Mycophenolate mofetil for lupus related myelopathy.
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Adult↗
Biomedical subjects
C H To
Publications and source records attributed to C H To.
Outcome of protein-losing gastroenteropathy in systemic lupus erythematosus treated with prednisolone and azathioprine.
OBJECTIVES: To report the efficacy of prednisolone and azathioprine (AZA) in the treatment of systemic lupus erythematosus (SLE)-related protein-losing gastroenteropathy (PLGE). METHODS: Between 1995 and 2002, 16 consecutive patients with SLE-related PLGE were treated with a regimen consisting of high-dose prednisolone (0.8-1 mg/kg/day for 6 weeks, then tapered to < or =10 mg/day) and AZA (2 mg/kg/day). Protein leakage from the gastrointestinal tract was confirmed by 99mTc-labelled human serum albumin scintigraphy and significant urinary loss of protein was excluded. Clinical response at 6 months of therapy was assessed and patients were followed for relapse of PLGE. RESULTS: Clinical characteristics of our patients at the time of PLGE were: age 36.2 +/- 8.7 (s.d.) yr; female:male ratio 15 : 1; mean SLE duration 29.6 +/- 65 months. Twelve patients had PLGE as the initial presentation of SLE. Fifteen (94%) patients had concomitant activity in other organs. All patients presented with oedema and eight patients (50%) had non-bloody diarrhoea. The mean serum albumin level was 22.8 +/- 5.7 g/dl. Protein leakage was at the small bowel in 11 (69%) patients and the large bowel in 5 (31%) patients. At 6 months of therapy, 14 (88%) patients had complete clinical response, 1 (6%) patient responded partially and 1 patient (6%) was treatment-refractory. Patients who responded were maintained on low-dose prednisolone (7.8 +/- 6.1 mg/day) and AZA (56.3 +/- 37 mg/day). Over a mean follow-up of 57.5 months, 1 (6%) patient had relapse of PLGE which responded to augmentation of prednisolone dosage. No patients developed alternative gastrointestinal diagnoses. Corticosteroid-induced psychosis, AZA-induced pancytopenia and herpes zoster occurred in three patients. CONCLUSION: PLGE is an uncommon manifestation of SLE. Treatment with a combination of prednisolone and AZA is effective and well tolerated.
Administration, Oral↗
Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus?
OBJECTIVE: To examine autoantibody clusters and their associations with clinical features and organ damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: The study group comprised 1,357 consecutive patients with SLE who were recruited to participate in a prospective longitudinal cohort study. In the cohort, 92.6% of the patients were women, the mean +/- SD age of the patients was 41.3 +/- 12.7 years, 55.9% were Caucasian, 39.1% were African American, and 5% were Asian. Seven autoantibodies (anti-double-stranded DNA [anti-dsDNA], anti-Sm, anti-Ro, anti-La, anti-RNP, lupus anticoagulant (LAC), and anticardiolipin antibody [aCL]) were selected for cluster analysis using the K-means cluster analysis procedure. RESULTS: Three distinct autoantibody clusters were identified: cluster 1 (anti-Sm and anti-RNP), cluster 2 (anti-dsDNA, anti-Ro, and anti-La), and cluster 3 (anti-dsDNA, LAC, and aCL). Patients in cluster 1 (n = 451), when compared with patients in clusters 2 (n = 470) and 3 (n = 436), had the lowest incidence of proteinuria (39.7%), anemia (52.8%), lymphopenia (33.9%), and thrombocytopenia (13.7%). The incidence of nephrotic syndrome and leukopenia was also lower in cluster 1 than in cluster 2. Cluster 2 had the highest female-to-male ratio (22:1) and the greatest proportion of Asian patients. Among the 3 clusters, cluster 2 had significantly more patients presenting with secondary Sjögren's syndrome (15.7%). Cluster 3, when compared with the other 2 clusters, consisted of more Caucasian and fewer African American patients and was characterized by the highest incidence of arterial thrombosis (17.4%), venous thrombosis (25.7%), and livedo reticularis (31.4%). By using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the greatest frequency of nephrotic syndrome (8.9%) was observed in patients in cluster 2, whereas cluster 3 patients had the highest percentage of damage due to cerebrovascular accident (12.8%) and venous thrombosis (7.8%). Osteoporotic fracture (11.9%) was also more common in cluster 3 than in cluster 2. CONCLUSION: Autoantibody clustering is a valuable tool to differentiate between various subsets of SLE, allowing prediction of subsequent clinical course and organ damage.
Adult↗
Monovision slows myopia progression.
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Accommodation, Ocular↗
Effects of melatonin on the nitric oxide treated retina.
AIMS: Nitric oxide (NO) is a free radical which reportedly causes damage to living cells. This study evaluated the damaging effect of NO and the protection of melatonin on the retina in vivo. METHODS: Female Wistar rats (230-250 g) received two intraperitoneal injections of either melatonin (5 mg/kg) or vehicle alone. After general anaesthesia, the animals received 1 microl intravitreal injections of 0.9% saline and 1 mM sodium nitroprusside (SNP) into the right eye and the left eye, respectively. The animals were divided into two groups and then sacrificed after 24 hours (day 1) and 96 hours (day 4). The mean inner retinal layer thickness (mIRLT), the number of retinas expressing hyperchromatic (HC) nuclei in the inner nuclear layer (INL) and the apoptotic ganglion cell detection were compared. RESULTS: After 1 day, SNP significantly increased the mIRLT by 45% (p = 0.004), initiated more INL nuclear HC expression (p = 0.01) and apoptotic nuclei (p<0.05) compared with the control eyes. Injection of melatonin ameliorated these changes. On day 4, SNP demonstrated similar effects in all parameters on the retina. After the injection of melatonin, both INL HC expression and apoptotic ganglion nuclei in the SNP treated eyes were similar to the controls but the mIRLT was significantly greater than in controls (p = 0.006). CONCLUSION: Uncontrolled NO elevation caused morphological and nuclear changes in the retina. Melatonin significantly suppressed the NO induced increase in mIRLT, INL HC expression, and apoptotic ganglion cells on day 1, but not after day 4. Melatonin may have a protective role in the NO elevated retina.
Animals↗
Successful treatment of dermatomyositis-related rapidly progressive interstitial pneumonitis with sequential oral cyclophosphamide and azathioprine.
Interstitial lung disease (ILD) is a major complication of idiopathic inflammatory myopathies (IIM). We report the successful use of oral cyclophosphamide, followed by azathioprine maintenance, in the treatment of a patient with dermatomyositis-related rapidly deteriorating ILD, resistant to steroid. Prompt recognition and early aggressive immunosuppressive therapy may improve the outlook of this condition.
Administration, Oral↗
Three patients with lead poisoning following use of a Chinese herbal pill.
We report on three patients with lead poisoning following use of the Chinese herbal pill Bao ning dan, prepared by the same traditional Chinese medicine practitioner. The patients had varying degrees of exposure to Bao ning dan and different clinical manifestations. Blood lead concentrations did not correlate with clinical severity. Two patients received chelating therapy and blood lead concentrations subsequently rapidly decreased. One patient was managed conservatively and end-organ complications resolved gradually. With increasing use of traditional Chinese medicines, related adverse reactions are expected to become increasingly common. Practitioners of western medicine should remain alert to this possibility. A comprehensive drug review, including the use of herbal medicines, should form a routine part of medical history taking.
Adult↗
N-acetyl-serotonin reduces copper (I) ion-induced lipid peroxidation in bovine retinal homogenates.
PURPOSE: Chalcosis is an ocular condition caused by penetration injury of copper or its alloy, which leads to extensive ocular inflammation. N-acetyl-serotonin has recently been identified as a potent antioxidant against free radical stress. In this study, we determined the efficacy of N-acetyl-serotonin against the copper (I)-induced retinal lipid peroxidation. METHODS: Copper (I)-treated (100 microM) bovine retinal homogenates were incubated with 6 different concentrations (i.e. 0.00, 0.25, 0.50, 1.00, 2.00 and 4.00 mM) of N-acetyl-serotonin or vitamin E. The malondialdehyde level was measured as an index of lipid peroxidation. RESULTS: Copper (I) ions induced a significant dose-dependent increase in malondialdehyde (p=0.007). Co-incubation with N-acetyl-serotonin or vitamin E significantly suppressed the copper (I)-induced malondialdehyde production (p<0.0001). The concentration to inhibit 50% of damage for N-acetyl-serotonin and vitamin E were found to be 1.54 mM and 0.45 mM, respectively. CONCLUSION: Although N-acetyl-serotonin is only 29% as effective as vitamin E in suppressing the copper (I)-induced lipid peroxidation, the present study supports a pharmacological potential of N-acetyl-serotonin combating free radical oxidative damages in the ocular tissues.
Animals↗
Model of ionic transport for bovine ciliary epithelium: effects of acetazolamide and HCO.
The possible existence of transepithelial bicarbonate transport across the isolated bovine ciliary body was investigated by employing a chamber that allows for the measurement of unidirectional, radiolabeled fluxes of CO2 + HCO. No net flux of HCO was detected. However, acetazolamide (0.1 mM) reduced the simultaneously measured short-circuit current (I(sc)). In other experiments in which (36)Cl- was used, a net Cl- flux of 1.12 microeq. h(-1). cm(-2) (30 microA/cm(2)) in the blood-to-aqueous direction was detected. Acetazolamide, as well as removal of HCO from the aqueous bathing solution, inhibited the net Cl- flux and I(sc). Because such removal should increase HCO diffusion toward the aqueous compartment and increase the I(sc), this paradoxical effect could result from cell acidification and partial closure of Cl- channels. The acetazolamide effect on Cl- fluxes can be explained by a reduction of cellular H+ and HCO (generated from metabolic CO2 production), which exchange with Na+ and Cl- via Na+/H+ and Cl-/HCO exchangers, contributing to the net Cl- transport. The fact that the net Cl- flux is about three times larger than the I(sc) is explained with a vectorial model in which there is a secretion of Na+ and K+ into the aqueous humor that partially subtracts from the net Cl- flux. These transport characteristics of the bovine ciliary epithelium suggest how acetazolamide reduces intraocular pressure in the absence of HCO transport as a driving force for fluid secretion.
Acetazolamide↗
Chloride secretion by bovine ciliary epithelium: a model of aqueous humor formation.
PURPOSE: To study the physiological mechanisms of the Cl transport across the bovine ciliary body-epithelium (CBE). METHODS: Fresh isolated bovine CBE was mounted in an Ussing-type chamber. The effects of ion substitution and transport inhibitors on electrical measurements and Cl transport were investigated. RESULTS: The potential difference (PD) across the preparation was 0.55 +/- 0.04 mV and was consistently negative at the aqueous side. The short-circuit current (SCC) and tissue resistance (Rt) were found to be 8.0 +/- 0.7 microA/cm2 and 72 +/- 3 omega/cm2, respectively. Both the PD and the SCC of the bovine CBE were found to depend primarily on the concentration of the Cl bath and to a lesser extent on the Na or HCO3 concentration. At 30 mM Cl, the polarity of the PD and the direction of the SCC were reversed. Reducing the extracellular Na or Cl concentration abolished the net Cl transport into the eye under the short-circuited condition. Bilateral bumetanide (0.1 mM), but not 4,4'-diisothiocyanatostilbene-2-2'-disulfonic acid (DIDS; 0.1 mM), greatly inhibited the Cl transport. Bumetanide, when applied to either side, inhibited the Cl transport. The effect, however, was three times greater on the stromal side than on the aqueous surface. Bilateral heptanol (3.5 mM) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB; 0.1 mM) on the aqueous side also inhibited the Cl transport by 80% and 92%, respectively. CONCLUSIONS: The results suggest that the major Cl influx pathway at the basolateral border in pigmented epithelial cells is through the Na-K-2Cl cotransporter, but not the Cl/HCO3 and Na/H double exchangers. Intercellular gap junctions between the two cell layers and the NPPB-sensitive Cl channels at the basolateral surface in nonpigmented epithelial cells also play a crucial role in regulating the Cl movement across the functional syncytium.
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
A preliminary study on the ocular blood flow (OBF) of Hong Kong Chinese.
The Ocular Blood Flow (OBF) Tonometer is an objective instrument to measure the Pulsatile Ocular Blood Flow (POBF), Pulse Amplitude (PA) and Pulse Rate (PR). It also provides the minimum intraocular pressure (IOPmin) simultaneously. This preliminary study applied the OBF Tonometer on 74 Hong Kong Chinese. They had their POBF measured followed by the Goldmann Applanation Tonometer (GAT). The OBF tonometer overestimates the IOP slightly. The average POBF result was smaller (661.2 microliters/min) than the previous studies. The effect of myopia of our sample (mean spherical equivalent -4.27 D) could be one of the contributing factors. Other factors include age and racial difference. Twenty-two subjects had their POBF measured again by the same practitioner and different practitioner for the reproducibility variation assessments. The POBF, PA and IOPmin were found to be repeatable between sessions. The POBF "norm" in Hong Kong Chinese needs to be established from a larger sample size and from a comparison on an age and refraction matched Caucasian group.
Adolescent↗
Pineal indoleamines and vitamin E reduce nitric oxide-induced lipid peroxidation in rat retinal homogenates.
Oxidative damage to retinal cell membranes can lead to sight-threatening ocular diseases. Pineal indoleamines are naturally located and synthesized in the retina, and they possibly protect the retina from oxidative cell damage. In this study, we compared the efficacy of three different pineal indoleamines (melatonin, N-acetylserotonin, and pinoline) with vitamin E, a well-known antioxidant, against nitric oxide (NO)-induced lipid peroxidation (LPO) in rat retinal homogenates. The possible synergistic effect of these agents was also studied. Retinal homogenates were incubated with sodium nitroprusside, which releases NO*. The LPO product, malondialdehyde (MDA), provided an index of cell damage. The results show that vitamin E and indoleamines significantly reduced MDA levels in a dose-dependent manner. When vitamin E was combined with the indoleamines, the protection was synergistically enhanced. In summary, under conditions where cellular homogenates are used (a) vitamin E and the three pineal indoleamines protected the retinal cells from NO-induced LPO damage; (b) the efficacies of each of these compounds had the following relationships: vitamin E > N-acetylserotonin > pinoline > melatonin; (c) vitamin E acted synergistically with indoleamines in combating oxidative retinal damage. Whether these same associations would exist in vivo after treatment with these compounds is unknown. The pharmacological potential of indoleamines, possibly in combination with vitamin E, in preventing retinal pathogenesis deserves further investigation.
Animals↗
A rapid method of preparing the plasma membrane enriched fraction of the bovine retinal pigment epithelial cells.
PURPOSE: To devise a rapid method of isolating the plasma membrane enriched fraction (PMEF) of the bovine retinal pigment epithelial (RPE) cells with Percoll centrifugation medium. METHODS: The bovine RPE was homogenised with a tight fit Dounce homogeniser and centrifuged in a 16.7% Percoll gradient for 20 minutes. The RPE particulate fractions were characterised in terms of their protein concentrations, Na/K-ATPase and bicarbonate stimulated ATPase activities. RESULTS: The total protein recovery was 88.7% of the RPE homogenate. The nucleus layer was identified at the first band. The mitochondrial fraction was at the second layer according to its bicarbonate stimulated ATPase activity. The 3rd and 4th bands were enriched with plasma membranes and their Na/K-ATPase activities were 31.5 and 34.6 mumol/mg/h respectively. The Na/K-ATPase activities were about six times that of the RPE homogenate. CONCLUSIONS: A rapid method of isolating the bovine RPE PMEF has been devised which involved a single centrifugation procedure in a Percoll gradient.
Animals↗
The glucose transport in retinal pigment epithelium is via passive facilitated diffusion.
The glucose transport across the bovine retinal pigment epithelium (RPE) was studied in a modified Ussing chamber. Unidirectional fluxes were recorded with radioactive tracers L-[14C]-glucose (LG) and 3-O-methyl-D-[3H]-glucose (MDG). There was no significant difference between the unidirectional MDG fluxes (retina to choroid, and choroid to retina directions) with or without ouabain. The effects of two glucose transporter inhibitors, phloretin and cytochalasin B, on the glucose fluxes from choroid to retina cells were also investigated. The MDG flux was found to be inhibited by 45.5% by phloretin (10(-4) M) and 87.4% by cytochalasin B (10(-4) M). These inhibitory characteristics resembled the facilitated diffusion mode of glucose transport. The glucose transporter protein in the plasma membrane of RPE was located by means of photolabeling [3H]-cytochalasin B. The labeled plasma membrane enriched fraction was analysed by SDS-PAGE. The glucose transporter of bovine RPE was found to have a molecular weight range of 46-53 kDa. The molecular weight range of this transporter protein agreed with those of facilitated glucose transporters in other tissues indicating a molecular similarity between them. The results indicated that the glucose transport across the RPE is via passive facilitated diffusion.
Animals↗
Chloride and sodium transport across bovine ciliary body/epithelium (CBE).
PURPOSE: To study the chloride and sodium ion transports across the bovine ciliary body/epithelium (CBE) by a modified Ussing-Zerahn type chamber. METHODS: Isolated bovine CBE preparations were mounted in a modified Ussing-type chamber and the transepithelial electrical parameters were monitored. The inward (stroma to aqueous) and outward (aqueous to stroma) fluxes of 36[Cl] chloride and 22[Na] sodium ions across the CBE were measured under short-circuited conditions. The effect of 0.1 mM of furosemide and bumetanide on the chloride transport were studied. RESULTS: The potential difference (PD), the resistance and the short-circuit current (SCC) across the isolated bovine ciliary body were found to be -0.20+/-0.01 mV (aqueous negative), 75+/-1 omegacm2 and -2.70+/-0.17 microAcm(-2) (mean+/-SEM, n=50) respectively. A statistically significant net inward chloride ion flux of 1.12+/-0.41 microEq h(-1)cm(-2) (p < 0.01) was found (n=15). The net chloride transport was abolished when 0.1 mM furosemide (82% inhibition) and 0.1 mM bumetanide (100% inhibition) were applied bilateral. No significant net sodium ion flux was detected. CONCLUSIONS: Electrolyte and fluid transport across the bovine CBE may be via a bumetanide and furosemide-sensitive chloride transport mechanism. The Na-K-2Cl cotransporter plays a significant role in the trans-CBE chloride transport. The net chloride flux/current was about 12 times higher than the measured SCC, suggesting that the chloride ion transport may be coupled to other ion species.
Animals↗
The efficacy of vitamin E and melatonin as antioxidants against lipid peroxidation in rat retinal homogenates.
Free radical-induced oxidation can cause severe cell damage in biological systems. Melatonin, a pineal secretory product, is a recently identified antioxidant that protects cells from the damaging effects of free radicals. We compared the effect of melatonin and vitamin E, another antioxidant, against lipid peroxidation (LPO) in rat retinal homogenates. The aim was to characterize the antioxidative efficacy of melatonin in retina, a tissue highly susceptible to oxidative damage. The LPO product, malondialdehyde (MDA), was determined to provide an index of cell damage in vitro. After the incubation with iron(II) ions, the free radical scavenging effectiveness of four different concentrations (i.e., 0.5, 1.0, 2.0, and 4.0 mM) of vitamin E and melatonin were determined by comparing the final levels of MDA. Lipid peroxidation product levels were significantly reduced in a dose-response manner by all concentrations of vitamin E. Melatonin, in concentrations of either 2.0 or 4.0 mM, also significantly reduced LPO. Statistical analysis of the data showed that vitamin E treatment always yielded a lower level of LPO products than did the same concentration of melatonin. The concentrations of each agent required to inhibit 50% of the lipid damage (IC50) were 0.69 mM and 4.98 mM for vitamin E and melatonin, respectively. Both vitamin E and melatonin protect the retina against LPO in a dose-dependent manner. Although the IC50 value for melatonin is about 7.2 times higher than that of vitamin E, melatonin's pharmacological and physiological role in the treatment and/or prevention of certain retinal diseases in vivo should be further investigated.
Animals↗
In vitro bovine ciliary body/epithelium in a small continuously perfused Ussing type chamber.
Our goal is to assess the viability of an in vitro preparation of bovine ciliary body/epithelium (CBE) in a small volume Ussing-type chamber. A new small volume Ussing-type chamber with continuous perfusion was developed for bovine CBE. The trans-CBE electrical parameters were monitored and the electrical responses of the CBE to ouabain (1 and 0.01 mM) were recorded. The trans-CBE fluxes of [14C]-L-ascorbate and [3H]-L-glucose were also studied. The bovine CBE preparation was stable inside the chamber in terms of its potential difference (PD), short circuit current (SCC) and trans-CBE resistance. They were -0.51+/-0.05 mV (aqueous side negative), -5.43+/-0.04 microAcm-2 and 94+/-2 Q.cm2 (mean s.e.m., n=35), respectively. The preparation hyperpolarised when 0.01 mM ouabain was administered to the aqueous side, depolarised when ouabain was applied to the stromal side. [3H]-L-glucose diffusion was about 74 nEq h(-1)cm(-2) in either direction (n=12). Taking the area magnification factor of the CBE into consideration, the diffusional L-glucose flux across the bovine CBE was comparable to other tight epithelia. A significant net ascorbate flux (0.26+/-0.05 nEq h(-1)cm(-2), n=4, p<0.01) was found in the stroma to aqueous direction. We have developed a viable in vitro bovine CBE preparation which was (1) electrically stable, (2) responsive to ouabain, (3) tight to L-glucose diffusion, and (4) capable of actively secreting ascorbate. A net trans-CBE chloride transport (0.81+/-0.30 microEq h(-1)cm(-2), n=12, p=0.01) from stromal to aqueous side was found in the present in vitro model under short-circuited conditions.
Animals↗
The saturation characteristics of glucose transport in bovine retinal pigment epithelium.
PURPOSE: To study the saturation characteristics of the glucose transport across the bovine retinal pigment epithelium(RPE). METHODS: The bovine RPE preparations were munted with a modified Ussing chamber. The L-[3H]-glucose and 3-O-methyl-D-[14C]-glucose fluxes across the RPE from the choroid to retina were studied at different glucose concentrations. RESULTS: The glucose transport was found to be stereospecific, with 3-O-methyl-D-glucose (MDG) being transported about three times faster than L-glucose. The glucose transport showed typical saturation characteristics in Michaelis-Menten fashion. The Vmax and the Km of corrected MDG were 2452 nmol cm-2h-1 and 30.8 mM respectively. It was shown that the glucose transport system was saturated at 61.6 mM. CONCLUSIONS: The saturation characteristics of the corrected MDG flux suggested that the capacity of glucose transport through the bovine RPE is immense.
3-O-Methylglucose↗