Evaluation of QSAR and ligand enzyme docking for the identification of ABCB1 substrates

P-glycoprotein (P-gp) is an efflux pump that belongs to ATP-binding cassette (ABC) transporter family embedded in the membrane bilayer. P-gp is a polyspecific protein that has demonstrated its function as a transporter of hydrophobic drugs as well as transporting lipids, steroids and metabolic products. Its role in multidrug resistance (MDR) and pharmacokinetic profile of clinically important drug molecules has been widely recognised. In this study, QSAR and enzyme-ligand docking methods were explored in order to classify substrates and non-substrates of P-glycoprotein. A set of 123 compounds designated as substrates (54) or non-substrates (69) by Matsson et al., 2009 was used for the investigation. For QSAR studies, molecular descriptors were calculated using ACD labs/LogD Suite and MOE (CCG Inc.). P-glycoprotein structures available in the Protein data bank were used for docking studies and determination of binding scores using MOE software. Binding sites were defined using co-crystallised ligand structures. Three classification algorithms which included classification and regression trees, boosted trees and support vector machine were examined. Models were developed using a training set of 98 compounds and were validated using the remaining compounds as the external test set. A model generated using BT was identified as the best of three models, with a prediction accuracy of 88%, Mathews correlation coefficient of 0.77 and Youden’s J index of 0.80 for the test set. Inclusion of various docking scores for different binding sites improved the models only marginally

Effect of dietary supplementation with arginine on haematological indices, serum chemistry, carcass yield, gut microflora, and lymphoid organs of growing turkeys

A 8-wk feeding experiment was conducted to investigate the effect of dietary supplementation with Arg on haematological indices, serum chemistry, carcass yield, gut microflora, and lymphoid organ weights of growing turkeys. A total of one hundred and eighty 56-d-old male grower turkeys were weighed individually and randomly assigned to 1 of 3 dietary treatments with 6 replicate pens, and 10 turkeys per pen in a completely randomized design. Dietary treatments consisted of basal diets supplemented with 0, 0.5, and 1.0 g Arg/kg. Haematological indices and serum chemistry were measured at 84 and 112 d of study. Carcass yield, relative weights of retail cuts, organ weights, and gut microflora were measured at d 112. Except eosinophil, no effect of Arg supplementation was obtained on haematological indices at d 84. At d 112, finisher turkeys fed the diet supplemented with 0.5 g Arg/kg had the greatest red blood cell (quadratic, P<0.001), lymphocyte (linear, P=0.011; quadratic, P<0.001), and basophil counts (quadratic, P<0.001). In grower turkeys at d 84, total serum protein (quadratic, P=0.030), and serum globulin concentrations (quadratic, P=0.043) increased initially as Arg supplementation increased from 0 to 0.5 g/kg, but decreased with the 1.0 g Arg/kg. Uric acid concentration and alanine aminotransferase activity reduced as Arg supplementation increased from 0 to 0.5 g/kg, but increased with the 1.0 g Arg/kg (quadratic, P=0.002). In finisher turkeys at d 112, total serum protein (linear, P=0.004; quadratic, P=0.002), serum globulin (linear, P=0.008; quadratic, P=0.030), serum albumin (linear, P=0.012; quadratic, P=0.040), and triodosterine concentrations (linear, P=0.025; quadratic, P=0.033) increased with increasing Arg supplementation. At d 112, spleen weights increased linearly (P=0.006), while thymus weights increased quadratically (P=0.003) with increasing dietary Arg supplementation. Salmonella counts in the small intestinal content of turkeys at d 112 reduced quadratically as Arg supplementation increased from 0 to 1.0 g/kg (P=0.029). In conclusion, Arg supplementation increased packed cell volume of finisher turkeys, improved serum chemistry of grower, and finisher turkeys as indicated by increased total serum protein, and reduced serum enzymes with appreciable improvement obtained when included at 0.5 g Arg/kg. Arginine supplementation enhanced the relative weights of thymus, spleen, and reduced Salmonella counts in small intestine of turkeys

Growth performance, nutrient digestibility, metabolizable energy, and intestinal morphology of growing turkeys fed diet supplemented with arginine

A 8-wk feeding experiment was conducted to investigate the effect of dietary supplementation with Arg on growth performance, nutrient digestibility, metabolizable energy, and intestinal morphology of growing turkeys. A total of one hundred and eighty 56-d-old male grower turkeys were weighed individually and randomly assigned to 1 of 3 dietary treatments with 6 replicate pens and 10 turkeys per pen in a completely randomized design. Dietary treatments consisted of basal diets supplemented with 0, 0.5, and 1.0 g Arg/kg. Growth response was measured during the grower (d 56–84) and finisher (d 84–112) phases, while nutrient digestibility, metabolizable energy, and intestinal morphology were measured at d 84 and 112. Arginine supplementation had no effect on growth response during the grower phase. During the finisher phase, feed conversion ratio decreased initially as Arg supplementation increased from 0 to 0.5 g/kg, but it increased with the 1.0 g Arg/kg (quadratic, P=0.028). At d 84, grower turkeys fed diets supplemented with 1.0 g Arg/kg had greater (linear, P<0.001) apparent dry matter, crude protein, and ether extract digestibility. At d 84, greatest apparent metabolizable energy, nitrogen corrected apparent metabolizable energy, and true metabolizable energy values were obtained with grower turkeys fed diet supplemented with 0.5 g Arg/kg (quadratic, P<0.001). At d 84, duodenum, and ileum villus height in grower turkeys increased linearly, and quadratically (P<0.001) with increasing Arg supplementation. Dietary supplementation with Arg reduced the apical widths in duodenum (linear, P=0.003; quadratic, P<0.001), jejunum (linear and quadratic, P<0.001), and ileum (linear, P=0.010; quadratic, P=0.004) of grower turkeys. At d 112, jejunum villus height (quadratic, P=0.042), and ileum villus height (linear, P=0.022; quadratic, P=0.042) of finisher turkeys increased, while duodenum apical widths reduced (quadratic, P=0.033) with increasing Arg supplementation. In conclusion, Arg supplementation showed a linear improvement in nutrient digestibility of grower turkeys at d 84, increased nutrient absorption in grower, and finisher turkeys as indicated by increased intestinal villus height at d 84, and 112. Furthermore, dietary supplementation with 0.5 g Arg/kg promoted a quadratic improvement in feed conversion ratio of finisher turkeys, and metabolizable energy values of grower turkeys at d 84

The effect of using solid-state fermented peeled and unpeeled cassava root tubers and limiting amino acid supplementation on metabolisable energy for meat-type cockerels

A preliminary in-vitro solid-state fermentation of peeled (PCRM) and unpeeled cassava root tuber meal (UCRM) using Aspergillus niger van Tieghem, was conducted, followed by a force-feeding experiment to investigate the effects of a diet of solid state fermented peeled (PCRM) and unpeeled (UPCRM) cassava root, supplemented with limiting amino acid, on metabolizable energy (ME) for meat-type cockerels. Forty eight, 84 d-old meat-type cockerels (Ross 308) were assigned to 8 treatments consisting of 6 birds per treatment laid out in a 2 × 2 × 2 factorial arrangement of treatment consisting of PCRM and UCRM subjected or not to solid-state fermentation and supplemented with or without limiting amino acids. An additional 6 cockerels were used for endogenous study. Peeling of cassava root increased (P < 0.05) gross energy content of the resultant cassava meal when compared with UCRM. Solid-state fermentation using Aspergillus niger increased (P < 0.05) the crude ash, ether extract and arginine concentration of PCRM and UCRM. Solid-state fermented PCRM recorded the highest (P < 0.05) amylopectin, least (P < 0.05) resistant starch and hydrocyanide concentration. Highest (P < 0.05) apparent metabolizable energy (AME) and nitrogen corrected AME (AMEn) values were obtained for cockerels fed with solid-state fermented PCRM supplemented with or without amino acid. However, supplementation of solid-state fermented PCRM with amino acid resulted in highest (P < 0.05) true metabolisable energy (TME) and nitrogen corrected TME (TMEn) for meat-type cockerels. Reduced (P < 0.05) AME and AMEn values were recorded for UCRM, regardless of solid-state fermentation and amino acid supplementation. In conclusion, solid-state fermentation and amino acid supplementation of PCRM resulted in improved AME, AMEn, TME and TMEn values for meat-type cockerels. Amino acid supplementation had no improvement on AME, AMEn and TME values of UCRM for meat-type cockerels

A meditation on boredom: Re-appraising its value through introspective phenomenology

Boredom is almost universally regarded as a dysphoric mental state, characterised by features such as disengagement and low arousal. However, in certain quarters (e.g., Zen Buddhism), boredom is seen as potentially having great value and even importance. The current study sought to explore boredom through a case study involving introspective phenomenology. The author created conditions in which he would experience boredom for an hour, and recorded his experience in real-time using a variant of the Experiencing Sampling Method. The data were analysed using an adaptation of Interpretative Phenomenological Analysis. The results indicated that the state of boredom contained three main sources of value: (a) altered perception of time; (b) awakened curiosity about the environment; and (c) exploration of self. Consequently, the paper offers a re-appraisal of boredom, suggesting that rather than necessarily being a negative state, if engaged with, boredom has the potential to be a positive and rewarding experience

Aplastic anaemia in a low resource economy: experience and survival of cases at University of Medical Sciences, Ondo, Southwest, Nigeria

Objective: The objective of the study is to determine the incidence, and discuss management practices currently in use alongside survival outcome at the University of Medical Sciences Teaching Hospital (UNIMEDTH), Ondo State, Nigeria over a 10-year period Design: This study utilized a retrospective research design Setting: The study was conducted at UNIMEDTH, Ondo State, Nigeria. Subject/Participant: Patients diagnosed with aplastic anaemia in the Haematology Department at the UNIMETH between 2012 to 2021. Intervention: Information on the age, sex, haematologic parameters at presentation (White blood cell count, Haematocrit, Platelet count) and survival outcome were retrieved from the case notes of all patient’s diagnosis with aplastic anaemia. Main outcome measures: Survival rate of the patients following a strictly monitored treatment over a 10 – year time span Results: A total of 13 patients were treated for aplastic anaemia over the 10 - year period giving an annual hospital incidence of 1.625 cases/year. Seven patients were diagnosed with severe Aplastic Anaemia, four with moderate AA and two with mild AA. The age of the patients ranged from 3 to 85 years with a male to female ratio of 0.54:0.46. The mean packed cell volume at presentation was 15.03%, white cell count was 2,323 x 109/L, and platelet count was 35,461/L. Conclusion: The evidence of improved survival rate in aplastic anaemia globally is apparent. However, this study has shown this to be hampered by various factors ranging from federal policies to reduce prices of drugs for patient

Physical masculization and growth performance of Oreochromis niloticus placed on 17α-methyltestosterone treated diet

Precocious reproduction of Nile tilapia still remains an impediment to its commercial culture. Various techniques have been used to solve this, including the culture of all male populations. The use of 17 α-methyl testosterone for sex reversal has been practiced but the effective dosage to maximize this technology is yet to be established for Oreochromis niloticus. This study was therefore conducted to evaluate the effect of different doses of 17 α-methyl testosterone (MT) on the sex reversal and growth performance of O. niloticus. Nile tilapia brood stocks with average weight of 220±7g were appropriately paired in happas. After two weeks, fertilized eggs were taken from the mouth of the female and hatched in jars. 300 fry were randomly stocked in 15 plastic aquarium tanks at a density of 33fish/m2, forming five treatments with three replicates. Fry feed of 45% crude protein was treated with different levels of 17 α-methyl testosterone to form five treatments (MT0, MT1, MT2, MT3, MT4 with 0mg, 20mg, 40mg, 60mg, and 80mg of MT/kg of feed respectively) fed to the tilapia fry after yolk absorption for 28 days. Percentage Specific Growth Rate (SGR), Mean Weight Gain (MWG), survival rates, and water quality were measured. Sex determination through histological examination was done following the gonadal squash method. Descriptive analysis and ANOVA were used to analyze the data collected. Results revealed that treatment MT3 had the highest SGR) of 7.57±0.3%, followed in descending order by treatments MT1, MT2, MT0 (control), and (MT4) with values 7.46±0.3%, 7.31%±0.2%, 7.28%±0.2% and 7.08%±0.5% respectively. The MWG (%) showed that treatment MT3 had the highest value of 11.0±13.1% while treatments MT4 had the least MWG of 8.2±21.5%, MT0, MT1 and MT2 had 9.1%±2.8, 10.2±9.9% and 9.3±4.3% respectively. Treatment MT3 also had the best survival rate percentage of 86.7±5.7% while the least was recorded in MT4 with value of 70%±5.0. Treatment MT3 with 60mg/kg of MT diet was the most efficient in sex reversal, resulting in 80±3.34% males, 20.0±7.8% intersex and no female, while MT4, MT1 MT2 and MT0 had 60±6.2% 50±4.2%, 50±6.9%, 25±2.9% respectively. Results showed that 17 α-methyl testosterone had a significant effect on the sex ratio of the fish. 60mg/Kg of MT in feed was the most effective of all the doses tested.Keywords: Sex reversal, Monosex, Precocious reproduction, Oreochromis niloticu

A profile of leukaemias in adults managed at the University Of Calabar Teaching Hospital in Nigeria

Background: Types and proportions of leukaemias in adults tend to vary from one institution to another. These are due to a variety of factors that may be examined after establishing and describing the status of leukaemias in a particular setting. The results inform planning for management and impacts on outcomes of intervention. Objective: To determine the types and trend of adult leukaemia managed at the University of Calabar Teaching Hospital. Design: This was a cross sectional retrospective study of the adult leukaemias seen at the Department of Haematology and Blood Transfusion, University of Calabar Teaching Hospital, Calabar (UCTH). Setting: The Haematology Department of the University of Calabar Teaching Hospital (UCTH) Nigeria. Population: All adults managed for haematological malignancies at the UCTH during the study period of ten-year from August 2009 to December 2018. Materials and Methods: Data were retrieved from the archives in the hospital including cancer registry, and departmental records. Information that met the study entry criteria was collected using a proforma questionnaire. The following were required for each case: dates of presentation, diagnosis, age, gender, and type of leukaemia. Data was also being further reviewed by the haematologist who had to corroborate with medical records and patients' case-notes. The data were then pooled, screened, collated and entered in a Microsoft Excel 2016 spreadsheet and analysed with IBM SPSS Version 22. Chi-square test was used to determine relationships between the variables. The results were presented using descriptive statistics (frequencies and percentages), and graphical charts. Results: A total of 138 haematological malignancies was seen over a period of ten years. Of which 70 were adult leukaemia, constituting the 50.72% of the total haematological malignancies. Male to female ratio was 1:1. Overall age characteristics; age ranges from 19 to 82 years, mode was 54 years, and median age was 53 years. Male age characteristics range 19 to 78, mean 48.72 ± 12.75, Female age characteristics range 26 to 82, mean 54.25± 10.50. Trend results for each type of leukaemia, in males, in females. The CLL was the most prevalent leukaemia variant with 26.09%, followed by CML 19.57%. The ALL and AML had a prevalence of 2.90% and 2.17% respectively. However, when leukaemia was categorised into types; females revealed CLL and CML 52.78 % and 59.26% of the leukaemias respectively. A peak was observed between 2014 and 2017. The mean age of the patients with leukaemia over the study period was 49.49 ± 16.95 (standard deviation) years. Gender distribution of all types, 4 males had ALL with no female, 17 males and 19 females had CLL, 3 males had AML with no female, 11 males and 16 females had CML. Conclusion: this study showed that leukaemias in adults in University of Calabar Calabar Teaching Hospital, Cross River State have variable patterns of age and sex. Type of leukaemia also showed similar variations. This study recommends further studies to understand causes of the variations in the profile of leukaemias