A case of anaphylactoid purpura associated with nephrosis followed by pulmonary tuberculosis

A 54-year old man was admitted to our hospital because of high fever, productive cough and purpura in both legs in June 2005. Urinalysis showed microscopic hematuria and proteinuria. Chest radiograph showed consolidation of right upper field. Because acid-fast bacilli and polymerase chain reaction test for Mycobacterium tuberculosis were positive in bronchial lavage fluid, we made a diagnosis of pulmonary tuberculosis, and prescribed antituberculosis therapy with isoniazid, rifampicin, ethambutol and pyrazinamide. In addition, anaphylactoid purpura was diagnosed by skin biopsy. In July 2005, renal function was deteriorated and nephrosis appeared. We treated with corticosteroid in addition to antituberculosis therapy. His symptoms and renal dysfunction improved. We report a rare case of an anaphylactoid purpura following occurence of pulmonary tuberculosis.     

Bezafibrate treatment: a new medical approach for PBC patients?

Background. A new medical approach to primary biliary cirrhosis (PBC) has been desired. We investigated the feasibility of using combination ursodeoxycholic acid (UDCA)-bezafibrate therapy in patients with PBC nonresponsive to UDCA monotherapy. Methods. During a 6-month period, 22 PBC patients with elevated serum alkaline phosphatase (ALP) despite UDCA monotherapy received either UDCA at 600 mg/day (control group) or UDCA at 600 mg/day plus bezafibrate at 400 mg/day (bezafibrate group). Each patient underwent detailed clinical and biochemical evaluation. Results. During treatment, changes in ALP level were greater in the bezafibrate group than in the control group (P < 0.01). During and at the end of treatment, serum ALP levels were significantly lower than those before treatment in patients receiving UDCA plus bezafibrate (P < 0.05). At the end of the 6 months, normalization of serum ALP was observed in 5 of 11 (45.4%) patients given bezafibrate and in 2 of 11 (18.1%) patients not given bezafibrate (P < 0.16). Bile acid proportions during the combination therapy did not change. Pruritus disappeared in 1 of 7 bezafibrate-group patients with this symptom. Conclusions. UDCA at 600 mg/day plus bezafibrate at 400 mg/day may be considered as a new therapeutic option for patients with PBC. Received: August 22, 2002 / Accepted: November 22, 2002 RID="*" ID="*" Reprint requests to: T. Kanda     

Exaggerated response to cold stress in a congenic strain for the quantitative trait locus for blood pressure

OBJECTIVE: Stroke-prone spontaneously hypertensive rats (SHRSP) are known to have sympathetic hyperactivity to various stimuli. In the search for 'intermediate phenotypes' inferring the function of hypertension genes, the present study assessed responsiveness to cold stress in a congenic strain derived from SHRSP/Izm and Wistar-Kyoto/Izm (WKY/Izm). DESIGN: A congenic strain, WKYpch1.0, was established by 10 generations of backcrossing to transfer the chromosomal fragment between D1Wox29 and D1Arb21 of SHRSP to WKY. This fragment covered the 100:1 confidence interval of the quantitative trait locus (QTL) for blood pressure identified in a previous study. Response to cold stress was studied by exposing rats to 4 degrees C for 4 h. Blood pressure was monitored with telemetry. Urine was collected during the exposure, and urinary concentrations of catecholamines were measured by high-performance liquid chromatography. RESULTS: Under the cold stress, urinary excretion of norepinephrine (NE) and vanillylmandelic acid (VMA), as well as the plasma level of NE, was significantly greater in WKYpch1.0 than in WKY. The increase in blood pressure during the cold stress was also greater in WKYpch1.0 than in WKY. Further, neonatal chemical sympathectomy using guanethidine abolished the exaggerated response in blood pressure and in urinary excretion of NE and VMA in WKYpch1.0. CONCLUSION: These results suggested that the QTL region on rat chromosome 1 harbored genes responsible for the exaggerated response of the sympathetic nervous system to the cold stress. The relationship of this with the pathogenesis of hypertension should be elucidated in future studies.     

Inhibitory effect of ceramide on insulin-induced protein kinase Czeta translocation in rat adipocytes

Ceramide has been confirmed to be a signal mediator of apoptosis that is induced by tumor necrosis factor-alpha (TNF-alpha). It has also been reported that ceramide may induce insulin resistance as well as TNF-alpha. We investigated the effect of ceramide on insulin signaling pathways, such as insulin receptor (IR) beta-subunit, insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and protein kinase Czeta (PKCzeta) in rat adipocytes. We examined insulin-stimulated [(3)H]2-deoxyglucose (2-DOG) uptake in rat adipocytes pretreated with N-hexanoylsphingosine (C(6)-ceramide, 10 to 30 micromol/L). Insulin-induced 2-DOG uptake was significantly reduced by C(6)-ceramide pretreatment. We also examined the effect of various concentrations of C(6)-ceramide pretreatment on insulin-induced autophosphorylation of the IR beta-subunit, tyrosine phosphorylation of IRS-1, enzyme activity of PI3K, and membrane-associated PKCzeta immunoreactivity. Pretreatment with C(6)-ceramide significantly reduced autophosphorylation of the IR beta-subunit, tyrosine phosphorylation of IRS-1, and enzyme activity of PI3K. Moreover, membrane-associated PKCzeta immunoreactivity and immunoprecipitable PKCzeta enzyme activity, downstream of PI3K, were significantly suppressed by C(6)-ceramide pretreatment. These results suggest that ceramide may induce insulin resistance via the suppression of IRS-1-PI3K signaling, and subsequent activation of PKCzeta.     

Angiogenesis in hepatocellular carcinoma as evaluated by CD34 immunohistochemistry

ABSTRACT— To clarify the relationship between angiogenesis and hepatocarcinogenesis on progression of hepatocellular carcinoma (HCC), we quantitatively evaluated angiogenesis by CD34 immunohistochemistry in liver cirrhosis (LC), adenomatous hyperplasia (AH), and HCC, and proliferative activity estimated by Ki-67 immunohistochemistry. Angiogenesis was evaluated by CD34 immunohistochemistry using monoclonal antibody HPCA-2, and tumor proliferative activity was evaluated using monoclonal antibody MIB-1. We used an image analysis system to assess the microvessel density as the area percentage of the endothelial area. Angiogenesis was generally observed in HCC and there was no significant difference among all clinical stages and histological grades of HCC. On the other hand, the staining of CD34 was partly observed in sinusoids of AH, although no positive staining was seen in any sinusoids of LC. The proliferative activity was significantly correlated with the clinical stage and histological grade of HCC. Our results indicate that the quantitation of angiogenesis does not provide significant prognostic information in HCC, but that it may have diagnostic value in distinguishing HCC from non-HCC. Meanwhile, AH, which is not morphologically diagnosed as cancer, shows positive staining for CD34, suggesting that some portion of AH contains cancerous characteristics.     

Erratum to: Antibacterial activity of Eucalyptus globulus on cariogenic bacteria and its inhibitory effect on glucosyltransferase

Journal of Natural Medicines -     

Protein C activation in NIDDM patients

Summary Enhanced activation of the clotting system has been recently implicated in the pathogenesis of vascular complications in patients with diabetes mellitus. Abnormalities of the anticoagulant system may constitute a potential trigger factor for the haemostatic activation observed in diabetic subjects. The current study aimed to evaluate anticoagulant activity in diabetic patients by assessing the plasma levels of activated protein C-protein C inhibitor complex; and by measuring the anticoagulant response to exogenous thrombomodulin. This study comprised 61 patients (34 men, 27 women) with non-insulin-dependent diabetes mellitus (NIDDM) of whom 22 showed microalbuminuria and 39 normoalbuminuria. Data obtained in 31 non-obese and non-diabetic subjects were available for comparison. The plasma levels of fibrinogen (p < 0.02), prothrombin fragment 1 + 2 (p < 0.05), fibrin monomer (p < 0.0001), protein C antigen (p < 0.005), total protein S antigen (p < 0.02), soluble thrombomodulin (p < 0.005) and soluble E-selectin (p < 0.005) were significantly higher in diabetic patients than in healthy subjects. The plasma level of activated protein C-protein C inhibitor complex (7.4 ± 3.8 vs 3.0 ± 0.4 pmol/l) was significantly higher (p < 0.0001) and the anticoagulant response to exogenous thrombomodulin (23.4 ± 2.6 vs 35.3 ± 3.0 ng/ml) was markedly lower (p = 0.005) in all diabetic patients than in healthy subjects. Cases with microalbuminuria presented low plasma levels of activated protein C-protein C inhibitor complex (5.5 ± 0.6 vs 8.6 ± 0.7 pmol/l, p < 0.05) and significantly decreased values of the anticoagulant response to exogenous thrombomodulin (16.5 ± 2.9 vs 23.4 ± 2.6 %, p = 0.03) as compared to those with normoalbuminuria. The present study suggests that the hyper-coagulable state in NIDDM is associated with an increased activation of protein C but with a poor plasma reactivity to the anticoagulant effect of thrombomodulin. [Diabetologia (1996) 39: 1455–1461] Received: 27 February 1996 and in revised form: 3 June 1996     

Clusters of proliferating endothelial cells and smooth muscle cells in rabbit carotid arteries

Schwarz and Benditt found clustering of replicating cells in aortic endothelium in 1976 and discussed how homeostasis of the arterial wall is maintained through this nonrandom distribution of replicating cells. However, it is still unclear how cells of vascular walls turnover. In order to address this issue, we evaluated distribution of the cells in mitotic cycle, labeled by Ki67‐immunostaining, in serial histological sections of twelve carotid arteries of six adult male Japanese rabbits. As a result, a total of 1713 Ki67‐positive endothelial cells (ECs) and 1247 Ki67‐positive smooth muscle cells (SMCs) were identified. The Ki67‐positivity rate in ECs and SMCs were about 0.048% and 0.0027%, respectively. Many of the Ki67‐positive cells clustered in two (EC, 37%; SMC, 33%), three to four (EC, 8%; SMC, 28%), and five to eight cells (EC, 5%; SMC, 10%). Clusters having more than eight cells were not found. Thus, it can be speculated that the cell division of proliferating ECs and SMCs occur four times at most. These novel findings offer great insights for better understanding of the mechanism that underlies cell number regulation of the blood vessel.