Lupus Nephritis in Indian Children: Flares and Refractory Illness

Objective: To evaluate the incidence of flares and treatment resistance in children with lupusnephritis and their association with renal outcomes. Methods: We retrospectively reviewedthe case records of 34 children treated for lupus nephritis (Class II-IV) at a single center.Patients were followed for a minimum of five years to evaluate treatment response, onset offlares, and renal survival. Regression analyses were performed to identify the factorsassociated with treatment refractoriness, incidence of flares and renal survival. Results: Theincidence of flares was 0.16 episodes/person/year. Eight patients (23.5%) were refractory totreatment. The five-year renal survival was 79%. Multiple episodes of flares (P=0.028) andtherapy refractoriness (P=0.003) were associated with poor renal survival. Conclusions:Prevention and aggressive management of renal flares is expected to prevent progression toend stage renal disease in lupus nephritis.

Probing tenability of biochemical vis-a-vis physicochemical interpretations of modulation of radiation damage by caffeine and cysteine in barley.

Cysteine (an aminothiol) is known to protect against radiation damage, and is understood to do so by generating hydrogen peroxide which subsequently inhibits RNA synthesis. Our results showed inability of catalase to remove or reduce the magnitude of radioprotection by caffeine and/or cysteine at optimal/suboptimal temperatures in barley. This observation was adequately corroborated by data on frequency of chromosomal aberration, peroxidase activity and total protein content. On the contrary, catalase tended to enhance the radioprotective effectiveness of cysteine. Macromolecular synthetic patterns in caffeine and/or cysteine treated embryos were too inconsistent to permit a logical conclusion with regard to their positive involvement in the biochemical pathway of chemical modification of radiation damage. On the other hand, mutually annihilatory reaction hypothesis based on physico-chemical principles provides a satisfactory explanation for the observed effects.

Radioprotective and antioxidant action of caffeine: mechanistic considerations.

Caffeine, a major constituent of coffee and other beverages has significant abilities to scavenge highly reactive free radicals and excited states of oxygen and to protect crucial biological molecules against these species. This is one of the possible reasons why caffeine acts as a radioprotector against oxygen-dependent ('oxic') pathway of radiation damage and as an antimutagen/anticarcinogen under certain conditions. The possible physicochemical and molecular mechanisms of caffeine action are briefly reviewed in the light of the recent findings.

Mechanistic aspects of modification of radiobiological damage in barley seeds by glutathione and buthionine sulfoximine.

Buthionine sulfoximine (BSO) enhances the radiosensitivity of in vitro mammalian cells, possibly by inhibiting de novo biosynthesis of glutathione (GSH); however, administration of BSO to intact animals results in no effect or possibly radioprotection. Keeping in view that BSO affords radioprotection its physico-chemical action in dry (metabolically inert) and pre-soaked (metabolizing) barley seeds has been investigated with a view that the effects of GSH and BSO on the radiation-induced O2-dependent and - independent components of damage could be unambiguously resolved. It was observed that (i) BSO does not inhibit the uptake of GSH in dry or metabolizing seeds, (ii) BSO also, like GSH, affords radioprotection against post-irradiation O2-dependent damage, and (iii) both additives enhance the O2-independent (i.e. N2- or N2O-mediated) component of damage. An equimolar mixture of these two additives also behaves as either alone on the oxic and anoxic components of radiation damage. Since GSH more efficiently reacts with electrons than it donates an H-atom to the damaged target molecules, and the glutamyl moiety is common to both GSH and BSO, physico-chemical mechanisms possibly involved in the differential modification of oxic and anoxic components are briefly discussed.

Post-exposure radioprotection by Chlorella vulgaris (E-25) in mice.

Oral administration of an algal mutant C. vulgaris E-25, 1 hr before or immediately after exposure to sublethal gamma-rays increased the number of endogenous spleen colony forming units (E-CFU). The magnitude of radioprotection was dependent on both, the dose of C. vulgaris fed and the time of administration. An optimal E-CFU was observed when 500 mg/kg body wt. of C. vulgaris was fed 1 hr before or immediately after irradiation. Significant recovery was observed in the number of bone marrow cells and the spleen weight. LD50/30 for Chlorella pre- and post-treated mice were 8.66 and 9.0 Gy, respectively compared to the control value of 7.8 Gy. The dose reduction factor (DRF) was 1.11 and 1.15 for pre-treated and post-treated mice respectively.

Maturation and externalization of EGF-receptor: a cell-surface located oncoprotein.

The EGF-receptor is a proto-oncogene encoded membrane protein related to the verb-B oncogene product of avian erythroblastosis virus. Here we report studies on expression and maturation characteristics of this receptor. The expression of intact 170 kDa EGF-receptor as well as a 100 kDa homologue that contains only the external domain is enhanced by the ligand EGF. EGF acts at transcriptional and post-transcriptional levels. To dissociate these pre-translational effects and the effects of EGF on receptor polypeptide synthesis from those on receptor export, pulse-chase experiments were conducted. These studies indicate that EGF stimulates post-translational transport and processing of the receptor, and this stimulation can occur in the absence of new protein synthesis. Other studies show that EGF accelerates at least two slow events in receptor maturation--the deoxynojirimycin-sensitive processing in endoplasmic reticulum (ER) and the swainsonine-sensitive processing in golgi, suggesting that EGF may influence one or more of the rate determining steps that control receptor export from ER. Overall the results demonstrate that EGF controls EGF-receptor expression at multiple levels, viz. at transcriptional, pre-translational and post-translational pathways of receptor biosynthesis.