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  1. Article ; Online: Clinical Pharmacy Practice in Low-and Middle-income Countries; Special Focus on Nepal

    Sitaram Khadka / Mahesh Khatri / Sabitri Lamichhane / Sagar Dhakal

    Journal of Karnali Academy of Health Sciences, Vol 5, Iss

    2022  Volume 1

    Abstract: The paradigm shift of pharmacy practice from the conventional compounding and dispensing role towards more advanced patient-centered care has a positive impact on the health care system. Not only has it rendered safe, appropriate, and cost-effective drug ...

    Abstract The paradigm shift of pharmacy practice from the conventional compounding and dispensing role towards more advanced patient-centered care has a positive impact on the health care system. Not only has it rendered safe, appropriate, and cost-effective drug therapy, but it also has optimized the therapeutic outcome. Though there is optimal growth of clinical pharmacy practice in the developed world, incorporating these new models into action has become a challenge for low-and middle-income countries (LMICs) like Nepal. Notably, the existing pharmacy curriculum is not updated to meet the current healthcare needs. Currently, the job opportunities are limited to manufacturing roles in pharmaceutical industries and as dispensers in community and retail pharmacies. Pharmacists and pharmacy practice have to evolve with the latest trends in demographics, epidemiology, societal factors, economy, and technological advances. It is high time that the policy-making bodies prepare and implement guidelines for strengthening clinical pharmacy practice in LMICs. The clinical pharmacy practice assures the rationalization of therapeutic outcomes with proper protocols, effort from the pharmacists, sound academic background and related training, and professional attitudes. This review sought to explore and expand the role of clinical pharmacists in healthcare settings, particularly in LMICs like Nepal.
    Keywords Pharmacists ; Developing Countries ; Nepal ; Professionalism ; Patient-Centered Care ; Medicine (General) ; R5-920
    Subject code 300
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Karnali Academy of Health Sciences
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Quantification of Cardiotonic Steroids Potentially Regulated by Paraoxonase 3 in a Rat Model of Chronic Kidney Disease Using UHPLC-Orbitrap-MS

    Sabitri Lamichhane / Chrysan J. Mohammed / Steven T. Haller / David J. Kennedy / Dragan Isailovic

    International Journal of Molecular Sciences, Vol 23, Iss 13565, p

    2022  Volume 13565

    Abstract: Endogenous cardiotonic steroids (CTSs), such as telocinobufagin (TCB) and marinobufagin (MBG) contain a lactone moiety critical to their binding and signaling through the Na + /K + -ATPase. Their concentrations elevate in response to sodium intake and ... ...

    Abstract Endogenous cardiotonic steroids (CTSs), such as telocinobufagin (TCB) and marinobufagin (MBG) contain a lactone moiety critical to their binding and signaling through the Na + /K + -ATPase. Their concentrations elevate in response to sodium intake and under volume-expanded conditions. Paraoxonase 3 (PON3) is an enzyme that can hydrolyze lactone substrates. Here, we examine the role of PON3 in regulating CTS levels in a rat model of chronic kidney diseases (CKD). TCB and MBG were extracted from rat urine samples, and the analyses were carried out using ultra-high pressure liquid chromatography–Orbitrap-mass spectrometry (UHPLC-Orbitrap-MS). Ten-week-old Dahl salt-sensitive wild type (SS-WT) and Dahl salt-sensitive PON3 knockout (SS-PON3 KO) rats were maintained on a high-salt diet (8% NaCl) for 8 weeks to initiate salt-sensitive hypertensive renal disease characteristic of this model. CTS extraction recovery from urine >80% was achieved. For animals maintained on a normal chow diet, the baseline amount of TCB excreted in 24 h urine of SS-PON3 KO rats (6.08 ± 1.47 ng/24 h; or 15.09 ± 3.25 pmol) was significantly higher than for SS-WT rats (1.48 ± 0.69 ng/24 h; or 3.67 ± 1.54 pmol, p < 0.05). Similarly, for the same animals, the amount of excreted MBG was higher in the urine of SS-PON3 KO rats (4.74 ± 1.30 ng/24 h versus 1.03 ± 0.25 ng/24 h in SS-WT; or 11.83 ± 2.91 pmol versus 2.57 ± 0.56 pmol in SS-WT, p < 0.05). For animals on a high-salt diet, the SS-PON3 KO rats had significantly increased levels of TCB (714.52 ± 79.46 ng/24 h; or 1774.85 ± 175.55 pmol) compared to SS-WT control (343.84 ± 157.54 ng/24 h; or 854.09 ± 350.02 pmol, p < 0.05), and comparatively higher levels of MBG were measured for SS-PON3 KO (225.55 ± 82.61 ng/24 h; or 563.19 ± 184.5 pmol) versus SS-WT (157.56 ± 85.53 ng/24 h; or 393.43 ± 191.01 pmol, p > 0.05) rats. These findings suggest that the presence and absence of PON3 dramatically affect the level of endogenous CTSs, indicating its potential role in CTS regulation.
    Keywords endogenous cardiotonic steroids ; telocinobufagin ; marinobufagin ; paraoxonase ; urine ; SPE ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 630 ; 333
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Management and Outcome of Severe Sepsis and Septic Shock Patients

    Sabitri Lamichhane / Nayan Manandhar / Shailendra Dhakal / Yagya Laxmi Shakya

    Journal of Nepal Health Research Council, Vol 16, Iss

    2018  Volume 2

    Abstract: Background: Severe sepsis and septic shock are major causes of morbidity and mortality worldwide and need immediate medical attention. Early recognition, fluid resuscitation and early antimicrobials are the mainstays of sepsis therapy. This study ... ...

    Abstract Background: Severe sepsis and septic shock are major causes of morbidity and mortality worldwide and need immediate medical attention. Early recognition, fluid resuscitation and early antimicrobials are the mainstays of sepsis therapy. This study analyzed the management strategies of severe sepsis and septic shock and evaluated its impact. Methods: A prospective study was conducted on patients admitted through emergency department of Tribhuvan University Teaching Hospital of Nepal, who were diagnosed with severe sepsis and septic shock. Results: A total of 85 patients were diagnosed as severe sepsis and septic shock with 45 female patients and mean age 47.69 years ranging from 18 to 83 years. Pneumonia (45.9%) was found to be the major source of infection. The most commonly prescribed antibiotics and vassopressor at emergency department were ceftriaxone (24.7%) and norepinephrine (44.7%) respectively. The mean length of stay in Emergency department was 13.01 ± 7.03 h, while it was 11.27 ± 5.26 days in hospital. A total of 31 (36.5%) septic patients died. Deceased patients were found to have greater age, higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score and presence of co-morbid conditions. Conclusions: This study looked in-depth on management and outcome of patients with severe sepsis and septic shock. Mortality from severe sepsis and septic shock were high, but similar to other studies. Keywords: Antimicrobial therapy; emergency department; mortality; septic shock; severe sepsis.
    Keywords Public aspects of medicine ; RA1-1270
    Subject code 616
    Language English
    Publishing date 2018-07-01T00:00:00Z
    Publisher Nepal Health Research Council
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Rational design of metabolically stable HDAC inhibitors: An overhaul of trifluoromethyl ketones.

    Riddhidev, Banerjee / Endri, Karaj / Sabitri, Lamichhane / Kotsull Lauren, N / Nishanth, Kuganesan / Dragan, Isailovic / Mary Kay H, Pflum / James, Slama / William, Taylor / L M Viranga, Tillekeratne

    European journal of medicinal chemistry

    2022  Volume 244, Page(s) 114807

    Abstract: Epigenetic regulation of gene expression using histone deacetylase (HDAC) inhibitors is a promising strategy for developing new anticancer agents. The most common HDAC inhibitors are hydroxamates, which, though highly potent, have limitations due to ... ...

    Abstract Epigenetic regulation of gene expression using histone deacetylase (HDAC) inhibitors is a promising strategy for developing new anticancer agents. The most common HDAC inhibitors are hydroxamates, which, though highly potent, have limitations due to their poor pharmacokinetic properties and lack of isoform selectivity. Trifluoromethylketones (TFMK) developed as alternatives to hydroxamates are rapidly metabolized to inactive trifluoromethyl alcohols in vivo, which prevented their further development as potential drug candidates. In order to overcome this limitation, we designed trifluoropyruvamides (TFPAs) as TFMK surrogates. The presence of an additional electron withdrawing group next to the ketone carbonyl group made the hydrate form of the ketone more stable, thus preventing its metabolic reduction to alcohol in vivo. In addition, this structural modification reduces the potential of the TFMK group to act as a covalent warhead to eliminate off-target effects. Additional structural changes in the cap group of the inhibitors gave analogues with IC
    MeSH term(s) Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/chemistry ; Ketones/pharmacology ; Epigenesis, Genetic ; Repressor Proteins/metabolism ; Hydroxamic Acids/chemistry ; Protein Isoforms/metabolism
    Chemical Substances Histone Deacetylase Inhibitors ; Ketones ; Repressor Proteins ; Hydroxamic Acids ; Protein Isoforms
    Language English
    Publishing date 2022-10-05
    Publishing country France
    Document type Journal Article
    ZDB-ID 188597-2
    ISSN 1768-3254 ; 0009-4374 ; 0223-5234
    ISSN (online) 1768-3254
    ISSN 0009-4374 ; 0223-5234
    DOI 10.1016/j.ejmech.2022.114807
    Database MEDical Literature Analysis and Retrieval System OnLINE

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