Andrographolide inhibits chikungunya virus infection by up-regulating host innate immune pathways

Objective:To investigate the therapeutic efficacy of andrographolide, a plant derived compound, against chikungunya virus (CHIKV) infection.Methods:Using flow cytometry and immunoblotting assay, in vitro viral protein expression was studied in THP-1 cells line. In Balb/c mouse neonates, viral RNA copy number was determined by real time PCR.Results:The results showed reduced CHIKV protein expression on andrographolide treatment in CHIKV-infected human peripheral blood mononuclear cells, Vero cells and THP-1 cell line. In vivo, andrographolide treatment to CHIKV-infected neonates reduced viral RNA copy number. Further, andrographolide also increased cytotoxic T lymphocytes both in vitro and in vivo. Andrographolide also activated host innate immune pathways, viz., protein kinase R, phosphorylated eukaryotic initiation factor 2α , retinoic acid inducible gene-I and interferon regulatory factor 3/7, thereby increasing IFN- α secretion. CHIKV-induced nuclear factor κ light chain enhancer of activated B cells and tumor necrosis factor- α was also reduced on andrographolide treatment.Conclusion:Andrographolide inhibits CHIKV by suppressing viral protein expression and up-regulating host innate immunity and hence could be an effective therapeutic agent against CHIKV infection.

Dengue virus non-structural 1 protein interacts with heterogeneous nuclear ribonucleoprotein H in human monocytic cells

OBJECTIVE@#To study protein-protein interaction between heterogeneous nuclear ribonucleoprotein H (hnRNP H) and Dengue virus (DENV) proteins.@*METHODS@#DENV proteins were screened against the host hnRNP H protein, in order to identify the host-viral protein-protein interactions in DENV infected THP-1 cells by co-immunoprecipitation. The co-localization of the interacting proteins was further confirmed by immunofluorescence microscopy.@*RESULTS@#The host protein hnRNP H was found to interact with DENV non-structural 1 protein and help the virus to multiply in the cell.@*CONCLUSIONS@#The non-structural 1 glycoprotein is a key modulator of host immune response and is also involved in viral replication. Therefore, disruption of this key interaction between hnRNP H and DENV non-structural 1 could be an important therapeutic strategy for management of DENV infection.

Prevalence of multidrug resistant uropathogenic bacteria in pediatric patients of a tertiary care hospital in eastern India

Today, because systemic infections such as urinary tract infection [UTI] affect even pediatric patients, antibiotic resistant bacteria have become a constant clinical challenge. In the present study, a total of 1054 urine samples were collected from pediatric patients over 18 months. From these samples, 510 isolates of pathogenic bacteria were collected using HiCrome UTI agar. Antibiotic sensitivity tests of isolates were performed using the Kirby-Bauer method. Two Gram-positive bacteria [Enterococcus faecalis and Staphylococcus aureus] and 7 Gram-negative bacteria [Citrobacter freundii, Enterobacter aerogenes, Escherichia coli, Kleb-siella oxytoca, K. pneumoniae, Proteus vulgaris and Pseudomonas aeruginosa] were isolated. Antibiograms of isolated bacteria were ascertained using antibiotics of 4 classes: aminoglycosides, p-lactams, fluoroquinolones and 2 stand-alones [co-trimoxazole and nitrofurantoin]. Based on percent values of antibiotic resistance, isolated bacteria were [in decreasing order of number of isolated isolates]: E. coli [109] > S. aureus [65] > E. faecalis [82] > E. aerogenes [64] > C. freundii [41] > P. aeruginosa [32] > K. pneumoniae [45] >K. oxytoca [50] >P. vulgaris [22]. Surveillance results show that MDR isolates of 9 pathogenic bacteria were prevalent in the environment around the hospital. Thus, revisions to the antimicrobial stewardship program in this area of the country are required to increase clinician confidence in empiric therapy, which is often used for UTI cases

Post monsoon spatial distribution of uranium in water of Alaknanda and Ganges river

Uranium poses both chemical and radiological hazard to the living system. Drinking water from river is one of the major sources of uranium intake. Dissolution of minerals, washout from rain water, rock-water interaction, agricultural run off, and industrial disposals are some of the sources of uranium in river water system. Present study was aimed to determine the uranium in the water Alaknanda and Ganges rivers and its post-monsoon spatial distribution from Nandprayag to Haridwar. River water samples were collected during the post monsoon period in pre-washed polypropylene bottles from the designated locations at both of the rivers. Samples were filtered and analyzed by fluorimetric technique. The measurements showed the concentration of uranium in water of Alaknanda river varied from 3.05 micro g/l to 2.53 micro g/l along the downstream sampled locations with a mean value of 2.75 micro g/l, whereas in water of Ganges river the concentration varied in the range 1.70 micro g/l to 2.00 micro g/l with a mean value of 1.86 micro g/l. The average concentration of uranium was found significantly higher [2.75 micro g/l] in water of Alaknanda river than in Ganges river the average values [1.86 micro g/l] of. However, both the values were far lower than the permissible limits at the sampled locations. The values obtained in present studies were notably higher than that reported elsewhere which seems partly attributable to post monsoon contributing factors

Synthesis of New VO(II), Co(II), Ni(II) and Cu(II) Complexes with Isatin-3-Chloro-4-Floroaniline and 2-Pyridinecarboxylidene-4-Aminoantipyrine and their Antimicrobial Studies

The complexes of tailor made ligands with life essential metal ions may be an emerging area to answer the problems of multi drug resistance. The coordination complexes of VO(II), Co(II), Ni(II) and Cu(II) with the Schiff bases derived from isatin with 3-chloro-4-floroaniline and 2-pyridinecarboxaldehyde with 4-aminoantipyrine have been synthesized by conventional as well as microwave methods. These compounds have been characterized by elemental analysis, molar conductance, electronic spectra, FT-IR, FAB mass and magnetic susceptibility measurements. FAB mass data show degradation of complexes. Both the ligands behave as bidentate and tridentate coordinating through O and N donor. The complexes exhibit coordination number 4, 5 or 6. The Schiff base and metal complexes show a good activity against the bacteria; Staphylococcus aureus, Escherichia coli and Streptococcus fecalis and fungi Aspergillus niger, Trichoderma polysporum, Candida albicans and Aspergillus flavus. The antimicrobial results also indicate that the metal complexes are better antimicrobial agents as compared to the Schiff bases. The minimum inhibitory concentrations of the metal complexes were found in the range 10~40 microg/mL.

Systemic adverse drug reactions: a preliminary report from the regional pharmacovigilance center, western Nepal

Present study analyzed the pattern, causality, severity and preventability of the systemic adverse drug reactions reported to the regional pharmacovigilance center during the period 14th September 2004 till 13th September 2005. Altogether the centre received 22 systemic adverse drug reactions [males 12 [54.55%], females 10 [45.45%]]. Among the total adverse drug reaction 5 [22.73%] were reported by the Department of Orthopedics. Of the 22 drugs responsible for the suspected adverse drug reaction, majority belongs to the class of Opoid analgesics [n=7, [31.82%]], followed by non steroidal anti-inflammatory drugs [n=5, [22.73%]]. Tramadol was the individual drug responsible for 6 [27.27%] adverse drug reactions and vomiting was the most common adverse drug reactions [n=6, [27.27%]]. The causality assessment revealed 7 [31.82%] of the adverse drug reaction to have a probable relationship with the suspected drugs

Can drug utilization help in promoting the more rational use of medicine? Experiences from western nepal

Drug utilization research describes the extent, nature and determinants of drug use in populations and aims to facilitate the more rational use of medicines. The departments of pharmacology and clinical pharmacy at the Manipal College of Medical Science, pokhara, Nepal are committed to promoting the more rational use of medicines. The departments run a Drug Information Center and Pharmacovigilance Center in the teaching hospital. Over the last eight years, the departments have conducted drug utilization studies in the teaching hospital and the community. A few of these were of the intervention type and drug use was studied before and after the intervention. Members of the departments are on the hospital Drug and Therapeutics Committee. Educational initiatives to improve prescribing have been carried out in a few instances. Restricting the number of brands in the hospital pharmacy and creation of a hospital drug list has been carried out. The impact of these initiatives has been studied only in a few cases. Generic prescribing was found to be low. The educational initiatives to improve prescribing had only limited success. The hospital is in the process of framing antimicrobial use guidelines for various departments. A hospital formulary is under preparation. The influence of drug utilization studies on the prescribing patterns has been low to moderate. The department of Clinical pharmacy runs a Medication Counseling Center in the hospital and teaches appropriate use of medicines to patients. The studies and initiatives to promote the more rational use of medicines should be continued and strengthened

Newer antibiotics

To combat the increasing problem of antibiotic resistance, newer antibiotics have been developed or are under development. This review focuses on the newer antibiotics, quinupristin-dalfopristin, linezolid, the newer glycopeptides, daptomycin, the cationic peptides and the newer fluoroquinolones

Dermatological adverse drug reactions due to systemic medications a review of literature

Cutaneous adverse drug reactions [ADRs] affect 2-3% of hospitalized patients. These reactions can arise as a result of immunologic or non-immunologic mechanisms. Extremes of age, female sex, previous history of ADRs and environmental factors are the major risk factors. The severity of the cutaneous ADRs may vary from a mild itching to a life threatening Stevens-Johnson syndrome [SJS]. In general, most are usually mild and respond to topical treatment. Different skin diseases and cutaneous manifestation of systemic diseases should be ruled out before diagnosing a cutaneous ADR. In order to establish the causal relationship between the offending drug and the reaction, causality assessment should be carried out. The Naranjo algorithm is widely used to determine the causality of an ADR. The cessation of the offending agent, along with the use of systemic and topical steroids, antipruritic agents and oral antihistamines may be helpful in the management. Patients with extensive skin involvement should be cared for as burns patients. High risk patients should be counseled regarding the possibility of developing a cutaneous ADR during the course of treatment and the strategies to be followed upon occurrence of a cutaneous ADR. This is a review article

Digital gangrene due to dopamine infusion- a case report

Dopamine is a vasopressor agent for the treatment of shock and hypotension in patients who do not respond to plasma volume expansion. Use of dopamine is associated with severe peripheral ischemia, particularly in patients in whom the peripheral circulation is already impaired. We describe a case of digital gangrene due to intravenous dopamine infusion in a 45-year-old man who did not have any predisposing factor. The patient developed digital gangrene within 24 hours of starting intravenous dopamine. Dopamine is one of the commonly used vasopressor agents in the treatment of shock and hypotension and measures should be taken to detect the possibility of the development of gangrene based on the predisposing factor and if gangrene occurs, immediate steps should be taken for management of the reaction

Cutaneous adverse drug reactions to modern medicines and initial experiences from a spontaneous adverse drug reaction reporting program in a tertiary care teaching hospital of Western Nepal

Cutaneous adverse drug reactions [ADRs] affect 2-3% of hospitalized patients; most are usually mild and respond to topical drugs. These reactions can arise as a result of immunologic or non-immunologic mechanisms. Extremes of age, female sex, previous history of ADRs and environmental factors are the major risk factors. The Naranjo algorithm is widely used to determine the causality of an ADR. To share the authors' experience of spontaneous adverse drug reaction reporting program Nepal. During a period from September, 2004 to March, 2005, any patient who experienced a dermatological ADR were asked to report the Pharmacovigilance Cell of the Manipal Teaching Hospital, Pokhara, Nepal. Morphology of the eruption was recorded. A total of 45 cutaneous ADRs were reported during the study period. Maculopapular rash [15 reports] was the most common, followed by contact dermatitis [7 reports], fixed drug eruptions [6 reports] and erythema [4 reports]. Considering its effectiveness, the pharmacovigilance program in Manipal Teaching Hospital should be strengthened and transformed to a full-fledged active reporting program. The nationwide extension of this program would be beneficial

Oxidative membrance damage and involvement in gamma radiation - induced apoptotic death

Recent results have provided increasing evidence to support involvement of membrane damage in the mechanism of ionizing radiation induced killing of mammalian cells. These findings have stimulated renewed interest in evaluating the damage to membrane as a primary initiator in radiation-induced cell killing especially in apoptotic death. The present study was aimed to gain deeper insight on the molecular mechanisms of radiation-induced damage at membrane level with consequences to apoptotic cell death. Materials and Radiation mediated changes in membrane fluidity in egg yolk lecithin [EYL] liposomal membrane were studied by employing 1,6-diphenyl hexatriene [DPH] fluorescence polarization and subsequent oxidative damage by measurement of malondialdehyde [MDA] by thiobarituric acid reactive species [TBARS] spectrophotometrically. Alterations in membrane permeability and nuclear dimensions in g -irradiated immature mouse thymocytes were investigated by fluorescein diacetate [FDA] and propidium iodide [PI] method, respectively. Results on irradiated liposomes have shown dose dependent lipid peroxidation with concomitant alterations in bilayer fluidity. These parameters were found significantly modified, when liposomes were prepared with a -tocopherol or cholesterol suggesting the contributions of both the radical scavenging and matrix modifying factors in membrane peroxidative damage. In addition, studies on mouse thymocytes labeled with FDA and PI have shown increased permeability of the plasma membrane and decreased nuclear diameter following g -irradiation of thymocytes. Alteration in membrane permeability with the time of post-irradiation incubation was found correlated with the induction of apoptotic death of thymocytes. These results suggest that membrane associated radiation damage were correlated with changes in the nucleus of cells. Moreover, the membrane damage seems a primary trigger in radiation-induced apoptosis which may have implications in cancer radiotherapy

Multiple central nervous system tumors and combined treatment modalities - an illustrative case

Multiple space occupying lesions in the craniospinal axis pose special type of challenges in their management. Surgeries for decompression or total excision of the symptomatic tumors at various sites and at different times are needed. Radiosurgery and administration of chemotherapeutic agents are other modalities for the treatment of such lesions caused by benign or malignant conditions and acute or chronic infections. We report a case of a young woman with central neurofibromatosis harbouring bilateral acoustic neurinomas multiple meningiomas and other cranial and spinal neurofibromas. she underwent radiosurgery for the right vestibular schwannoma [VS] and surgery for the left sphenoidal wing meningioma and a large right C5 nerve root neurofibroma. There was no evidence of tumor necrosis or shrinkage 4 years after the radiosurgery. Brain stem compression increased over 4 years period. she is likely to need futher intervention for symptomatic lesions

Multiple primary skin cancers a case report

Basal Cell Carcinoma [BCC] is the most common of all skin cancers especially among the people of European race. In pigmented races it is associated with pre-disposing conditions such as naevus sebaceous, albinism or Xeroderma Pigmentosum. We are reporting a 64-year old gentleman of European origin working in Oman since 25 years who presented with multiple primary skin cancers on the scalp, face and upper trunk at different occasions

Early exploration or appendicular mass

The management of an appendicular mass has traditionally been conservative, involving a long hospital stay. The patients in whom mass resolves have to be readmitted for interval appendicectomy at a later stage. Those who develop an appendicular abscess during admission need to be operated upon for drainage of the abscess and still called later for elective appendicectomy. A prospective study was carried out to compare the merits and demerits of early exploration vs. conservative treatment of appendicular mass in the Department of Surgery, Unit-I, Lahore General Hospital attached to Postgraduate Medical Institute, Lahore. Fifty patients were admitted and divided in two equal group. One group was managed conservatively and the other underwent early exploration of the appendicular mass of five days or lesser duration. The mean hospital stay in the operated group was 3.48 days and in the other it was 5.7 days. No major complication occurred in patients who had early exploration except wound infection rate of 8 percent. We found that early exploration was not only safe and advantageous but cost effective as well. We recommend early exploration of appendicular mass of five days or lesser duration