Efficacy of mitiglinide and sitagliptin,alone or in combination,on postprandial excursion and glycemic variability assessed by continuous glucose monitoring: a post hoc analysis with single-day treatment

Objective: To compare the efficacy of mitiglinide and sitagliptin, alone or in combination, on postprandial excursion and glycemic variability assessed by continuous glucose monitoring (CGM) in a single-day treatment setting.

Methods: This was a post hoc analysis of a randomized crossover study comparing the efficacy of sitagliptin, mitiglinide and the combination of these two drugs. Twenty-four hour CGM was performed before and after a single-day treatment with each drug alone or in combination.

Results: Mean glucose levels were decreased in all groups. The average of three postprandial glucose excursions AUC (average of all three 4-h postprandial periods throughout the day) (AUCpp-average) decreased in the mitiglinide and combination treatment groups, but not in the sitagliptin group. The lowering effect on AUCpp-average was greater in patients given mitiglinide (–47 mg/dl, p < 0.001) or combination treatment (–66 mg/dl, p < 0.001) compared with sitagliptin alone (–18 mg/dl). The reduction in mean amplitude of glycemic excursion was greater with mitiglinide (–29.3 mg/dl, p < 0.001) and combination treatment (–28.3 mg/dl, p < 0.01) than with sitagliptin alone (–8.9 mg/dl).

Conclusions: Mitiglinide or combination treatment resulted in lower glycemic variability and postprandial glucose excursion than sitagliptin alone; however, the results of this single-day pharmacodynamics study cannot be generalized to a clinical setting.     

Acute retrobulbar optic neuritis with anti-myelin oligodendrocyte glycoprotein antibody-associated disease complicated with microscopic polyangiitis: A case report

Rationale:Anti-myelin oligodendrocyte protein antibody-associated disease (MOGAD) is a new disease entity with various clinical phenotypes. MOGAD often present with recurrent optic neuritis (ON), and it can also develop as a compartment of neuromyelitis optica spectrum disorder (NMOSD). Moreover, multiple autoantibodies such as an anti-myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) had been reported in the serum of patients with NMOSD.Patient concerns:We report an 86-year-old woman with a 2-year history of microscopic polyangiitis (MPA). The patient had a rapid loss of vision in her left eye. No abnormal findings were observed on her left fundus, and she tested negative for MPO-ANCA upon admission. However, anti-MOG antibodies were observed in the patient''s serum and cerebrospinal fluid.Diagnosis:A diagnosis of MOGAD complicated with MPA was made.Interventions:The patient received twice steroid pulse therapy and oral azathioprine as maintenance therapy.Outcomes:Her vision rapidly recovered, and no subsequent relapse was observed during the 8-month observation period.Conclusion:To the best of our knowledge, this is the first case of MOGAD complicated with MPA, and steroid pulse therapy and azathioprine therapy were effective for ON caused by MOGAD.     

Antimicrobial susceptibility of common pathogens isolated from postoperative intra-abdominal infections in Japan

The principle of empirical therapy for patients with intra-abdominal infections (IAI) should include antibiotics with activity against Enterobacteriaceae and Bacteroides fragilis group species. Coverage of Pseudomonas aeruginosa, Enterobacter cloacae, and Enterococcus faecalis is also recommended for hospital-associated IAI. A nationwide survey was conducted to investigate the antimicrobial susceptibility of pathogens isolated from postoperative IAI. All 504 isolates were collected at 26 institutions and referred to a central laboratory for susceptibility testing. Lower susceptibility rates to ciprofloxacin and cefepime were demonstrated in Escherichia coli. Among E. coli, 24.1% of strains produced extended-spectrum β-lactamase (ESBL). Carbapenems, piperacillin/tazobactam, cephamycins/oxacephem, aminoglycosides, and tigecycline had high activity against E. coli, including ESBL-producing isolates. Among E. cloacae, low susceptibility rates to ceftazidime were demonstrated, whereas cefepime retained its activity. P. aeruginosa revealed high susceptibility rates to all antimicrobials tested except for imipenem. Among B. fragilis group species, low levels of susceptibility were observed for cefoxitin, moxifloxacin, and clindamycin, and high susceptibility rates were observed for piperacillin/tazobactam, meropenem, and metronidazole. Ampicillin, piperacillin, and glycopeptides had good activity against E. faecalis. Imipenem had the highest activity against E. faecalis among carbapenems. In conclusion, we suggested the empirical use of antimicrobials with the specific intent of covering the main organisms isolated from postoperative IAI. Piperacillin/tazobactam, meropenem, or doripenem, are appropriate in critically ill patients. Combination therapy of cefepime (aztreonam in patients with β-lactam allergy) plus metronidazole plus glycopeptides, imipenem/cilastatin or cephamycins/oxacephem plus ciprofloxacin plus metronidazole are potential therapeutic options.     

Ventilatory efficiency during ramp exercise in relation to age and sex in a healthy Japanese population

BackgroundThe current understanding of ventilator efficiency variables during ramp exercise testing in the normal Japanese population is insufficient, and the responses of tidal volume (VT) and minute ventilation (V?E) to the ramp exercise test in the normal Japanese population are not known.MethodsA total of 529 healthy Japanese subjects aged 20–78 years underwent cardiopulmonary exercise testing using a cycle ergometer with ramp protocols. VT and V?E at rest, at anaerobic threshold, and at peak exercise were determined. The slope of V?E versus carbon dioxide (V?CO₂) (V?E vs. V?CO₂ slope), minimum V?E/V?CO₂, and oxygen uptake efficiency slope (OUES) were determined.ResultsFor males and females in their 20 s, peak VT (VTpeak) was 2192 ± 376 and 1509 ± 260 mL (p < 0.001), peak V?E (V?Epeak) was 80.6 ± 18.7 and 57.7 ± 13.9 L/min (sex differences p < 0.001), the V?E vs. V?CO₂ slope was 24.4 ± 3.2 and 25.7 ± 3.2 (p = 0.035), the minimum V?E/V?CO₂ was 24.2 ± 2.3 and 27.0 ± 2.8 (p < 0.001), and the OUES was 2452 ± 519 and 1991 ± 315 (p < 0.001), respectively. VTpeak and V?Epeak decreased with age and increased with weight and height. The V?E vs. V?CO₂ slope and minimum V?E/V?CO₂ increased with age, while conversely, the OUES decreased with age.ConclusionsWe have established the normal range of VT and V?E responses, the V?E vs. V?CO₂ slope, the minimum V?E/V?CO₂, and the OUES for a healthy Japanese population. Some of these parameters were influenced by weight, height, sex, and age. These results provide useful reference values for interpreting the results of cardiopulmonary exercise testing in cardiac patients.     

Changes in sodium-22 turnover and total body potassium in two-kidney, one-clip renovascular hypertension

Changes in sodium-22 turnover and total body potassium (TBK) were studied during acute (within 2 weeks after clipping) and chronic (12-14 weeks after clipping) phases in two-kidney, one-clip (2k, 1c) hypertensive rabbits by using a whole body counter. Sodium-22 injected intravenously was eliminated more rapidly in hypertensive rabbits than in controls. The biological half-life (BHL) of sodium-22 was shorter in hypertensive rabbits during both acute (p less than 0.05) and chronic phases (p less than 0.001). A significant negative correlation was obtained between the BHL of sodium-22 and blood pressure (r = -0.588, p less than 0.05) in hypertensive rabbits. TBK decreased significantly at the chronic phase in hypertensive rabbits (p less than 0.05), while TBK showed no significant change in controls. Serum sodium and potassium did not change during the observation period. Increased plasma aldosterone concentration was observed during the acute phase in hypertensive rabbits. These results suggested that sodium retention was not a major factor in the acute and chronic phases of 2k, 1c hypertension in rabbits and that pressure natriuresis could explain, at least in part, the lack of sodium retention. Furthermore, there appears to be a derangement in the intracellular potassium metabolism which may be associated with the maintenance rather than the development of hypertension.     

Preload-adjusted 2 wave-intensity peaks reflect simultaneous assessment of left ventricular contractility and relaxation.

BACKGROUND: The magnitudes of the first (WI1) and the second wave-intensity peak (WI2) during the ejection period can be used as indices of left ventricular (LV) contractility and relaxation, respectively. However, use of WI to characterize LV dp/dt and the end-diastolic volume (V ed) relationship may be more problematic, as WI may be affected by changes in preload. METHODS AND RESULTS: The LV pressure-volume data sets, consisting of 23 recordings obtained by the conductance method from 12 heart disease patients, were studied. End-systolic elastance (E es) and volume-axis-intercept (V0) were calculated with varying preload. Time constant of LV relaxation (tau), V ed, and WI were calculated from steady-state averaged data. The E es showed a weak correlation with WI1 (r = 0.46, p < 0.05) but a better correlation with preload-adjusted WI1 [WI1/V ed; r=0.86, WI1/V(ed)2; r = 0.92, WI1/(V ed - V0)2; r = 0.89, all p < 0.01]. Similarly, tau did not correlate with WI2 but did correlate with preload-adjusted WI2 [WI2/V ed; r = -0.73, WI2/V(ed) 2; r = -0.63, WI2/(V ed - V0)2; r = -0.78, all p < 0.01]. CONCLUSIONS: These data demonstrate the importance of preload-adjustment when using the WI index for simultaneous assessment of LV contractility and relaxation.     

Anti-monocyte chemoattractant protein 1 gene therapy attenuates experimental chronic pancreatitis induced by dibutyltin dichloride in rats

BACKGROUND: Monocyte chemoattractant protein 1 (MCP-1) is a member of the C-C chemokine family and exerts strong chemoattractant activity in monocytes, macrophages, and lymphocytes. Rat pancreatic fibrosis induced by dibutyltin dichloride (DBTC) is considered to be an appropriate chronic pancreatitis model histologically and enzymatically, as has demonstrated in a previous study. AIM: We examined the effect of human dominant negative inhibitor of MCP-1 (mutant MCP-1) on progression of chronic pancreatitis induced by DBTC in a rat model. METHODS: We used the experimental model of chronic pancreatitis induced by DBTC in rats. Mutant MCP-1 or empty plasmid at a dose of 50 microg/body weight was administrated into rat thigh muscles on days 4, 11, and 18 after administration of DBTC. On days 14 and 28, we evaluated the effect of mutant MCP-1 morphologically and biochemically. RESULTS: The mutant MCP-1 treated group inhibited early pancreatic inflammation and later pancreatic fibrosis histologically, and showed a decrease in serum MCP-1 concentration, intrapancreatic hydroxyproline, alpha-smooth muscle actin, and an increase in intrapancreatic amylase and protein content compared with the empty plasmid treated group. The mutant MCP-1 group also inhibited intrapancreatic mRNA expression of cytokines and chemokines. CONCLUSIONS: : Our findings suggest that monocyte/macrophage recruitment and the systemic MCP-1 signal pathway contribute to progression of chronic pancreatitis, and that blockade of MCP-1 may suppress the development of pancreatic fibrosis.     

Cardiopulmonary exercise variables in diastolic versus systolic heart failure

The response to cardiopulmonary exercise (CPX) in patients with heart failure (HF) with normal left ventricular (LV) ejection fractions (EFs) is not well characterized. To determine if CPX testing could distinguish between patients with HF with normal EFs (>50%; i.e., diastolic HF) and those with decreased EFs (> or =50%; i.e., systolic HF), CPX responses were compared between 185 patients with systolic HF (79% men, mean age 62.6 +/- 10.9 years) and 43 with diastolic HF (54% men, mean age 67.4 +/- 9.8 years) enrolled in a phase II multicenter clinical trial. All patients were evaluated with echocardiography and a standardized CPX test as part of the trial. CPX variables, including oxygen uptake at peak exercise (peak VO(2)) and the slope of the ventilation/carbon dioxide production ratio (VE/VCO(2)), were determined and analyzed by core laboratory personnel. Echocardiographic measurements included the LV EF, the E/A ratio, filling time, cavity volumes, right ventricular function, and mitral regurgitation. Patients in the diastolic HF group tended to be older (p <0.08), with more women (p <0.006) and with greater body mass indexes (p <0.02), than those in the systolic HF group. There was no significant difference in the use of beta blockers or the incidence of coronary artery disease. Patients with diastolic HF had decreased E/A ratios (0.9 +/- 0.4 vs 1.4 +/- 1.1, p <0.02, diastolic HF vs systolic HF) and increased filling times (30.4 +/- 3.2 vs 26.5 +/- 4.7 ms, p <0.01, diastolic HF vs systolic HF). No significant differences in peak VO(2) (14.4 +/- 1.9 vs 15.6 +/- 3.2 ml/kg/min, p = 0.06, diastolic HF vs systolic HF) were observed. The VE/VCO(2) ratios for the 2 groups were abnormal and comparable (32 2 +/- 7.5 vs 34.0 +/- 8.3, p = 0.3, diastolic HF vs systolic HF). In conclusion, the CPX response in patients with diastolic HF and systolic HF is markedly abnormal and indistinguishable with regard to peak VO(2) and ventilation despite marked differences in the LV EF.     

Depressed myocardial contractility in mitral stenosis--an analysis by force-length and stress-shortening relationships

To determine whether low ejection fraction (EF) in mitral stenosis (MS) is the result of depressed contractility or is mediated by other factors, left ventricular (LV) function was analyzed by force-length and stress-shortening relationships. Thirty patients without heart disease served as normal controls (Group 1). Forty-three patients with MS were divided into 2 subgroups: Group 2 (n = 19) had EF within one standard deviation of the mean of Group 1, and Group 3 (n = 24) had EF below it. Normal EF (Group 2) was associated with low preload (end-diastolic stress) and low afterload (end-systolic stress), and preload and afterload were in the normal range in patients with low EF (Group 3). A significant negative correlation was observed in the whole group of patients with MS between EF and end-systolic stress (Y = -0.14X + 72.8, r = -0.61, p less than 0.001), and a positive correlation between end-systolic stress and volume (Y = 1.39X + 65.4, r = 0.45, p less than 0.01). These observations suggest that systolic shortening and end-systolic volume of the left ventricle are in part governed by afterload in this disease. It is concluded that low EF of MS is not mediated by reduced preload or inappropriately elevated afterload, and contractility of the ventricle is mildly depressed in MS.