Predictors of Efavirenz Plasma Exposure, Auto-Induction Profile, and Effect of Pharmacogenetic Variations among HIV-Infected Children in Ethiopia: A Prospective Cohort Study

(1) Background: Efavirenz plasma concentration displays wide between-patient variability partly due to pharmacogenetic variation and autoinduction. Pediatric data on efavirenz pharmacokinetics and the relevance of pharmacogenetic variation are scarce, particularly from sub-Saharan Africa, where >90% of HIV-infected children live and population genetic diversity is extensive. We prospectively investigated the short- and long-term effects of efavirenz auto-induction on plasma drug exposure and the influence of pharmacogenetics among HIV-infected Ethiopian children. (2) Method: Treatment-naïve HIV-infected children aged 3–16 years old (n = 111) were enrolled prospectively to initiate efavirenz-based combination antiretroviral therapy (cART). Plasma efavirenz concentrations were quantified at 4, 8, 12, 24, and 48 weeks of cART. Genotyping for CYP2B6, CYP3A5, UGT2B7, ABCB1, and SLCO1B1 common functional variant alleles was performed. (3) Results: The efavirenz plasma concentration reached a peak at two months, declined by the 3rd month, and stabilized thereafter, with no significant difference in geometric mean over time. On average, one-fourth of the children had plasma efavirenz concentrations ≥4 µg/mL. On multivariate analysis, CYP2B6*6 and ABCB1c.3435 C > T genotypes and low pre-treatment low-density lipoprotein (LDL) were significantly associated with higher plasma efavirenz concentration regardless of treatment duration. Duration of cART, sex, age, nutritional status, weight, and SLCO1B, CYP3A5, UGT2B7, and ABCB1 rs3842 genotypes were not significant predictors of efavirenz plasma exposure. (4) Conclusion: Pre-treatment LDL cholesterol and CYP2B6*6 and ABCB1c.3435 C > T genotypes predict efavirenz plasma exposure among HIV-infected children, but treatment-duration-dependent changes in plasma efavirenz exposure due to auto-induction are not statistically significant.

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Prevalence of urogenital and intestinal schistosomiasis among school children in South-west Nigeria

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009628 ◽

2021 ◽

Vol 15 (7) ◽

pp. e0009628

Author(s):

Johnson A. Ojo ◽

Samuel A. Adedokun ◽

Akeem A. Akindele ◽

Adedolapo B. Olorunfemi ◽

Olawumi A. Otutu ◽

...

Keyword(s):

School Children ◽

Mixed Infection ◽

Schistosoma Haematobium ◽

Geometric Mean ◽

Harmful Effect ◽

Infection Intensity ◽

Sub Saharan Africa ◽

South West ◽

Significant Difference ◽

And Control

Background The risk of co-infection with Schistosoma haematobium and S. mansoni and the potential harmful effect on morbidity and control is enhanced by the overlapping distribution of both species in sub-Saharan Africa. Despite the reported high endemicity of both species in Nigeria, studies on the spread and effect of their mixed infection are limited. Therefore, a cross-sectional survey was conducted among school children in two communities in South-west Nigeria to investigate the prevalence of mixed human schistosome infection, intensity, and possible ectopic egg elimination. Methods Urine and stool samples were collected from consenting school children in Ilie and Ore communities of Osun State, Nigeria. Schistosoma haematobium eggs were detected in urine using the urine filtration technique, while S. mansoni eggs were detected in stool using the Kato–Katz thick smear technique. Results The study enrolled 466 primary and secondary school children (211; 45.3% males vs. 255; 54.7% females; mean age 11.6 ± 3.16 years). The overall prevalence of schistosomiasis was 40% (185/466), with 19% (89/466) recording single S. haematobium infection while 9% (41/465) had a single S. mansoni infection. The geometric mean egg count for S. haematobium was 189.4 egg/10ml urine; 95% CI: range 115.9–262.9, while for S. mansoni, it was 115.7 epg; 95% CI: range 78.4–152.9. The prevalence of ectopic S mansoni (S. mansoni eggs in urine) was 4.7%, while no ectopic S. haematobium (S. haematobium eggs in stool) was recorded. Mixed infection of S. haematobium/S. mansoni had a prevalence of 9.5% (44/466). More females (54.5%) presented with S. haematobium/S. mansoni co-infection. For both parasites, males had higher infection intensity, with a significant difference observed with S. haematobium (p = 0.0004). Hematuria was significant in individuals with single S. haematobium infection (p = 0.002), mixed ectopic S. haematobium/S. mansoni (p = 0.009) and mixed S. haematobium/S. mansoni/ectopic S. mansoni (p = 0.0003). Conclusions These findings suggest the probability of interspecific interactions between S. haematobium and S. mansoni. Scaling up of mass administration of praziquantel and control measures in the study areas is highly desirable.

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The Effect of Antiplatelet Drugs on Plasma Betathromboglobulin in Coronary Artery Disease

10.1055/s-0038-1665677 ◽

1979 ◽

Cited By ~ 1

Author(s):

P Han ◽

A Turpie ◽

E Genton ◽

M Gent

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Crossover Trial ◽

Specific Protein ◽

Antiplatelet Drugs ◽

Significant Difference ◽

Pre Treatment ◽

Artery Disease ◽

Therapeutic Doses ◽

Granule Release

Platelets play a role in the development and complications of coronary artery disease (CAD) and a number of abnormalities of platelet function which can be corrected by antiplatelet drugs have been described. Betathromboglobulin (BTG), a platelet-specific protein which is released from α-granules during platelet activation is significantly elevated in patients with angiographically demonstrated CAD (51.0 ± 31.0 ng/ml., n = 50) compared to normal (28.0 ± 8.0 ng/ml., n = 70) p < 0.001. The effect of sulphinpyrazone (800 mg.) or aspirin (1200 mg.)/dipyridamole (200 mg.) on plasma BTG in CAD was studied in a blind prospective crossover trial in 25 patients. Mean BTG concentration pre-treatment was 52.3 ng/ml. and after 1 month’s treatment with placebo, sulphinpyrazone or aspirin/dipyridamole mean plasma BTG concentrations were 53.5, 49.6 and 56.7 ng/ml. respectively. Analysis of variance showed no significant difference between the means (p > 0.1) . This study confirms increased plasma BTG concentrations in patients with CAD and indicates that therapeutic doses of these antiplatelet drugs do not significantly effect the BTG level and thus appear not to prevent α-granule release in CAD.

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STUDIES ON SULFATION FACTOR (SF) ACTIVITY OF HUMAN SERUM

Acta Endocrinologica ◽

10.1530/acta.0.xxxv0381 ◽

1960 ◽

Vol XXXV (III) ◽

pp. 381-396 ◽

Cited By ~ 14

Author(s):

Sven Almqvist

Keyword(s):

Human Serum ◽

Normal Serum ◽

Treatment Level ◽

Response Curves ◽

Normal Children ◽

Significant Difference ◽

Human Sera ◽

Normal Humans ◽

Pre Treatment ◽

Dose Levels

ABSTRACT The sulfation factor (SF) activity of human sera has been estimated using a modification of the method of Daughaday et al. (1959). Each assay was statistically evaluated. The method had a mean precision of 0.14 and, used as an assay of GH of human serum, a sensitivity in three pituitary dwarfs of 0.1 to 0.6 μg of HGH/ml of serum. SF activity was found at all ages between 1 month and 75 years. There was a significantly lower mean SF activity below the age of half a year. Three cases of pituitary dwarfism had significantly low SF activities of sera. There was no significant difference between the SF activities of sera from untreated pituitary dwarfs and the sera from normal children below half a year of age. Dose-response curves with large volumes of sera from pituitary dwarfs and small volumes of sera from normal humans had the same slopes. Four mg of HGH prepared according to the method of Li & Papkoff (1956) resulted in a normal serum SF activity in each of the three dwarfs. A significant (P < 0.01) linear relationship was found between the concentration of SF activity of sera from these subjects and the logarithm of the dose of HGH given with dose levels of 1, 2 and 4 mg daily for three days. The decline of serum SF activity to the pre-treatment level following HGH in one dwarf suggested a half life not different from that indicated by others for growth hormone.

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Isolation of an Anti-fatigue Preparation from Cellulase-treated Maca by Hydroalcoholic Extraction

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.17:93-98 ◽

2017 ◽

Vol 17 (1) ◽

pp. 93-98

Author(s):

Zheng Yue ◽

Zhang Wen-Cheng ◽

Wu Ze-Yu ◽

Fu Chuan-Xiang ◽

Gao Han ◽

...

Keyword(s):

Positive Control ◽

Glycogen Storage ◽

Hepatic Glycogen ◽

Time To Exhaustion ◽

High Dose ◽

Hydroalcoholic Extract ◽

Swimming Time ◽

Significant Difference ◽

Pre Treatment ◽

Better Than

The purpose of this study was to evaluate the anti-fatigue activity of maca hydroalcoholic extract (ME), which mainly contains macamides and polysaccharides. ME was prepared by circumfluence extraction with enzymatic pre-treatment. Anti-fatigue activity of ME was investigated in weight-loaded forced swimming mice, with pure macamides and commercially available maca tablet as positive control. Compared with normal group, pure macamides treatment group could prolong the swimming time to exhaustion, but there was no statistically significant difference (P > 0.05); while ME (middle-dose and high-dose groups) could effectively prolong the swimming durations (P < 0.05). Supplementation with pure macamides significantly decreased blood lactic acid (BLA), whereas ME significantly increased hepatic glycogen (HG), decreased BLA, and blood urea nitrogen (BUN) compared with those in normal control (P < 0.05). The results suggested that the anti-fatigue effect of ME was better than that of pure macamides, which can be explained by the increase of glycogen storage and the reduction of metabolites accumulation.

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Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

Current Drug Metabolism ◽

10.2174/1389200221666200218121050 ◽

2020 ◽

Vol 21 (2) ◽

pp. 126-131

Author(s):

Bhuvanachandra Pasupuleti ◽

Vamshikrishna Gone ◽

Ravali Baddam ◽

Raj Kumar Venisetty ◽

Om Prakash Prasad

Keyword(s):

Plasma Concentration ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Plasma Concentrations ◽

Control Group ◽

Drug Concentrations ◽

Significant Difference ◽

Post Hoc ◽

Hydrolysis Of ◽

Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

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Effects of n-3 Polyunsaturated Fatty Acid Supplementation in the Prevention and Treatment of Depressive Disorders—A Systematic Review and Meta-Analysis

Nutrients ◽

10.3390/nu13041070 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1070

Author(s):

Maike Wolters ◽

Annkathrin von der Haar ◽

Ann-Kristin Baalmann ◽

Maike Wellbrock ◽

Thomas L. Heise ◽

...

Keyword(s):

Depressive Symptoms ◽

Treatment Duration ◽

Depressive Disorders ◽

Meta Analysis ◽

Pufa Supplementation ◽

Depressive Symptomology ◽

Beneficial Effects ◽

Randomized Controlled ◽

Significant Difference

N-3 polyunsaturated fatty acids (PUFAs) have been suggested to affect depressive disorders. This review aims to determine the effect of n-3 PUFAs on depressive symptoms in people with or without diagnosed depression. Medline, PsycINFO, and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) assessing the association between n-3 PUFAs and depressive symptoms or disorders as outcomes. A random-effects meta-analysis of standardized mean difference (SMD) with 95% confidence intervals (CI) was performed. Twenty-five studies (7682 participants) were included. Our meta-analysis (20 studies) indicated that n-3 PUFA supplementation lowered depressive symptomology as compared with placebo: SMD = −0.34, 95% CI: −0.55, −0.12, I2 = 86%, n = 5836, but a possible publication bias cannot be ruled out. Subgroup analyses indicated no statistically significant difference by treatment duration of <12 vs. ≥12 weeks, presence of comorbidity, or severity of depressive symptoms. Nevertheless, beneficial effects were seen in the subgroups of studies with longer treatment duration and with no depression and mild to moderate depression. Subgroup analysis by eicosapentaenoic acid (EPA) dosage revealed differences in favor of the lower EPA dosage. Sensitivity analysis including studies with low risk of bias seems to confirm the overall result. Supplementation of n-3 PUFA appears to have a modest beneficial effect on depressive symptomology, although the quality of evidence is still insufficient.

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Unravelling the Perspectives of Day and Night Traders in Selected Markets within a Sub-Saharan African City with a Malaria Knowledge, Attitude and Practice Survey

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18073468 ◽

2021 ◽

Vol 18 (7) ◽

pp. 3468

Author(s):

Patience B. Tetteh-Quarcoo ◽

Nicholas T. K. D. Dayie ◽

Kevin Kofi Adutwum-Ofosu ◽

John Ahenkorah ◽

Emmanuel Afutu ◽

...

Keyword(s):

Cross Sectional Study ◽

Malaria Treatment ◽

Sub Saharan Africa ◽

African City ◽

Cross Sectional ◽

Attitudes And Practices ◽

Treatment Type ◽

Significant Difference ◽

High Knowledge ◽

Sub Saharan

Background: Malaria is still endemic in sub-Saharan Africa, with a high disease burden. Misconceptions about malaria contribute to poor attitudes and practices, further increasing the burden in endemic countries. Studies have examined the knowledge, attitudes, and practices (KAP) of malaria among different populations. However, there seems to be no available literature reporting on the perspectives of day and night market traders. To the best of our knowledge, this is the first report on malaria KAP with a focus on day and night market traders. Methods: A descriptive cross-sectional study involving day and night market traders in 10 selected markets within the Greater Accra Region of Ghana was carried out. Data were collected from consenting respondents using a structured questionnaire. Results: Of the 760 respondents (33.3% (n = 253) night and 66.7% (n = 507) day traders) interviewed, there was no significant difference between the day and night market traders in terms of malaria KAP. Although the market traders had an overall moderate knowledge (54.0% of the day traders and 56.5% of the night traders), misconceptions about malaria (especially that it could be caused by exposure to the sun) still existed among the traders. Moreover, the majority of the traders who demonstrated high knowledge (43.98%, n = 250) did not always take laboratory tests to confirm their suspicion, indicating poor attitude. Furthermore, the market traders’ choice of drug for malaria treatment (p = 0.001) and preferred malaria treatment type (orthodox or herbal) (p = 0.005) were significantly associated with their knowledge level. Conclusions: Despite the observation that no significant difference in KAP exists between day and night market traders, appropriate health education programs and interventions still need to be directed at misconceptions, poor attitudes, and poor practices revealed by this study. This will ultimately help in the prevention and control of malaria in Ghana, and globally.

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The effect of table olive wastewater extract administration on the adult ovariectomized rat model of osteoporosis

British Journal Of Nutrition ◽

10.1017/s0007114521000465 ◽

2021 ◽

pp. 1-26

Author(s):

Alexandros S. Zervas ◽

Pavlos P. Lelovas ◽

Antonios Galanos ◽

Dimitris Galanis ◽

Maria Makropoulou ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Biomechanical Testing ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Abdominal Fat ◽

Ovariectomized Rats ◽

Mineral Density ◽

Final Body Weight ◽

Significant Difference ◽

Table Olive

Abstract Recent efforts for alternative non-pharmaceutical treatments for postmenopausal osteoporosis are focused on nutritional measures. The aim of this study was to investigate the effect of table olive wastewater extract (OE) administration on bone mineral density (BMD) and biomechanical strength in ovariectomized rats. Thirty mature 9-month-old female Wistar rats were separated into 3 groups of ten; Control, Ovariectomized (OVX) and OVX+OE. BMD was measured before ovariectomy, 3 and 6 months afterwards. At the end of the study, blood, both femurs and tibias, internal organs and abdominal fat were collected. After three months, the percentage changes from baseline of the total and proximal tibial BMD of the OVX+OE group were both higher compared to the OVX group (p<0.005). Similar results were found after six months, when the percentage changes from baseline of the total and proximal tibial BMD of the OVX+OE group were both higher compared to the OVX group (p<0.005). Biomechanical testing of the femurs did not reveal any statistically significant difference between the groups. Body weights throughout the study, organs’ and abdominal fat ratios to final body weight, blood results (alanine aminotransferase; ALT, Gamma-glutamyltransferase; γ-GT, total cholesterol, high-density lipoprotein; HDL-cholesterol, low-density lipoprotein; LDL-cholesterol, calcium, phosphorus) were within normal limits and did not show any significant difference between the treated and untreated groups. As a conclusion, the administration of table olive wastewater extract for 6 months protected tibial BMD loss in comparison to the untreated OVX group without causing adverse effects.

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Control trial of porcine cysticercosis in Uganda using a combination of the TSOL18 vaccination and oxfendazole

Infectious Diseases of Poverty ◽

10.1186/s40249-021-00823-6 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Zachary Nsadha ◽

Chris Rutebarika ◽

Chrisostom Ayebazibwe ◽

Bukenya Aloys ◽

M. Mwanja ◽

...

Keyword(s):

Taenia Solium ◽

Control Program ◽

Control Area ◽

Sub Saharan Africa ◽

Intermediate Hosts ◽

Porcine Cysticercosis ◽

Intervention Area ◽

Significant Difference ◽

Sub Saharan ◽

Village Communities

Abstract Background Neurocysticercosis caused by Taenia solium when the parasite lodges in the central nervous system, is an important cause of human seizures and mortality in sub-Saharan Africa. The parasite is prevalent in many regions of Uganda. Pigs are intermediate hosts for T. solium, and we evaluated a T. solium control program in pigs, involving vaccination of pigs with the TSOL18 vaccine and treatment with oxfendazole. Methods The study was conducted in two districts of Eastern Uganda involving the rural village communities of Bukedea (intervention area) and Kumi (control area) during 2016–2017. Seven hundred and thirty-four households were enrolled in the study. Pigs in the intervention area received intramuscular immunizations with TSOL18 (Cysvax™) and an oral medication with 30 mg/kg oxfendazole (Paranthic™) at approximately 3-monthly intervals for 18 months. Porcine cysticercosis was evaluated by post-mortem examination. At the beginning of the study, 111 pigs were examined. In an interim evaluation in the intervention area, 55 pigs were evaluated 12 months after starting the project. At the end of the study approximately 3 months after the final intervention, 55 pigs from the intervention area and 56 pigs from the control area were evaluated. Results The prevalence of porcine cysticercosis for the two sites was 16.2% at the beginning of the study (17.2% in the intervention area and 15.1% in the control area) with no statistically significant difference (P = 0.759) between the two study sites. Among the 110 animals assessed from the intervention site (55 at the interim evaluation and 55 at the final evaluation), no pig with viable T. solium cysts was found. There was a statistically significant difference between the prevalence at baseline (17.2%) and at the end of the study (0%) in the intervention area (P = 0.001) and a statistically significant difference between the intervention (0%) and control areas (5.4%) (P = 0.041) at the end of the study. Conclusions Three-monthly concurrent vaccination of pigs with the TSOL18 vaccine and medication with oxfendazole eliminated T. solium transmission by the animals involved in the study. Application of vaccination with medication in pigs has the potential to reduce transmission of T. solium in Uganda and other endemic countries.

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Organ motion in linac-based SBRT for glottic cancer

Radiation Oncology ◽

10.1186/s13014-021-01833-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Annarita Perillo ◽

Valeria Landoni ◽

Alessia Farneti ◽

Giuseppe Sanguineti

Keyword(s):

Early Stage ◽

Displacement Vector ◽

Thyroid Cartilage ◽

Three Dimensional ◽

Target Volume ◽

Glottic Cancer ◽

Organ Motion ◽

Delivery Times ◽

Significant Difference ◽

Pre Treatment

Abstract Purpose The purpose of this study is to evaluate inter- and intra-fraction organ motion as well as to quantify clinical target volume (CTV) to planning target volume (PTV) margins to be adopted in the stereotactic treatment of early stage glottic cancer. Methods and materials Stereotactic body radiotherapy (SBRT) to 36 Gy in 3 fractions was administered to 23 patients with early glottic cancer T1N0M0. Patients were irradiated with a volumetric intensity modulated arc technique delivered with 6 MV FFF energy. Each patient underwent a pre-treatment cone beam computed tomography (CBCT) to correct the setup based on the thyroid cartilage position. Imaging was repeated if displacement exceeded 2 mm in any direction. CBCT imaging was also performed after each treatment arc as well as at the end of the delivery. Swallowing was allowed only during the beam-off time between arcs. CBCT images were reviewed to evaluate inter- and intra-fraction organ motion. The relationships between selected treatment characteristics, both beam-on and delivery times as well as organ motion were investigated. Results For the population systematic (Ʃ) and random (σ) inter-fraction errors were 0.9, 1.3 and 0.6 mm and 1.1, 1.3 and 0.7 mm in the left-right (X), cranio-caudal (Y) and antero-posterior (Z) directions, respectively. From the analysis of CBCT images acquired after treatment, systematic (Ʃ) and random (σ) intra-fraction errors resulted 0.7, 1.6 and 0.7 mm and 1.0, 1.5 and 0.6 mm in the X, Y and Z directions, respectively. Margins calculated from the intra-fraction errors were 2.4, 5.1 and 2.2 mm in the X, Y and Z directions respectively. A statistically significant difference was found for the displacement in the Z direction between patients irradiated with > 2 arcs versus ≤ 2 arcs, (MW test, p = 0.038). When analyzing mean data from CBCT images for the whole treatment, a significant correlation was found between the time of delivery and the three dimensional displacement vector (r = 0.489, p = 0.055), the displacement in the Y direction (r = 0.553, p = 0.026) and the subsequent margins to be adopted (r = 0.626, p = 0.009). Finally, displacements and the subsequent margins to be adopted in Y direction were significantly greater for treatments with more than 2 arcs (MW test p = 0.037 and p = 0.019, respectively). Conclusions In the setting of controlled swallowing during treatment delivery, intra-fraction motion still needs to be taken into account when planning with estimated CTV to PTV margins of 3, 5 and 3 mm in the X, Y and Z directions, respectively. Selected treatments may require additional margins.

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