Long-term dietary antioxidant cocktail supplementation effectively reduces renal inflammation in diabetic mice

Diabetic nephropathy is a serious complication for diabetic patients, yet the precise mechanism that underlies the development of diabetic complications remains unknown. We hypothesised that dietary antioxidant supplementation with single N-acetylcysteine (NAC) or vitamin C combined with either vitamin E or vitamin E and NAC improves diabetic renal inflammation through the modulation of blood glucose levels, oxidative stress and inflammatory response. Experimental animals were treated with alloxan monohydrate to induce diabetes. Mice were divided into five groups and supplemented with single or a combination of antioxidants. Body weights and blood glucose levels were measured once a week. After 8 weeks of dietary antioxidant supplementation, mice were killed and blood urea N (BUN) and plasma creatinine levels were measured to evaluate renal function. NF-κB protein was indirectly demonstrated by the phosphorylated IκBα (pIκBα) level, and the expressions of oxidative stress- and inflammatory response-related proteins were also determined. We demonstrated that dietary antioxidant supplementation decreased lipid peroxidation levels demonstrated by thiobarbituric acid-reacting substances, BUN and plasma creatinine levels in diabetic kidneys. Moreover, dietary antioxidant cocktail supplementation improved blood glucose levels and selectively regulated the expressions of Cu-Zn superoxide dismutase, haeme oxygenase-1, pIκBα, inducible NO synthase, cyclo-oxygenase-2 and C-reactive protein in diabetic kidneys effectively. These findings demonstrated that diabetic renal failure was associated with inflammatory responses induced by hyperglycaemia. In addition, results in the study suggest that antioxidant cocktail supplementation may have beneficial effects on diabetic nephropathy through selective reduction of blood glucose levels and inflammatory response.     

Regulation of 1-cys peroxiredoxin expression in lung epithelial cells

1-cys peroxiredoxin (1-cys Prx), the only member of a Prx subfamily that contains a single conserved cysteine residue, is abundant in lung. This bifunctional protein has both glutathione peroxidase and phospholipase A2 activities compatible with a role both in protection against lung oxidant injury and also in lung phospholipid metabolism. Here we studied the developmental expression of 1-cys Prx in rat lungs and hormonal effects on protein expression in human and rat lung cells. There was little change in 1-cys Prx expression during the prenatal period, but a marked increase in expression immediately after birth. Enzymatic (peroxidase and phospholipase) activities increased gradually after birth and reached adult level at 7-14 postnatal days. Expression of the protein was induced in the presence of dexamethasone (Dex) in cultured human and rat lung epithelial cells and also was upregulated in neonatal rat lung in vivo. cAMP treatment had no effect on expression, although there was a modest synergistic effect when combined with Dex in human fetal lung epithelial cells. The increased expression of 1-cys Prx at birth may be important for surfactant phospholipid turnover related to the phopholipase A2 activity of the protein and for antioxidant defense based on its peroxidase function.     

Cellular electrophysiologic properties of old canine atria provide a substrate for arrhythmogenesis

OBJECTIVE: The incidence of atrial fibrillation increases with age. We hypothesized that aging-associated changes in the atrial action potential (AP) and conduction velocity provide a substrate for abnormal conduction and arrhythmogenesis. METHODS: We used microelectrode techniques to record AP from the endocardium of the right atrial wall of dogs aged 1-5 (adult) and >8 years (old). Conduction velocity was measured between two microelectrodes 3-10 mm apart. Histological study was carried out to assess fibrosis. RESULTS: Whereas resting potential, AP amplitude and V(max) did not differ with age, the plateau was more negative and AP duration was longer in old tissue. The L-type calcium current (I(Ca,L)) agonist Bay K8644 (10(-8)-10(-6) mol/l) elevated the plateau and shortened APD more in old than in adult, such that AP contour in old atria approached that of adult. In contrast, the I(Ca,L) blocker nisoldipine (10(-8)-10(-5) mol/l) depressed the plateau in adult and had no effect in old. There was no difference between the two groups in conduction velocity of normal beats, whereas for early premature impulses, reduced conduction velocity and a wider time window manifesting slow conduction were detected in old in comparison to adult tissue. A twofold increase in the amount of fibrous tissue was detected in old atria. CONCLUSIONS: Our data show significant differences in contour of AP in adult and old atria. The responses to Bay K8644 and nisoldipine suggest a decreased I(Ca,L) in old atrial tissue. The alterations in AP contour and increased fibrosis may be responsible for slower conduction of early premature beats in old atria. The age-related changes in conduction of premature beats are consistent with those observed in patients with paroxysmal atrial fibrillation and may contribute to the greater propensity to atrial fibrillation in the aged.     

Dietary zinc alters early inflammatory responses during cutaneous wound healing in weanling CD-1 mice

Zinc deficiency is a well-known health problem associated with delayed wound healing, yet the precise mechanisms that underlie the delay remain unknown. We hypothesized that zinc deficiency delays wound healing as a result of decreased nuclear factor (NF)kappaB activation, reduced expression of proinflammatory cytokines [interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha], and a decrease in neutrophil infiltration during the early stage of cutaneous wound healing. We used a cutaneous, full-thickness excisional wound model in CD-1 mice to examine the rate of wound closure as well as mRNA levels of inhibitory (I)kappaBalpha, IL-1beta, and TNF-alpha and infiltration of neutrophils at the wound site of mice fed a diet containing <1 (deficient), 50 (control), 500, or 1000 microg zinc/g diet. Zinc deficiency reduced the rate of wound closure and mRNA levels of IL-1beta and TNF-alpha and attenuated infiltration of neutrophils at the wound site compared with controls. Interestingly, zinc supplementation at 1000 microg/g delayed the rate of wound closure and decreased mRNA levels of TNF-alpha and infiltration of neutrophils compared with mice fed the control diet. These findings demonstrate that zinc deficiency and high-dose zinc supplementation delay wound healing as a result of altered inflammatory responses and suggest that adequate zinc supplementation may have beneficial effects on the inflammatory responses to enhance cutaneous wound healing.     

Immunohistochemical analysis for cytokeratin 7, KIT, and PAX2: value in the differential diagnosis of chromophobe cell carcinoma

Immunohistochemical staining for cytokeratin 7 (CK7), KIT, and PAX2 expression was performed on 91 renal neoplasms, 37 conventional (clear cell) renal cell carcinomas (CRCCs), 20 papillary RCCs (PRCCs), 11 chromophobe RCCs (ChCs), and 23 oncocytomas, with available karyotypes. All ChCs, 19 PRCCs, 2 CRCCs, and 1 oncocytoma were CK7+; all ChCs, 22 oncocytomas, 2 CRCCs, and no PRCCs expressed KIT; PAX2 was positive in 31 CRCCs, 17 PRCCs, 20 oncocytomas, and 1 ChC. The predominant expression profiles were as follows: CRCC, CK7-/KIT-/PAX2+ (26/37); PRCC, CK7+/KIT-/PAX2+ (17/20); ChC, CK7+/KIT+/PAX2- (10/11); and oncocytoma, CK7-/KIT+/PAX2+ (19/23). Cytogenetic analysis showed that the sole PAX2+ ChC had a retained chromosome 10, and all ChCs with chromosome 10 loss were PAX2-. These results identify specific staining patterns of the 4 major histologic subtypes of renal neoplasms and raise the question of a relationship between chromosome 10 loss and loss of PAX2 expression in ChC.     

Real-World Data Regarding Satisfaction to Botulinum Toxin A Injection into the Urethral Sphincter and Further Bladder Management for Voiding Dysfunction among Patients with Spinal Cord Injury and Voiding Dysfunction

Purpose: This study aimed to investigate improvement in voiding condition after the initial botulinum toxin A (BoNT-A) injection into the urethral sphincter among patients with chronic spinal cord injury (SCI) and voiding dysfunction. Moreover, subsequent surgical procedures and bladder management were evaluated. Materials and Methods: From 2011 to 2020, 118 patients with SCI and dysuria who wanted to void spontaneously received their first BoNT-A injection at a dose of 100 U into the urethral sphincter. Improvement in voiding and bladder conditions after BoNT-A treatment were assessed. Next, patients were encouraged to continually receive BoNT-A injections into the urethral sphincter, convert to other bladder managements, or undergo surgery. After undergoing bladder management and surgical procedures, the patients were requested to report improvement in voiding condition and overall satisfaction to bladder conditions. Then, data were compared. Results: In total, 94 male and 24 female participants were included in this analysis. Among them, 51 presented with cervical, 43 with thoracic, and 24 with lumbosacral SCI. After BoNT-A injections into the urethral sphincter, 71 (60.2%) patients, including 18 (15.3%) with excellent, and 53 (44.9%) with moderate improvement, had significant improvement in voiding condition. Patients with cervical SCI (66.6%), detrusor overactivity and detrusor sphincter dyssynergia (72.0%), partial hand function (80.0%), and incomplete SCI (68.4%) had a better improvement rate than the other subgroups. Only 42 (35.6%) patients continually received treatment with BoNT-A injections into the urethral sphincter. Meanwhile, more than 60% of patients who converted their treatment to augmentation enterocystoplasty (n = 5), bladder outlet surgery (n = 25), BoNT-A injections into the detrusor muscle (n = 20), and medical treatment (n = 55) had moderate and marked improvement in voiding dysfunction and overall satisfaction. Discussion: Although BoNT-A injections into the urethral sphincter could improve voiding condition, only patients with SCI who presented with voiding dysfunction were commonly satisfied. Those whose treatments were converted to other bladder managements, which can promote urinary continence, or to surgical procedures, which can facilitate spontaneous voiding, had favorable treatment outcomes.     

The outcome of open heart surgery for congenital heart disease in infants with low body weight less than 2500 g

Although the outcome of neonatal cardiac surgery has dramatically improved, low body weight (LBW) is still considered an important risk for open heart surgery. The factors contributing to poor outcomes in LBW infants, however, are still unclear. We investigated risk factors for poor outcomes in infants weighing <2500 g who underwent surgical correction with cardiopulmonary bypass (CPB). From January 1995 to December 2009, 102 consecutive patients were included in this study. Median age and body weight at the time of surgery was 19 (range 1 to 365) days and 2.23 kg (range 1.3 to 2.5), respectively. Corrective surgery was performed on 75 infants. The median follow-up duration was 45.03 months (range 0.33 to 155.23). There were 23 (22.5%) hospital mortalities. Emergency surgery and low cardiac output (LCO) were associated with early mortality; however, body weight, Aristotle basic complex score, and type of surgery was not. Early morbidities, including delayed sterna closure, arrhythmia, and chylothorax, occurred in 39 (38.2%) infants. The overall actuarial survival rate at 10 years was 74.95% ± 4.37%. In conclusion, among infants weighing <2500 g who underwent open heart surgery with CPB, perioperative hemodynamic status, such as emergency surgery and LCO, strongly influenced early mortality. In contrast, LBW itself was not associated with patient morbidity or mortality.