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Notes: We examined changes in O2 uptake, CO2 output, blood pressure and heart rate following tourniquet deflation in 23 patients undergoing orthopaedic surgery of the lower extremities. A pneumatic tourniquet was applied for periods ranging from 21 to 106 min (mean 51 min). Prerelease values of V̇o2 (O2 uptake at each min) and V̇co2 (CO2 output at each min) were 201 (37) and 174 (38) (mean (SD)) ml.min−1 respectively. Significantly, V̇o2 and V̇co2 increased by 55% and 80%, respectively, at 2 min after tourniquet release and returned to prerelease values within 8 min. The blood pressure fell significantly and the heart rate rose significantly. The increases in CO2 output and O2 uptake were dependent on the length of tourniquet inflation time; Y = 4.7 X (tourniquet time) +54, r = 0.88, (p 〈 0.001) for CO2, and Y = 1.3 X (tourniquet time) +99, r = 0.52, (p 〈 0.05) for O2. The slope of the increase in CO2 output as a function in inflation time was 3.6 times greater than that of O2 uptake. In conclusion, CO2 output and O2 uptake increased transiently after tourniquet deflation and the extent of the increase in CO2 output is more than threefold as compared with that in O2 uptake.

Notes: DNA damage generated by reactive oxygen species (ROS) has been implicated in ageing and in the pathogenesis of cardiovascular disease. Reactive oxygen species have also been demonstrated to play a crucial role in the pathophysiology of various renal diseases. They are extremely vulnerable to oxidative stress because mitochondria are the major intracellular source of ROS and have limited protection from oxidative stress. We have found increased accumulation of 8-hydroxy-2′-deoxyguanosine (8-OH-dG), which is a product and bio-marker of oxidative DNA damage, in the mitochondria of glomeruli and tubules in patients with IgA GN. The hOGG1 gene encodes a DNA glycosylase that excises 8-OH-dG from damaged DNA. Recently, genetic polymorphism of Ser(S)326Cys(C) has been reported. In addition, the enzymatic activity of hOGG1 in the repair of 8-OH-dG has been reported to be greater with S than with C.In this study, we investigated the correlation between hOGG1 polymorphism and the clinical phenotypes in Japanese patients with IgA GN. A total of 100 patients with IgAGN with a clinical course of over 7 years duration whose diagnosis was made by renal biopsy were divided into the ‘CRF group’ and the ‘fair group’. The CRF group consisted of 30 patients whose creatinine clearance (Ccr) had fallen to less than 50% of that during the initial period or they had developed end stage renal failure (ESRF). The fair group consisted of 62 patients whose Ccr had been kept at over 80% of that during the initial period, even 7 years after the diagnosis. The patients were genotyped and their clinical findings were compared. One hundred healthy Japanese subjects with normal urinalysis and renal function were analysed. The patients and controls were informed of the ethical approval of this study before entry into the study. The genotype of the hOGG1 gene was determined using the PCR-SSCP method followed by direct sequencing analysis. The details of PCR-SSCP methods have been previously described.1 Clinical and biochemical data were extracted from case records. Blood pressure was evaluated as the average during 1 week of the patient’s hospitalization for a first renal biopsy. Proteinuria was also evaluated as the average data obtained from 24 h collected urine samples for a week. Significant differences in allele frequency and genotype between groups were tested by χ2 test. Biochemical and clinical data were tested by ANOVA and the t-test.We found a high frequency of the C allele in the CRF group compared to the fair group and controls (P 〈 0.05, 〈link href="#t1"〉Table 1). The frequency of ESRF patients was significantly higher among the patients with the CC genotype than in those woth the CS and SS genotype (CC, CS, SS = 50%, 27%, 16%; CC vs CS, P 〈 0.05; CC vs SS, P 〈 0.01; 〈link href="#f1"〉Fig. 1).〈tabular xml:id="t1"〉1〈title type="main"〉 Genotype and allele frequencies in each group 〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP7:NEP_7_t1"/〉〈figure xml:id="f1"〉1〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP7:NEP_7_f1"/〉Frequency of ESRF patients in each group.The creatinine increase rate CC, CS, SS = 0.6090 ± 0.924, 0.1998 ± 0.561, 0.0766 ± 0.2558 mg/dL per year, P 〈 0.05, 〈link href="#t2"〉Table 2) and proteinuria (CC, CS, SS = 1.89 ± 2.24, 1.02 ± 1.07, 1.17 ± 1.57 (g/24 h), P 〈 0.05) were significantly higher in the patients with the C allele than in those with the S allele.〈tabular xml:id="t2"〉2〈title type="main"〉 Creatinine increase rate and proteinuria in each group 〈table frame="topbot"〉〈tgroup cols="5" align="left"〉〈colspec colnum="1" colname="col1" align="left"/〉〈colspec colnum="2" colname="col2" align="center"/〉〈colspec colnum="3" colname="col3" align="center"/〉〈colspec colnum="4" colname="col4" align="center"/〉〈colspec colnum="5" colname="col5" align="left"/〉〈thead valign="bottom"〉〈row rowsep="1"〉CCCSSS〈tbody valign="top"〉Crn increase rate0.6090 ± 0.9240.1998 ± 0.5610.0766 ± 0.2558(mg/dL per year)Proteinuria1.89 ± 2.241.02 ± 1.071.17 ± 1.57(g/24 h)〈note xml:id="t2_note4" numbered="no"〉 P 〈 0.05These findings indicate that the polymorphism of the hOGG1 gene is associated with progression of IgA GN. hOGG1 polymorphism correlates with the amount of proteinuria and a decreasing speed of renal function. In this study, the patients with the CC genotype tended to fall into ESRF. A previous study disclosed that the ability to excise 8-OH-dG is greater with the S allele than with the C allele.2 These facts suggest that accumulation of oxidative DNA damage might be an important factor in the progression of IgA GN. Excision oxidative DNA damage, which is genetically decided, may play an important role in IgA GN.

Notes: Summary The involvement of various cytokines and chemokines has been reported in the pathogenesis of bullous pemphigoid (BP). Double-filtration plasmapheresis (DFPP) is an effective treatment for BP but the mechanism of action remains unclear. Using semiquantitative reverse transcription–polymerase chain reaction, we examined levels of transcripts for various cytokines and chemokines in freshly isolated peripheral blood mononuclear cells in a patient with BP before and after DFPP treatment. DFPP was performed four times. Relative levels of transcripts for interleukin (IL)-8, macrophage inflammatory protein (MIP)-1α and IL-5, and the ratio of relative levels of transcripts for IL-4 and interferon (IFN)-γ, were higher, before treatment, than in healthy controls, and decreased when the extent of the lesions was reduced. Relative levels of transcripts for tumour necrosis factor (TNF)-α and IL-4 also decreased with regression of lesions, although they were similar to or lower than the corresponding levels in healthy individuals. When eruptions recurred, relative levels of transcripts for IL-8, MIP-1α, RANTES (regulated upon activation normal T cell expressed and secreted), IL-2, IFN-γ and TNF-α were very much higher than those prior to the recurrence, while relative levels of mRNAs for IL-4 and IL-5 did not increase. Relative levels of transcripts for IL-8, MIP-1α, TNF-α and IL-2 were lower at the end of each individual DFPP and after the four treatments than at the beginning of treatment. Our observations suggest that cytokines and chemokines produced in mononuclear cells play important roles in the pathogenesis of BP and that regulation of their expression might be involved in the therapeutic effects of DFPP in BP.