Measurement of erythrocyte creatine might be useful for diagnosing latent hemolysis.

OBJECTIVES: Whereas HbA1c values are low relative to glycemia in patients with hemolytic anemia, including compensatory anemia, low HbA1c levels along with negative results for conventional hemolysis indicators have been reported in patients with latent hemolysis. Conversely, glycated albumin (GA) is a glycemic control indicator unaffected by hemolysis. Erythrocyte creatine (EC) is a hemolysis indicator that reflects the mean age of red blood cells (MRBC). We recently reported a formula for obtaining MRBC based on EC. The present study examined the usefulness of EC measurements and MRBC calculated with EC for diagnosing latent hemolysis. MATERIALS AND METHODS: Two patients with latent hemolysis and low HbA1c values relative to glycemia were investigated, while controls comprised 214 patients (including patients with hemolysis and/or type 2 diabetes mellitus). HbA1c was expressed in International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) units (iA1c). GA/iA1c ratios, reticulocyte counts, EC, and MRBC in patients with latent hemolysis were compared to non-hemolysis, compensatory hemolysis, and hemolytic anemia patients. RESULTS: Both reticulocyte counts and haptoglobin levels were within reference ranges in patients with latent hemolysis. GA/iA1c ratios and EC were higher than reference values in patients with latent hemolysis, and MRBC values were 41.6 and 48.4 days, respectively, shorter than the reference range (49.1-66.8 days). CONCLUSIONS: EC measurement and MRBC values calculated on the basis of EC might be useful for diagnosing latent hemolysis.

Estimation of the hemoglobin glycation rate constant.

In a previous study, a method of obtaining mean erythrocyte age ([Formula: see text]) from HbA1c and average plasma glucose (AG) was proposed. However, the true value of the hemoglobin glycation constant ([Formula: see text] dL/mg/day), required for this model has yet to be well characterized. Another study also proposed a method of deriving [Formula: see text] from erythrocyte creatine (EC). Utilizing these formulae, this study aimed to determine a more accurate estimate of [Formula: see text]. One hundred and seven subjects including 31 patients with hemolytic anemia and 76 subjects without anemia were included in this study. EC and HbA1c data were analyzed, and [Formula: see text] using HbA1c, AG and the newly-derived constant, [Formula: see text] were compared to [Formula: see text] using traditional [Formula: see text] in three patients whose data were taken from previous case studies. A value of [Formula: see text] dL/mg/day was determined for [Formula: see text]. [Formula: see text] using HbA1c, AG and [Formula: see text] were found to no be significantly different (paired t-test, [Formula: see text]) to [Formula: see text] using traditional [Formula: see text]. [Formula: see text] enables the estimation of [Formula: see text] from HbA1c and AG.

Therapeutic effect of Chinese prescription Kangen-karyu in patients with diabetic nephropathy.

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. A number of new therapies have been developed based on the pathogenic factors of diabetic nephropathy such as intensive glycemic control, precise hypertension control, lifestyle modifications including exercise and an energy-restricted diet, and numerous novel agents. The utilization of traditional Chinese medicine for patients with diabetic nephropathy has also received increasing attention due to its wide availability, weak side-effects, and proven therapeutic mechanisms and benefits. In this paper, we report the case of patients with diabetic nephropathy, stage 2 or 3. Kangen-karyu extract (7.5 g/day) was administered three times per day for 6 months. The estimated glomerular filtration rate was increased at the 6-month follow-up. The serum creatinine level decreased following administration. At that time, somatic and subjective symptoms had partially disappeared. Here, we present evidence that Kangen-karyu exerts a renoprotective effect against the development of diabetic nephropathy.

Efficacy of Chinese prescription Kangen-karyu for patient with metabolic syndrome.

Metabolic syndrome is a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. The risk factors include hypertension, dyslipidemia, hyperglycemia, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. The utilization of traditional Chinese medicine to treat metabolic syndrome has received increasing attention due to its wide availability. In this paper, we report the case of a 68-year-old patient with hypertension, hypercholesterolemia, borderline diabetes, and obesity, who showed an improvement in metabolic syndrome on the administration of 7.5 g of Kangen-karyu extract per day. After 6 months, the levels of serum total cholesterol, low-density lipoprotein-cholesterol, triglycerides, hemoglobin A1c were decreased. The abdominal circumference and body weight were decreased following administration. At that time, the somatic and subjective symptoms had partially disappeared. Herein, we present and discuss the evidence supporting the use of Kangen-karyu extract against metabolic syndrome.

Community-acquired pneumonia distinguished from influenza infection based on clinical signs and symptoms during a novel (swine) influenza A/H1N1 pandemic.

AIMS: The numbers of patients with influenza-like illnesses increase during influenza outbreaks. A study was undertaken to distinguish community-acquired pneumonia (CAP) from influenza based on clinical signs and symptoms. METHODS: This retrospective study investigated patients with positive results in the rapid influenza antigen test and those diagnosed with CAP during an influenza A/H1N1 pandemic. Significant factors for predicting risk for CAP within 48 hrs from onset and at diagnosis were selected by multiple regression analysis. RESULTS: Within 48 hrs of onset and at diagnosis, age and coarse crackles significantly increased the risk of CAP whereas sick contact, sore throat, and rhinorrhoea significantly decreased the risk of CAP. Duration of illness, sputum, dyspnoea, chest pain, and coarse crackles also significantly increased the risk of CAP at diagnosis. CONCLUSIONS: CAP differed somewhat from influenza even within 48 hrs of onset and the differences became even more evident thereafter.

Significance of the progression of respiratory symptoms for predicting community-acquired pneumonia in general practice.

BACKGROUND AND OBJECTIVE: Early diagnosis improves outcomes in patients with community-acquired pneumonia (CAP). However, prediction of CAP based on symptoms and signs is difficult. The present study investigated the evaluation of progression of symptoms as a factor for predicting the occurrence of CAP in general practice. METHODS: Consecutive patients (n = 406) suspected of having CAP on routine clinical examination were studied retrospectively. Selection of patients with suspected CAP was based on progression of symptoms after 5 days, as well as published criteria. Diagnostic yields for the recommended criteria and our proposed criteria were then compared. Scoring systems for the prediction of CAP were designed, based on the results of multiple regression analysis. The diagnostic performance of these systems, including or excluding symptom progression, was compared using the areas under receiver operating characteristic curves. RESULTS: The sensitivity and specificity of the recommended criteria and our proposed criteria were 0.75 and 0.44, and 0.93 and 0.38, respectively. Sputum production, dyspnoea, fever > 38 degrees C, heart rate > 100 beats/min, decreased breath sounds, coarse crackles and progression of symptoms significantly increased the likelihood of CAP. Areas under receiver operating characteristic curves analysis showed that the diagnostic prediction of CAP was significantly improved when the scoring system included progression of symptoms. CONCLUSIONS: Progression of symptoms was a significant factor for predicting CAP and selecting patients who required CXR. Inclusion of progression of symptoms among the other recommended criteria, namely, dyspnoea, fever > 38 degrees C, heart rate > 100 beats/min and abnormal chest findings, improved prediction of the incidence of CAP in general practice.

Chronic tumor necrosis factor-alpha treatment causes insulin resistance via insulin receptor substrate-1 serine phosphorylation and suppressor of cytokine signaling-3 induction in 3T3-L1 adipocytes.

Serine phosphorylation of insulin receptor substrate (IRS)-1 and the induction of suppressor of cytokine signaling 3 (SOCS3) is recently well documented as the mechanisms for the insulin resistance. However, the relationship between these two mechanisms is not fully understood. In this study, we investigated the involvement of SOCS3 and IRS-1 serine phosphorylation in TNFalpha-induced insulin resistance in 3T3-L1 adipocytes. TNFalpha transiently stimulated serine phosphorylation of IRS-1 from 10 min to 1 h, whereas insulin-stimulated IRS-1 tyrosine phosphorylation was inhibited only after TNFalpha treatment longer than 4 h. These results suggest that serine phosphorylation of IRS-1 alone is not the major mechanism for the inhibited insulin signaling by TNFalpha. TNFalpha stimulation longer than 4 h enhanced the expression of SOCS3 and signal transducer and activator of transcription-3 phosphorylation, concomitantly with the production of IL-6. Anti-IL-6 neutralizing antibody ameliorated suppressed insulin signaling by 24 h TNFalpha treatment, when it partially decreased SOCS3 induction and signal transducer and activator of transcription-3 phosphorylation. These results suggest that SOCS3 induction is involved in inhibited insulin signaling by TNFalpha. However, low-level expression of SOCS3 by IL-6 or adenovirus vector did not affect insulin-stimulated IRS-1 tyrosine phosphorylation. Interestingly, when IRS-1 serine phosphorylation was enhanced by TNFalpha or anisomycin in the presence of low-level SOCS3, IRS-1 degradation was remarkably enhanced. Taken together, both IRS-1 serine phosphorylation and SOCS3 induction are necessary, but one of the pair is not sufficient for the inhibited insulin signaling. Chronic TNFalpha may inhibit insulin signaling effectively because it causes both IRS-1 serine phosphorylation and the following SOCS3 induction in 3T3-L1 adipocytes.

Interleukin-1alpha inhibits insulin signaling with phosphorylating insulin receptor substrate-1 on serine residues in 3T3-L1 adipocytes.

Proinflammatory cytokines are recently reported to inhibit insulin signaling causing insulin resistance. IL-1alpha is also one of the proinflammatory cytokines; however, it has not been clarified whether IL-1alpha may also cause insulin resistance. Here, we investigated the effects of IL-1alpha treatment on insulin signaling in 3T3-L1 adipocytes. IL-1alpha treatment up to 4 h did not alter insulin-stimulated insulin receptor tyrosine phosphorylation, whereas tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and the association with phosphatidylinositol 3-kinase were partially inhibited with the maximal inhibition in around 15 min. IRS-1 was transiently phosphorylated on some serine residues around 15 min after IL-1alpha stimulation, when several serine kinases, IkappaB kinase, c-Jun-N-terminal kinase, ERK, and p70S6K were activated. Chemical inhibitors for these kinases inhibited IL-1alpha-induced serine phosphorylation of IRS-1. Tyrosine phosphorylation of IRS-1 was recovered only by the IKK inhibitor or JNK inhibitor, suggesting specific involvement of these two kinases. Insulin-stimulated Akt phosphorylation and 2-deoxyglucose uptake were not inhibited only by IL-1alpha. Interestingly, Akt phosphorylation was synergistically inhibited by IL-1alpha in the presence of IL-6. Taken together, short-term IL-1alpha treatment transiently causes insulin resistance at IRS-1 level with its serine phosphorylation. IL-1alpha may suppress insulin signaling downstream of IRS-1 in the presence of other cytokines, such as IL-6.

Roles of mTOR and JNK in serine phosphorylation, translocation, and degradation of IRS-1.

In 3T3-L1 adipocytes, insulin or anisomycin stimulated phosphorylation of IRS-1 at Ser(307) and Ser(636/639), both of which were partially reduced by the mTOR inhibitor, rapamycin, or the JNK inhibitor, SP600125, and were further inhibited by a combination of them. Interestingly, anisomycin-induced p70(S6K) phosphorylation was reduced by SP600125, while insulin-induced p70(S6K) phosphorylation was not. Furthermore, unlike insulin, anisomycin failed to elicit translocation or degradation of IRS-1. These results indicate that mTOR and JNK play roles in phosphorylating IRS-1 serine residues, and that insulin and anisomycin are different in terms of the relationship of activation between mTOR and JNK, and the effects on IRS-1 localization and stability.