Abiola S. Babatunde

Normal CD4 Count Range among Healthy Nigerian Population in Ilorin

Background: For the establishment and monitoring of the immune status, CD4 count is critical. Objectives: To determine the CD4 count range of apparently healthy Nigerians resident in Ilorin and compare with the national value. Methods: An automated blood analyzer was used to determine the full blood count and CD4 count. The percentage of CD4 count was derived by using other variables. Results: Of the 1205 participants, the reference CD4 count (percentage of CD4) range for adult was 400 to 1288 cells/mm3 (19%-48%) and for children was 582 to 3652 cells/mm3 (17%-50%). CD4 count and percentage of CD4 were significantly (P = .001) higher in females than in males, and the CD4 count declined significantly with increasing age (r = −.174, P ≤ .0001). The percentage of CD4 count shows less variation with age (r = −.051, P = .076). Adult residents of Ilorin had significantly lower absolute mean CD4 count (808 ± 260) than that of the national reference values of 847.0 ± 307.0 cells/mm3 (P = .001). Conclusion: We therefore advocate the use of CD4 count range derived in this study is lower than that of the national reference values.

Characterization of hemopoietic engraftment kinetics and development of secondary cytopenia in AML post auto-SCT and its correlation with survival outcome

We performed a single center retrospective analysis of 84 autologous hemopoietic stem cell transplants done for AML to characterize the pattern of hemopoietic engraftment, post-transplant cytopenia and their impact on survival outcome. Following autologous transplant and engraftment, 30 patients (35.7%) had a transient secondary decline in their plt counts, which was not associated with graft rejection, relapse or infection. The median time to onset of thrombocytopenia was 59 days post transplant, with spontaneous recovery after a median period of 41 days. A secondary decline in ANC also occurred in eight patients. Patients with secondary plt decline had a significantly earlier primary plt engraftment (median 15 days) and a trend towards earlier neutrophil engraftment compared with patients who maintained steady plt counts (median 21 days). There was a trend towards a lower incidence of secondary plt decline in patients who received BM stem cells compared with those who received PBSC. No cause was evident for the occurrence of a secondary cytopenia, and it did not adversely affect survival. We conclude that secondary cytopenia is a common and harmless occurrence after autologous transplant especially from PBSC graft.

Graviola (Annona muricata) Exerts Anti-Proliferative, Anti-Clonogenic and Pro-Apoptotic Effects in Human Non-Melanoma Skin Cancer UW-BCC1 and A431 Cells In Vitro: Involvement of Hedgehog Signaling

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: (i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; (ii) induce G0/G1 cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iii) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs.

Anticancer Properties of Graviola (Annona muricata): A Comprehensive Mechanistic Review

Graviola (Annona muricata) is a small deciduous tropical evergreen fruit tree, belonging to the Annonaceae family, and is widely grown and distributed in tropical and subtropical regions around the world. The aerial parts of graviola have several functions: the fruits have been widely used as food confectionaries, while several preparations, especially decoctions of the bark, fruits, leaves, pericarp, seeds, and roots, have been extensively used in traditional medicine to treat multiple ailments including cancers by local communities in tropical Africa and South America. The reported therapeutic benefits of graviola against various human tumors and disease agents in in vitro culture and preclinical animal model systems are typically tested for their ability to specifically target the disease, while exerting little or no effect on normal cell viability. Over 212 phytochemical ingredients have been reported in graviola extracts prepared from different plant parts. The specific bioactive constituents responsible for the major anticancer, antioxidant, anti-inflammatory, antimicrobial, and other health benefits of graviola include different classes of annonaceous acetogenins (metabolites and products of the polyketide pathway), alkaloids, flavonoids, sterols, and others. This review summarizes the current understanding of the anticancer effects of A. muricata and its constituents on diverse cancer types and disease states, as well as efficacy and safety concerns. It also includes discussion of our current understanding of possible mechanisms of action, with the hope of further stimulating the development of improved and affordable therapies for a variety of ailments.

Chitosan-based nanoformulated (–)-epigallocatechin-3-gallate (EGCG) modulates human keratinocyte-induced responses and alleviates imiquimod-induced murine psoriasiform dermatitis

Background Psoriasis is a chronic and currently incurable inflammatory skin disease characterized by hyperproliferation, aberrant differentiation, and inflammation, leading to disrupted skin barrier function. The use of natural agents that can abrogate these effects could be useful for the treatment of psoriasis. Earlier studies have shown that treatment of keratinocytes and mouse skin with the green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG) mitigated inflammation and increased the expression of caspase-14 while promoting epidermal differentiation and cornification. However, bioavailability issues have restricted the development of EGCG for the treatment of psoriasis. Materials and methods To overcome these limitations, we employed a chitosan-based polymeric nanoparticle formulation of EGCG (CHI-EGCG-NPs, hereafter termed nanoEGCG) suitable for topical delivery for treating psoriasis. We investigated and compared the efficacy of nanoEGCG versus native or free EGCG in vitro and in an in vivo imiquimod (IMQ)-induced murine psoriasis-like dermatitis model. The in vivo relevance and efficacy of nanoEGCG formulation (48 µg/mouse) were assessed in an IMQ-induced mouse psoriasis-like skin lesion model compared to free EGCG (1 mg/mouse). Results Like free EGCG, nanoEGCG treatment induced differentiation, and decreased proliferation and inflammatory responses in cultured keratinocytes, but with a 4-fold dose advantage. Topically applied nanoEGCG elicited a significant (p<0.01) amelioration of psoriasiform pathological markers in IMQ-induced mouse skin lesions, including reductions in ear and skin thickness, erythema and scales, proliferation (Ki-67), infiltratory immune cells (mast cells, neutrophils, macrophages, and CD4+ T cells), and angiogenesis (CD31). We also observed increases in the protein expression of caspase-14, early (keratin-10) and late (filaggrin and loricrin) markers of differentiation, and the activator protein-1 factor (JunB). Importantly, a significant modulation of several psoriasis-related inflammatory cytokines and chemokines was observed compared to the high dose of free EGCG (p<0.05). Taken together, topically applied nanoEGCG displayed a >20-fold dose advantage over free EGCG. Conclusion Based on these observations, our nanoEGCG formulation represents a promising drug-delivery strategy for treating psoriasis and possibly other inflammatory skin diseases.

Triglyceride/HDL-cholesterol ratio and plasminogen activator inhibitor-1 independently predict high pulse pressure in sickle cell trait and disease

Abstract We hypothesised that TG/HDL-C ratio and PAI-1 would be associated with high pulse pressure (PP) in young adults with sickle cell trait (SCT) and sickle cell disease (SCD). We compared the clinical, biochemical, and cardiometabolic parameters among individuals with normal genotype (HbAA; n = 60), SCT (HbAS; n = 60), and SCD (HbSS; n = 60), all in steady state. Using multivariate linear regression analysis, high PP was positively related to TG/HDL-C ratio in SCT (β = 0.307; p = .014) and PAI-1 (β = 0.499; p = .001) in SCD. The curve of receiver operating characteristic also showed that TG/HDL-C ratio and PAI-1 are efficient predictors of high PP in SCT carriers and SCD patients, respectively. This study suggests that increased levels of TG/HDL-C ratio and PAI-1 may be salient risk factors that would promote the development of arterial stiffness and other CVD in SCT carriers and SCD patients.

Fibrinolytic proteins of normal pregnancy and pre-eclamptic patients in North West Nigeria

Background The hypercoagulability of pregnancy is exaggerated in pre-eclamptic state because of endothelial activation with resultant production of some endothelial derived proteins that are said to be inhibitors of fibrinolysis. This study compares these proteins like tPA, PAI-1 and D-dimers in normal pregnant women and the pre-eclamptic women. Methodology This was a comparative cross-sectional study. Eighty-five pre-eclamptic women were recruited as subjects and eighty five age, trimester and parity matched normotensive pregnant women as controls. Levels of PT, aPTT, tPA, PAI-1, D-dimer protein were determined in blood samples of subjects and controls. Urinalysis was performed with dipstick method on their urine samples. Data generated was analysed using the IBM®SPSS 20.0 (2011) soft ware packages and the level of significance was a p-value <0.05. Results The mean age of the respondents was 29.9±5.2 years. The median(25th–75th percentile) values of D-dimer, tPA, and PAI-1 of subjects were 730 (305.000–1560.000ng/ml), 0.11 (0.065–0,300ng/ml) and 3.65 (2.970–4,400ng/ml) respectively which were significantly higher than the corresponding values in the controls of 520 (24.000–1030.000ng/ml), 0.05 (0.040–0.090ng/ml and 2.650 (2.125–3.400ng/ml) respectively, p<0.05 each. Conclusion The abnormal levels of PAI-1, D-dimer and tPA imply that they contribute to the exaggerated hypercoagulabilty state in pre-eclampsia thus, measuring their levels can help in the management of the condition.

Iloneoside: a cytotoxic ditigloylated pregnane glycoside from the leaves of Gongronema latifolium Benth

Abstract Gongronema latifolium Benth (Asclepiadaceae) is an edible-green-leafy vegetable with known medicinal value. A chemical investigation of the 80% methanolic extract of the leaves led to the isolation of a new pregnane glycoside: iloneoside (3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→14)-β-D-oleandropyranosyl]-11,12-di-O-tigloyl-17β-marsdenin), together with four known constituents. Their chemical structures were determined by spectroscopic analysis. The isolates were tested for their in vitro growth inhibitory activity against human leukemia HL-60 cells. Iloneoside was the most active and gave apoptotic response. Molecular docking analysis demonstrated that iloneoside could be accommodated within hot spots of anti-apoptotic protein Bcl-2. These results suggest G. latifolium as a reliable source of potent anticancer compounds.

MPS 15-01 TRIGLYCERIDE-GLUCOSE INDEX IS AN INDEPENDENT DETERMINANT OF HIGH PULSE PRESSURE IN SICKLE CELL ANEMIA

Objective: Sickle cell anemia (SCA) patients do not suffer from arterial hypertension in spite of high incidence of cardiovascular disease (CVD). However, some SCA patients have elevated pulse pressure (PP), which is a surrogate of arterial stiffness and an independent risk factor for CVD. Studies have reported an association between insulin resistance (IR) and increased arterial stiffness. Triglyceride-glucose (TyG) index is a simple and reliable indicator of IR. We hypothesized that TyG index would be an independent determinant of elevated PP in young adults with SCA in steady state. Design and Method: We compared the anthropometrical, haematological and IR indices between SCA patients with normal (PP < 55 mmHg; n = 43) and those with high PP (PP ≥ 55 mmHg, n = 20), all in steady state. Results: Our results showed that SCA with high PP had significantly higher waist circumference (WC) and IR markers (TyG, TyG-BMI, TyG-WC). Using multivariate regression analysis, results showed that TyG index (R2 = 0.643; p < 0.001) was an independent determinant of high PP in SCA. A receiver operating characteristic (ROC) curve analysis also showed that TyG index was the most efficient predictor of high PP than other IR indices. The area under the ROC curve for TyG (0.750) was larger than that of TyG-BMI (0.741) and TyG-WC (0.741). Conclusions: These findings suggest that increased TyG index may be a salient risk factor that would promote the development of arterial stiffness and CVD in SCA.

LBPS 02–29 NECK CIRCUMFERENCE IS AN INDEPENDENT PREDICTOR OF RELATIVE SYSTEMIC HYPERTENSION IN YOUNG ADULT WITH SICKLE CELL ANAEMIA

Objective: A seemingly interesting observation in patients with sickle cell anaemia (SCA) is that they usually have lower systemic blood pressures (BP) and insulin resistance (IR) than persons in the general population in spite of endothelial dysfunction, chronic inflammation and vasculopathy. However, the relative systemic hypertension (rHTN) has been linked to increased risk of pulmonary hypertension, increased blood viscosity and renal insufficiency, which could indicate a risk of developing cardiometabolic disorder (CMD) in SCA. We therefore hypothesized that neck circumference (NC) and CMD marker; triglyceride-glucose (TyG) index would independently predict rHTN in young adults with SCA in steady state. Design and Method: We compared the anthropometrical, hematological, hemorheological and CMD markers between SCA patients with normal BP < 120/70 mmHg; nHTN, n = 65) and those with rHTN (BP ≥ 120/70 mmHg, n = 32). Results: Our results showed that SCA with rHTN had significantly higher body weight, waist circumference, NC, plasma viscosity, systolic and diastolic BP. Results also indicated that NC (OR: 2.98; 95% CI 1.46 to 6.10, p < 0.01) was a predictor of rHTN in SCA independent of gender, age, weight, waist circumference, BMI, blood viscosity, triglyceride or TyG. A receiver operating characteristic curve analysis also showed that NC was the most efficient predictor of rHTN than other CMD markers. Conclusions: The present study demonstrates that increased NC is a salient risk factor that would promote the development of rHTN in SCA. The finding therefore underscores the utility of NC in early detection and stratification of systemic hypertension, particularly in individuals with SCA.