CD59 protects rat kidney from complement mediated injury in collaboration with Crry

CD59 protects rat kidney from complement mediated injury in collaboration with Crry.BackgroundAs previously reported, the membrane-bound complement regulator at the C3 level (Crry/p65) is important in maintaining normal integrity of the kidney in rats. However, the role of a complement regulator at the C8/9 level (CD59) is not clear, especially when activation of complement occurs at the C3 level. The aim of this work was to elucidate the in vivo role of CD59 under C3 activating conditions.MethodsTwo monoclonal antibodies, 5I2 and 6D1, were used to suppress the function of Crry and CD59, respectively. In order to activate alternative the pathway of complement, the left kidney was perfused with 5I2 and/or 6D1 and was recirculated.ResultsIn the kidneys perfused with 5I2 alone, deposition of C3 and membrane attack complex (MAC) was observed in the peritubular capillaries, vasa recta, and tubular basement membranes. Cast formation, tubular dilation and degeneration, and cellular infiltration were observed at days 1 and 4, and they recovered by day 7. Further suppression of CD59 by 6D1 significantly enhanced the deposition of MAC and worsened the already exacerbated tubulointerstitial injury. These effects of 6D1 were dose dependent. Perfusion with 6D1 alone did not induce histologic damage or MAC deposition in the tubulointerstitium.ConclusionsIn rats, CD59 maintains normal integrity of the kidney in collaboration with Crry in rats against complement-mediated damage in vivo

Aldose reductase inhibition ameliorates pupillary light reflex and F-wave latency in patients with mild diabetic neuropathy

WSTĘP. Zbadanie wpływu inhibitora reduktazy aldozy, epalrestatu, na wczesną fazę neuropatii autonomicznej i somatycznej u chorych na cukrzycę typu 2 przez ocenę odruchu źrenicznego na światło oraz minimalnej latencji fali F. MATERIAŁ I METODY. Badanie objęło 30 chorych na cukrzycę z podkliniczną lub łagodną neuropatią cukrzycową, których losowo przydzielono do grupy kontrolnej (n = 15) lub do grupy leczonej epalrestatem (150 mg/d., n = 15). Po 24 tygodniach przeprowadzono badanie odruchu źrenicznego na światło, testy włókien autonomicznych układu sercowo-naczyniowego oraz badanie przewodzenia nerwowego. WYNIKI. Korzystny wpływ epalrestatu na odruch źreniczny na światło zaobserwowano w odniesieniu do minimalnej średnicy po bodźcu świetlnym (p = 0,044), wskaźnika zwężenia (p = 0,014) oraz maksymalnej szybkości zwężania (p = 0,008). Spośród testów autonomicznych układu sercowo-naczyniowego leczenie epalrestatem spowodowało poprawę wskaźnika najdłuższego odstępu RR podczas wydechu do najkrótszego odstępu RR w czasie wdechu obserwowanego podczas testu głębokiego oddychania (p = 0,037). Minimalna latencja fali F nerwów pośrodkowego oraz piszczelowego uległa istotnemu skróceniu w grupie chorych leczonych epalrestatem (odpowiednio p = 0,002 oraz p = 0,001); nie stwierdzono jednak istotnego wpływu na prędkość przewodzenia nerwowego w nerwach czuciowych oraz ruchowych. WNIOSKI. Powyższe obserwacje sugerują, że epalrestat może korzystnie działać we wczesnej fazie neuropatii cukrzycowej oraz że odruch źreniczny na światło i minimalna latencja fali F mogą stanowić przydatne wskaźniki neuropatii cukrzycowej.INTRODUCTION. The present study was conducted to investigate the effect of an aldose reductase inhibitor, epalrestat, on autonomic and somatic neuropathy at an early stage in type 2 diabetic patients by assessing the pupillary light reflex and minimum latency of the F-wave. MATERIAL AND METHODS. A total of 30 diabetic patients with subclinical or mild diabetic neuropathy were randomly allocated to a control group (n = 15) and epalrestat (150 mg/day) group (n = 15). After 24 weeks, the pupillary light reflex test, cardiovascular autonomic function tests, and nerve conduction study were performed. RESULTS. The beneficial effect of epalrestat on the pupillary light reflex was observed in the minimum diameter after light stimuli (P = 0.044), constriction ratio (P = 0.014), and maximum velocity of constriction (P = 0.008). Among cardiovascular autonomic nerve functions, the ratio of the longest expiratory R-R interval to the shortest inspiratory R-R interval during deep breathing was significantly improved by epalrestat (P = 0.037). Minimum latencies of F-wave of median and tibial motor nerves were significantly shortened by epalrestat (P = 0.002 and P = 0.001, respectively); however, no significant effects were observed in motor or sensory nerve conduction velocity. CONCLUSIONS. These observations suggest that epalrestat may have therapeutic value at the early stage of diabetic neuropathy and that the pupillary light reflex and minimum latency of F-wave may be useful indicators of diabetic neuropathy

Association of Chronic Kidney Disease and Cerebral Small Vessel Disease with Cognitive Impairment in Elderly Patients with Type 2 Diabetes

Background/Aims: In recent years, the relationship between chronic kidney disease (CKD) and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD) is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. Methods: Seventy-nine type 2 diabetic patients (mean age, 76.0 years) were enrolled in the present study. CKD was defined as the presence of albuminuria and/or a low estimated glomerular filtration rate (eGFR 2). SVD was evaluated by the presence and severity of silent brain infarcts (SBIs) and white matter lesions (WMLs) on brain magnetic resonance imaging. Neuropsychological tests were assessed using four validated cognitive instruments. Results: In multiple linear regression analyses, albuminuria was associated with worse modified Stroop Color Word scores (β = 0.284, p = 0.017) and low eGFR was associated with reduced Digit Symbol Substitution scores (β = -0.224, p = 0.026) after adjustment for age, sex, education years, diabetes duration, hypertension, multiple SBIs, and advanced WMLs. In contrast, there were no significant associations between CKD markers and Mini-Mental State Examination or Word Recall scores. Conclusion: Our findings suggest that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients