CHALLENGES IN THE MANAGEMENT OF BRONCHIOLITIS

ABSTRACTObjective: This study aims to review and evaluate current medication and to provide practical guidelines to the practitioners managing children withbronchiolitis.Methods: A 6-month retrospective study was carried out in the Department of Paediatrics in Tertiary Care Hospital, a 350-bedded multispecialtyhospital to review the management of bronchiolitis. A total of 60 cases selected from July 2014 to December 2014 were included in the study. Patientdata and prescription details were recorded and analyzed accordingly.Results: About 58.3% of bronchiolitis cases were reported in the age group of <1 year, 26.6% in the age group of 1-2 years and 15% casesreported at the age >2 years. Commonly reported symptoms in different cases include 85% of cases with fever, 90% with a cough, 93.3% withcold, 30% with vomiting, 35% with breathlessness, 33.3% with loose motions, and 68.3% with wheezing. A single broad-spectrum antibioticwas used in 68.3% cases, two broad spectrum antibiotics in 26.6% of cases, and three or more combinations in 5% of cases to prevent bacterialcoinfections. A careful assessment of study has evaluated that antiviral therapy was not used in any of the cases to avoid antiviral resistancebut broad-spectrum antibiotics were most commonly prescribed for a viral respiratory illness which is generally self-limiting adding to thethreat of antibiotic resistance. Bronchodilators and corticosteroids were routinely used. As per current Standard Treatment Guidelines for themanagement of bronchiolitis, the priority has been given to adequate rest, intravenous fluids, symptomatic therapy, and reserve antiviral therapyfor special cases. This study demonstrated the importance of routine medication review and the need of a clinical pharmacist at various levelsof clinical setup.Conclusion: From this study, it can be concluded that interventions by a clinical pharmacist are needed in taking a special effort to analyze prescriptionsand provide clinicians with a feedback involving available antiviral medications, antiviral resistance, prescription costs, limitations of antiviral agentsand updated current standard treatment guidelines.Keywords: Self-limiting, Antiviral therapy, Antiviral resistance, Antibiotic use, Antibiotic resistance

Sulfated Multivalent Polymers for inhibition of L-selectin and LOX-1 Receptors

Within the scope of this thesis, multivalent sulfated polymers were synthesized and investigated concerning their targeting properties towards two proteins: L-selectin, a cell adhesion molecule expressed on leukocytes and LOX-1, a scavenger receptor from macrophages. Whereas L-selectin plays a dominant role in chronic diseases, LOX-1 can contribute to atherosclerosis. In both cases, a targeted intervention is desired. In the first part, b-cyclodextrin vesicles were non-covalently functionalized with oligosulfate-adamantyl conjugates as guest molecules. The supramolecular assemblies were evaluated for L-selectin binding in solution by microscale thermophoresis. An increase in binding affinity was observed with respect to the sulfate valency of the ligands. The adamantly conjugates with 4 and 8 sulfate groups revealed KD values of 34 and 25 μM, respectively. Unfunctionalized vesicles and sulfate-adamantly conjugates alone did not show any effect. However, the complex stability was limited. In the second part, sulfated oligoglycerol dendrons were conjugated to polyethylene linkers yielding mono- and bi-functionalized compounds. For binding studies, a soluble recombinant fusion protein was expressed that carries two LOX-1 dimers. Targeting of the positively charged, linearly aligned arginine residue on the dimer surface was evaluates for all polymeric architectures by surface plasmon resonance and two of the molecules gave binding affinities in the low nM range (~50 nM). In cell-based assays the sulfated polymers were able to reduce the binding of soluble LOX-1 to target cells. Recognition of a physiological ligand, oxidized low density lipoprotein particle (oxLDL) by LOX-1 expressing cells was reduced upon preincubation with the sulfated polymers. As a result, the work demonstrates that multivalent compounds enhance binding affinity and therefore, multivalency is a useful concept to interfere with planar biological surfaces.Ziel der Doktorarbeit war die Synthese multivalenter sulfatierter Polymere und Untersuchungen der Bindung an zwei Zielproteine: L-Selektin, einem Zell- Adhäsionsmolekül, das auf Leukozyten exprimiert wird und LOX-1, ein Scavenger- Rezeptor der auf Makrophagen vorkommt. Während L-Selektin eine wichtige Rolle bei chronischen Erkrankungen spielt, kommt LOX-1 eine zentrale Rolle bei der Entwicklung der Atherosklerose zu. In beiden Krankheitsbildern ist eine zielgerichtete medizinische Intervention wünschenswert. Im ersten Teil der Arbeit wurden b-Cyclodextrinvesikel mit Oligosulfat- Adamantylkonjugaten als Gast-Moleküle nicht-kovalent funktionalisiert. Diese supramolekularen Systeme wurden in Lösung mittels mikroskalarer Thermophorese hinsichtlich ihrer L-Selektinbindung untersucht. Dabei wurde eine Steigerung der Bindungsaffinität in Abhängigkeit von der Anzahl an Sulfatgruppen nachgewiesen. Die Adamantylkonjugate mit 4 bzw. 8 Sulfatgruppen ergaben KD-Werte von 34 und 25 μM. Nicht funktionalisierte Vesikel und die sulfatierten Adamantylkonjugate allein zeigten keine Bindung. Auffällig war, dass die Stabilität der Komplexe begrenzt war. Im zweiten Teil der Arbeit wurden sulfatierte Oligoglyceroldendrone an mono- und bifunktionelle Polyethylenlinker konjugiert. Zur Untersuchung der Funktionalität der Konjugate wurde ein lösliches Fusionsprotein exprimiert, dass aus zwei LOX-1 Dimeren besteht. Die Bindung an eine positiv geladene, lineare Poly-Argininsequenz auf der Oberfläche des LOX-1 Proteins wurde mit allen synthetisierten Konjugaten mittels Oberflächenplasmonresonanz-Spektroskopie bestimmt. Zwei Konjugate zeigten dabei Bindungsaffinitäten im unteren nM Bereich (~50 nM). In zellbasierten Experimenten reduzierten die sulfatierten Polymere die Bindung des rekombinanten löslichen LOX-1 an Zielzellen. Durch Vorinkubation eines physiologischen Liganden, dem oxidierten Lipoprotein Partikel (oxLDL) mit den sulfatierten Polymeren konnte die Bindung des Liganden an membranständiges LOX-1 auf Zielzellen reduziert werden. Als Ergebnis zeigt die Arbeit, dass multivalente Systeme geeignet sind Bindungsaffinität zu erhöhen und Multivalenz ein geeignetes Konzept ist, um planare biologische Oberflächen zu adressieren

Immune Dysfunction during Enteric Protozoal Infection: The Current Trends

Enteric protozoa usually cause severe morbidity and mortality in humans. Protozoal infections contribute to the high burden of infectious diseases. Despite recent advances in the epidemiology, diagnostic tool, molecular biology, and treatment of protozoan illnesses, gaps in knowledge still exist; hence, protozoal infections require further research. We are describing here some important enteric protozoal infections along with the immune dysfunction produced by them. Genus- 1. Entamoeba; 2. Giardia; 3. Cryptosporidium; 4. Cyclospora; 5. Cystoisospora; 6. Dientamoeba; 7. Blastocystis; 8. Balantidium

EFFECT OF BOILING AND MICROWAVE ASSISTED PROCESSING ON THE ANTIMICROBIAL EFFICACY OF VITAMIN–C IN EMBLICA OFFICINALIS

Objective: The present work aimed to expand the awareness of restoring vitamin-C in its active form on different heat exposures. The effect of microwave-assisted processing and boiling of the aqueous crude extract of citrus fruit Emblica officinalis (amla) has been correlated with its antimicrobial efficacy against E. coli. Methods: The aqueous crude extract of dried amla pulp exposed to microwave radiation(600W,5 min) and boiling (5 min) were titrimetrically estimated for vitamin-C content by DCPIP-(2,6, Dinitrophenol indophenol) method and compared the same with the untreated sample. These three samples were studied for their effect on the growth pattern of E. coli turbidimetrically. The antimicrobial susceptibility test by agar cup well diffusion method was further followed to measure the zone of inhibitions (ZOI) for these three test extracts against E. coli. Results: The total estimated vitamin-C content was 26.76 mg/100g, 25.35 mg/100g and 21.12 mg/100g in the untreated extract (UTE), microwaved extract (MWE) and boiled extract (BE) respectively. At a higher concentration (0.8 mg/ml), the UTE showed a greater ZOI of 20 mm and a comparable ZOI of 18 mm for the MWE against E. coli. In addition, a reduced ZOI of 10 mm was recorded in case of the BE. At a lowest concentration (0.05 mg/ml), the UTE inhibited the growth with a least ZOI of 7 mm, whereas no inhibition zones were detected for MWE and BE at this concentration. Conclusion: The present investigation demonstrated the effect of boiling and microwave-assisted processing on the content of bioactive vitamin-C and its antimicrobial activity. The DCPIP method calculated a more vitamin-C retention in the MWE than the BE. As the boiling method destroyed the vitamin more rapidly, a higher growth rate of E. coli was measured in the presence of BE than the UTE and MWE. In addition, the antimicrobial assay also showed a least inhibitory effect against E. coli in the presence of the BE. A moderate inhibitory effect for MWE was also detected. Thus the present investigation proved that the boiling process destroys vitamin-C present in a food sample to a higher extent than the microwave-assisted processing

(R1513) The Dynamical Study of Variable Mass Test Particle in Nonlinear Sense of Restricted 3-body Problem with Heterogeneous Primaries

The main idea of this paper is to study the non-linear stability property of the motion of the test particle which is moving under the influence of heterogeneous primaries having N-layers with different densities as well as varying its mass according to Jeans law. The system is also perturbed by the small perturbations in Coriolis as well as centrifugal forces. We evaluate the equations of motion of the test particle under the influence of the above said perturbations. From this system of equations of motion, we reveal analytically the locations of stationary points as well as the non-linear stability

Population Dynamics of Helminth Parasites in Fresh Water Fishes Channa punctatus and Heteropneustes fossilis in Moradabad, U.P., India

In the present report two types of fish Channa punctatus (Bloch) and Heteropneustes fossilis (Bloch) were examined to explore the status of helminthic infection in fishes from various water bodies of Moradabad district. The Acanthocephalans, Nematodes and Trematode parasites were detected from gastrointestinal tract and body cavity of host during the study period from January 2017 to March 2017. Intestine was found to be highly infected site in the host fish Channa punctatus while in Heteropneustes fossilis, trematodes were localized in skin muscles only and the highest prevalence (70%) of all the parasites was observed in the month of February 2017, however highest abundance (0.89), highest intensity (1.34) and highest index of infection (0.61) was recorded in the month of March 2017 along with the highest loss in body weight (0.153kg.) along with highest mortality

ANTIHYPERGLYCEMIC ACTIVITY OF PITHECELLOBIUM DULES PLANT EXTRACTS ON BLOOD GLUCOSE LEVELS OF STREPTOZOCIN-INDUCED DIABETIC RATS

Background: The prevalence of diabetes mellitus continues to rise worldwide and treatment with oral hypoglycemic drugs leads to numerous side effects and huge monetary expenditure. Therefore active research on identification of new antidiabetic drugs with minimal side effects from medicinal plants is a challenge according to WHO recommendations. In this aspect, the present study was undertaken to evaluate the antihyperglycemic potential of Pithecellobium dules plant in streptozotocin (STZ) induced diabetic rats. Methods: Diabetes was induced in male wister rats by intraperitoneal administration of STZ (45 mg/kg.b.w).Fasting blood glucose (FBG) levels were measured by glucose-oxidase & peroxidase method. The statistical analysis of results was carried out using and one-way analysis (ANOVA) followed by Student t-test. Results and Discussion: Antihyperglycemic potentials of plant of Pithecellobium dules extract has been investigated at the doses of 150, 300 and 600 mg/kg body weight orally administered to streptozocin-induced diabetes male wistar rats. Treatment of streptozocin diabetic male wistar rats with the extracts caused a significant (P<0.01) reduction in the blood glucose levels. The highest activity resides at the dose of 600 mg/kg body weight with mean percentage blood glucose level change of 55.32% after 6 hours of extract administration while the other two doses 150 and 300 mg/kg have blood glucose level change of 40.45% and 47.14% respectively after 6 hours of extract administration. This result suggests that the Pithecellobium dules plant extracts possess antihyperglycemic effect on streptozocin-induced diabetic male wistar rats. Conclusions: The plant extract is capable of managing antihyperglycemia and complications of diabetes in STZ induced diabetic rats. Hence, this plant may be considered as one of the potential sources for the isolation of new oral anti hypoglycemic agent(s) Keywords: Antihyperglycemic activity, Streptozocin, Pithecellobium dules, Diabetes mellitu

Prevalence of thyroid disorders among pregnant women at a tertiary care hospital in Rajasthan

Background: Hormonal changes and metabolic demands during pregnancy result in profound alterations in the biochemical parameters of thyroid function. Screening for thyroid disorders and initiation of its management at the earliest stage during first trimester is essential as maternal thyroid failure during the first half of pregnancy has been associated with several pregnancy complications and intellectual impairment in offspring. Aim was to evaluate the prevalence of thyroid dysfunction during the first and second trimester of pregnancy among women of Rajasthan state in India.Methods: The study comprised a cohort of 313 consecutive pregnant women in the first and second trimester that attended the OPD and were admitted as pregnant women in Obstetrics and Gynecology Department of the NIMS Medical College and Hospital, Jaipur, Rajasthan. Thyroid stimulating hormone (TSH) levels and free T4 (fT4) were estimated. The subjects were grouped into six groups based on the value of serum TSH and fT4.Results: Out of 313 antenatal women enrolled in the study, 213 (68%) attended antenatal clinic in first trimester of pregnancy and 100 (32%) women in their second trimester. The prevalence of thyroid dysfunction was 15.97% (overt hypothyroidism 1.28%, subclinical hypothyroidism 4.79%, isolated hypothyroxinemia 4.47%, overt hyperthyroidism 1.92%, and subclinical hyperthyroidism 3.51%). The women with overt hypo- or hyperthyroidism and subclinical hypothyroidism were older than euthyroid women. Maternal weight was high in pregnant women with overt hypothyroidism (58.22±6.18 kg) and subclinical hypothyroidism (52.04±2.94 kg). Gravid status was high in pregnant women with overt hypothyroidism, subclinical hypothyroidism and isolated hypothyroxinemia, but low in hyperthyroid group. History of miscarriage was high in pregnant women with subclinical hypothyroidism.Conclusions: With this study, it was concluded that there is high prevalence of thyroid dysfunction in pregnancy predominantly in rural population of Rajasthan. Majority among these being subclinical hypothyroidism and hypothyroxinemia

(R1985) Study the Effect of Modified Newtonian Force on the Restricted 3-body Configuration in Non-Linear Sense

This paper aims to investigate the non-linear stability of the triangular libration point in the restricted three-body problem (R3BP). The model, we use for our problem consists of a primary body as a heterogeneous spheroid with N-layers having different densities of each layer and a secondary body as a point mass that is producing the modified Newtonian Potential. We determine the equation of motion of the smallest body which is under the influence of the above-mentioned perturbations and also influenced by Coriolis as well as Centrifugal forces and then evaluated the Lagrangian for the evaluated system of equations. Afterwards, we write the first and second-order normalization of the Hamiltonian of the problem. By implying KAM theorem and the techniques used by Bhatnagar and Hallan, we discuss the non-linear stability analytically