Increased response of renal perfusion to the antioxidant vitamin C in type 2 diabetes.

BACKGROUND: Reactive oxygen species play a major role in the development of endothelial dysfunction. It is as yet unspecified whether increased oxidative stress contributes to endothelial dysfunction of the renal vasculature in patients with type 2 diabetes. METHODS: Renal haemodynamics were studied in 20 patients with type 2 diabetes and arterial hypertension (age 62 +/- 5 years) and 20 non-diabetic hypertensive patients at baseline and following infusions of the nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg); the substrate of nitric oxide synthase, L-arginine (100 mg/kg); and the antioxidant, vitamin C (3 g, co-infused with L-arginine 100 mg/kg). RESULTS: The response of renal plasma flow (RPF) to L-NMMA (-54 +/- 62 and -45 +/- 42 ml/min/1.73 m(2); P = NS) and L-arginine (+46 +/- 36 and +49 +/- 25 ml/min/1.73 m(2); P = NS) was not different between diabetic and non-diabetic patients. In contrast, vitamin C induced a more pronounced increase in RPF in diabetic than in non-diabetic patients when co-infused with L-arginine (+71+/-47 and +43+/-33 ml/min/1.73 m(2); P<0.05). CONCLUSIONS: The difference in the response of renal perfusion to an antioxidant suggests increased formation of reactive oxygen species and thereby reduced nitric oxide bioavailability in the renal vasculature of patients with type 2 diabetes.     

Changes in temporal gait characteristics and pressure distribution for bare feet versus various heel heights

The purpose of this study was to identify changes in temporal gait characteristics and pressure generation across the sole of the foot due to various heel heights in women's dress pumps. Thirty female subjects, aged 18-30 years, volunteered to participate. Subjects were required to have normal gait and to wear comfortably either size 7 or size 9 shoes. Subjects were tested initially in bare feet using electrodynography (Langer Biomechanics Group, 21 East Industry Court, Deer Park, NY 11729-9986) (EDG) at a cadence of ~100 steps/min set by metronome. EDG trials with 4 pairs of shoes were then performed in random order. Shoes were women's dress pumps identical except for heel height. Heel heights were 1.75, 3.12, 5.72 and 8.74 cm. Data were collected over ~ 30 steps and averaged over this period. Data were analyzed using a one-way ANOVA, and changes were only considered significant if the ANOVA identified significant variations bilaterally. Considering temporal gait variables, we concluded that: (1) stance phase was shortened in shoes vs. bare feet but was unaffected by heel height, (2) the percentage of stance spent in weight bearing on the lateral and medial calcaneus decreased above a 3.12 cm heel height, (3) the percentage of stance spent in weight bearing on the first and second metatarsal heads increased in shoes vs. bare feet but was unaffected by heel height, (4) the percentage of stance spent in weight bearing on the fifth metatarsal was less in the 8.74 cm heel than in any other shoe or in bare feet. With regard to pressure variables, we found that: (1) peak pressure under the fifth metatarsal head was inversely related to heel height, (2) pressure under the third metatarsal head peaked earliest in heels greater than 5.72 cm high, and (3) pressure under the medial calcaneus peaked latest in heels greater than 5.72 cm high.     

Guidance of dopaminergic neuritic growth by immature astrocytes in organotypic cultures of rat fetal ventral mesencephalon.

Astrocytes, with their many functions in producing and controlling the environment in the brain, are of great interest when it comes to studying regeneration after injury and neurodegenerative diseases such as in grafting in Parkinson's disease. This study was performed to investigate astrocytic guidance of growth derived from dopaminergic neurons using organotypic cultures of rat fetal ventral mesencephalon. Primary cultures were studied at different time points starting from 3 days up to 28 days. Cultures were treated with either interleukin-1 beta (IL-1 beta), which has stimulating effects on astrocytic proliferation, or the astrocytic inhibitor cytosine arabinoside (Ara-C). Tyrosine hydroxylase (TH)-immunohistochemistry was used to visualize dopaminergic neurons, and antibodies against glial fibrillary acidic protein (GFAP) and S100 beta were used to label astrocytes. The results revealed that a robust TH-positive nerve fiber production was seen already at 3 days in vitro. These neurites had disappeared by 5 days. This early nerve fiber outgrowth was not guided by direct interactions with glial cells. Later, at 7 days in vitro, a second wave of TH-positive neuritic outgrowth was clearly observed. GFAP-positive astrocytic processes guided these neurites. TH-positive neurites arborized overlying S100 beta-positive astrocytes in an area distal to the GFAP-positive astrocytic processes. Treatment with IL-1 beta resulted in an increased area of TH-positive nerve fiber network. In cultures treated with Ara-C, neither astrocytes nor outgrowth of dopaminergic neurites were observed. In conclusion, this study shows that astrocytes play a major role in long-term dopaminergic outgrowth, both in axonal elongation and branching of neurites. The long-term nerve fiber growth is preceded by an early transient outgrowth of dopamine neurites.     

Hypoplasia of the Posterior Leaflet as a Rare Cause of Congenital Mitral Insufficiency

A bstract A rare case of congenital mitral insufficiency characterized by the hypoplasia of the posterior leaflet is reported. At operation, the mitral valve was successfully repaired by a ring annuloplasty, which created a satisfactory surface of coaptation between the anterior leaflet and the bulky posterior muscular structure. The presence of this posterior muscular structure represents a developmental arrest at the stage of conversion from muscular chordae and leaflets to thin connective structures.     

Infantile autism—fragile X: Molecular findings support genetic heterogeneity

Twenty-two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR-1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR-1 region in infantile autists negative for fragile X expression. © 1992 Wiley-Liss, Inc.     

Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.

The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats.     

Initial 5-fluorouracil trabeculectomy in young patients.

The effectiveness of initial trabeculectomy with adjunctive 5-fluorouracil (5-FU) for uncomplicated glaucoma in patients age 40 years or younger at the time of surgery was evaluated retrospectively in a consecutive series of 20 eyes of 20 patients. Fifteen patients had juvenile primary open-angle glaucoma, 4 had pigmentary glaucoma, and 1 had glaucoma associated with angle recession. Mean patient age was 26.8 +/- 9.7 years (range, 13 to 40 years) at the time of surgery. The mean total 5-FU dose administered was 27.8 +/- 8.8 mg (range, 15 to 45 mg). The intraocular pressure (IOP) decreased from 34.4 +/- 11.5 mmHg preoperatively to 10.5 +/- 4.0 mmHg postoperatively after a mean follow-up of 31.1 +/- 17.3 months (range, 11.5 to 70 months). Nineteen eyes (95%) had a postoperative IOP of 20 mmHg or less without pressure-lowering medications. One patient required additional medical therapy to control the IOP. Complications included bleb-related endophthalmitis (2 eyes) and hypotony maculopathy (1 eye).     

Differences in CMV-Specific T-Cell Levels and Long-Term Susceptibility to CMV Infection after Kidney, Heart and Lung Transplantation

Patients after kidney, heart and lung transplantation differ in their immunosuppressive drug regimens and in susceptibility to infectious complications with cytomegalovirus (CMV). In this study, CMV-specific T-cell responses were characterized in long-term transplant recipients and associated with the frequency of infectious complications. CMV-reactive CD4 T cells from 50 healthy controls, 68 renal, 14 heart and 24 lung transplant recipients were flow cytometrically quantified by the induction of cytokines after specific stimulation. Moreover, the immunosuppressive effect of calcineurin inhibitors on specific T-cell reactivity was quantified in vitro and compared with responses in vivo. Median CMV-specific T-cell frequencies in long-term renal (1.48%; range 0.06-17.26%) and heart transplant recipients (0.90%; 0.13-12.49%) did not differ from controls (1.82%; 0.26-21.00%). In contrast, CMV-specific T-cell levels were significantly lower in lung transplant recipients (0.50%; <0.05-4.98%) and showed a significant correlation with the frequency of infectious episodes (r =-0.57, p = 0.005). The differences within the groups were associated with increasing dosages of immunosuppressive drugs, as exemplified for calcineurin inhibitors that dose dependently reduced specific T-cell reactivity in vitro. In conclusion, monitoring CMV-specific CD4 T cells may serve as a measure for long-term disease susceptibility and may contribute to an improved management of CMV complications after lung transplantation.