Sildenafil Increases the p50 and Shifts the Oxygen-Hemoglobin Dissociation Curve to the Right.

INTRODUCTION: Sildenafil (Viagra®) is a selective phosphodiesterase type 5 (PDE5) inhibitor that block the breakdown of cyclic guanyl monophosphate (cGMP) leading to relaxation of the smooth muscles of the corpus cavernous and an increase in blood flow resulting in penile erection. It is hypothesized that sildenafil will increase the release of oxygen from erythrocytes and shift the oxygen-hemoglobin curve to the right. AIM: The aim of this study was to investigate the effect of varying doses of sildenafil on the p50 of the oxygen-hemoglobin dissociation curve in blood samples from eight (8) healthy adult male volunteers with normal hemoglobin HbAA. METHOD: The hemox-analyzer was used to generate the p50 and the oxygen-hemoglobin dissociation curves. MAIN OUTCOME MEASURES: The effect of different doses of sildenafil on the p50 values and shift of the oxygen-hemoglobin curve were the main outcome measures. RESULT: Sildenafil caused a statistically significant increase in the p50 values and rightward shift of the oxygen-hemoglobin dissociation curve. CONCLUSION: Sildenafil caused a dose-dependent increase in the release of oxygen from the erythrocytes as shown by the increased p50 values and rightward shift of the oxygen-hemoglobin dissociation curve. Ellis SS and Pepple DJ. Sildenafil increases the p50 and shifts the oxygen-hemoglobin dissociation curve to the right.

In vitro hemolytic effect of sulfadoxine/pyrimethamine and artemether/lumefantrine on malaria parasitized erythrocytes of female patients.

G6PD is an X-linked gene enzyme that protects erythrocytes from hemolysis when they are exposed to antimalarial drugs because of the effects of the free radicals generated by these drugs. We investigated the effects of Fansidar ™ (Sulfatoxine/Pyrimethamine) and Coartem ™ (Artemether/Lumefantrine) on the hemolysis of malaria parasitized female erythrocytes. Twelve (12) malarious patients attending the University of Benin Teaching Hospital, Benin City, Nigeria, were used in this study. Ten (10) apparently healthy female students from the Medical School, University of Benin, acted as control. Low, normal (the recommended adult dose) and high doses of Fansidar ™ and Coartem ™ were used to determine the percentage hemolysis by checking the absorbance of the various samples. Data was analyzed by the Student's t-test and ANOVA with p<0.05 indicating the level of significance. At low doses of Fansidar ™ and Coartem ™, no hemolysis occurred, while at normal doses, Fansidar ™ showed no hemolysis but significant hemolysis (p<0.05) was observed in the Coartem ™ group. At high doses, both FansidarTM and CoartemTM caused significant (p<0.05) hemolysis. High doses of both drugs and normal dose of CoartemTM caused significant hemolysis. There was no hemolysis observed in the normal dose of FansidarTM and low doses for both drugs, similar to the trend reported for male subjects.

Artocarpus Altilis (Breadfruit) could Reverse Myocardial Infarction Through the Normalization of the Oxygen Haemoglobin Dissociation Curve.

OBJECTIVE: The study was performed to assess if hematological mechanisms such as blood flow modulation, P50 and Oxygen haemoglobin dissociation are involved in Artocarpus altilis leaf extract amelioration of Isoproterenol-Induced Myocardial Damage in rats. METHODS: Twenty (20) adult male Sprague-Dawley rats were randomly divided into 5 groups. Group 1 served as the control, group 3 and 5 received 50 and 100 mg/kg Artocarpus altilis water extract, respectively, after being induced with Isoproterenol twice (85 mg/ kg) at a 24-hour period. Group 2 received 85mg/kg isoproterenol only, while group 4 received 50 mg/kg Artocarpus altilis extract only for 6 days. The Hematological parameters were assessed using an automatic Coulter Counter, blood flow was assessed with the CODA machine using the tail cuff method, while blood viscosity was measured at native hematocrit and the oxygen haemoglobin dissociation curves were assessed with the BioProfiler and Hemox Analyzer at the end of seven days. RESULTS: Artocarpus altilis treatment ameliorated the ISO induced increases in viscosity, increased the ISO induced decreased blood flow and influenced oxygen release through its effects on the P50 of the oxygen hemoglobin dissociation curve, AA treatment also reversed the ISO induced weight loss. Apart from the changes in MCH, MCV, there were no significant differences in hematological parameters. CONCLUSION: This study reported the effects of Artocarpus atilis on the improvement of oxygen availability, the reduction of blood viscosity, and the improvement of blood flow through its influence on endothelial functions and NO availability. Our study further highlights The usefulness of A.atilis, as having a beneficial cardiovascular and haematological outcome in experimental myocardial infarction and as such, potential drug discovery for diseases of cardiovascular & hematological involvement.

The in vitro effect of delta-9-tetrahydrocannabinol and cannabidiol on whole blood viscosity, elasticity and membrane integrity.

BACKGROUND: The main biological activities of cannabis are due to the presence of several compounds known as cannabinoids. Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are two of the main cannabinoids. Studies have shown that the effects of THC can be modulated by CBD. OBJECTIVE: This study aims to look at the effect of different concentrations of THC and CBD separately and in combination, on blood viscosity, elasticity and membrane integrity. METHODS: Blood samples were collected from twenty-four healthy adult non-smokers. Blood viscosity and elasticity were determined using the Vilastic Scientific Bioprofiler for different concentrations (0, 2.5, 25, 50 and 100 ng/ml) of CBD and THC respectively, as well as in extracts with combinations of CBD and THC in 4:1 and 1:1 ratios respectively. Repeated measures analysis of variance (ANOVA) was used to determine the difference between the means of the groups. RESULTS: Blood viscosity increased significantly with increasing concentrations of both THC and CBD from 25 ng/ml up to 100 ng/ml ranging from 6.45 ± 0.36 mPa·s to 11.60 ± 1.12 mPa·s for THC and ranging from 5.46 ± 0.24 mPa·s to 9.91 ± 1.10 mPa·s for CBD respectively, being more pronounced in the extracts at 21.33 ± 2.17 mPa·s for the 4THC:1CBD extract and 21.76 ± 1.88 mPa·s for the 1THC:1CBD extract. There was no significant increase in elasticity for THC and CBD separately. However, a significant increase in elasticity was observed in the extracts. THC and CBD affected red cell morphology resulting in complete disintegration at the highest concentrations. CONCLUSIONS: THC and CBD increased red blood cell viscosity and elasticity separately and in combination. They also adversely affected membrane integrity.

A comparison of student performance in multiple-choice and long essay questions in the MBBS stage I physiology examination at the University of the West Indies (Mona Campus).

This retrospective study compared the performance of preclinical medical students in the multiple-choice question (MCQ) and long essay question components of a comprehensive physiology final examination. During the 3 yr analyzed, 307 students had an average score of 47% (SD 9.9) in the long essay questions and 64% (SD 9.9) in the MCQs. Regression analysis showed a significant correlation (r = 0.62, P < 0.01) between MCQs and long essay questions. When student performance was grouped by final course grade, a statistically significant correlation between MCQ and long essay scores existed only for the 210 students who received a passing grade (r = 0.20, P < 0.01). The MCQ and long essay question scores were not correlated for the 57 students who failed (r = 0.25, P = 0.06) or for the 40 students who achieved honors and distinctions (r = -0.27, P = 0.11). MCQ scores were significantly higher (P < 0.01) than essay scores for each of the groups when analyzed by two-way ANOVA. The results of this study suggest that for most students, the strong correlation between scores on MCQs and essay questions indicates that student performance was independent of testing format. For students at either end on the performance spectrum, the lack of correlation suggests that the performance in one of the testing formats had a strong influence on the final course grade. In addition, those students who failed the course were likely to be weak in both testing modalities, whereas students in all grade groups were more likely to perform better in the MCQs than in the long essay questions.

The effect of delta-9-tetrahydrocannabinol and cannabidiol on p50 of the oxygen haemoglobin dissociation curve.

Cannabis is one of the most chemically complex plants containing a large number of compounds, among which are cannabinoids; the main biologically active constituents of the plant. Delta-9-tetrahydrocannabinol (THC) is known as the main psychoactive cannabinoid. Studies have shown that the effects of THC can be modulated by cannabidiol (CBD), another major cannabinoid which has several beneficial effects of its own. This study aims to look at the effect of different concentrations of THC and CBD separately and in combination on the release of oxygen from erythrocytes by measuring the p50 of the oxygen haemoglobin dissociation curve. Blood samples were collected from twenty four healthy adult male and female non-smokers. P50 values were measured using the Hemox Analyzer for different concentrations (0, 2.5, 25, 50 and 100 ng/ml) of THC and CBD respectively, as well as with combinations of THC and CBD in 4:1 and 1:1 ratios. The results indicate that there is a decrease in P50 with increasing concentrations of both THC and CBD separately and in combination. The decrease in P50 was significant (p < .05) at all concentrations of THC and CBD. The changes observed with increasing concentrations of both THC and CBD suggests that they have an increased affinity for oxygen. This may have implications for individuals who consistently use cannabis.

In vitro effect of dibenzyl trisulfide on the p50 of the oxygen haemoglobin dissociation curve.

OBJECTIVES: Dibenzyl trisulfide (DTS) has been reported to have cytotoxic and anti-inflammatory effects. It also affects erythrocyte deformability. We investigated the effects of DTS on the p50 of the oxygen haemoglobin dissociation curve. METHODS: Blood samples from 10 healthy male volunteers with normal haemoglobin AA were exposed to 50, 100, 200 and 400 ng/mL, respectively, of DTS. A hemox-analyzer was used to obtain the p50 values. RESULTS: The mean p50 value for the control samples was 25.89 ± 2.18 mm Hg. The values for the samples exposed to 50, 100, 200 and 400 ng/mL were 23.53 ± 1.81 mm Hg, 22.62 ± 1.61 mm Hg, 21.88 ± 1.67 mm Hg and 21.68 ± 1.88 mm Hg, respectively. CONCLUSIONS: DTS caused a significant (p<0.001) reduction in p50 values indicating a shift of the oxygen- haemoglobin dissociation curve to the left in all the samples compared with control, suggesting that the administration of DTS could result in decrease in oxygen supply to tissues.

Alterations in hemorheological determinants and glycated hemoglobin in black diabetic patients with retinopathy.

Alterations of hemorheological determinants and glycated hemoglobin levels are prominent features of diabetic retinopathy, resulting in the increased whole-blood and plasma viscosities observed in this condition. These variables have been reported to show ethnic variations. The present study was designed to investigate the pattern of alterations in these variables and the possible influence of plasma viscosity in black diabetic retinopathy patients. Forty-two patients, who included 14 males and 28 females (mean age, 62.81 +/- 11.38 years) were studied. The control group consisted of 30 black, nondiabetic, age-matched subjects, including 10 males and 20 females. Relative plasma viscosity, plasma fibrinogen concentration, packed cell volume, and mean glycated hemoglobin were significantly higher in the diabetic subjects compared with the controls. We observed an increase in plasma viscosity in our study population, similar to those reported in previous studies for Caucasians.

Red blood cell deformability is reduced in homozygous sickle cell disease patients with leg ulcers.

Previous reports differ as to whether a decreased elongation index (EI), a proxy for red blood cell (RBC) deformability, is associated with leg ulcers (LU) in people with homozygous sickle cell disease (SCD). We sought to determine whether erythrocyte deformability (ED) and haematological indices were associated with the presence of LU in patients with SCD. The study design was cross-sectional. Twenty-seven patients with LU and 23 with no history of ulceration were recruited into the study. A laser assisted rotational red cell analyzer was used in the determination of the EI. Haematological indices were determined using a CELL-DYN Ruby haematology analyzer. Data were normally distributed and presented as means±SD. Two-sample t-test was used to test for associations between haemorheological variables in SCD patients with and without LU. Statistical significance was taken as p < 0.05. The EI was significantly lower in the group with ulcers (0.30±0.07 vs. 0.35±0.07, p = 0.02). Haematological indices were comparable in patients with and without LU. Erythrocyte deformability, but not haematological indices, was associated with LU in patients with SCD.

Effect of cilostazol on the p50 of the oxygen-hemoglobin dissociation curve.

Cilostazol is a drug used for the treatment of intermittent claudication caused by narrowing of the blood vessels and reduced oxygen supply, characterized by intense pain in the leg when walking. This study was designed to investigate the effect of cilostazol on the P50 of the oxygen hemoglobin dissociation curve. A total of eight healthy adult subjects were studied. Blood samples (0.5 mL) from each subject were mixed with 5, 10, and 20 µL of the 0.5 mg/mL stock solution of cilostazol to give concentrations of 10, 20, and 40 µg/mL equivalent to adult doses of 50, 100, and 200 mg, respectively. The control sample had no drug added. The oxygen hemoglobin dissociation curve of each sample was plotted and the P50 determined with a Hemox-Analyzer (TCS, Medical Products Division, Southampton, PA). The mean P50 for the control samples was 28.27 ± 0.43 mm Hg. The values of the samples exposed to 10, 20, and 40 µg/mL cilostozol were 29.63 ± 0.66, 30.15 ± 0.77, and 31.66 ± 0.62 mm Hg, respectively. There was a statistically significant difference (p < 0.01) between the control and samples exposed to 40 µg/mL cilostazol. This study suggests that cilostazol caused an increase in the release of oxygen from hemoglobin as shown in the P50 values. This effect was significant at the highest concentration of 40 µg/mL.

Comparison of Outcome of Students' Performance Using the Standard Setting Method with the Absolute Grading Method in Preclinical Examination.

This study compared the outcome of students' performance using the standard setting method with the equivalent outcome they would have obtained using the absolute grading method. It involved the comparison of fail, pass, honors and distinction grades in Digestive System, Endocrine System, Cardiovascular System and Health and the Environment courses in the MBBS Stage I examination. The performance in Cardiovascular System was significantly better with the standard setting method (χ2 = 27.53; p < 0.01), median score in the honors range compared with the absolute grading method where the median score was in the pass range. On the other hand, the performance in Endocrine System was significantly better using the absolute grading method (χ2 = 27.30; p < 0.01), with median score in the honors range compared with the standard setting method where the median score was in the pass range. There was no difference in the performance in Digestive System (χ2 = 7.45; p = 0.06), median score in the pass range and Health and the Environment (χ2 = 6.34; p = 0.09), median score in the honors range; between the standard setting and absolute grading methods (Wilcoxon's signed rank). The overall pass, honors, distinction and failure rates were also identical in both methods (Mann Whitney U test). This suggests that overall the outcome of the students' performance in the standard setting method compared with the absolute grading method were not significantly different.

Maternal blood viscosity and perinatal outcome in steady-state homozygous sickle cell disease.

Homozygous sickle cell disease (HbSS) is a complicating factor in pregnancy resulting in perinatal morbidity and mortality. One of the hallmarks of sickle cell disease is increased whole blood viscosity. The present study was designed to investigate the effect of the maternal blood viscosity on perinatal outcome in steady-state homozygous sickle disease in 19 women admitted to the labor ward of the University Hospital of the West Indies, Mona. Whole blood viscosity was measured with the Wells-Brookfield viscometer at 370C at low (23 sec-1) and high (230 sec-1) shear rates. Measurements were done at native hematocrit. Perinatal outcome was classified as adverse if there was one or more of the following: admission to nursery, birth weight less than 2.5 kg, 5 minute Apgar score less than 7, caesarean section for fetal distress, perinatal death or death before discharge from nursery. The whole blood viscosity value (mean ± SD) at low shear rate was 2.04 ± 0.55 mPa.s and 2.96 ± 0.80 mPa.s at high shear rate. The hematocrit was 25.13 ± 4.18%. The perinatal outcome was good in 10 (53%) subjects and adverse in 9 (47%) subjects. There was no statistically significant difference in the incidence of adverse perinatal outcome between women with low and high blood viscosities in either the low or high shear rates. Similarly, low or high hematocrit did not significantly affect the incidence of adverse perinatal outcome. This could be attributed to their similarity in the whole blood viscosity and hematocrit values.

Pre-clinical grades predict clinical performance in the MBBS stage II examination at the University of the West Indies, Mona Campus.

In the preclinical sciences, statistically significant predictive values have been reported between the performances in one discipline and the others, supporting the hypothesis that students who perform well in one discipline were likely to perform well in the other disciplines. We therefore decided to conduct a retrospective study to investigate the predictive effects of preclinical subjects on clinical subjects from 87 students of The University of the West Indies (UWI), Mona Campus who took the MBBS Stage II examination at various times between May 2000 and May 2002. The grade in Pathology was significantly predicted by scores in Anatomy and Pharmacology; Medicine by Physiology and Pharmacology scores; Surgery by Anatomy and Social and Preventive Medicine scores; while, the Obstetrics and Gynecology grade was predicted by the Anatomy score. The results support the hypothesis that the scores in some preclinical subjects can predict the performance in specific clinical subjects, which could be interpreted to suggest that poor performance in specific preclinical disciplines could be a warning sign of future poor performance in the related clinical disciplines.

Comparison and prediction of preclinical students' performance in the MBBS stage I examination at the University of the West Indies, Mona Campus.

This retrospective study involved the analysis of the grades of ninety-four preclinical students who took the Bachelor of Medicine and Bachelor of Surgery (MBBS) Stage I Examination in Anatomy, Biochemistry, Physiology, Social and Preventive Medicine, and Pharmacology between December 1997 and May 1999 at the Mona Campus of The University of the West Indies (UWI). A statistically significant correlation was observed among the basic science subjects. Additionally, a statistically significant prediction was found between the performances of the students in one discipline and the others, with Physiology being the most predicted. The data support the hypothesis that students who performed well in one discipline were likely to perform well in the other disciplines; and also that the performance in some subjects could predict the performance in others. This result may also justify further investigation as to whether the performance in certain basic sciences disciplines at the preclinical stage can be used to predict performance in the clinical disciplines.

The effect of sildenafil on the elasticity of erythrocytes in homozygous sickle cell disease.

PURPOSE: One of the features of homozygous sickle cell disease (HbSS) is the impaired elasticity of the erythrocyte membrane that could impede microcirculatory blood flow and cause hypoxia and tissue damage. We investigated the effect of sildenafil, a phosphodiesterase 5 (PDE5) inhibitor that inhibits the breakdown of cyclic guanosine monophosphate (cGMP) resulting in vasodilatation, on the elasticity of HbSS erythrocyte. MATERIALS AND METHODS: Blood samples from ten HbSS patients in steady state was exposed to different doses (5, 10, 20, and 40 µg/mL) of sildenafil and the elasticity of the erythrocytes measured at native hematocrit with the BioProfiler. An equal number of subjects with normal hemoglobin (HbAA) served as the control group. RESULTS: There was a marginal increase in elasticity with 5 µg/mL of the drug and this became significant (P<0.05) with the 10 µg/mL dose. Thereafter, gradual nonsignificant decreases were observed with the 20 and 40 µg/mL doses. A similar trend was observed for the control group. The elasticity values for the HbSS subjects at native hematocrit were significantly (P<0.05) less when compared with the corresponding concentrations for the HbAA controls. This was reversed at a corrected hematocrit of 45%. CONCLUSION: The result of this study shows that sildenafil caused an initial increase in erythrocyte membrane elasticity in both HbSS and HbAA subjects, and this later decreased with increasing concentration of the drug possibly due to the dual effect of cyclic adenosine monophosphate (cAMP).