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Ntirenganya C.,University of Kigali | Manzi O.,University of Kigali | Muvunyi C.M.,National University of Pharmacy | Ogbuagu O.,Yale University
American Journal of Tropical Medicine and Hygiene | Year: 2015

Antimicrobial resistance (AMR) is a serious public health threat in both developed and developing countries. Many developing countries, including Rwanda, lack adequate surveillance systems, and therefore, the prevalence of AMR is not well-known. We conducted a prospective observational study to assess the prevalence of AMR among common bacterial isolates from clinical specimens obtained from patients on the medical wards of Kigali University Teaching Hospital (KUTH). We evaluated the antibiotic sensitivity patterns of bacterial pathogens cultured from urine, blood, sputum, and wound swab specimens obtained over a 6-month period (July 1 toDecember 30, 2013). There were 154 positive cultures from specimens obtained from 141 unique patients over the study period. Urine, blood, wound swab, and sputum cultures comprised 55.2%, 25.3%, 16.2%, and 3.3% of the total specimens evaluated; 31.4% and 58.7% of Escherichia coli and Klebsiella isolates, respectively, were resistant to at least one of the third generation cephalosporins. Eight percent of E. coli isolates were resistant to imipenem; 82% and 6% of Staphylococcus aureus strains were oxacillin-and vancomycin-resistant respectively. Antimicrobial resistance rates are high in Rwanda and pose a serious therapeutic challenge to the management of common infections. Copyright © 2015 by The American Society of Tropical Medicine and Hygiene.

BACKGROUND: Several antibiotics have shown promising anti-malarial effects and have been useful for malarial chemotherapy, particularly in combination with standard anti-malarial drugs. Tigecycline, a semi-synthetic derivative of minocycline with a unique and novel mechanism of action, is the first clinically available drug in a new class of glycylcycline antibiotics.METHODS: Tigecycline was tested in vitro against chloroquine (CQ)-sensitive (D6) and resistant strains (W2) of Plasmodium falciparum alone and in combination with CQ. Tigecycline was also tested in vivo in combination with CQ in Plasmodium berghei-mouse malaria model for parasitaemia suppression, survival and cure of the malaria infection.RESULTS: Tigecycline was significantly more active against CQ-resistant (W2) than CQ-susceptible (D6) strain of P. falciparum. Tigecycline potentiated the anti-malarial action of CQ against the CQ-resistant strain of P. falciparum by more than seven-fold. Further, treatment of mice infected with P. berghei with tigecycline (ip) produced significant suppression in parasitaemia development and also prolonged the mean survival time. Treatment with as low as 3.7 mg/kg dose of tigecycline, once daily for four days, produced 77-91% suppression in parasitaemia. In vivo treatment with tigecycline in combination with subcurative doses of CQ produced complete cure in P. berghei-infected mice.CONCLUSION: Results indicate prominent anti-malarial action of tigecycline in vitro and in vivo in combination with CQ and support further evaluation of tigecycline as a potential combination candidate for treatment of drug-resistant cases of malaria.

Prada G.I.,National University of Pharmacy
Acta Endocrinologica | Year: 2014

Researches on ageing phenomenon offer significant information regarding the consequences of stressors on immune system that affects longevity in the elderly. Immunosenescence has become the most common immunodeficiency state in humans, occurring in over 30% of community - dwelling elderly, and greater than 90% of elderly who are ill, taking medication, or residing in longterm care facilities. Immunosenescence may reflect tandem changes in neuroendocrine responses. There are several agingrelated changes in cortisol, DHEA and catecholamines, which are considered to set up a “vicious cycle of endocrinosenescence and immuno-senescence”. The low-level, chronic increase in innate, inflammatory response observed in older adults ultimately results in tissue damage and disease; the key inflammatory mediators in this process are CRP, nuclear factor (NF)-kB, IL-1-beta, IL-6, TNF-alpha, cyclooxygenase-2 (COX-2), and inducible nitric oxide (NO) synthase. Further, glucocorticoid inhibition of IL-6 production was observed to be lower in older compared to younger men following psychological stress. There are individual differences that protect aged people from stressors and strains, and it will be important to identify biological mechanisms of protection and those at risk who might benefit from early behavioral interventions. © 2014, Acta Endocrinologica Foundation. All rights reserved.

Park H.Y.,Korea University | Park H.Y.,National University of Pharmacy | Kim G.-Y.,Jeju National University | Choi Y.H.,Korea University | Choi Y.H.,University Graduate Center
International Journal of Molecular Medicine | Year: 2012

Naringenin, one of the most abundant flavonoids in citrus fruits and grapefruits, has been reported to exhibit anti-inflammatory and antitumor activities. However, the cellular and molecular mechanisms underlying the naringenin anti-inflammatory activity are poorly understood. In this study, we conducted an investigation of the inhibitory effects of naringenin on the production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators in BV2 microglial cells. We found that pre-treatment with naringenin prior to treatment with LPS significantly inhibited excessive production of nitric oxide (NO) and prostaglandin E 2 (PGE 2) in a dose-dependent manner. The inhibition was associated with downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Naringenin also attenuated the production of pro-inflammatory cytokines and chemokines, including interleukin-1β (IL-1β), tumor necrosis factor-α(TNF- α) and monocyte chemoattractant protein-1 (MCP-1) by suppressing expression of mRNAs for these proteins. In addition, the molecular mechanism underlying naringenin-mediated attenuation in BV2 cells has a close relationship to suppressing translocation of the nuclear factor-κB (NF-κB) p65 subunit into the nucleus and the phosphorylation of Akt and mitogen-activated protein kinases (MAPKs). These findings suggest that naringenin may provide neuroprotection through suppression of pro-inflammatory pathways in activated BV2 microglial cells.

Zdoryk O.A.,National University of Pharmacy
International journal of pharmaceutical compounding | Year: 2013

Pharmaceutical compounding in modern Ukraine has a rich history and goes back to ancient times. Today in the Ukraine, there is a revival of compounding practice, the opening of private compounding pharmacies, updating of legislative framework and requirements of the State Pharmacopeia of Ukraine for compounding preparations, and the introduction of Good Pharmaceutical Practice.

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