Permeacija losartana kroz humani respiratorni epitel: In vitro ispitivanja na Calu-3 stanicama

The potential for nasal delivery of losartan, a drug with poor oral bioavailability, was investigated using Calu-3 cells. Epithelial permeation of the drug with or without dimethyl-β-cyclodextrin (DM--CD) and glycocholate was investigated. Possible transport mechanism of the compound and epithelial mucosal tolerance were screened. Reversibility of epithelial membrane perturbation was also investigated by measuring transepithelial electrical resistance (TEER) recovery over a 24-h period following drug formulation exposure. The permeability coefficient of losartan was 1.3 ± 0.5 × 10-6 cm s-1. This flux was not significantly different from that of formulations containing DM--CD (0.5 and 1.0 %) or glycocholate (0.5 %). However, the formulation with 1.0 % glycocholate significantly increased losartan permeation 7-fold. Losartan flux across the cells was concentration-dependent. Serosal to mucosal permeation was significantly higher than mucosal to serosal permeation. Concentration-dependency, as well as polarity in transport indicated that the flux of the compound across Calu-3 cells was not limited to passive diffusion. Cells exposed to DM--CD (0.5 and 1.0 %) and glycocholate (0.5 %) caused no significant change in TEER and mitochondrial dehydrogenase activity (MDH). The results of the study showed that losartan may be a suitable drug candidate for nasal delivery.U radu je ispitivana mogućnost nazalne primjene losartana, lijeka sa slabom bioraspoloživošću nakon peroralne uporabe, koristeći Calu-3 stanice. Ispitivana je permeacija lijeka kroz epitel u prisutnosti dimetil-β-ciklodekstrina (DM--CD) i glikokolata te bez njihove prisutnosti. Predložen je mogući mehanizam transporta kroz epitel i određena je tolerancija epitelne mukoze. Reverzibilnost promjena u epitelu praćena je mjerenjem povrata transepitelnog električnog otpora (TEER) kroz razdoblje od 24 h nakon izlaganju pripravku lijeka. Koeficijent permeabilnosti losartana bio je 1.3 ± 0.46 × 106 cm s1. Taj se dotok značajno ne razlikuje od pripravaka koji sadrže DM--CD (0,5 i 1,0 %), odnosno glikokolat (0,5 %) (faktor povećanja 1,0). Međutim, iz pripravka s 1,0 % glikokolata povećala se permeacija losartana 7 puta. Protok losartana kroz stanice ovisio je o koncentraciji. Permeacija iz seruma u mukozu bila je značajno veća nego u obrnutom smjeru. Ovisnost o koncentraciji te polarnost u transportu ukazuju na to da protok losartana kroz Calu-3 stanice nije ograničen samo na pasivnu difuziju. Stanice izložene dimetil-β-ciklodekstrinu (0,5 i 1,0 %) i glikokolatu (0,5 %) nisu uzrokovale značajne promjene TEER-a i aktivnosti mitohondrijske dehidrogenaze (MDH). Rezultati pokazuju da je losartan pogodan za nazalnu isporuku

Effect of Corruption on Corporate Governance in Selected Area Offices of Deposit Money Banks in Enugu State, Nigeria

The study seeks to examine the effect of corruption on corporate governance in selected area offices of deposit money banks in Enugu State, Nigeria. The specific objectives were to; (i) determine the extent to which bribery affects the board of directors\u27 functions, (ii) ascertain the extent to which fraud affects the managers\u27 accountability, and (iii) identify the nature of the relationship existing between money laundering and shareholders\u27 investment in selected area offices of deposit money banks in Enugu State, Nigeria. The study adopted a descriptive survey design. The population of the study was 1197, which comprised the senior and junior staff members of the five selected banks (United Bank for Africa Plc, First Bank of Nigeria Plc, Access Bank Plc, Fidelity Bank Plc, and Skye Bank Plc.). The sample size of 316 was obtained from the population using Freud and William\u27s formula at 5% error tolerance and 95% level of confidence. Data collection was done via a questionnaire and an oral interview guide. Simple Linear Regression Analysis and Pearson Product Moment Correlation were used for data analysis

Treatment Outcomes in Patients Receiving Combination Antiretroviral Therapy in Central Hospital, Benin City, Nigeria

Purpose: This study investigated mortality rate, early CD4 responses, pattern of ARVs substitutions and medication adherence of HIV-infected patients on first-line triple combination antiretroviral therapy (ART) in Central Hospital, Benin City, Nigeria. Methods: A retrospective assessment of 196 HIV-infected patients on first-line combination ART regimens was performed following 18 months of therapy. Medication adherence assessment of a 69- patient follow-up target group was based on a study-specific questionnaire. Paired sample t-test and simple linear correlation were used to test the association of the CD4-cell counts at different time intervals. Kaplan-Meier model was used to assess survival functions while log-rank test was applied to assess statistical difference at 95 % confidence interval (CI). Mean age of participants was 33.6 years (95 % CI, 32.1 - 35.2; 67.9 % were females. Results: At ART initiation, 27.0 % were at WHO clinical stage II, 47.0 % at stage III. Mortality rate (N = 196) was 20.3 deaths per 100 patient-months; 31.6 % occurred in < 30 days while 52.6 % occurred post-120 days of treatment. The mean CD4-cell count (cells/mm3) at ART initiation was 179.2 which increased to 328.5 at 3 months, 325.6 at 6 months, 357.4 at 12 months, and 366.7 at 18 months, (p < 0.01). Patients started on stavudine-based or efavirenz-based regimens were considerably more likely to have that drug substituted, compared to patients started on zidovudine-based or nevirapine-based regimens. The level of adherence reported after 18 months on ART was 73.8 %. Conclusion: In this setting, patients receiving ART showed significant improvements in CD4-cell status but adherence level was relatively poor. Patients were more stable on zidovudine-based or nevirapinebased regimens than on stavudine-based or efavirenz-based regimens. Early mortality rate was high, indicating a need for early interventions.Keywords: Antiretroviral therapy; HIV/AIDS; Mortality; Therapy outcomes, Nigeri

The Impact of Mentoring as a GMP Capability Building Tool in The Pharmaceutical Manufacturing Industry in Nigeria

Good Manufacturing Practices (GMP), a component of Pharmaceutical Quality Systems, is aimed primarily at managing and minimizing the risks inherent in pharmaceutical manufacture to ensure the quality, safety and efficacy of products. Provision of adequate number of personnel with the necessary qualifications/practical experience and their continuous training and evaluation of effectiveness of the training is the responsibility of the manufacturer. (World Health Organization [WHO], 2014; International Organization for Standardization [ISO], 2015). The classroom method of training that has been used for GMP capacity building in the pharmaceutical manufacturing industry in Nigeria over the years, delivered by experts from stringently regulated markets, have not yielded commensurate improvement in the Quality Management Systems (QMS) in the industry. It is necessary and long over-due to explore an alternative training method that has a track record of success in other sectors. A lot of studies carried out on mentoring as a development tool in several fields such as academia, medicine, business, research etc., reported positive outcomes. The aim of this study was to explore mentoring as an alternative GMP training method in the pharmaceutical manufacturing industry in Nigeria. Specifically, the aim of this study was to evaluate the impact of mentoring as a GMP capability building tool in the pharmaceutical manufacturing industry in Nigeria, with focus on GMP documentations in XYZ pharmaceutical manufacturing company located in South-Western region of Nigeria. The methodology comprised gap assessment of GMP documentation of XYZ company to generate current state data, development of training materials based on the identified gaps and use of the training materials for the mentoring sessions. The outcome of the study was outstanding as gap assessment identified the areas of need that enabled development efforts to be targeted at these areas, unlike generic classroom training. The mentees’ acceptance of the mentoring support was evident by their request for additional training in some other areas related to the microbiology operations that were not covered in the gap assessment. This result portrays mentoring as a promising tool for GMP capacity building, but more structured studies need to be conducted in this area to generate results that can be generalized

Mullerian adenosarcoma of the cervix: case report

Mullerian adenosarcomas are rare tumours that may be found in any part of the female genital tract including cervix. They are more common in the reproductive age group and rare among blacks. When they present in the cervix they may be clinically misdiagnosed as an endocervical polyp and histologically as an adenofibroma. Clinical presentation is mostly as irregular vagina bleeding and as a mass in the vagina. Meticulous histopathological evaluation is crucial for its optimum management

Impact of Talent Management Strategies on Organizational Performance in Selected Deposit Money Banks in Lagos State, Nigeria

This study critically examined the Impact of Talent Management Strategies on Organizational Performance in Selected Deposit Money Banks (DMB) in Lagos State, Nigeria. Specifically, the study sought to; (i) determine the extent succession planning relates to sustainability; (ii) ascertain to what extent human capital development impacts on innovative capabilities of employees; and, (iii) examine the degree compensation impacts on employee engagement, in selected DMBs under study. The study adopted the survey design. The population of the study was 3126 comprising management and junior staff drawn from the selected DMBs in Lagos state, Nigeria. These include First Bank of Nigeria Plc, United Bank for Africa Plc, Zenith Bank Plc, Access Bank Plc, and Ecobank Plc. The sample size of 359 was obtained from the population using Bill Godden\u27s formula at 5% error margin and 90% level of confidence. Data were collected using the questionnaire research instrument and interview guide which was designed in a 5-point Likert Scale and was manually administered to the respondents. The validity of the instrument was measured using content validity, and this was done by three management experts from both the industry and the academia

Prevalence and associations of symptomatic renal papillary necrosis in sickle cell anemia patients in South‑Eastern Nigeria

Aim: To assess the prevalence and associations of symptomatic renal papillary necrosis (RPN) in sickle cell anemia patients.Patients and Methods: The case notes of homozygous hemoglobin (Hb) S patients diagnosed with RPN were retrospectively assessed. Diagnosis was based on microscopic hematuria and positive ultrasound findings. Their steady state diastolic blood pressure, Hb, leukocyte count, platelet count, serum direct bilirubin, and aspartate transaminase, were obtained by automated analyzers. These were evaluated for any relationship with the occurrence of RPN.Results: Two hundred and twenty patients were assessed aged 6–55 years with a median age of 24 years. The prevalence of symptomatic RPN was found to be 2.3%. RPN was positively associated with the female gender (Chi‑square P value 0.001), but not with any other clinical or laboratory variable. However, other predictors of disease severity were positively associated with RPN such as age, diastolic blood pressure 0.180 (P = 0.016), serum aspartate transaminase, serum bilirubin 0.145 (0.027), Hb, and leukocyte count − 0.155 (P = 0.003).Conclusion: The prevalence of symptomatic RPN is low in this group of homozygous S patients and occurs more commonly in females. Improvement in care for these patients will reduce these chronic complications.Keywords: Female gender, microscopic hematuria, renal papillary necrosis, sickle cell anemi

360-Degree Complex Primary Reconstruction Using Porous Tantalum Cages for Adult Degenerative Spinal Deformity

Study Design: Retrospective cohort study. Objective: To assess both implant performance and the amount of correction that can be achieved using multilevel anterior lumbar interbody fusion (ALIF). Methods: Retrospective cohort study (n = 178) performed over a 4-year period. Surgical variables examined included blood loss, operative time, perioperative complications, and secondary/revision procedures. Follow-up radiographic assessment was performed to record implant-related problems. Radiographic parameters were examined pre- and postoperatively. Health-related quality of life (HRQOL) outcome measures were collected preoperatively and at 6 weeks, 6 months, 1 year, and 2 years postoperatively. Descriptive and comparative statistical analysis, using paired-sample t test and repeated-measures analysis of variance (rANOVA), was performed. Results: Lumbar lordosis increased from 42° ± 17° preoperatively to 55° ± 11° postoperatively (P < .001). The visual analog scale back pain mean score improved from 8.3 ± 1.5 preoperatively to 2.6 ± 2.4 at 2 years (P < .001). The mean Oswestry Disability Index improved from 69.5 ± 21.5 preoperatively to 19.9 ± 15.2 at 2 years (P < .001). The EQ-5D mean score improved from 0.2 ± 0.2 preoperatively to 0.8 ± 0.1 at 2 years (P = .02). There were no neurological, vascular, or visceral approach-related injuries reported. No rod breakages and no symptomatic nonunions occurred. There was one revision procedure performed for fracture. Conclusions: The use of porous tantalum cages as part of a 360-degree fusion to treat adult degenerative spinal deformity has been demonstrated to be a safe and effective strategy, leading to good clinical, functional, and radiographic outcomes in the short term

Making Study Populations Visible through Knowledge Graphs

Treatment recommendations within Clinical Practice Guidelines (CPGs) are largely based on findings from clinical trials and case studies, referred to here as research studies, that are often based on highly selective clinical populations, referred to here as study cohorts. When medical practitioners apply CPG recommendations, they need to understand how well their patient population matches the characteristics of those in the study cohort, and thus are confronted with the challenges of locating the study cohort information and making an analytic comparison. To address these challenges, we develop an ontology-enabled prototype system, which exposes the population descriptions in research studies in a declarative manner, with the ultimate goal of allowing medical practitioners to better understand the applicability and generalizability of treatment recommendations. We build a Study Cohort Ontology (SCO) to encode the vocabulary of study population descriptions, that are often reported in the first table in the published work, thus they are often referred to as Table 1. We leverage the well-used Semanticscience Integrated Ontology (SIO) for defining property associations between classes. Further, we model the key components of Table 1s, i.e., collections of study subjects, subject characteristics, and statistical measures in RDF knowledge graphs. We design scenarios for medical practitioners to perform population analysis, and generate cohort similarity visualizations to determine the applicability of a study population to the clinical population of interest. Our semantic approach to make study populations visible, by standardized representations of Table 1s, allows users to quickly derive clinically relevant inferences about study populations.Comment: 16 pages, 4 figures, 1 table, accepted to the ISWC 2019 Resources Track (https://iswc2019.semanticweb.org/call-for-resources-track-papers/