Emphysematous pyelonephritis with complete duplication of the left urinary tract

Emphysematous pyelonephritis (EPN) is a life-threatening bacterial infection and should be treated rapidly and carefully. We report a case of EPN with complete duplication of the left urinary tract. A 68-year-old woman was admitted to our hospital complaining of high-grade fever and left flank pain. An abdominal computed tomography scan showed gas was presented in the renal parenchyma, not only the pelvis and ureter. Based on these findings, a diagnosis of left EPN was made. A partial nephrectomy of the affected left upper pole moiety was performed and the patient underwent additional medical management. Other 83 cases of EPN from the Japanese literature were reviewed.     

Parkin-mediated protection of dopaminergic neurons in a chronic MPTP-minipump mouse model of Parkinson disease

Loss-of-function mutations in the ubiquitin ligase parkin are the major cause of recessively inherited early-onset Parkinson disease (PD). Impairment of parkin activity caused by nitrosative or dopamine-related modifications may also be responsible for the loss of dopaminergic (DA) neurons in sporadic PD. Previous studies have shown that viral vector-mediated delivery of parkin prevented DA neurodegeneration in several animal models, but little is known about the neuroprotective actions of parkin in vivo. Here, we investigated mechanisms of neuroprotection of overexpressed parkin in a modified long-term mouse model of PD using osmotic minipump administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Recombinant adeno-associated viral vector-mediated intranigral delivery of parkin prevented motor deficits and DA cell loss in the mice. Ser129-phosphorylated α-synuclein-immunoreactive cells were increased in the substantia nigra of parkin-treated mice. Moreover, delivery of parkin alleviated the MPTP-induced decrease of the active phosphorylated form of Akt. On the other hand, upregulation of p53 and mitochondrial alterations induced by chronic MPTP administration were barely suppressed by parkin. These results suggest that the neuroprotective actions of parkin may be impaired in severe PD.     

Therapeutic efficacy of interferon β-1b in Japanese patients with optic-spinal multiple sclerosis

Most cases of ovarian torsion require emergency surgery; the ovary has become necrotic and cannot be conserved. Preoperative determination of the ovarian necrosis extent is difficult but it may increase the likelihood of the ovary conservation. In this study, we retrospectively evaluated the findings in ovarian torsion among patients with ovarian tumors who underwent emergency surgery at a single hospital for possible preoperative indicators of ovarian viability. We thus evaluated 77 patients who were intraoperatively diagnosed with torsion of ovarian tumor between 1995 and 2010. These patients were classified into three groups depending on the postoperative histopathological findings: necrotic, congestive, and normal. Preoperative C-reactive protein (CRP) level, leukocyte count, and body temperature, along with tumor size, degree of torsion, time from the onset of abdominal pain to surgery, and incidence of acute abdomen were compared among the three groups. The sensitivity, specificity, and positive and negative predictive values of the preoperative serum CRP levels for ovarian necrosis were calculated. The CRP level, degree of torsion, and time from the onset of abdominal pain to surgery were significantly higher in the necrotic group than in the normal group. The sensitivity and specificity of the CRP level for necrosis were 35% and 83%, respectively, and positive and negative predictive values were 38% and 82% respectively. The potential for ovary conservation in suspected ovarian torsion should be greater if the tumor is non-malignant, the time from the onset of abdominal pain to operation is short, and the CRP level is < 0.3 mg/dl.     

Circadian rhythms in the CNS and peripheral clock disorders: function of clock genes: influence of medication for bronchial asthma on circadian gene

Bronchial asthma is a chronic inflammatory disorder of the airways, in which inflammation causes bronchial hyper-responsiveness and flow limitation in the presence of various stimuli. Pulmonary function in asthmatic patients frequently deteriorates between midnight and early morning, which has suggested a role for chronotherapy. Although relationships between bronchial asthma and the function of clock genes remain unclear, some medications given for asthma such as glucocorticoids or beta(2)-adrenoceptor agonists may influence clock genes in vivo. In our studies of clock gene mRNA expressions in human bronchial epithelial cells in vitro and peripheral blood cells in vivo, we demonstrated that glucocorticoid or beta(2)-adrenoceptor agonist treatment strongly induced human Per1 mRNA expression both in vitro and in vivo. Human peripheral blood cells provide a useful indication of peripheral clock gene mRNA expression in vivo.     

Comparison of Allergenic Properties of Salmon (Oncorhynchus nerka) between Landlocked and Anadromous Species

BackgroundSalmon is one of the most widely consumed seafoods in Japan and many other countries around the world. Due to the confirmed cases of salmon-induced allergy, the food sanitation law in Japan stipulates salmon as one of the specific food items for which labeling is recommended when used as an ingredient of processed foods. However, trout, the landlocked form of anadromous salmon, is not subject to the allergenlabeling requirements, even though both populations belong to a single species. Since no supporting data have been demonstrated to make a clear distinction between these two populations in terms of allergenicity, we comparatively examined their allergenic properties using sera from patients allergic to fish.MethodsExtracts of Oncorhynchus nerka from different habitats were obtained: kokanee (landlocked) and red salmon (anadromous). Control extracts were derived from four other species. This study focused on the (1) IgE-binding capacity of the fish extracts in patients' sera (n = 50), (2) ELISA inhibition test (n = 6), and (3) inhibition immunoblot test (n = 8) between the kokanee and red salmon.ResultsThe extracts from kokanee and red salmon showed the highest correlation with each other in terms of the IgE-binding capacity, and showed complete (100%) reciprocal cross-inhibition in the ELISA inhibition test. On immunoblotting, there was no marked difference in the staining pattern between the two extracts, and each IgE-binding band gradually disappeared when the patients' sera were preincubated with the counterpart antigen in a dose-dependent manner.ConclusionsThese results suggest that kokanee has similar allergenic properties to red salmon.     

Monocyte chemoattractant protein-1 ?2518 polymorphism is not associated with diabetic retinopathy in Japanese type 2 diabetes

To clarify whether polymorphism of monocyte chemoattractant protein-1 (MCP-1) were related to diabetic retinopathy (DR), we performed a case–control study in 175 Japanese type 2 diabetic patients participating in a multi-center research protocol. Genetic analysis was performed using a fluorescent allele-specific DNA primer assay system. DR was diagnosed in a masked manner by an independent ophthalmologist using fundus photographs and was classified as non-diabetic retinopathy (NDR), non-proliferative retinopathy (NPDR), and proliferative retinopathy (PDR). The results showed that the genotype frequencies of the MCP-1 gene at position ?2518 were not significantly different among patients with NDR, NPDR and PDR. Multivariate logistic regression analyses showed that significant associations were observed between DR and age, diabetes duration, systolic pressure, and HbA₁c, but not polymorphisms of the MCP-1 gene at position ?2518. In conclusion, the present study demonstrated no association between polymorphism of MCP-1 gene at position ?2518 and DR in Japanese type 2 diabetic patients.     

Angiotensinogen gene polymorphism (Met235Thr) influences visceral obesity and insulin resistance in obese Japanese women

To investigate the relationship between angiotensinogen (AGT) Met235Thr polymorphism (M235T) and human obesity, because AGT is regarded as one of the cytokines produced from adipocytes and serum AGT concentrations are reported to be positively correlated with body mass index. One hundred and twenty obese Japanese women (age, 58.8+/-9.4 years; body mass index, 32.2+/-4.9 kg/m(2)) were enrolled. Angiotensinogen genotypes were determined with a fluorescent allele-specific DNA primer assay system. Subjects were divided into M/M, M/T, and T/T groups. Control subjects comprised 146 healthy age-matched women. Clinical characteristics and the effects of diet and exercise therapy for 6 months were compared among the 3 genotypes. The genotype frequencies of AGT M235T polymorphism were in accordance with the Hardy-Weinberg equation (obese: M/M, 6.7%; M/T, 27.5%; T/T, 65.8%; control: M/M, 6.8%; M/T, 21.2%; T/T, 71.9%). The frequency of the T allele did not differ between obese and control subjects (0.80 vs 0.83). As the number of obese women with M/M genotype was only 8, comparisons of the characteristics and outcomes of weight reduction therapy were performed only between subjects with M/T genotype and T/T genotype. In the T/T group, % body fat and waist circumference at baseline were significantly greater than in the M/T group (36.3%+/-4.8% vs 33.8%+/-4.7%, P=.0105; 107.9+/-10.9 vs 102.6+/-7.9 cm, P=.0428, respectively). Before the weight reduction therapy, significantly higher insulin and higher homeostasis model assessment (HOMA-R) were demonstrated in the T/T group than in the M/T group (9.1+/-5.5 microU/mL vs 5.9+/-4.4 microU/mL, P=.0056; 2.3+/-1.4 vs 1.6+/-1.3, P=.0252, respectively). Both systolic and diastolic blood pressure at baseline in the T/T group tended to be higher than those in the M/T group, but the differences were not significant. No genotype-dependent difference in energy expenditure or outcome of weight reduction therapy was observed with respect to AGT M235T polymorphism. After the diet and exercise therapy, the blood pressure in the T/T group tended to be higher than that in the M/T group, but the difference was not significant. We demonstrated that the T/T genotype of the AGT M235T gene polymorphism was positively related to visceral obesity and hyperinsulinemia in obese Japanese women. Blood pressure did not show genotype-specific differences before or after the treatment. Further studies of the association between obesity and this gene polymorphism should contribute to understanding and treating obesity-related diseases.     

The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis

Background

The single nucleotide polymorphism (SNP) rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with hepatic fat accumulation and disease progression in patients with non-alcoholic fatty liver disease and alcoholic liver disease (ALD). This study was conducted to determine whether PNPLA3 rs738409 SNPs affect development and prognosis of hepatocellular carcinoma (HCC) in patients with various liver diseases.

Methods

We enrolled 638 consecutive Japanese patients newly diagnosed with HCC between 2001 and 2010: 72 patients with hepatitis B virus (HBV), 462 with hepatitis C virus (HCV), and 104 with non-B non-C (NBNC).

Results

NBNC patients exhibited large tumors of advanced TNM stages at HCC diagnosis, and had significantly poorer prognosis than HBV or HCV patients (P < 0.001 and <0.001, respectively; log-rank test). The G/G genotype of PNPLA3 rs738409 SNP had significantly higher distribution in NBNC patients (P < 0.001) and was significantly associated with higher body mass index (BMI) and an increased aspartate aminotransferase to platelet ratio index. No significant differences were observed in survival with differences in PNPLA3 SNP genotypes among the patients, although ALD patients with the G/G genotype of PNPLA3 SNP and low BMI had significantly poorer survival than those with high BMI (P = 0.028).

Conclusions

The G/G genotype of PNPLA3 rs738409 SNP was more frequently distributed, and associated with BMI and fibrosis among NBNC-HCC patients but not among HBV or HCV patients. These genotypes might affect HCC prognosis in ALD patients, but not in HBV, HCV, or NAFLD patients.     

A shear-induced in vitro platelet function test can assess clinically relevant anti-thrombotic effects

Morphological features of haemostatic plugs formed in vitro under high shear forces were investigated. Electron microscopy confirmed the relevance of such haemostatic plug to a platelet-rich arterial thrombus, which is formed in vivo. In rat blood samples, the effects of anticoagulants and various antiplatelet agents on platelet reactivity (rate of haemostatic plug formation) and subsequent coagulation of the flowing blood were investigated. Haemostasis did not occur in citrated blood, and heparin greatly inhibited the shear-induced platelet reaction. Aspirin (1 mM), a thromboxane A₂ receptor antagonist (5 μM), a stable prostacyclin (0.55 nM), a stable prostaglandin E₁ (141 nM) and a phosphodiesterase inhibitor (100 μM) were tested. All these agents exerted significant inhibitory effect on shear-induced platelet reaction, including the inhibition of the very first phase of platelet plug formation, due to aggregation of shear-activated platelets. Except for the phosphodiesterase inhibitor, which prolonged clotting time, none of the above agents affected dynamic coagulation. These results suggest that the employed in vitro shear-induced thrombosis/haemostasis test can reveal in vivo the antithrombotic effect of various agents independently of their mechanism of action.     

Crocetin,a Carotenoid from Gardenia jasminoides Ellis,Protects against Hypertension and Cerebral Thrombogenesis in Stroke‐prone Spontaneously Hypertensive Rats

Crocetin is a natural carotenoid dicarboxylic acid that is found in the fruit of Gardenia jasminoides Ellis (Cape Jasmine) and in the stamen and pistil of Crocus sativus L. (saffron). It is used worldwide as an important spice, food colorant, and herbal medicine. In the current investigation, we have examined the cardiovascular effects of crocetin using stroke‐prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs (6 weeks old) were classified into three groups: a control group and two crocetin groups (25 and 50 mg/kg/day). The animals were given crocetin for 3 weeks. Body weights in each group were not significantly different during the treatment period, but the increase in systolic blood pressures observed with age was significantly moderated by crocetin. Thrombogenesis, assessed using a He‐Ne laser technique in pial vessels, was significantly decreased. Antioxidant activity, assessed by measuring urinary 8‐hydroxy‐2′‐deoxyguanosine levels, together with urinary nitric oxide (NO) metabolite levels, was increased significantly after treatment. Acetylcholine‐induced vasodilation was measured using the aorta and indicated that endothelial function was significantly improved by crocetin. These results strongly suggest that the antihypertensive and antithrombotic effects of crocetin were related to an increase in bioavailable NO, possibly mediated by decreased inactivation of NO by reactive oxygen species. Copyright © 2014 John Wiley & Sons, Ltd.