Effect of Pluchea lanceolata bioactives in LPS-induced neuroinflammation in C6 rat glial cells

Neuroinflammation plays a significant role in various chronic and acute pathological conditions of the central nervous system. In the Indian system of medicine, Pluchea lanceolata is used to treat the neurological disorders. We investigated the effect of major pentacyclic triterpene and its naturally occurring acetate derivative isolated from P. lanceolata on lipopolysaccharide (LPS)-stimulated neuroinflammatory condition associated to inflammatory cytokine production in rat astrocytoma cell line (C6). The log concentration dependence of Pluchea bioactive taraxasterol (Tx) significantly (p?<?0.05) attenuates the release of pro-inflammatory cytokines, such as TNF-α, IFN-γ, and IL-6, while its in situ produced acetyl derivative, i.e., taraxasterol acetate (TxAc), did not inhibit the LPS-induced IL-6 production at lower concentration (p?>?0.05). Surflex-Dock molecular modeling study was performed to simulate the binding capacity of compounds into the active site of the TNF-α (2AZ5), tumor protein P53 (2VUK), and NF-kappa-B (1RAM). The differential inhibition of cytokines by Tx and TxAc was further confirmed by high docking scores showing the high affinity to target proteins. Findings of the study demonstrated the comparatively greater role of Pluchea triterpene than its in situ produced acetate derivate in neuroinflammation-associated disorders.     

Scrub typhus: Clinical spectrum and outcome

Background:

Scrub typhus is one of the differential diagnoses for fever with thrombocytopenia. ARDS associated with Scrub typhus has high morbidity and mortality.

Aims:

To evaluate clinical features, lab values, and outcome in patients with scrub typhus and comparison in patients with or without ARDS.

Methods:

A prospective observational study was conducted on 109 patients with febrile illness and thrombocytopenia during a period of 12 months. All 109 patients were tested with both Immune-chromatography test and Weil felix test. Patients having either Immune-chromatography test/Weil felix test positive have been included and considered as scrub typhus positive whereas negative for both Immune-chromatography and Weil felix test were excluded. Clinical features, lab parameters, and outcome were evaluated in all patients with scrub typhus. Statistical analysis used in this study was T-test.

Results:

Among 58 patients who were included (After exclusion of 51 patients among total of 109 patients) 34 patients had no ARDS and 24 patients had ARDS. The clinical feature like dyspnoea, cough, low blood pressure (MAP<65 mmHg), IVC collapsibility (by ultrasound) and laboratory parameters like decreased Hemoglobin, Hematocrit, Serum albumin, and increased serum creatinine, serum total bilirubin, SGOT, SGPT, LDH, CPK, and serum lactate were statistically significant (P < 0.0001) in scrub typhus patients group with ARDS. The higher titers of Weil-felix can be correlated with more severe form of disease according to our observation. All 34 Scrub typhus patients without ARDS recovered completely. Among 24 Scrub typhus patients with ARDS, 22 patients recovered, and 2 patients died.

Conclusion:

Scrub typhus is an important differential diagnosis in a patients having fever with thrombocytopenia. Scrub typhus associated with ARDS has high morbidity and mortality. Early diagnosis and treatment with doxycycline can prevent the occurrence of ARDS     

Evaluation of wound healing activity of root of Mimosa pudica

Ethno pharmacological relevance

Mimosa pudica, commonly known as touch-me-not, is used in folklore medicine in arresting bleeding and in skin diseases.

Aim

There was no scientific evidence justifying the use of Mimosa pudica, therefore the present study was aimed at evaluation of wound healing activity of the plant.

Materials and methods

In the present study the roots of Mimosa pudica were studied for wound healing activity by incorporating the methanolic and the total aqueous extract in simple ointment base B.P. in concentration of 0.5% (w/w), 1% (w/w) and 2% (w/w). Wound healing activity was studied in three types of model in rats viz. excision, incision and estimation of biochemical parameter. In case of the excision wound model wound contraction and period of epithelization was studied while in incision wound model was evaluated by determining tensile strength and hydroxyproline content in the scab.

Results

Treatment of wound with ointment containing 2% (w/w) the methanolic and 2% (w/w) the total aqueous extract exhibited significant (P < 0.001) wound healing activity. The methanolic and total aqueous extracts were analyzed for total phenols content equivalent to Gallic acid. The content of total phenols was 11% (w/w) and 17% (w/w) in methanolic and total aqueous extract respectively.

Conclusion

The methanolic extract exhibited good wound healing activity probably due to phenols constituents.     

Evaluation of antiasthmatic activity of Clitoria ternatea L. roots

Aim of study

Clitoria ternatea L. (Family: Fabaceae) is being used in traditional medicine for the treatment of severe bronchitis and asthma. So the aim of study was to evaluate antiasthmatic activity of ethanol extract of Clitoria ternatea roots.

Materials and methods

In the present study ethanol extract of Clitoria ternatea root (ECTR) was evaluated for preliminary phytochemical screening, acute toxicity studies and antiasthmatic activity using milk induced leucocytosis and eosinophilia in mice, egg albumin induced mast cell degranulations in rats and passive cutaneous anaphylaxis in rats at doses (100-150 mg/kg ip).

Results

The results of present investigation showed that the LD₅₀ of ECTR is more than 1300 mg/kg. ECTR significantly decreases milk induced leucocytosis and eosinophilia, protects egg albumin induced degranulations of mast cells in mice and inhibits area of blue dye leakage in passive cutaneous anaphylaxis in rats at (100-150 mg/kg, i.p.). Phytochemical studies observed the presence of steroids, saponin, flavonoids, and glycosides.

Conclusion

The present investigation concludes that the antiasthmatic activity of ECTR may be due to the presence of flavonoids or saponins.     

Prognostic significance of the distortion of terminal portion of QRS complex on admission electrocardiogram in ST segment elevation myocardial infarction

BackgroundECG on admission has been used in predicting prognosis and risk stratification in ST segment elevation acute myocardial infarction (STEMI).ObjectiveTo analyze the admission ECG in STEMI based on abnormality observed in terminal portion of QRS and its correlation to hospital mortality.Method160 consecutive patients of STEMI were classified into subjects without (Group I) and with distortion of terminal QRS (Group II), Pattern A – Emergence of J point at ≥50% of the R wave amplitude in leads with qR configuration or Pattern B – Absence of the S waves, in leads with Rs configuration in two consecutive leads.ResultsOut of 160 patients of STEMI, 69 (43.1%) had distortion of QRS. There were 13 deaths (8.1%). Hospital mortality was found to be significantly more in subjects with distortion than those without (15.9% V/S 2.1%, p < 0.001). Patients with QRS distortion tended to have larger infarction as assessed by Killip class on admission (p < 0.05), anterior location of MI (p < 0.01) and presence of significant Q waves in leads with ST segment elevation (p < 0.0001).With multiple logistic regression analysis using hospital mortality as a dependent variable and all studied risk factors as independent variables, QRS distortion on admission ECG was the only variable found to be statistically significant (Adjusted OR = 7.161, p < 0.05).ConclusionECG on admission is a simple, cheap, universally available investigation that can predict the short term prognosis in STEMI and would help in deciding which patients should go for other myocardial revascularization procedures.     

QT dispersion and early arrhythmic risk in acute myocardial infarction

BACKGROUND: This study sought to find out QT dispersion in healthy individuals and patients of acute myocardial infarction and to find correlation, if any, between QT dispersion and the incidence of ventricular arrhythmias in acute myocardial infarction. METHODS AND RESULTS: QT dispersion was calculated from a 12-lead electrocardiogram in 100 patients of acute myocardial infarction admitted in intensive coronary care unit and 100 age- and sex-matched healthy individuals. In patients of acute myocardial infarction, QT dispersion was calculated on admission, 24 hours after admission and at the time of discharge from intensive coronary care unit. Average QT dispersion in acute myocardial infarction was found to be significantly higher on admission (76.4 +/- 18.3 ms), 24 hours after admission (62.88 +/- 17.52 ms) and at the time of discharge from intensive coronary care unit (51.79 +/- 16.79 ms) than in healthy individuals (29.76 +/- 6.06 ms; p<0.05). QT dispersion was found to be significantly increased in patients of acute myocardial infarction with ventricular arrhythmias (82.06 +/- 16.86 ms) than in those without (66.75 +/- 16.28 ms; p<0.01). Patients of acute myocardial infarction with ventricular tachycardia or ventricular fibrillation had significantly increased QT dispersion (96.25 +/- 15.97 ms) than those who had only ventricular premature beats (80 +/- 15.04 ms; p<0.01). QT dispersion was found to be significantly greater in patients with anterior wall acute myocardial infarction (79.80 +/- 18.19 ms) than in those with inferior wall acute myocardial infarction (71.9 +/- 17.48 ms; p<0.05). At the time of discharge from intensive coronary care unit no statistically significant difference was found in QT dispersion in those who received thrombolysis (51.58 +/- 16.05 ms) and those who did not (48.18 +/- 14.68 ms; p>0.05). QT dispersion was found to be significantly higher in those who died (88.66 +/- 15.97 ms) than in those who survived (74.23 +/- 17.91 ms; p<0.05). QT dispersion was significantly higher in ventricular arrhythmic deaths (97.14 +/- 17.04 ms) than those who had non-arrhythmiac deaths (81.25 +/- 11.25 ms; p<0.05). CONCLUSIONS: Interlead QT variation and its measure as QT dispersion challenges our current approach to the electrocardiographic assessment of arrhythmic risk. QT dispersion may provide a potentially simple, cheap, non-invasive method of measuring underlying dispersion of ventricular excitability.     

Association of apolipoproteins C3 and E with metabolic changes in HIV-infected adults treated with a protease-inhibitor-containing antiretroviral therapy

OBJECTIVE: To examine the relationship between plasma levels of apolipoproteins C3 (APOC3) and E (APOE) and the presence of lipid and carbohydrate metabolism abnormalities or clinical signs of lipodystrophy in HIV-1-infected patients started with a protease-inhibitor-containing antiretroviral therapy. METHODS: The Aproco (Antiproteases Cohort) Study enrolled 1,181 HIV-1-infected adults in 47 French healthcare centres from May 1997 to June 1998. From December 1998 through July 1999, the APROCO-Metabolic Complications (APROCO-MC) cross-sectional study was performed at the month 20 visit for those patients enrolled in 1997 and at the month 12 visit for those enrolled in 1998. The current analysis presents results from a subset of patients who had undergone additional tests to measure APOC3 and APOE in order to study their relationship with metabolic syndrome (n=157) and abnormal results in an oral glucose tolerance test (n=135). RESULTS: Increases in triglycerides and non-high-density lipoprotein (HDL) cholesterol were associated with significantly higher levels of APOC3, in both Lp B (lipoproteins containing apolipoprotein B) and Lp non-B (lipoproteins free of apolipoprotein B), and a significant higher level of APOE Lp B. APOC3 and APOC3 Lp non-B were increased when glucose metabolism abnormalities were more severe. The presence of a metabolic syndrome was associated with increased plasma APOC3, APOC3 Lp B and APOC3 Lp non-B levels. In a multiple regression analysis, high levels of APOC3 in Lp B and APOC3 Lp non-B were associated with the presence of clinical signs of lipodystrophy, even after adjustment for triglycerides and HDL-cholesterol levels. CONCLUSIONS: Lipid and/or glucose metabolism abnormalities in treated HIV-1-infected patients are associated with increased levels of APOC3 and, to a lesser extent, APOE plasma concentrations. Increased values are also related to clinical signs of insulin resistance and lipodystrophy.     

Homotypic aggregation of CD103 (αEβ7)+ lymphocytes by an anti-CD103 antibody,HML-4

One monoclonal antibody, HML-4, directed against the αEβ7 integrin (CD103), an integrin preferentially expressed on human intestinal intraepithelial lymphocytes (IEL), induced the homotypic aggregation of IEL and of a CD103⁺ MOLT16 cell line. Aggregation was an active adhesion event dependent on an intact cytoskeleton, on tyrosine phosphorylation but not on activation of protein kinase C. It was blocked by four other anti-CD103 antibodies but by none of the antibodies blocking known adhesion lymphocyte pathways. It was associated with a redistribution of the CD103 integrin in the areas of cell-cell contacts. These results indicated that HML-4zx-induced homotypic adhesion was mediated via CD103 and resulted from the binding of the integrin to an as yet undefined ligand expressed by CD103⁺ cells. This ligand was distinct from the epithelial ligand of CD103: in contrast with homotypic adhesion, heterotypic adhesion of CD103⁺ MOLT16 cells on two epithelial intestinal cell lines (DLD1 and HT29) was dependent on the presence of divalent cations, was not enhanced by HML-4, was inhibited by HML-1 but not by the three other antibodies with an inhibitory effect on homotypic adhesion. Finally, the study of conjugates between CD103⁺ and CD103^- sublines derived from the MOLT16 cell line suggested that HML-4-induced homotypic aggregation resulted from homophilic CD103-CD103 interactions.     

What is the Responsiveness and Respondent Burden of the New Knee Society Score?

Background

Although the new Knee Society score (NKSS) has been validated by a task force, a longitudinal study of the same cohort of patients to evaluate the score’s responsiveness and respondent burden has not been reported, to our knowledge.

Questions/Purposes

We analyzed the NKSS for (1) responsiveness; (2) respondent burden; and (3) convergent validity in 148 patients studied longitudinally during more than 1 year.

Methods

During an 8-month period, 165 patients underwent TKA by the same surgeon at our institution, of whom 148 (90%) completed this study; the others were excluded because of distance to travel or loss to followup at the specified time. The NKSS, WOMAC, and SF-12 were completed by each patient 1 day before surgery and at 3 and 12 months postoperatively. At the same times, the original KSS (OKSS) which is designed as an observer’s assessment, was completed by the same orthopaedic fellow for all patients. Responsiveness of the NKSS was assessed by determining effect size, standardized response mean (SRM), and ceiling and floor effects. Respondent burden was assessed through time to completion recorded in minutes and ease of completion which was measured objectively on a Likert scale of 1 to 5 by the patients. Convergent validity was assessed by correlating the NKSS with the WOMAC, SF-12, and OKSS (current, widely used scales) by Pearson’s correlation coefficient.

Results

Effect size was largest (2.83 and 3.38) and SRM was highest (2.29 and 2.68) for the NKSS at 3 and 12 months respectively, indicating the NKSS to be the most-responsive score followed by the OKSS, WOMAC, and SF-12. The NKSS exhibited no ceiling and floor effects. The NKSS took a longer time to complete (5.49 ± 3.56 minutes) compared with the WOMAC (4.64 ± 3.19 minutes) and SF-12 (4.35 ± 3.27 minutes). The mean difference in time taken for the NKSS versus the WOMAC was 0.85 minutes (95% CI, 0.54–1.17 minutes; p < 0.001) and the mean difference for the NKSS versus the SF-12 was 1.14 minutes (95% CI, 0.76–1.15 minutes; p < 0.001). Its ease of completion generally was comparable to that of the WOMAC and SF-12. Convergent validity showed a strong correlation (r > 0.6; p < 0.001) of the NKSS with the WOMAC at all times and moderate to strong correlation (r = 0.4–0.6; p < 0.001) with the SF-12 and OKSS at the first two assessments, which became strong (r > 0.6; p < 0.001) at 12 months.

Conclusions

The NKSS exhibited greater responsiveness than the WOMAC, SF-12, and OKSS scales and showed no ceiling effect, indicating adequate potential for recording future improvement. The NKSS also showed reliable convergent validity when correlated with these other scores. However, it posed a greater respondent burden in terms of time to completion.

Clinical Relevance

As independent nondevelopers of the NKSS, we found it to be a responsive tool for assessment of TKA outcomes. We have confirmed that the NKSS can be used interchangeably for this purpose with the WOMAC scale and that it correlates positively with other established scales of the SF-12 and OKSS. Further study of the short-form version will establish whether it also can be used effectively while reducing the respondent burden.