Arginine supplementation for prevention of necrotising enterocolitis in preterm infants.

BACKGROUND: Immaturity, ischemia, and disturbances in gut mucosal integrity due to infections or hyperosmolar feeds are some of the suspected mechanisms in the development of necrotising enterocolitis (NEC) in preterm infants. Decreased concentration of nitric oxide is proposed as one of the possible cellular mechanisms for NEC. Plasma arginine concentrations were found to be lower in infants who developed NEC. Arginine can act as a substrate for the production of nitric oxide in the tissues and arginine supplementation may help in preventing NEC. OBJECTIVES: To examine the effect of arginine supplementation on the incidence of NEC in preterm neonates. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966 - April 2007), EMBASE (1980 - April 2007), CINAHL (1982 - April 2007), Cochrane Controlled Trials Register (Issue 2, 2007 of Cochrane Library) and abstracts from the annual meetings of the Society for Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2007). No language restrictions were applied. STUDY DESIGN: randomized or quasi-randomized controlled trials. POPULATION: preterm neonates. INTERVENTION: enteral or parenteral arginine supplementation (in addition to what an infant may be receiving from enteral or parenteral source), compared to placebo or no treatment; arginine administered orally or parenterally for at least seven days in order to achieve adequate plasma arginine levels (145 umol/l). OUTCOMES: any of the following outcomes - NEC, death prior to discharge, death due to NEC, surgery for NEC, duration of total parenteral nutrition, plasma concentrations of arginine and glutamine at baseline and seven days after intervention, side effects of arginine. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the author. Data on relevant outcomes were extracted and the effect size was estimated and reported as relative risk (RR), risk difference (RD) and mean difference (MD) as appropriate. MAIN RESULTS: Only one eligible study was identified. The methodological quality of the included study was good. There was a statistically significant reduction in the risk of developing NEC (any stage) in the arginine group compared with the placebo group [RR 0.24 (95% CI 0.10, 0.61), RD -0.21 (95% CI -0.32, -0.09)]. No significant side effects directly attributable to arginine were observed. In this updated version, follow up data from this trial were available that revealed no statistically significant difference in the adverse outcomes. AUTHORS' CONCLUSIONS: The data are insufficient at present to support a practice recommendation. A multicentre randomized controlled study of arginine supplementation in preterm neonates is needed, focusing on the incidence of NEC, particularly the more severe stages (2 or 3).

Arginine supplementation for prevention of necrotising enterocolitis in preterm infants.

BACKGROUND: Immaturity, ischemia, and disturbances in gut mucosal integrity due to infections or hyperosmolar feeds are some of the suspected mechanisms in the development of necrotising enterocolitis (NEC) in preterm infants. Decreased concentration of nitric oxide is proposed as one of the possible cellular mechanisms for NEC. Plasma arginine concentrations were found to be lower in infants who developed NEC. Arginine can act as a substrate for the production of nitric oxide in the tissues and arginine supplementation may help in preventing NEC. OBJECTIVES: This review examines the efficacy and safety of arginine supplementation in decreasing the incidence of NEC among preterm neonates. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966 - June 2004), EMBASE (1980 - June 2004), CINAHL (1982 - June 2004), Cochrane Controlled Trials Register (Issue 2, 2004 of Cochrane Library) and abstracts from the annual meetings of the Society for Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2004). No language restrictions were applied. STUDY DESIGN: randomized or quasi-randomized controlled trials. POPULATION: preterm neonates. INTERVENTION: enteral or parenteral arginine supplementation (in addition to what an infant may be receiving from enteral or parenteral source), compared to placebo or no treatment; arginine administered orally or parenterally for at least 7 days in order to achieve adequate plasma arginine levels (145 umol/l). OUTCOMES: any of the following outcomes - NEC, death prior to discharge, death due to NEC, surgery for NEC, duration of total parenteral nutrition, plasma concentrations of arginine and glutamine at baseline and seven days after intervention, side effects of arginine. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the author. Data on relevant outcomes were extracted and the effect size was estimated and reported as relative risk (RR), risk difference (RD) and mean difference (MD) as appropriate. MAIN RESULTS: Only one eligible study was identified. The methodological quality of the included study was good. There was a statistically significant reduction in the risk of developing NEC (any stage) in the arginine group compared with the placebo group (RR 0.24 [95% CI 0.10, 0.61], RD -0.21 [95% CI -0.32, -0.09]). No significant side effects directly attributable to arginine were observed. REVIEWERS' CONCLUSIONS: The data are insufficient at present to support a practice recommendation. A multicentre randomized controlled study of arginine supplementation in preterm neonates is needed, focusing on the incidence of NEC, particularly stage 2 or 3.

Management of vitreous loss during cataract surgery under topical anesthesia with transconjunctival vitrectomy system.

PURPOSE: A new technique to manage posterior capsular rupture with vitreous prolapse into the anterior chamber during phacoemulsification under topical anesthesia using the sutureless self-sealing 25-gauge transconjuctival vitrectomy system. METHOD: In the event of vitreous prolapse into the anterior chamber, the corneal wound is sutured and cleared of vitreous. A trans conjunctival 25-gauge sclerotomy through the pars plana is made. The high speed 25-guage trans-conjunctival vitrectomy system (TVS-25) under topical anesthesia is introduced and vitrectomy is performed to clear the anterior chamber of vitreous. An anterior vitrectomy is also done. A foldable intraocular lens is subsequently inserted. RESULTS: The vitrectomy is performed in a closed chamber maintaining normal intraocular pressure. The high-speed cutter exerts minimal traction on the vitreous. The accessibility to vitreous improves through the pars plana route ensuring more complete removal of the vitreous and restoration of normal anatomy. Topical anesthesia avoids the risks of globe perforation, retrobulbar hemorrhage, and prolonged postoperative akinesia of the eye. CONCLUSIONS: The 25-gauge pars plana incision is small and self-sealing. This makes the procedure fast, effective, painless and safe.

Pycnogenol protects vascular endothelial cells from beta-amyloid-induced injury.

The neuropathological hallmarks of Alzheimer's disease (AD) are senile plaques, cerebrovascular beta-amyloidosis, neurofibrillary tangles, and selective neuronal loss. Beta-amyloid (Abeta) has been shown to cause vascular damage mediated by generation of reactive oxygen species and this damage is considered an early event in the development of AD. In this study, we determined the effect of pyenogenol, a potent antioxidant phytochemical, on Abeta-induced cellular injury. Pulmonary artery endothelial cells (PAEC) were exposed to Abeta for 24 h. Cell injury was assessed by measuring cell viability with methylthiazol tetrazolium (MTT) assay, and by determining the release of intracellular lactate dehydrogenase (LDH). Lipid peroxidation products of PAEC were determined by measuring thiobarbituric acid-reactive substances (TBARS). Exposure of PAEC to Abeta resulted in a decrease in cell viability, an increase of LDH release indicating membrane damage, and an elevated level of TBARS. Preincubation of PAEC with pycnogenol significantly minimized these changes. This study demonstrated that pycnogenol can protect vascular endothelial cells from Abeta-induced injury. The data suggest that pycnogenol may be useful for the prevention and/or treatment of vascular or neurodegenerative diseases associated with Abeta toxicity.

Ginkgo biloba inhibits hydrogen peroxide-induced activation of nuclear factor kappa B in vascular endothelial cells.

The present study determined the effects of Ginkgo biloba extract (GBE) on the activation of nuclear factor kappa B (NF-kappaB) and the level of hydrogen peroxide (H2O2) in bovine pulmonary artery endothelial cells (PAEC). H2O2 showed a concentration-dependent activation of NF-kappaB. GBE demonstrated a concentration-dependent suppression of NF-kappaB activated by H2O2. GBE directly scavenged H2O2 in a cell-free system; it also decreased H2O2 levels in PAEC. These results suggest that the inhibitory effect of GBE on H2O2-induced NF-kappaB activation may be caused by its scavenging and suppression of H2O2. Our experiments demonstrate that GBE can inhibit NF-kappaB activation induced by H2O2 and may thus be effective for the prevention or treatment of atherosclerosis and other disorders related to NF-kappaB activation.

Effect of cyclosporin A on glomerular filtration rate in children with minimal change nephrotic syndrome.

Cyclosporin A (CyA) is now commonly used in the management of children with steroid-dependent nephrotic syndrome. In order to assess nephrotoxicity related to CyA therapy, we measured glomerular filtration rate (GFR) on 123 occasions in 24 children with minimal change nephrotic syndrome receiving CyA. GFR was estimated from the plasma clearance of 51chromium-EDTA every 3 months during CyA therapy of up to 27 months duration. There was a significant reduction in GFR after 3 months of CyA therapy [118 +/- 33 (SD) to 93 +/- 24 ml/min per 1.73 m2] but no further fall thereafter, although the reduction in GFR was sustained for the duration of CyA therapy. This reduction in GFR appeared to be reversible upon cessation of CyA, but careful monitoring of renal function is necessary in such patients to prevent the development of longer term nephrotoxic sequelae.

Terminal differentiation and senescence in the human melanocyte: repression of tyrosine-phosphorylation of the extracellular signal-regulated kinase 2 selectively defines the two phenotypes.

Melanocytes are pigmented cells distributed in humans in several organs like the epidermis, the leptomeninges, the eye, and the inner ear. Epidermal melanocytes, whether derived from adult or neonatal skin, proliferate well in a medium supplemented with phorbol esters and other mitogens before they undergo senescence. Potent cAMP inducers like cholera toxin are also growth promoters for neonatal melanocytes but only transient growth stimulators for cells derived from adults. We used this cellular system to delineate biochemical pathways involved in proliferation and in terminal differentiation. Here we show that after a period of 4-8 wk of sustained proliferation in the presence of cholera toxin, the adult melanocytes became round, flat, and enlarged. These changes were associated with terminal growth and preceded by a five- to sixfold increase in cAMP levels and an 8- to 10-fold increase in melanin content. The simultaneous addition of phorbol esters and cholera toxin did not prevent cells from reaching terminal differentiation. Identified targets for phorbol esters are protein kinase C (PKC) and the mitogen-activated kinases (MAPKs), also called extracellular signal-regulated kinases (ERKs). PKC was found to be similarly regulated in proliferating and in terminally differentiated melanocytes. Proliferating melanocytes in early or late passage showed identical activation of the kinase ERK2. This kinase was rapidly phosphorylated upon phorbol 12-myristate 13-acetate (PMA) addition and specifically accumulated in the nucleus of the cells, whereas in unstimulated cells it had a perinuclear distribution. In contrast, senescent and terminally differentiated cells were unable to phosphorylate tyrosine residues of the ERK2 gene product in spite of presenting normal amounts of ERK2 protein. In addition, ERK2 did not show the nuclear accumulation observed in proliferating melanocytes after PMA activation and remained localized in the perinuclear area. These results demonstrate that senescent and terminally differentiated melanocytes share a common block in a critical pathway thought to integrate multiple intracellular signals transmitted by various second messengers and specifically prevent the continuation of the signal transduction cascade initiated by PMA activation of PKC.

Pycnogenol protects vascular endothelial cells from t-butyl hydroperoxide induced oxidant injury.

The active oxygen induced and free radical mediated oxidation of biological molecules, membranes, and tissues has been suggested as a major cause of cancer, atherosclerosis, and aging. Damage of endothelial cells may lead to cardiovascular and cerebrovascular diseases. In the present study, the antioxidant effect of pycnogenol (procyanidins extracted from Pinus maritima) was investigated in vitro using vascular endothelial cells. Confluent monolayers of bovine pulmonary artery endothelial cells (PAEC) were preincubated with different concentrations of pycnogenol for 16 h, washed, and then exposed to an organic oxidant t-butyl hydroperoxide (tBHP) for 3 or 4 h. Cellular injury was assessed by measuring cell viability with methylthiazol tetrazolium (MTT) assay and by determining the release of intracellular lactate dehydrogenase (LDH). Lipid peroxidation products of PAEC were monitored as malondialdehyde (MDA) with a thiobarbituric acid fluorometric assay. Incubation of tBHP (75, 100, or 125 microM) with PAEC decreased cell viability, increased LDH release, and elevated MDH production. Preincubation of PAEC with pycnogenol (10-80 micrograms/mL) before tBHP exposure significantly increased cell viability, decreased LDH release, and reduced MDA production. These results demonstrate that pycnogenol can protect vascular endothelial cells from oxidant injury. The data thus suggest that pycnogenol may be useful for the prevention of disorders associated with oxidative damage.

Topical corticosteroids: quality control considerations.

A simple procedure is developed, which can be used as a quality control test. The method utilizes commercially available diffusion cell assembly, synthetic membrane, and an appropriate receptor phase. The amount of drug released over time is determined using an HPLC method. From this, the drug release rate, flux, microgram/cm2/min0.5 is calculated. This drug release rate can serve as a good quality control test to assure batch-to-batch uniformity.

Glycemic index of traditional Indian carbohydrate foods.

The glycemic index (GI) was determined in 36 non-insulin-dependent diabetes mellitus patients who were fed 50 g carbohydrate portions of six Indian conventional foods, including rice, a combination of rice-legume (Bengalgram, peas, and greengram), and a combination of rice-dal (greengram dal and redgram dal -- dal is dehusked and split legume). In addition to the GI, triglyceride (TG) responses of these foods were also determined. A higher GI was obtained for rice and for rice with peas; all other combinations yielded lower glycemic indices. However, all the foods produced significantly lower blood glucose response 2 hours postprandially as compared with blood glucose responses to a 50 g glucose load for the same group. No significant difference was observed for TG responses to the different foods.

Chonemorphine, stigmasterol, and ecdysterone: steroids isolated through bioassay-directed plant screening programs.

In a bioassay-directed screening programme of plants for the identification of active constituents the following steroids were isolated. Chonemorphine was identified as the antiamoebic and antitrichomonad principle of Chonemorpha fragrans. Stigmasterol from Coleus forskohlii and ecdysterone from Diploclisia glaucescens were inactive constituents isolated during the process of purifying the active principles of the plants. D. glaucescens roots are a high-yielding source (0.5% of the dry root weight) of ecdysterone.

Use of oxidizing dyes in combination with 2-cyanocinnamic acid to enhance hyperthermic cytotoxicity in L929 cells.

Two widely used oxidizing dyes, 2,3,5-triphenyltetrazolium chloride and methylene blue, can greatly potentiate hyperthermic cytotoxicity when administered simultaneously with 2-cyanocinnamic acid. The same compounds are virtually nontoxic to L929 cells if administered alone at 42 degrees C or in combination with 2-cyanocinnamic acid at 37 degrees C. Cytotoxicity was synergistically enhanced by the combined regimens after 3 h of heat exposure. Quercetin, a bioflavonoid known to enhance hyperthermic cytotoxicity, also acts synergistically when administered in combination with 2-cyanocinnamic acid and this effect is apparent after 1 h of heat exposure. Since these compounds do not greatly interfere with pyruvate metabolism at either normal or heat shock temperatures, a mechanism of action based on depletion of NAD(P)H is considered.

Bartter's syndrome: 10 cases in childhood. Results of long-term indomethacin therapy.

Ten children with Bartter's syndrome are described. Their ages at diagnosis ranged from three months to 15 years and there was an equal sex distribution. A wide spectrum of severity of clinical and biochemical features was found. Hypercalcaemia, hypophosphataemia, hypercalcuria, nephrocalcinosis, rickets and urine acidification defects were seen in some patients. Two affected children were siblings. Six children were treated over periods of six to 24 months with indomethacin with remarkable clinical and biochemical improvement. Catch-up growth was demonstrated in all treated cases. Tolerance to indomethacin appeared to develop in some children. Only one serious complication was seen with this therapy, a duodenal ulcer in a child on high dosage. Of those children not treated with indomethacin, one died, one is now on indomethacin elsewhere and two are well without therapy.