Effects of fasting on hypoxic ventilatory responses and the contribution of histamine H1 receptors in mice

We tested the hypothesis that fasting affects hypoxic ventilatory responses through metabolic changes via histamine H1 receptors. Wild-type (WT) and histamine H1 receptor knockout (H1RKO) mice were studied in fed and fasted states. In the fed WT, hypoxic-gas exposure elicited an increase and a subsequent decline in ventilation (hypoxic ventilatory decline or HVD). HVD was influenced by fasting in breathing pattern with metabolic rate. Fasting elicited hypoglycemia, a drop in R, and increases in free fatty acid and ketone bodies in the serum. In H1RKO, HVD was blunted in the fed state, but it appeared in the fasted state. There was a minimal drop in R following fasting and a low triglyceride concentration. Thus, fasting affects HVD through a change in energy mobilization from glucose to lipid metabolism. Histamine H1 receptors are involved in HVD during fed and fasted states, resulting in adaptation to the environmental conditions.     

Assessment of Interleukin‐6 Receptor Inhibition Therapy on Periodontal Condition in Patients With Rheumatoid Arthritis and Chronic Periodontitis

Background: Overproduction of interleukin (IL)‐6 may play a pathologic role in rheumatoid arthritis (RA) and chronic periodontitis (CP). The present study assesses IL‐6 receptor (IL‐6R) inhibition therapy on the periodontal condition of patients with RA and CP. Methods: The study participants were 28 patients with RA and CP during treatment with IL‐6R inhibitor, and 27 patients with RA and CP during treatment without IL‐6R inhibitor. Periodontal and rheumatologic parameters and serum levels of cytokine and inflammatory markers and immunoglobulin G against periodontopathic bacteria were examined after medication with IL‐6R inhibitor for 20.3 months on average (T1) and again 8 weeks later (T2). Results: No differences were observed between the groups in any parameter values at T1, except for serum IL‐6 levels. The anti–IL‐6R group showed a significantly greater decrease in gingival index, bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and serum levels of IL‐6 and matrix metalloproteinase (MMP)‐3 from T1 to T2 than the control group (P <0.05). A significant correlation was found between changes in serum anticyclic citrullinated peptide levels and those in PD and CAL in the anti–IL‐6R group (P <0.05), whereas both groups exhibited a significant association between changes in serum MMP‐3 levels and those in BOP (P <0.05). Conclusion: Changes in periodontal and serum parameter values were different between the patients with RA and CP during treatment with and without IL‐6R inhibitor.     

Safety and efficacy of fluvastatin in hyperlipidemic patients with chronic renal disease

BACKGROUND: There are few reports on the safety and efficacy of long-term treatment with statins in patients with chronic renal disease and hyperlipidemia. We evaluated these subjects treated with fluvastatin. METHODS: After a 4-week run-in period, a total of 80 patients with diabetic nephropathy or chronic glomerulonephritis were randomly allocated to receive dietary therapy and fluvastatin 20 mg/day (n=39), or dietary therapy alone (n=41) for a period of 48 weeks. Lipid parameters, rhabdomyolysis-related indicators, 24-hour urinary albumin excretion and creatinine clearance were measured. The pharmacokinetics of fluvastatin was examined in 8 patients. RESULTS: Creatinine clearance and 24-hour urinary albumin excretion did not differ between the two groups. The peak serum fluvastatin concentration (Cmax) was 141+/-67 microg/L and the mean AUC0-6 h was 341+/-149 microgh/L. Fluvastatin treatment significantly lowered serum total cholesterol, low-density lipoprotein (LDL) cholesterol and apo-lipoprotein B concentrations by 16%, 25%, and 22%, respectively, compared with patients receiving dietary therapy alone. There were no significant differences in serum triglyceride and high-density lipoprotein (HDL) cholesterol concentrations between the two treatment groups. Serum creatine kinase and aldolase concentrations did not change throughout treatment in both groups. CONCLUSIONS: Fluvastatin treatment significantly improved lipid parameters in patients with chronic renal disease. Fluvastatin was well tolerated, with no adverse effects on renal function and no muscular toxicity. However, the drug showed no direct renoprotective effects.     

Histological differences in new-onset IgA nephropathy between children and adults.

BACKGROUND: It is suggested that IgA nephropathy (IgAN) manifests differently in children vs adults on the basis of biopsy findings. However, this has been difficult to establish owing to the uncertainty of the timing of disease onset in adult IgAN. We addressed this question by comparing both histology and leucocyte accumulation in biopsies of recently diagnosed childhood and adult IgAN. METHODS: Biopsies taken within 2 years from the onset of renal abnormalities in 33 childhood (10 +/- 3 years of age) and 38 adult (35 +/- 6 years) cases of IgAN were examined for histological changes (cellularity in mesangial, endocapillary and extracapillary areas, matrix expansion, adhesions/crescents and interstitial damage), glomerular deposition of immunoglobulin and complement, and the presence of macrophages, activated macrophages and T cells by immunohistochemistry. RESULTS: Glomerular hypercellularity owing to increased cells in mesangial area was prominent in paediatric IgAN and significantly greater than in adult IgAN. In contrast, glomerular matrix expansion, crescent formation and interstitial damage were more severe in adults compared to paediatric IgAN. Indeed, glomerular hypercellularity correlated with proteinuria in paediatric but not in adult IgAN, whereas glomerular matrix correlated with proteinuria and renal function in adult but not in paediatric IgAN. The degree of C3c deposition was significantly greater in paediatric IgAN, while deposition of fibrinogen was greater in adult IgAN. Glomerular and interstitial CD68+ macrophages and a subset of sialoadhesin (Sn)+ activated macrophages were identified in both paediatric and adult IgAN, being significantly greater in number in adult IgAN. Glomerular leucocyte infiltration correlated with proteinuria while interstitial leucocyte infiltration correlated with interstitial damage in both groups. However, only the subset of Sn+ macrophages gave a significant correlation with renal function, glomerular hypercellularity and glomerular matrix. CONCLUSIONS: This study has demonstrated significant differences in the early glomerular lesions of IgAN in children vs adults. Furthermore, Sn+ activated macrophages are implicated in the pathogenesis of IgAN in both patient groups. The prognostic significance of these findings warrants further study.     

Comparison of methods of steroid administration combined with tonsillectomy for IgA nephropathy patients

Background

IgA nephropathy (IgAN) is a chronic glomerular disease that causes end-stage renal disease in 20–40 % of patients within 20 years. The efficacy of tonsillectomy combined with steroid pulse (SP) administration (TSP) for clinical remission of IgAN has been reported. Particularly in Japan, TSP has been performed widely. However, the optimum method for steroid administration in TSP has not been established.

Methods

We retrospectively compared clinical remission in IgAN patients treated with tonsillectomy combined with two different steroid administration methods: (1) three courses of SP therapy and oral prednisolone administered on alternate days (group 3A; n = 25); and (2) one course of SP therapy and oral prednisolone administered on consecutive days (group 1C; n = 22).

Results

There was no significant difference in the clinical remission rates between the two groups at 12 (48.0 vs. 40.9 %, P = 0.77) and 24 months after starting treatment (68.0 vs. 72.7 %, P = 0.76) and at the final observation (76.0 vs. 81.8 %, P = 0.73). The mean period from starting treatment to remission of hematuria in group 3A was significantly shorter than that in group 1C (5.7 ± 4.4 vs. 9.9 ± 5.9 months, P = 0.03). Dyslipidemic patients treated for the first time with statin after the SP therapy were more present in group 3A at 24 months (P = 0.02).

Conclusions

In IgAN patients, treatment of group 3A may be effective for inducing rapid remission of hematuria. Further studies are needed to establish an appropriate protocol for TSP.

     

Upregulation of prolactin receptor in proximal tubular cells was induced in cardiac dysfunction model mice

Background

In order to clarify the interaction between cardiac dysfunction and sodium homeostasis in the kidney, we used a murine model of cardiac dysfunction and investigated the effect on sodium transporters in renal tubular cells.

Methods

Cardiac function was deteriorated by abdominal aortic banding, and the gene expression of sodium transporters in the kidneys was evaluated by real-time RT-PCR and compared with that in the kidneys of control mice.

Results

Gene expression of all three variants of the murine prolactin receptor was enhanced by aortic banding. Upregulated prolactin receptor was distributed in the proximal tubular cells of the pars recta in the deep inner cortex and the outer stripe of the outer medulla. Prolactin has been reported to be a natriuretic hormone that inhibits proximal tubular Na⁺/K⁺-ATPase activity, resulting in reduced sodium reabsorption and the acceleration of natriuresis. Inhibition of endogenous prolactin secretion by bromocriptine administration decreased the urine sodium excretion in both aortic banding and control mice. On the other hand, excess exogenous prolactin administration enhanced urine potassium excretion in aortic banding mice. Furthermore, a high-sodium diet accelerated urinary sodium excretion, which was also significantly decreased by inhibition of endogenous prolactin secretion in aortic banding mice.

Conclusion

We reported that the prolactin receptor was upregulated by aortic banding treatment. Prolactin-prolactin receptor interaction in the proximal tubular cells of the pars recta should involve a different mechanism of kaliuresis other than inhibition of Na⁺/K⁺-ATPase.     

Hypersensitivity to paraoxybenzoic Acid esters (parabens) in a dialysis patient

A 24-year-old woman undergoing chronic dialysis therapy who had been diagnosed as having 'heparin allergy' presented acute allergic reaction after the intracatheter injection of a heparin agent. Further investigation revealed that mild eosinophilia had persisted for more than 3 years before this incidence despite avoiding the use of heparin agents. The leukocyte migration inhibition test (LMIT) showed that heparin agent A which was used for the patient showed positive reaction while heparin agent B which was not used for the patient showed a negative reaction. Paraoxybenzoic acid esters (parabens) are contained in heparin agent A but not in heparin agent B. Parabens showed positive reactions on LMIT. Parabens are the most common preservatives in drugs, foods, and cosmetics and they sometimes induce allergic reactions through percutaneous and possibly ingestive sensitization. However, they cause more severe allergic reactions when used intravenously. We concluded that the allergen in this patient was not heparin but parabens. Hypereosinophilia of unknown origin often occurs in dialysis patients. Such patients may be hypersensitive to parabens.     

Comparison of fluorine-18 fluorodeoxyglucose positron emission tomography and Ga-67 scintigraphy in evaluation of lymphoma

BACKGROUND: The accuracy of fluorodeoxyglucose positron emission tomography (FDG-PET; dual-head camera with attenuation correction) and Ga-67 scintigraphy was compared to identify disease sites in patients with Hodgkin disease (HD) and intermediate and high-grade non-Hodgkin lymphoma (NHL) at initial diagnosis or clinical recurrence. METHODS: Fifty-one contemporaneous FDG-PET and Ga-67 scintigraphies were performed on patients with NHL (35 intermediate grade, 3 high grade) or HD (13 patients). Sites of disease were correlated on a site-by-site basis on FDG-PET and Ga-67 images. Tumor-to-background (T/B) ratios were obtained for both techniques. Discordant FDG-PET and Ga-67 findings were correlated with computed tomography findings or clinical evaluation including repeat FDG-PET scans obtained after therapy. RESULTS: Fluorodeoxyglucose positron emission tomography was positive at all 158 sites in 51 patients compared with 113 sites in 41 positive studies with Ga-67 scintigraphy (single positron emission computed tomography [SPECT] and/or planar images). In 44 patients who had complete Ga-67 SPECT data on all tumor sites, FDG-PET was positive at 126 sites and Ga-67 SPECT was positive at 81 sites. Ga-67 SPECT failed to demonstrate disease at 45 sites (35.7%). In 10 of 44 patients, Ga-67 SPECT completely failed to detect any disease at 22 of 45 sites (17.5%) and partially identified disease sites at 23 of 45 sites (18.2%) in 11 patients regardless of the tumor site and histology. In these patients, the lesions measured between 0.6 and 14.0 cm by CT. Fluorodeoxyglucose positron emission tomography revealed higher stage disease in 13 patients compared with Ga-67 imaging. Tumor-to-background ratios were statistically different between the two techniques with higher ratios obtained with FDG-PET (P < 0.0001). CONCLUSIONS: In imaging aggressive lymphoma and HD before therapy, FDG-PET has significantly higher site and patient sensitivity than Ga-67 scintigraphy (100% vs. 71.5% and 100% vs. 80.3%, respectively). The change in disease stage by FDG-PET may result in a change in therapy strategy.     

An Accurate and Rapid Gender Determination Assay in Single Cells by the Capillary Polymerase Chain Reaction Method

Purpose: In preimplantation genetic diagnosis (PGD), a rapid and accurate assay has been required. We have therefore developed a capillary polymerase chain reaction (PCR) method using rapid thermal cycling programs to determine the gender of single amniocytes. Methods: Single amniocytes from each amniotic fluid sample were isolated by micromanipulation and their gender was determined by a multiplex PCR assay in a capillary tube, using primers that amplify a 308-bp DXZ1 and a 154-bp DYZ1 repeat sequence on the X and Y chromosomes, respectively. Results: All four thermal cycling programs, which took 180, 150, 120, and 90 min, were 100% accurate in diagnosing the gender of single amniocytes. No DNA contamination was observed in any samples. Conclusions: The multiplex PCR assay was rapid and accurate in diagnosing gender in single cells and may be clinically applicable in PGD.     

A novel type of encephalopathy associated with mushroom Sugihiratake ingestion in patients with chronic kidney diseases

BACKGROUND: The etiology of encephalopathy in uremic patients is multiple. We recently encountered a novel type of encephalopathy which occurred exclusively in patients with chronic kidney diseases after ingestion of a mushroom called Sugihiratake. While the exact etiology of this encephalopathy remained mysterious, we aimed to describe its clinical features. METHODS: A total of 32 patients with chronic kidney diseases who had presented with encephalopathy following ingestion of Sugihiratake were enrolled from seven prefectures in Japan., with 24 of the 32 patients undergoing regular hemodialysis. The patient's clinical data were from surveillance by The Japanese Society of Nephrology. RESULTS: There was a significant association between Sugihiratake ingestion and the occurrence of encephalopathy in 524 hemodialysis patients questioned for a recent ingestion of this mushroom (P= 0.0006). The latent asymptomatic period before the onset of symptoms varied from 1 to 31 days (mean 9.1 +/- 7.3) days. The patient's symptoms consisted of disturbed consciousness in 30 patients (93.8%), convulsions in 25 (78.1%), myoclonus in 15 (46.9%), dysarthria in ten (31.3%), ataxia in eight (25.0%), paresis or paralysis in seven (21.9%), and skin parasthesia in two patients (6.3%). Nine (27.2%) patients died, mostly due to respiratory failure. The other patients were either discharged or still in hospitals with various degrees of clinical improvement. CONCLUSION: Patients with chronic kidney diseases are at risk of having serious encephalopathy following Sugihiratake ingestion and must refrain from eating it. Physicians, in those parts of the world, where this mushroom harvesting is common, should be aware of this complication.