Safe and Simple Emergency Department Discharge Therapy for Patients with Type 2 Diabetes Mellitus and Severe Hyperglycemia

ObjectiveTo investigate the safety and effectiveness of 2 simple discharge regimens for use in patients with type 2 diabetes mellitus (DM2) and severe hyperglycemia, who present to the emergency department (ED) and do not need to be admitted.MethodsWe conducted an 8-week, open-label, randomized controlled trial in 77 adult patients with DM2 and blood glucose levels of 300 to 700 mg/dL seen in a public hospital ED. Patients were randomly assigned to receive glipizide XL, 10 mg orally daily (G group), versus glipizide XL, 10 mg orally daily, plus insulin glargine, 10 U daily (G + G group). The primary outcome was to maintain safe fasting glucose and random glucose levels of < 350 and < 500 mg/dL up to 4 weeks and < 300 and < 400 mg/ dL, respectively, thereafter and to have no return ED visits (responders).ResultsBaseline characteristics were similar between the 2 treatment groups. The primary outcome was achieved in 87% of patients in both treatment groups. The enrollment mean blood glucose values of 440 and 467 mg/dL in the G and G + G groups, respectively, declined by the end of week 1 to 298 and 289 mg/dL and by week 8 to 140 and 135 mg/dL, respectively. Homeostasis model assessment of b-cell function and early insulin response improved 7-fold and 4-fold, respectively, in responders at the end of the 8-week study.ConclusionSulfonylurea with and without use of a small dose of insulin glargine rapidly improved blood glucose levels and b-cell function in patients with DM2. Use of sulfonylurea alone once daily can be considered a safe discharge regimen for such patients and an effective bridge between ED intervention and subsequent follow-up. (Endocr Pract. 2009;15:696-704)     

Update on Inpatient Glycemic Control in Hospitals in the United States

ObjectiveTo provide data on glucose control in hospitals in the United States, analyzing measurements from the largest number of facilities to date.MethodsPoint-of-care bedside glucose (POC-BG) test results were extracted from 575 hospitals from January 2009 to December 2009 by using a laboratory information management system. Glycemic control for patients in the intensive care unit (ICU) and non-ICU areas was assessed by calculating patient-day-weighted mean POC-BG values and rates of hypoglycemia and hyperglycemia. The relationship between POC-BG levels and hospital characteristics was determined.ResultsA total of 49,191,313 POC-BG measurements (12,176,299 ICU and 37,015,014 non-ICU values) were obtained from 3,484,795 inpatients (653,359 in the ICU and 2,831,436 in non-ICU areas). The mean POC-BG was 167 mg/dL for ICU patients and 166 mg/dL for nonICU patients. The prevalence of hyperglycemia (> 180 mg/ dL) was 32.2% of patient-days for ICU patients and 32.0% of patient-days for non-ICU patients. The prevalence of hypoglycemia (< 70 mg/dL) was 6.3% of patient-days for ICU patients and 5.7% of patient-days for non-ICU patients. Patient-day-weighted mean POC-BG levels varied on the basis of hospital size (P < .01), type (P < .01), and geographic location (P < .01) for ICU and non-ICU patients, with larger hospitals (≥ 400 beds), academic hospitals, and US hospitals in the West having the lowest mean POC-BG values. The percentage of patient-days in the ICU characterized by hypoglycemia was highest among larger and academic hospitals (P < .05) and least among hospitals in the Northeast (P < .001).ConclusionHyperglycemia is common in hospitals in the United States, and glycemic control may vary on the basis of hospital characteristics. Increased hospital participation in data collection may support a national benchmarking process for the development of optimal practices to manage inpatient hyperglycemia. (Endocr Pract. 2011;17:853-861)     

Glycemic Control and Outcomes of Hospitalization in Noncritically Ill Patients With Type 2 Diabetes Admitted With Cardiac Problems or Infections

ObjectiveAlthough the importance of glycemic control is well established for patients with diabetes hospitalized for surgical problems, it has not been supported by clinical studies for patients with diabetes hospitalized on the medical floors.MethodsWe conducted a retrospective study of 378 patients with type 2 diabetes admitted for cardiac or infectious disease (ID) diagnosis between September 1, 2011, and August 1, 2012. Exclusion criteria included type 1 diabetes, admission to the intensive care unit (ICU), hospital stay shorter than 3 days, and daily glucocorticoid dose > 20 mg of methylprednisolone. The primary composite outcome included death during hospitalization, ICU transfer, initiation of enteral or parenteral nutrition, line infection, deep vein thrombosis, pulmonary embolism, rise in plasma creatinine by 1 or > 2 mg/dL, new infection, an infection lasting for more than 20 days, and readmission within 30 days and between 1 and 10 months after discharge.ResultsPatients were stratified by mean blood glucose (BG) level: group 1 had mean BG of < 180 mg/dL (n = 286; mean BG, 142 ± 23 mg/dL), whereas group 2 had mean BG levels > 181 mg/dL (n = 92; mean BG, 218 ± 34 mg/dL; P < .0001). Group 2 had a 46% higher occurrence of the primary outcome (P < .0004). The rate of unfavorable events was greater in cardiac and ID patients with worse glycemic control (group 2).ConclusionOur data strongly support a positive influence of better glycemic control (average glycemia < 180 mg/dL or 10 mmol/L) on outcomes of hospitaliza-tion in patients with type 2 diabetes. (Endocr Pract. 2014; 20:1303-1308)     

Characterizing Glucose Changes Antecedent to Hypoglycemic Events in the Intensive Care Unit

ObjectiveTo determine whether patterns of glucose changes before hypoglycemia vary according to the severity of the event.MethodsIn this retrospective analysis, point-ofcare blood glucose (POC-BG) data were obtained from the intensive care units (ICUs) of a convenience sample of hospitals that responded to a survey on inpatient diabetes management quality improvement initiatives. To evaluate POC-BG levels before hypoglycemic events, data from patients who experienced hypoglycemia during their time in the ICU were examined, and their glucose changes were assessed against a comparison group of patients who achieved a glycemic range of 80 to 110 mg/dL without ever experiencing hypoglycemia. Absolute glucose decrease, glucose rate of change, and glucose variability before hypoglycemic events (< 40, 40-49, 50-59, and 60-69 mg/ dL) were calculated.ResultsA total of 128 419 POC-BG measurements from 2942 patients in 89 ICUs were analyzed. Patients who experienced the most severe hypoglycemic episodes had the largest absolute drop in their glucose levels before the event (P < .001). The glucose rate of change before a hypoglycemic event increased with worsening hypoglycemia: mean (± standard deviation) glucose rate of change was-1.69 (± 2.98) mg/dL per min before an episode with glucose values less than 40 mg/dL, -0.56 (± 2.65) mg/dL per min before an episode with glucose values 60 to 69 mg/dL, but only -0.39 (± 0.70) for patients who attained a glucose range of 80 to 110 mg/dL without hypoglycemia (P < .001). Glucose variability before an event progressively increased with worsening biochemical hypoglycemia and was least among patients achieving glucose concentrations in the 80 to 110-mg/dL range without hypoglycemia (P < .001).ConclusionsAntecedent glucose change and variability were greater for patients who experienced hypoglycemia. If monitored, these patterns could potentially alert clinicians and help them take preventive measures. Further examination of how these parameters interact with other predisposing risk factors for hypoglycemia is warranted. (Endocr Pract. 2012;18:317-324)     

Influence Of Diabetes And Hyperglycemia On Duration Of Stay In Patients Hospitalized With Congestive Heart Failure

ObjectiveTo analyze the influence of diabetes and hyperglycemia on duration of stay in patients hospitalized with congestive heart failure (CHF).MethodsWe conducted a retrospective review of data for patients admitted during a 6-month period with CHF to a community teaching hospital in Baltimore, Maryland. Patients were divided into diabetic and nondiabetic groups, and patients with diabetes were stratified by mean fasting plasma glucose levels into the following groups: < 110 mg/dL, 110 to 180 mg/dL, and > 180 mg/dL. The primary outcome was duration of hospitalization. Other variables included sex, age, ejection fraction, admission glucose, brain natriuretic peptide, creatinine, and other comorbidities.ResultsThe study cohort consisted of 142 patients, 49% of whom had diabetes. The duration of hospitalization was 3.23 days in the patients with diabetes versus 3.11 days in those without diabetes (P = .875). Patients with diabetes were significantly younger (71.8 versus 76.6 years; P = .027) and had a higher baseline mean creatinine level (1.4 versus 1.2 mg/dL; P = .010). Patients with diabetes in the 110 to 180 mg/dL blood glucose group had shorter hospitalizations than did those in the < 110 mg/dL group (2.94 versus 3.41 days; P = .259). Only 9 patients had blood glucose levels > 180 mg/dL, and these patients had the longest hospitalizations (mean duration, 3.78 days).ConclusionThe prevalence of diabetes was higher in our study than in previously published studies of patients with CHF. Although patients with diabetes did not have significantly longer hospitalizations than those without diabetes, they were significantly younger and had higher baseline creatinine values. Hyperglycemia was an infrequent phenomenon among patients without diabetes. The patients with diabetes in the 110 to 180 mg/dL blood glucose group had shorter hospitalizations than did those in the < 110 mg/dL group, although this difference did not reach statistical significance. Many of the initial studies of tight glucose control were conducted in the surgical intensive care unit, but recently published evidence has raised doubt about applying these results to medical patients. We conclude that there may be no significant benefit in terms of duration of hospitalization in assigning patients with diabetes who have CHF exacerbations to tight glucose control regimens. A more liberal approach of maintaining glucose levels at 110 to 180 mg/dL may be acceptable. (Endocr Pract. 2008;14:691-696)     

Colesevelam Hydrochloride to Treat Hypercholesterolemia and Improve Glycemia in Prediabetes: A Randomized,Prospective Study

ObjectiveTo assess the effect of the bile acid sequestrant colesevelam hydrochloride in patients with hypercholesterolemia and prediabetes.MethodsIn this 16-week, randomized, double-blind study, adults with untreated prediabetes (2-hour postoral glucose tolerance test [OGTT] glucose ≥ 140 to 199 mg/dL, fasting plasma glucose [FPG] ≥ 110 to 125 mg/ dL, or both), low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL, and triglycerides < 500 mg/dL were randomly assigned to receive colesevelam (3.75 g/d) or placebo. The primary end point was percent change in LDL-C from baseline to week 16 with last observation carried forward. Secondary end points included change in FPG, hemoglobin A1c (A1C), and 2-hour post-OGTT glucose level from baseline to week 16 and attainment of LDL-C and FPG targets.ResultsIn total, 216 patients were randomized (colesevelam, 108; placebo, 108). In comparison with placebo, colesevelam significantly reduced LDL-C (mean treatment difference, -15.6%), non-high-density lipoprotein cholesterol (-9.1%), total cholesterol (-7.2%), apolipoprotein B (-8.1%) (P < .001 for all the foregoing), FPG (median, -2.0 mg/dL; P = .02), and A1C (mean, -0.10%; P = .02). Colesevelam did not significantly change 2-hour post-OGTT glucose (-1.9 mg/dL; P = .75) or high-density lipoprotein cholesterol (-0.5%; P = .80). In addition, colesevelam significantly increased triglyceride levels relative to placebo (median, 14.3%; P < .001). The proportion of patients achieving target levels with colesevelam versus placebo, respectively, was as follows: LDL-C < 100 mg/dL (29% versus 11%; P < .001), A1C < 6.0% (37% versus 25%; P = .05), FPG < 110 mg/dL (48% versus 56%; P = .97), and normalization of glucose (FPG < 100 mg/dL [40% versus 23%; P = .06]). Colesevelam had a weight-neutral effect and was well tolerated.ConclusionColesevelam is an option for managing the lipid profile and normalizing glucose levels in patients with hypercholesterolemia and prediabetes. Further study is warranted to determine whether colesevelam slows or prevents progression of prediabetes to type 2 diabetes. (Endocr Pract. 2010;16:617-628)     

An association among iron,copper, zinc,and selenium,and antioxidative status in dyslipidemic pediatric patients with glycogen storage disease types IA and III

Dyslipidemia in patients with glycogen storage disease types Ia (GSD Ia) and III (GSD III) does not lead to premature atherosclerosis. The aim of this study was to investigate the association among serum copper (Cu), zinc (Zn), iron (Fe), and selenium (Se) concentrations, and their carrier proteins: ceruloplasmin, albumin, and related antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), paraoxonase (PON), and arylesterase (ARYL)] in 20 GSD Ia and 14 III patients compared to age and sex matched 20 healthy subjects. Erythrocyte oxidative stress was measured by erythrocyte thiobarbituric acid reactive substances (eTBARSs). Hypertriglyceridemia [333 (36–890) mg/dL] in GSD Ia and hypercholesterolemia with elevated LDL-cholesterol [188 (91–313) mg/dL] and decreased HDL-cholesterol [32(23–58) mg/dL] levels in GSD III were found. Serum Cu, Fe, and Zn showed no significant differences between groups. However, Se 60 (54–94), 81 (57–127) μg/L, ceruloplasmin 21 (10–90), 27 (23–65) μg/L, and albumin 2.4 (1.7–5.1), 2.8 (1.8–4.06) g/dL levels were decreased in GSD Ia and III groups, respectively, in comparison with the controls [Se 110 (60–136) μg/L, ceruloplasmin 72 (32–94) μg/L, and albumin 4.4 (4–4.8) g/dL)]. In spite of high oxidative stress in erythrocyte detected by elevated eTBARS/Hb levels in GSD group [674.8 (454.6–948.2) for GSD Ia, 636.3 (460.9–842.1) for GSD III, and 525.6 (449.2–612.6)], the activities of CAT, SOD, ARYL, and PON in GSD patients were not different from the controls. GPx activity was decreased in GSD Ia [3.7 (1.8–7.1) U/mL] and GSD III [4.2 (2.2–8.6) U/mL] compared with healthy controls [7.1 (2.9–16.2) U/mL].In conclusion, this study supplied the data for trace elements, their carrier, and antioxidative enzymes in the patients with GSD Ia and III. The trace elements and anti-oxidative enzyme levels in GSD patients failed to explain the atherosclerotic escape phenomenon reported in these patients.     

High-Dose Glucocorticoid Treatment Does Not Induce Severe Hyperglycemia in Young Patients with Autoimmune Diseases by Cgms

Objective: High-dose glucocorticoids (HDG) are used in the treatment of autoimmune diseases. Glucocorticoids-induced hyperglycemia (GIH) is often described in elderly patients. In young patients with autoimmune diseases, however, the risk for GIH has not been well characterized.Methods: We recruited 24 inpatients (median age, 32 years; interquartile range, 25–42) with exacerbations of autoimmune diseases, receiving 1 to 2 mg/kg/day prednisone or equivalent methylprednisone. Fourteen subjects were naïve to glucocorticoids (group 1) and 10 subjects were on glucocorticoid maintenance (≤15 mg/day prednisone at least 3 months) (group 2) prior to HDG. All subjects were monitored by continuous glucose monitoring system (CGMS) for 3 days.Results: GIH developed in 21 (91%) subjects, 11/13 in group 1 and 10/10 in group 2. The main peak of glucose excursion (128.7 ± 6.4 mg/dL, group 1; 143.9 ± 10.0 mg/dL, group 2) occurred at 2 to 3 pm. Another peak occurred before sleep. Two-hour mean postprandial glucose levels were normal in both groups: breakfast, 105.0 ± 28.4 versus 125.6 ± 24.4 mg/dL, P = .065; lunch, 115.7 ± 21.1 versus 135.9 ± 29.0 mg/dL, P = .082; dinner, 122.8 ± 18.5 versus 137.8 ± 26.4 mg/dL, P = .144 in groups 1 and 2, respectively. There was a positive association between pretreatment hemoglobin A1C and peak glucose levels (P<.0001). Notably, 35% of our subjects experienced early morning hypoglycemia (65.2 ± 2.8 mg/dL).Conclusion: In hospitalized young patients with auto-immune diseases, CGMS data revealed that short-term consistent HDG treatment induced mild hyperglycemia, peaking in the early afternoon and before sleep. Early morning hypoglycemia was found in 35%.Abbreviations: A1C = hemoglobin A1C; AUC = the area under the curve; BG = blood glucose; BMI = body mass index; CGMS = continuous glucose monitoring system; DM = diabetes mellitus; FBG = fasting blood glucose; GA = glycated albumin; GCs = glucocorticoids; GIH = glucocorticoids-induced hyperglycemia; HDG = high-dose glucocorticoids; HOMA-IR = Homeostasis Model Assessment-Insulin Resistance; IG = interstitial glucose; IQR = interquartile range; PUMCH = Peking Union Medical College Hospital; SLE = systemic lupus erythematosus     

Prevalence of Anemia Among Unselected Adults with Diabetes Mellitus and Normal Serum Creatinine Levels

ObjectiveTo determine the prevalence of anemia in a cohort of patients with diabetes and normal serum creatinine concentration in a primary care clinic.MethodsWe undertook a retrospective cohort study, comparing adult patients who had diabetes, with or without anemia. Patients older than 18 years who had diabetes were identified by using the computerized database for the years 2006 and 2007 in a primary care clinic. Patients with hemoglobin levels < 13.7 g/dL (men < 60 years old), ≤ 13.2 g/dL (men ≥ 60 years old), or < 12.2 g/dL (women) with no known cause of anemia were identified and compared with patients who had diabetes but not anemia. All patients had normal serum creatinine levels (men ≤ 1.5 mg/dL and women ≥ 1.4 mg/dL).ResultsOf 594 eligible patients with diabetes, 192 (32%) had anemia. Older age, higher serum urea and creatinine levels, lower estimated glomerular filtration rates, and reduced serum iron levels were more common in the patients with diabetes who had anemia than in those without anemia. The prevalence of anemia was higher in patients treated with “glitazones,” insulin, and angiotensin receptor blockers in comparison with those receiving other orally administered hypoglycemic medications. In stepwise logistic regression analysis, only serum creatinine, age, and use of glitazones retained statistical significance.ConclusionIn a community clinic, the prevalence of anemia in unselected patients with diabetes and normal serum creatinine levels was 32%. Factors associated with anemia were older age, higher serum creatinine levels, and use of glitazone therapy. (Endocr Pract. 2009;15:714-719)     

Diabetes Status and Race are Associated With Cardiovascular Risk Markers in Obese Adolescents

ObjectiveThe objective of this study was to evaluate differences in cardiovascular disease (CVD) risk markers in obese adolescents based on diabetes status and race in order to improve risk-reduction intervention strategies.MethodsThis was a retrospective, cross-sectional study of obese adolescents, age 10 to 21 years, who were evaluated at Children’s of Alabama between 2000 and 2012. Subjects were classified by glycated hemoglobin (HbA_1c) as having normoglycemia, prediabetes, or type 2 diabetes mellitus (T2DM).ResultsThere were a total of 491 African American (AA) or Caucasian American (CA) subjects. Body mass index was not different between HbA_1c and racial groups. Compared to subjects with normoglycemia or prediabetes, subjects with T2DM had higher levels of total cholesterol (TC) (178.6 ± 43.8 mg/dL vs. 161.5 ± 32.5 mg/dL vs. 162.4 ± 30.6 mg/dL; P < .0001) and low-density-lipoprotein cholesterol (107.4 ± 39.2 mg/dL vs. 97.0 ± 31.0 mg/dL vs. 97.5 ± 26.9 mg/dL; P = .0073). Compared with AA subjects, CA subjects had lower high-density-lipoprotein cholesterol (HDL-C) levels (40.4 ± 10.4 mg/dL vs. 44.3 ± 11.9 mg/dL; P = .0005) and higher non-HDL-C levels (129.6 ± 36.2 mg/dL vs. 122.5 ± 37.5 mg/dL; P = .0490). Of the characteristics studied, HbA_1c had the most significant positive association with dyslipidemia and was strongly correlated with both TC (β, 4.21; P < .0001) and non-HDL-C (β, 4.3; P < .0001).ConclusionObese adolescents with T2DM have more abnormal lipoprotein profiles than those with normoglycemia or prediabetes. Obese CA adolescents have more abnormal lipids than obese AA adolescents. HbA_1c was the characteristic most highly associated with abnormal lipoprotein profiles in our subjects. Our results show that CVD risk markers in obese adolescents vary by race and HbA_1c concentration. (Endocr Pract. 2015;21:165-173)     

Elevated Fructosamine Levelsin Acquired Immunodeficiency Syndrome

ObjectiveTo investigate whether the mechanism of increased glycation in acquired immunodeficiency syndrome (AIDS) is due to an alteration in a circulatory plasma enhancer.MethodsWe assessed glycation of serum protein and hemoglobin in patients with AIDS without altered carbohydrate metabolism. Fasting concentrations of glucose, ethanol, vitamin E, fructosamine, hemoglobin, hemoglobin A1c (A1C), and partial pressure of alveolar oxygen (Pao₂) were determined in 50 men with AIDS and in 25 age-matched healthy men in whom normal glucose tolerance was established by oral glucose tolerance tests.ResultsFasting serum glucose was not significantly different between the men with AIDS (87 ± 4 mg/dL) and the healthy male volunteers (84 ± 6 mg/dL); however, A1C (6.9 ± 0.2%) and serum fructosamine levels (288 ± 15 μmol/L) were significantly higher (P < .01) in the patients with AIDS than in the normal subjects (A1C, 5.6 ± 0.1%; fructosamine, 204 ± 14 μmol/L). Moreover, both A1C and fructosamine concentrations were significantly higher (P < .01) in the patients with AIDS than in the normal subjects divided into subgroups on the basis of fasting plasma glucose concentrations (70 to 79 mg/dL, 80 to 89 mg/dL, and 90 to 99 mg/dL). None of the study participants had anemia (hemoglobin < 12 g/dL) or hypoxia (Pao₂ < 95 mm Hg), and serum ethanol was undetectable. Furthermore, vitamin E concentrations were not significantly different between the patients with AIDS (25 ± 3 mg/L) and the normal subjects (22 ± 4 mg/L).ConclusionOn the basis of this study, glycation of some circulating proteins appears to be enhanced in AIDS and may be induced by an undetermined plasma enhancer, inasmuch as known circulating factors promoting glycation were absent. (Endocr Pract. 2008;14:686-690)     

The hypoglycemic activity of Euclea undulata Thunb. var. myrtina (Ebenaceae) root bark evaluated in a streptozotocin–nicotinamide induced type 2 diabetes rat model

The hypoglycemic activity of a crude acetone extract of the root bark of Euclea undulata var. myrtina was evaluated in a streptozotocin–nicotinamide induced type 2 diabetes rat model after positive results were obtained by in vitro screening of glucose utilization by C2C12 myocytes, 3T3-L1 preadipocytes and Chang liver cells and alpha-glucosidase inhibition. Thirty male Wistar rats were used for the experiment. Type 2 diabetes was induced by a single intraperitoneal injection of streptozotocin and administration of nicotinamide 15 min after. Animals exhibiting fasting glucose levels of 140–200 mg/dl after 7 days were screened as type 2 diabetes. Extract was administered for 21 days orally at a concentration of 50 mg/kg and 100 mg/kg respectively. Glibenclamide (1 mg/kg) was used as positive control. On day 21, blood lipid profiles and body weight were determined by using standard enzymatic colorimetric kits before the rats were sacrificed by cervical decapitation. The crude acetone extract of E. undulata root bark at a concentration of 100 mg/kg body weight significantly lowered fasting blood glucose levels as well as elevated cholesterol and triglyceride levels to near normal without any weight gain. The results indicate that the crude acetone root bark extract of E. undulata exhibit antidiabetic activity in type 2 induced diabetic rats. It confirms the in vitro screening results as well as its use in the treatment of diabetes by traditional healers and herbalists in southern Africa.     

A comparative evaluation of efficacy of chemotherapy,immunotherapy and immunochemotherapy in visceral leishmaniasis-an experimental study

Visceral leishmaniasis (VL) represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. Ninety per cent of VL cases occur in five countries namely Bangladesh, India, Nepal, Sudan and Brazil. No licensed vaccine is available till date against any form of leishmaniasis. High toxicity and increasing resistance to the current chemotherapeutic regimens have further complicated the situation in VL endemic regions of the world. To combat this situation, immunochemotherapy can provide a solution. In the present study, an attempt has been made to assess the in vivo antileishmanial efficacy of chemotherapy, immunotherapy and immunochemotherapy with the use of a first generation antigen Killed Leishmania donovani (KLD) along with a standard drug sodium stibogluconate (SSG) and a newly tested antileishmanial cisplatin. Inbred BALB/c mice were infected with 10⁷ promastigotes/0.1 ml of Leishmania donovani. A month after infection, these animals were given specific immunotherapy (KLD/KLD + MPL-A) or chemotherapy (SSG/cisplatin) or immunochemotherapy (SSG + KLD/SSG + KLD + MPL-A/cisplatin + KLD/cisplatin + KLD + MPL-A). Animals were sacrificed on 1, 15 and 30^th day post treatment. The efficacy of these combinations was assessed in terms of parasite load and by immunological investigations. Infected mice and normal mice served as controls. Results showed that combination of drug and KLD significantly reduced the parasite burden, enhanced the DTH (Delayed Type Hypersensitivity) responses, showed increased levels of IgG2a and decreased levels of IgG1 as compared to mice given chemotherapy or immunotherapy alone. Further maximum protection was provided by SSG + KLD + MPL-A and it was most effective as depicted by 98.5% reduction in parasite load, a potent increase in IFN-γ levels and a significant decrease in IL-10 and IL-4 levels thus skewing the immune response towards Th1 type. Hence, immunochemotherapy is more effective in control of VL in comparison to chemotherapy or immunotherapy.     

Tratamiento y evolución del síndrome de tormenta de citoquinas asociados a infección por SARS-CoV-2 en pacientes octogenarios

IntroductionCytokine storm syndrome (CTS) is a serious complication of patients with SARS-CoV-2 infection. Treatment and evolution in octogenarians are not well defined. Our objective is to describe its clinical characteristics, the treatments and its clinical evolution.Patients and methodRetrospective observational study of consecutive patients admitted in the period between March 23 and April 12, 2020 with confirmed SARS-CoV-2 infection, with pneumonia by radiological study or chest tomography, whith STC criteria and who received treatment. We classified patients as those who received only glucocorticoid (GC) pulses, or GC and tocilizumab pulses. We determined serum levels of ferritin, CRP and D-dimers. The final variable was survival.Results21 patients, (80-88 years). The mean ferritin was 1056 microg/L (317-3,553), CRP 115.8 mg/dL (22-306) and D-dimers 2.9 m/L (0.45-17.5). All patients received GC pulses and in 2 cases simultaneously tocilizumab. The mean follow-up time was 13.7 days (8-21). The overall mortality was 38.1% (8/21 patients). The 2 patients who received tocilizumab died. The deceased had significantly higher levels of ferritin (1,254 vs. 925 microg/L; P = .045) and CRP (197.6 vs. 76 mg / dL; P = .007). At the end of the follow-up, a decrease in the biochemical parameters was observed with ferritin of 727 microg/L, CRP of 27 mg/dl and D-dimers of 1.18 mg/L. In 13/21 patients (61.9%), the CTS was controlled without the need to add other treatments.ConclusionsSTC mortality from SARS-CoV-2 is high despite treatment. A greater inflammatory response was associated with a higher mortality. Although it seems that the early use of GC pulses could control it, and the use of other treatments such as tocilizumab shouldo be, with the study design and its limitations, this conclusion cannot be stablished.     

Effect of dietary cobalt supplementation on plasma and rumen metabolites in Mehraban lambs

Two experiments were conducted to study the effects of different levels of dietary cobalt on performance, plasma and rumen metabolites and nutrient digestibility in Mehraban male lambs. Experiment 1: 28, 8–9-month-old lambs were randomly divided into four groups. Animals were fed a basal diet containing 0.088 mg Co/kg DM and were supplied with 0 (control), 0.25, 0.50, or 1.00 mg Co/kg DM as reagent grade CoSO₄·7H₂O. The experiment lasted for 70 days. Experiment 2: four lambs from each group in Experiment 1 were randomly allocated to the individual metabolic crates to measure the effects of dietary Co on nutrient digestibility. Final body weight, average daily gain and gain efficiency were higher (p < 0.05) in the group supplemented with 0.50 mg Co/kg DM compared to other groups. Plasma glucose and vitamin B₁₂ concentrations increased (p < 0.05) at all levels of Co supplementation on day 68 of the experiment and for vitamin B₁₂ were higher (p < 0.05) at 0.50 and 1.00 mg Co/kg DM compared to 0.25 mg Co/kg DM. There was no significant difference among treatments for TVFA and ruminal fluid pH. Digestibility of dry matter, organic matter, crude protein and neutral detergent fiber increased (p < 0.05) by Co supplementation, but did not differ among Co supplied treatments. The obtained results showed that lambs fed the control diet containing 0.088 mg Co/kg DM had a reduced appetite and gained less than the supplemented animals, suggesting that the level of 0.088 mg Co/kg DM was inadequate for normal growth of Mehraban male lambs, and a total level of 0.58 mg Co/kg DM might be optimum level for enhancing performance.     

Renal protective effects of arjunolic acid in a cisplatin-induced nephrotoxicity model

Cisplatin is the first platinum-containing anti-cancer drugs. Cisplatin notable side effect of nephrotoxicity limits its use in clinic. Meanwhile, arjunolic acid possesses anti-inflammatory properties and plays protective roles against chemically induced organ pathophysiology. This study was conducted to find out whether arjunolic acid could attenuate kidney damage in rats, and to elucidate its possible mechanism of action. Fifty rats were treated with cisplatin (10 mg/kg) in the presence/absence of 100 or 250 mg/kg arjunolic acid. Arjunolic acid is given 1 h after cisplatin. Morphological changes were assessed in kidney sections stained with Hematoxylin/Eosin and Masson Trichrome. Kidney samples were used for measurements of transforming growth factor (TGF)-β1 and its type 1 receptor (TGF-βR1), tumor necrosis factor (TNF)-α and interleukin (IL)-1β by ELISA. Gene expression NFκB was determined by real time-PCR. Kidney tissue apoptosis was assessed by measuring the activities of caspase-3/8/9. The renal protective effect of arjunolic acid was confirmed by approximately normal appearance of renal tissue and the relatively unaffected serum creatinine and urea levels. Furthermore, arjunolic acid showed dose dependent reduction in cisplatin-induced elevation in renal levels of TGF-βR1, TGF-β1, TNF-α, IL-1β and caspases. These findings demonstrated that arjunolic acid attenuates cisplatin nephrotoxicity either indirectly by enhancing body antioxidant activity or directly through several mechanisms, including inhibition of pro-inflammatory cytokines, blocking activation of TGF-β1, and anti-apoptotic effects.     

Changes of ginsenosides in Korean red ginseng (Panax ginseng) fermented by Lactobacillus plantarum M1

To obtain microorganisms for the microbial conversion of ginsenosides in red ginseng powder (RGP), Lactobacillus species (M1–M4 and P1–P4) were isolated from commercial ginseng products. Strain M1 was determined to be L. plantarum by 16S rRNA sequencing. Red ginseng powder (RGP) fermented by L. plantarum M1 had a high total content of ginsenosides (142.4 mg/g) as compared to the control (121.8 mg/g). In particular, the ginsenoside metabolites Rg3, Rg5, Rk1, Compound K (CK), Rh1, and Rg2 showed a high level in the fermented RGP (65.5 mg/g) compared to the control (32.7 mg/g). During fermentation for 7 days, total sugar content decreased from 8.55 mg/g to 4 mg/g, uronic acid content reached its maximum (53.43 μg/g) at 3 days, and total ginsenoside content increased to 176.8 mg/g at 4 days. In addition, ginsenoside metabolites increased from 38.0 mg/g to 83.4 mg/g at 4 days of fermentation. Using everted instestinal sacs of rats, the fermented red ginseng showed a high transport level (10.3 mg of polyphenols/g sac) compared to non-fermented red ginseng (6.67 mg of polyphenols/g sac) after 1 h. These results confirm that fermentation with L. plantarum M1 is very useful for preparing minor ginsenoside metabolites while being safe for foods.     

Variation of quercetin glycoside derivatives in three onion (Allium cepa L.) varieties

The aim of this study was to quantify the contents of individual quercetin glycosides in red, yellow and chartreuse onion by High Performance Liquid Chromatography (HPLC) analysis. Acid hydrolysis of individual quercetin glycosides using 6 M hydrochloric acid guided to identify and separate quercetin 7,4′-diglucoside, quercetin 3-glucoside, quercetin 4′-glucoside, and quercetin. The contents of total quercetin glycosides varied extensively among three varieties (ranged from 16.10 to 103.93 mg/g DW). Quercetin was the predominant compound that accounted mean 32.21 mg/g DW in red onion (43.6% of the total) and 127.92 mg/g DW in chartreuse onion (78.3% of the total) followed by quercetin 3-glucoside (28.83 and 24.16 mg/g DW) respectively. Quercetin 3-glucoside levels were much higher in yellow onion (43.85 mg/g DW) followed by quercetin 30.08 mg/g DW. Quercetin 4′-glucoside documented the lowest amount that documented mean 2.4% of the total glycosides. The varied contents of glycosides present in the different onion varieties were significant.     

Association Between Blood Glucose Levels and Development of Candidemia in Hospitalized Patients

ObjectiveTo examine the relationship between blood glucose levels in hospitalized patients and the risk of occurrence of candidemia.MethodsWe undertook a retrospective review of medical records and hospital computerized database information to compare blood glucose levels in 48 patients with nosocomial candidemia and 144 contemporaneous matched control subjects without candidemia at a tertiary teaching hospital.ResultsThe proportions of days (for patients with candidemia versus control subjects without candidemia) with blood glucose levels ≥ 100 mg/dL (293 of 325 [90%] versus 849 of 1,007 [84%]; P = .009), ≥ 140 mg/dL (184 of 325 [57%] versus 507 of 1,007 [50%]; P = .049), and ≥ 200 mg/dL (80 of 325 [25%] versus 163 of 1,007 [16%]; P = .001) were significantly higher during the 7 days preceding the diagnosis of candidemia than during a 7-day period of hospitalization of control subjects. Blood glucose levels exceeding 200 mg/dL for 4 or more days of the week preceding the diagnosis of candidemia were significantly associated with its development (P = .04; odds ratio, 2.44; and 95% confidence interval, 1.01 to 5.94).ConclusionInpatient hyperglycemia is an important—and potentially modifiable—risk factor for development of nosocomial candidemia. These findings have implications for innovative infection control strategies that focus on glycemic control. (Endocr Pract. 2009;15:111- 115)