Melatonin reduces OGD/R-induced neuron injury by regulating redox/inflammation/apoptosis signaling.

OBJECTIVE: To investigate the roles and underlying mechanisms of melatonin in oxygen-glucose deprivation/reoxygenation (OGD/R)-insulted SH SY5Y cells. MATERIALS AND METHODS: SH SY5Y cells were cultured for OGD/R stimulation. Cell viability and cytotoxicity were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, lactate dehydrogenase (LDH), and Hoechst 33258/propidium iodide (PI) staining assays. The mRNA levels of high mobility group box-1 (HMGB1), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS) were analyzed by quantitative Real Time-PCR assays. Nitric oxide (NO) production was assessed by Griess reagent. Reactive oxygen species (ROS) production was detected by fluorescent probe. Malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were examined by commercial kits. Cell apoptosis was analyzed by flow cytometry and caspase-3 activity. The protein levels were detected by Western blot. RESULTS: Melatonin enhanced the viability and reduced the death and LDH release of OGD/R exposed SH SY5Y cells. Melatonin repressed the HMGB1, TNF-α, and iNOS mRNA expression, NO production, and nuclear factor κB (NF-κB) activation in OGD/R challenged SH SY5Y cells. Melatonin reduced the ROS, MDA, 4-HNE, and 8-OHdG contents but further enhanced the levels of the nuclear factor E2-related factor-2 (Nrf2) and heme oxygenase (HO-1). Melatonin-increased viability and melatonin-decreased LDH release were also mediated by the blockage of NF-κB or reversed by Nrf2 or HO-1 knockdown. Melatonin exerted antiapoptotic effect on OGD/R treated SH SY5Y cells partly by activating Akt signaling. OGD/R challenged SH SY5Y cell autophagy was also repressed by melatonin, as evidenced by the decreased levels of LC-II and beclin-1 and the increased phosphorylation of mammalian target of rapamycin (mTOR), p70 ribosomal protein S6 kinase (p70S6K), and eukaryotic initiation factor 4E binding protein 1 (4E-BP-1). CONCLUSIONS: Melatonin protected SH SY5Y cells from OGD/R induced oxidative stress, inflammation, apoptosis, and autophagy by blocking NF-κB signaling and activating Nrf2/HO-1, Akt, and mTOR/p70S6K/4E-BP-1 pathways, thereby indicating that melatonin is a potential and novel therapeutic drug for ischemic stroke.

[Clinical observation of saccharomyces boulardii combined with cetirizine hydrochloride in children allergic rhinitis].

Objective:To study the treatment efficacy of Saccharomyces boulardii combined with Cetirizine Hydrochloride of children with allergic rhinitis (AR) and the influence of IFN-γ and interleukin-4 (IL-4) Level in serum.Method:Ninty cases of children were randomly divided into observation group and control group (both n=45).The control group with levocetirizine hydrochloride drops, 5 mL/time for 2-6 years old, 10 mL/time for >6 years old , qd oral. Group based on the combination of Saccharomyces boulardi, 0.25 g/time for <3 years old, qd, > 3 years old, 0.25 g, bid. Four weeks for a course of treatment, and set 30 cases for the health group.Result:The level of serum IFN-γ was significantly lower in the two groups than in the healthy group (P < 0.01), while the level of IL-4 was significantly higher than that of the healthy group (P < 0.01). After treatment, the levels of IFN-γ of both groups were up-regulated And the level of IL-4 were down-regulated , but the effect of the treatment group was more obvious (P < 0.01). The total effective rate was 91.11% in the observation group, which was significantly higher than that in the control group (68.89%,χ2=6.94, P < 0.01). After treatment, the symptom scores of the two groups were lower than those before treatment, but the observation group was significantly lower than the control group (P < 0.01). Compared with the control group, the observation group was significantly better than the control group (P < 0.01).Conclusion:The combination of Saccharomyces boulardi and levocetirine hydrochloride in the treatment of children with AR has obvious clinical efficacy, and its mechanism may be related to the correction of interferon IFN-γ and IL-4.

Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group.

BACKGROUND: The combination of cyclophosphamide and prednisolone is effective for the treatment of severe lupus nephritis but has serious adverse effects. Whether mycophenolate mofetil can be substituted for cyclophosphamide is not known. METHODS: In 42 patients with diffuse proliferative lupus nephritis we compared the efficacy and side effects of a regimen of prednisolone and mycophenolate mofetil given for 12 months with those of a regimen of prednisolone and cyclophosphamide given for 6 months, followed by prednisolone and azathioprine for 6 months. Complete remission was defined as a value for urinary protein excretion that was less than 0.3 g per 24 hours, with normal urinary sediment, a normal serum albumin concentration, and values for serum creatinine and creatinine clearance that were no more than 15 percent above the base-line values. Partial remission was defined as a value for urinary protein excretion that was between 0.3 and 2.9 g per 24 hours, with a serum albumin concentration of at least 30 g per liter. RESULTS: Eighty-one percent of the 21 patients treated with mycophenolate mofetil and prednisolone (group 1) had a complete remission, and 14 percent had a partial remission, as compared with 76 percent and 14 percent, respectively, of the 21 patients treated with cyclophosphamide and prednisolone followed by azathioprine and prednisolone (group 2). The improvements in the degree of proteinuria and the serum albumin and creatinine concentrations were similar in the two groups. One patient in each group discontinued treatment because of side effects. Infections were noted in 19 percent of the patients in group 1 and in 33 percent of those in group 2 (P = 0.29). Other adverse effects occurred only in group 2; they included amenorrhea (in 23 percent of the patients), hair loss (19 percent), leukopenia (10 percent), and death (10 percent). The rates of relapse were 15 percent and 11 percent, respectively. CONCLUSIONS: For the treatment of diffuse proliferative lupus nephritis, the combination of mycophenolate mofetil and prednisolone is as effective as a regimen of cyclophosphamide and prednisolone followed by azathioprine and prednisolone but is less toxic.

A randomized prospective comparison of oral levofloxacin plus intraperitoneal (IP) vancomycin and IP netromycin plus IP vancomycin as primary treatment of peritonitis complicating CAPD.

OBJECTIVE: To compare the therapeutic efficacy of daily oral levofloxacin plus intermittent intraperitoneal (IP) vancomycin (group 1) versus daily IP netromycin and intermittent IP vancomycin (group 2) in the primary treatment of peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD). DESIGN: A randomized multicenter prospective open-label comparative clinical study. SETTING: University and Hospital Authority hospitals in Hong Kong. PATIENTS: All CAPD patients who developed bacterial or culture-negative peritonitis beyond 28 days of a previous episode and without evidence of septicemia, associated tunnel infection, or known sensitivity to trial medications were accepted into the clinical trial. RESULTS: A total of 101 patients entered the trial. The primary cure rate was 74.5% for group 1 and 73.6% for group 2. Baseline culture results appeared to influence the clinical outcome: the primary cure rate for culture-negative, gram-positive, and gram-negative episodes was 83.3%, 78.6%, and 42.9% for group 1 and 69.1%, 76.9%, and 71.3% for group 2, respectively. The primary cure rate also varied considerably among individual centers and was particularly noticeable in group 1. In the latter group, it correlated closely with in vitro levofloxacin resistance which in turn correlated closely with previous exposure to fluoroquinolones. CONCLUSION: Oral levofloxacin in combination with intermittent IP vancomycin has comparable efficacy to IP netromycin combined with intermittent IP vancomycin as primary treatment in CAPD peritonitis, but is simpler and more cost-effective to administer. It may be recommended as primary therapy in centers with relatively low exposure and, therefore, low background resistance to fluoroquinolones.

Correction of anemia in patients on continuous ambulatory peritoneal dialysis with subcutaneous recombinant erythropoietin twice a week: a long-term study.

Subcutaneous recombinant human erythropoietin (rHuEPO) was given for 12 months twice weekly to 10 patients on continuous ambulatory peritoneal dialysis (CAPD) with anemia (hemoglobin less than 9.0 mg/dl). All patients responded to a median weekly dose of between 37.5 to 100 (mean 55 to 105) units/kg and reached a target hemoglobin of 10-12 mg/dl in a mean of 11.7 weeks (range 5-24). Serum iron, iron saturation and ferritin were significantly lower and serum potassium was significantly higher than the pre-treatment level from 1 month onwards. Five patients without pre-treatment iron overload required oral iron supplement and 3 required oral potassium-binding resin. No significant change in other serum biochemical parameters was observed. Blood pressure remained stable during the treatment period but additional or increased dosage of antihypertensive drugs was required in 5 patients. Peritoneal small solute clearance and ultrafiltration and residual renal clearance did not change significantly after correction of anemia. The incidence of peritonitis and exit site infection was similarly unaffected. One patient developed a severe headache which was not associated with hypertension and responded to withdrawal of rHuEPO treatment. Most of the remaining patients showed improvement in subjective well-being. It was concluded that the subcutaneous route twice a week is a safe, convenient and cost-effective way to administer rHuEPO to patients on CAPD.

Factors affecting lymphatic absorption in Chinese patients on continuous ambulatory peritoneal dialysis (CAPD).

The pathways and physiology of lymph absorption (LA) from the peritoneal cavity are well documented; however, much uncertainty still exists as to the various clinical and demographic factors affecting LA. We studied LA measured by the albumin instillation method, in adult Chinese CAPD patients, and showed that it was independent of age, sex, body surface area, duration of dialysis, intrinsic renal disease, use of intraperitoneal drugs (heparin/antibiotics/deferroxamine) and frequency of past bacterial peritonitis. High lymph absorbers had a relatively higher transcapillary cumulative ultrafiltration than low lymph absorbers. An enhanced LA was associated with a high initial intraperitoneal volume. Assessment of diaphragmatic strength by the decrement in vital capacity on changing from an erect to a supine position failed to distinguish patients with high and low LA.

Haematological changes after renal transplantation: differences between cyclosporin-A and azathioprine therapy.

Haematological changes after renal transplantation in 76 patients were reviewed and the differences observed between patients treated with cyclosporin-A and prednisolone and those treated with azathioprine and prednisolone were compared. Erythrocytosis defined as haemoglobin concentration equal to or exceeding 17 g/dl occurred in 25% of patients treated with cyclosporin-A and in 11.4% of patients treated with azathioprine. Only one patient, who received cyclosporin-A, had clinical evidence of thrombosis. Eight patients treated with cyclosporin-A and five treated with azathioprine had therapeutic venesections. There was no difference in the incidence of putative risk factors for post-transplant erythrocytosis between the two groups.

[Clinical features and long-term outcome of 91 cases of adult onset post-streptococcal glomerulonephritis in Hong Kong].

The clinical features and long-term outcome of 91 cases of adult-onset PSGN in Hong Kong were reported. There were 46 male and 45 female with age ranging from 13 to 56 yrs (mean 18.6). The diagnosis was based on clinical manifestations and renal biopsy was performed in 29 cases. The main manifestations were acute nephritic syndrome (72.5%) and acute nephritic-nephrotic syndrome (27.5%). Serum creatinine was increased in 48.4% of the patients at presentation. Four cases presented with acute renal failure. Serial serum C3 levels were determined in 48 patients. It was decreased in all patients at presentation but returned to normal within 15 weeks. The follow-up duration of this series ranged from I to 19 yrs (mean 4.73 yr) 67.03% recovered early (within 3 mts); 14.29% recovered later (from 6 mts to 7 yrs): 16.48% had persistent or intermittent proteinuria and or haematuria. Two cases developed chronic renal insufficiency. Our results suggested that the prognosis of PSGN in adults is relatively good and the indications for renal biopsy in adult-onset PSGN were discussed.

Adult-onset mesangiocapillary glomerulonephritis: a disease with a poor prognosis.

A retrospective analysis of the records of 46 patients with adult-onset mesangiocapillary glomerulonephritis seen over a period of 15 years is reported. There were 28 males and 18 females with a mean age of 34 years. Mean observation period was 60 months. All patients had renal biopsies and characteristic changes, but no dense deposit variant was seen. HBsAg was positive in 20 per cent of the patients tested whereas in the general population it was about 10 per cent. Nephrotic syndrome was the commonest presentation. There was a mean delay of 8.5 months between the onset of symptoms and renal biopsy. Nineteen patients were given steroid/immunosuppressive therapy while 27 received no specific treatment. At the time of review, renal function was stable in 13 patients but progressively deteriorating in 33. In the latter, the slope of the graph of reciprocal of creatinine versus time could be accurately determined. Steroid/immunosuppressive therapy did not influence the rate of progression of renal failure but appeared to hasten and induce more partial remissions of the nephrotic state. There was no difference in cumulative renal survival between treated and untreated patients, and between HBsAg-positive and negative patients. Overall, 23 patients required dialysis/renal transplantation and an additional four had died of end-stage renal failure at the time of this review.

Fungal peritonitis complicating peritoneal dialysis: report of 27 cases and review of treatment.

The clinical features, treatment and outcome of 27 cases of fungal peritonitis were studied. Twenty-one cases occurred in patients receiving CAPD and six in patients on intermittent peritoneal dialysis. Twenty-five cases were due to Candida spp., one was due to Trichosporon spp. and in one, both Candida and Trichosporon and an unidentified acid-fast bacillus were isolated. Clinical features of fungal peritonitis and bacterial peritonitis were the same. A direct comparison with patients without fungal peritonitis failed to reveal an increased incidence of diabetes mellitus. However, a history of recent bacterial peritonitis and antibiotic treatment was frequently obtained. We found that the combination of oral ketoconazole and intraperitoneal miconazole is successful in treating fungal peritonitis complicating peritoneal dialysis but catheter removal and replacement is often necessary. Analysis of the relationship between clinical outcome and various treatment strategies in cases reported in the literature and in our own showed that an initial trial of antifungal drugs consisting of oral ketoconazole and i.p. 5-fluorocytosine or miconazole is warranted in most cases before contemplating catheter removal.

[Long-term results of an operation alone and postoperative adjuvant chemotherapy in advanced gastric cancer--report of 265 patients].

During the period from June 1973 to December 1978, 338 patients with advanced gastric cancer were treated in our hospital. By retrospective grouping, 142 out of 265 patients with tumor resected received postoperative adjuvant chemotherapy (MMC + 5FU + Ara-C), 123 operated alone were taken for comparison. These two groups were similar in: age, sex, location of tumor, mode of resection, histological type, clinical stage and follow-up rate. The results indicated that the 1, 3 and 5 year survival rates of the combined group were much higher than those of the operation only group. Further analysis showed that the supplementary chemotherapy was particularly valid in stages III and IV. In stage III patients, the 5 year survival rate was increased by 27.8%. In stage IV patients, the 3 and 5 year survival rates of the combined group were 16.3% and 9.8% but none survived over 3 years in the operation only group. The authors believe that postoperative adjuvant chemotherapy plays an important role in controlling the micrometastatic and residual cancer foci.