Immunomodulatory activity of Asparagus racemosus on systemic Th1/Th2 immunity: Implications for immunoadjuvant potential

Ethnopharmacological relevance

Roots of Asparagus racemosus Willd (Shatavari in vernacular) are widely used in Ayurveda as Rasayana for immunostimulation, galactogogue as also in treatment of conditions like ulcers and cancer. Various studies have indicated immunomodulatory properties of Shatavari root extracts and formulations.

Aim of the study

To study the effect of standardized Asparagus racemosus root aqueous extract (ARE) on systemic Th1/Th2 immunity of SRBC sensitized animals.

Materials and methods

We used HPTLC to quantify steroidal saponins (Shatavarin IV, Immunoside^®) and flow cytometry to study effects of ARE on Th1/Th2 immunity. SRBC specific antibody titres and DTH responses were also monitored as markers of Th2 and Th1 responses, respectively. We also studied lymphocyte proliferation. Cyclosporin, cyclophosphamide and levamisole were used as controls.

Results

Treatment with ARE (100 mg/(kg b.w. p.o.)) resulted in significant increase of CD3⁺ and CD4/CD8⁺ percentages suggesting its effect on T cell activation. ARE treated animals showed significant up-regulation of Th1 (IL-2, IFN-g) and Th2 (IL-4) cytokines suggesting its mixed Th1/Th2 adjuvant activity. Consistent to this, ARE also showed higher antibody titres and DTH responses. ARE, in combination with LPS, Con A or SRBC, produced a significant proliferation suggesting effect on activated lymphocytes.

Conclusion

The study suggests mixed Th1/Th2 activity of ARE supports its immunoadjuvant potential.     

Dry powder aerosols of polyethylenimine (PEI)-based gene vectors mediate efficient gene delivery to the lung

Aerosol gene delivery holds great therapeutical potential for many inherited and acquired pulmonary diseases. The physical instability of aqueous suspensions of non-viral vector complexes is a major limitation for their successful application. In this study, we investigated dry powder aerosols as novel gene vector formulations for gene transfer in vitro and murine lungs in vivo. Lyophilization was used to produce dry powder cakes followed by powderization to produce dry powder aerosols. Different sugars, namely lactose, sucrose and trehalose, were tested as lyoprotectants for gene delivery complexes consisting of branched polyethylenimine 25 kDa and plasmid DNA. Biophysical particle characterization demonstrated that lyophilization and powderization in the presence of lyoprotectants were well tolerated. In vitro transfection efficiency remained unaffected by the choice of lyoprotectant and subsequent lyophilization and/or powderization. In vivo screening of powderized samples, by applying the powder with an insufflator, resulted in highest gene expression with lactose as lyoprotectant. Delivering a plasmid coding for murine erythropoietin together with lactose as lyoprotectant resulted in increased blood hematocrit values post application thereby demonstrating the potential of dry powder aerosol as a promising method for pulmonary gene delivery.     

Intestinal parasites in children with diarrhea in Delhi,India

The parasitic causes of diarrhea in children in Delhi were determined by the direct smear technique; stool specimens of 127 children were examined for intestinal parasites. In 59 cases (46.5%) intestinal helminths and protozoa were demonstrated. Ascaris lumbricoides was observed in 1 (0.8%) case, while Trichuris trichiura was the finding in 3 (2.4%). Protozoal parasites included Giardia intestinalis and Entamoeba histolytica in 14 (11%) cases each, Balantidium coli in 3 (2.4%) cases and Cryptosporidium spp in 24 (18.9%) patients. Mixed infection was not seen in any of the cases. Intestinal parasites may increase susceptibility to infection with other intestinal pathogens and therefore with the help of a simple technique, like direct fecal smear examination. rapid diagnosis can be made and specific therapy instituted.     

Septic shock in chronic dialysis patients: clinical characteristics,antimicrobial therapy and mortality

Objectives

To describe the clinical characteristics and in-hospital mortality of chronic dialysis-dependent end-stage kidney disease patients with septic shock in comparison to septic shock patients not receiving chronic dialysis.

Methods

Using an international, multicenter database, we conducted a retrospective analysis of data collected from 10,414 patients admitted to the intensive care unit (ICU) with septic shock from 1989 to 2013, of which 800 (7.7 %) were chronic dialysis patients. Data on demographic characteristics, sites of infection, microbial pathogens, antimicrobial usage patterns, and in-hospital mortality were aggregated and compared for chronic dialysis and non-dialysis patients. Multivariate time-varying Cox models with and without propensity score matching were constructed to determine the association between dialysis and in-hospital death.

Results

Septic shock secondary to central venous catheter infection, peritonitis, ischemic bowel, and cellulitis was more frequent in chronic dialysis patients. The isolation of resistant organisms (10.7 vs. 7.1 %; p = 0.005) and delays in receiving antimicrobials (6.0 vs. 5.0 h) were more common in chronic dialysis patients than in non-dialysis patients. Delayed appropriate antimicrobial therapy was associated with an increased risk of death in chronic dialysis patients (p < 0.0001). In-hospital death occurred in 54.8 and 49.0 % of chronic dialysis and non-dialysis patients, respectively. After propensity score matching, there was no difference in overall survival between chronic dialysis and non-dialysis patients, but survival in chronic dialysis patients decreased over time compared to non-dialysis patients.

Conclusions

The demographic and clinical characteristics of chronic dialysis patients with septic shock differ from those of similar non-dialysis patients. However, there was no significant difference in mortality between the chronic dialysis and non-dialysis patients with septic shock enrolled in this analysis.

     

Outcomes of Patients With Syncope and Suspected Dementia

Objectives

Syncope and near‐syncope are common in patients with dementia and a leading cause of emergency department (ED) evaluation and subsequent hospitalization. The objective of this study was to describe the clinical trajectory and short‐term outcomes of patients who presented to the ED with syncope or near‐syncope and were assessed by their ED provider to have dementia.

Methods

This multisite prospective cohort study included patients 60 years of age or older who presented to the ED with syncope or near‐syncope between 2013 and 2016. We analyzed a subcohort of 279 patients who were identified by the treating ED provider to have baseline dementia. We collected comprehensive patient‐level, utilization, and outcomes data through interviews, provider surveys, and chart abstraction. Outcome measures included serious conditions related to syncope and death.

Results

Overall, 221 patients (79%) were hospitalized with a median length of stay of 2.1 days. A total of 46 patients (16%) were diagnosed with a serious condition in the ED. Of the 179 hospitalized patients who did not have a serious condition identified in the ED, 14 (7.8%) were subsequently diagnosed with a serious condition during the hospitalization, and an additional 12 patients (6.7%) were diagnosed postdischarge within 30 days of the index ED visit. There were seven deaths (2.5%) overall, none of which were cardiac‐related. No patients who were discharged from the ED died or had a serious condition in the subsequent 30 days.

Conclusions

Patients with perceived dementia who presented to the ED with syncope or near‐syncope were frequently hospitalized. The diagnosis of a serious condition was uncommon if not identified during the initial ED assessment. Given the known iatrogenic risks of hospitalization for patients with dementia, future investigation of the impact of goals of care discussions on reducing potentially preventable, futile, or unwanted hospitalizations while improving goal‐concordant care is warranted.

     

Intensive care management of patients with acute intermittent porphyria: Clinical report of four cases and review of literature

Acute intermittent porphyria (AIP), the most common and the most severe form of acute hepatic porphyria, is an autosomal dominant condition. It results from lower-than-normal levels (less than 50%) of porphobilinogen (PBG) deaminase. Patients may present commonly with gastrointestinal complaints and neuropsychiatric manifestations. Diagnosis may be confirmed with the presence of intermediary metabolites of haem synthesis, amino levulinic acid (ALA) and PBG in urine or with specific enzyme assays. Abdominal pain is the most common symptom (90%). Peripheral polyneuropathy, primarily motor with flaccid paresis of proximal musculature, with or without autonomic involvement, is characteristic. Respiratory failure necessitates ventilator and intensive care support. Avoidance of precipitating factors and the use of haem preparations and intravenous dextrose form the basis of management. Gabapentin and propofol, rather than the conventional antiepileptics appear to be the appropriate choice for seizure control. Here, we present intensive care management of four cases of AIP with varying clinical presentation.     

Synthesis, molecular docking and PTP1B inhibitory activity of functionalized 4,5-dihydronaphthofurans and dibenzofurans

Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that plays a critical role in down-regulating insulin signaling through dephosphorylation of the insulin receptor. Inhibitors of PTP1B showed increased insulin sensitivity and normalize plasma glucose level and thus are useful therapeutic agents for the treatment of diabetes. A series of functionalized 4,5-dihydronaphthofurans and dibenzofurans were synthesized, studied through molecular docking and evaluated for their PTP1B inhibitory activity.     

Microwave-induced CAN promoted atom-economic synthesis of 1H-benzo[b]xanthene and 4H-benzo[g]chromene derivatives of N-allyl quinolone and their antimicrobial activity

Some new 1H-benzo[b]xanthene and 4H-benzo[g]chromene derivatives of N-allyl quinolone were efficiently synthesized via microwave-induced one-pot three component reaction of N-allyl quinolones, 2-hydroxy-1,4-naphthoquinone and cyclic β-diketones/malononitrile, and iso-propylcyanoacetate in the presence of catalytic amount of ceric ammonium nitrate under solvent-free condition. This methodology allowed us to achieve the desired products in excellent yields in a very short time without the use of solvent. The % atom economy was calculated for all the newly synthesized compounds and found in the range of 92–96 %. Titled derivatives were elucidated by ¹H NMR, ¹³C NMR, FT-IR, elemental analysis, and mass spectral data as well as tested against a panel of pathogenic strains of bacteria and fungi using by microdilution minimum inhibitory concentration method. The structural activity relationship analysis demonstrated that electronic influence and lipophilicity of different groups make much difference in the antimicrobial potency.