be regulated by separate or synergistic action of hormone-dependent adenylate cyclase and of inositol phospholipid turnover systems and might be important for maintenance of endothelial monolayer integrity under normal physiological and pathological conditions.