Donovan McGrowder

Publications of Donovan McGrowder

• The effect of nitric oxide inhibitors and Snitroso-Nacetylpenicillamine on glucose concentration in an animal model.

  Authors: Sophia Bryan, Ruby Alexander-Lindo, Tara Dasgupta, Donovan McGrowder

  Journal of natural science, biology, and medicine. 01/2011; 2(1):80-6.

  Nitric oxide (NO) is becoming an increasingly important signaling molecule implicated in a growing number of physiological and pathophysiological processes. Research on the effect of NO donors onNitric oxide (NO) is becoming an increasingly important signaling molecule implicated in a growing number of physiological and pathophysiological processes. Research on the effect of NO donors on glucose metabolism in peripheral tissues have grown rapidly in the last decade. This study examined the effects of N(G)methyl-L-arginine acetate (L-NMMA) and N(G)methyl-L-arginine ester (L-NAME) on fasting and postprandial blood glucose concentrations. The study also investigated if L-NMMA and L-NAME decrease the hyperglycemic effect caused by the NO donor S-nitrosoN-acetylpenicillamine (SNAP) in normoglycemic rats. L-NAME and L-NMMA significantly lowered the postprandial blood glucose concentrations. Mean postprandial blood glucose concentrations in rats treated with L-NAME were 5.04 ± 0.07 mmol/L at 120 min, 4.62 ± 0.19 mmol/L at 150 min and 4.36 ± 0.17 mmol/L at 180 min time points compared with 5.46 ± 0.14 (P = 0.029), 5.20 ± 0.17 mmol/L (P = 0.036), and 4.89 ± 0.14 mmol/L (P = 0.015) at the same time points respectively for saline control. Mean blood glucose concentrations in rats treated with L-NMMA were 4.35 ± 0.23 mmol/L (P = 0.0018) at 120 min, 4.60 ± 0.14 mmol/L (P = 0.090) at 150 min and 3.88 ± 0.16 mmol/L (P 0.001) at 180 min. There were significant differences in mean postprandial blood glucose concentrations in rats treated with SNAP, compared with those treated with L-NAME and SNAP at 90 min (P = 0.012), 180 min (P = 0.013) and 210 min (P < 0.0001). In addition, there were significant differences in mean postprandial blood glucose concentrations in rats treated with SNAP compared with those treated with L-NMMA and SNAP at 90 min (P = 0.0011), 180 min (P = 0.015) and 210 min (P = 0.0077). The nitric oxide synthase [NOS] inhibitors were effective in reducing postprandial blood glucose concentration in rats treated with SNAP. This suggests that although SNAP is an effective antihypertensive agent it decreases glucose tolerance which can be improved by the use of NOS inhibitors such as L-NMMA or L-NAME. These drugs could be beneficial in controlling blood glucose tolerance in rats administered with SNAP, and possibly in humans.

• The role of high-density lipoproteins in reducing the risk of vascular diseases, neurogenerative disorders, and cancer.

  Authors: Donovan McGrowder, Cliff Riley, Errol Y St A Morrison, Lorenzo Gordon

  Cholesterol. 01/2011; 2011:496925.

  High-density lipoprotein (HDL) is one of the major carriers of cholesterol in the blood. It attracts particular attention because, in contrast with other lipoproteins, as many physiological functionsHigh-density lipoprotein (HDL) is one of the major carriers of cholesterol in the blood. It attracts particular attention because, in contrast with other lipoproteins, as many physiological functions of HDL influence the cardiovascular system in favourable ways unless HDL is modified pathologically. The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High anti-oxidant and anti-inflammatory activities of HDL are associated with protection from cardiovascular disease. Atheroprotective activities, as well as a functional deficiency of HDL, ultimately depend on the protein and lipid composition of HDL. Further, numerous epidemiological studies have shown a protective association between HDL-cholesterol and cognitive impairment. Oxidative stress, including lipid peroxidation, has been shown to be the mediator of the pathologic effects of numerous risk factors of Alzheimer's disease. Lifestyle interventions proven to increase HDL- cholesterol levels including "healthy" diet, regular exercise, weight control, and smoking cessation have also been shown to provide neuro-protective effects. This review will focus on current knowledge of the beneficial effects of HDL-cholesterol as it relates to cardiovascular diseases, breast and lung cancers, non-Hodgkin's lymphoma, as well as its neuroprotective potential in reducing the risk of Alzheimer's disease and dementia.

• Factors affecting prostate cancer screening behaviour in a discrete population of doctors at the University Hospital of the West Indies, Jamaica.

  Authors: Dawn McNaughton, William Aiken, Donovan McGrowder

  Asian Pacific journal of cancer prevention : APJCP. 01/2011; 12(5):1201-5.

  To determine the knowledge, attitudes and practices of Jamaican male medical consultants regarding prostate cancer screening in three departments within the University Hospital of the West Indies.To determine the knowledge, attitudes and practices of Jamaican male medical consultants regarding prostate cancer screening in three departments within the University Hospital of the West Indies. The research design was a cross-sectional quantitative survey utilising a self administered questionnaire. All 36 male consultants between 40 and 70 years from the Departments of Surgery Radiology Anaesthesia and Intensive Care, Obstetrics and Gynaecology/Child Health, and Medicine participated in the survey. Bivariate analyses were used to determine the relationship between the three constructs with P < 0.05 taken as statistically significant. The majority (97%) of the respondents were aware that prostate cancer among Jamaicans account for one of the highest incidences in the world and 85% believed that screening for prostate cancer should begin at age 40 years. Approximately two-fifths (44.4%) reported that they usually encourage their patients to be screened. Nearly all (97%) of the respondents agreed that performing both the prostate specific antigen (PSA) test and digital rectal examination (DRE) are more effective in assessing for the presence of prostate cancer. Just over one-third (36%) found the DRE embarrassing and 41% had never had a DRE. The results showed a significant positive correlation (r = 0.374, P = 0.032) between knowledge and attitude, and an even stronger correlation between attitude and prostate cancer screening practice (r = 0.395, P = 0.025). However there was no direct correlation between knowledge and practice. Physicians' knowledge of prostate cancer does not predict their personal prostate cancer screening behaviour. Knowledge of prostate cancer is not enough to result in screening behavior of men in Jamaica.

• Dyslipidaemia in hypertensive obese type 2 diabetic patients in Jamaica.

  Authors: Lorenzo Gordon, Dalip Ragoobirsingh, Errol Morrison, Donovan McGrowder, Eric Choo-Kang, E Martorell

  Archives of medical science : AMS. 10/2010; 6(5):701-8.

  Hypertension and obesity are common problems among diabetic patients accelerating progression of vascular diabetic complications. A two-stage stratified random sampling design was used, andHypertension and obesity are common problems among diabetic patients accelerating progression of vascular diabetic complications. A two-stage stratified random sampling design was used, and individuals aged 15 years and over were interviewed. This cross-sectional study evaluated lipid abnormalities of 117 obese type 2 diabetic patients (28 males and 89 females), and 56 hypertensive obese type 2 diabetic patients (22 males and 34 females). Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C) and high-density lipoprotein cholesterol (HDL-C) concentrations were assayed using standard biochemical methods. Hypertensive obese type 2 diabetic females had significantly higher mean serum concentrations of TC (p = 0.043), TG (p = 0.046), LDL-C (p= 0.040), TC/HDL-C ratio (p = 0.001) and LDL-C/HDL-C ratio (p = 0.003) compared with hypertensive obese non-diabetic females. Similar results were found in hypertensive obese type 2 diabetic males compared with hypertensive obese non-diabetic males. Hypertensive obese type 2 diabetic females had significantly higher serum TC, TG and TC/HDL-C ratio (p < 0.05) than hypertensive obese type 2 diabetic males. Hypertensive obese type 2 diabetic females had significantly higher mean serum concentrations of TG (p = 0.03) and TC (p = 0.01) than obese type 2 diabetic females. There was a significant association between blood glucose and LDL-C concentrations in type 2 diabetic subjects (r = 0.36; p< 0.05). Obese hypertensive type 2 diabetic females are exposed more profoundly to risk factors including atherogenic dyslipidaemia compared with males.

• Late-onset Fanconi anemia in an African-Caribbean patient.

  Authors: Roslyn Alfred, Loretta Buchner-Daley, Adedamola Soyibo, Doreen Brady-West, Rochelle Hardie, Donovan McGrowder

  Journal of the National Medical Association. 02/2010; 102(2):132-4.

  A 38-year-old female of African-Caribbean origin presented with symptomatic anemia and was found to have hypoplastic thumbs and patchy hypopigmentation. Peripheral blood examination revealedA 38-year-old female of African-Caribbean origin presented with symptomatic anemia and was found to have hypoplastic thumbs and patchy hypopigmentation. Peripheral blood examination revealed pancytopenia and the bone marrow biopsy confirmed marrow hypoplasia. Fanconi anemia was later confirmed by flow cytometry and diepoxybutane testing. Treatment was limited to transfusions after development of toxicity with cyclosporine and androgen therapy. She manifested classical features of transfusion-related hemosiderosis and died 12 years after initial presentation.

• Lipid profile of type 2 diabetic and hypertensive patients in the jamaican population.

  Authors: Lorenzo Gordon, Dalip Ragoobirsingh, Errol Y A Morrison, Eric Choo-Kang, Donovan McGrowder, E Martorell

  Journal of laboratory physicians. 01/2010; 2(1):25-30.

  Previous studies have shown that diabetes mellitus (DM) increases the risk of cardiovascular diseases in females to a greater extent than in males. In this cross-sectional study, we evaluated thePrevious studies have shown that diabetes mellitus (DM) increases the risk of cardiovascular diseases in females to a greater extent than in males. In this cross-sectional study, we evaluated the lipid profiles of type 2 diabetic males and females. The study included 107 type 2 diabetic patients (41 males and 66 females), and 122 hypertensive type 2 diabetic patients (39 males and 83 females), aged 15 years and older. Total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) and high density lipoprotein-cholesterol (HDL-C) concentrations were assayed for each group using standard biochemical methods. The mean TC, TG, VLDL-C, HDL-C and LDL-C concentrations, TG/HDL and LDL/HDL ratios were higher in type 2 diabetic and hypertensive type 2 diabetic patients compared with non-diabetic, and hypertensive non-diabetic control subjects, although these were not significant (P > 0.05). Hypertensive type 2 diabetic females had significantly higher serum TC (7.42 ± 1.63 mmol/L) than hypertensive non-diabetic males (5.76±1.57 mmol/L; P < 0.05). All the other lipid and lipoprotein parameters except HDL-C were non-significantly higher in females with type 2 DM and those with hypertension and type 2 DM, compared with type 2 diabetic and hypertensive type 2 diabetic males, respectively (P > 0.05). This study demonstrated that dyslipidemia exists in our type 2 diabetic population with greater TC in hypertensive type 2 diabetic females compared with hypertensive type 2 diabetic males. This suggests that hypertensive type 2 diabetic females are exposed more profoundly to risk factors including atherogenic dyslipidemia compared with males.

• Prevalence of injuries and reporting of accidents among health care workers at the University Hospital of the West Indies.

  Authors: Kurt Vaz, Donovan McGrowder, Tazhmoye Crawford, Ruby Lisa Alexander-Lindo, Rachael Irving

  International journal of occupational medicine and environmental health. 01/2010; 23(2):133-43.

  This study investigated the knowledge, awareness and practices of health care workers towards universal precautions at the University Hospital of the West Indies. The study also examined theThis study investigated the knowledge, awareness and practices of health care workers towards universal precautions at the University Hospital of the West Indies. The study also examined the prevalence of injuries experienced by health care workers, as well as incidence of accidents and compliance with post-exposure prophylaxis. A cross sectional survey was conducted in September and October 2007. A 28-item self-administered questionnaire was provided to two hundred health care workers including medical doctors, medical technologists, nurses and porters to assess knowledge and practices regarding universal precautions, prevalence of injuries and incidence of accidents. Almost two-thirds (62.3%) of the respondents were aware of policies and procedures for reporting accidents while one-third (33.2%) were unsure. All nurses were aware of policies and procedures for reporting accidents, followed by medical doctors (88%) and medical technologists (61.2%). The majority (81.5%) of the respondents experienced splashes from bodily fluid. Over three-quarters of medical doctors (78%) and two-thirds of nurses (64%) reported having experienced needle stick injuries, while the incidence among medical technologists was remarkably lower (26%). The majority of the respondents (59%) experienced low accident incidence while just over one-tenth (14%) reported high incidence. Eighty four respondents reported needle stick injuries; just under two-thirds (59.5%) of this group received post-exposure treatment. The study found that majority of health care workers were aware of policies and procedures for reporting accidents. Splashes from body fluids, needle stick injuries and cuts from other objects were quite prevalent among health care workers. There is a need for monitoring systems which would provide accurate information on the magnitude of needle stick injuries and trends over time, potential risk factors, emerging new problems, and the effectiveness of interventions at The University Hospital of the West Indies and other hospitals in Jamaica.

• The prevalence of other sexually transmitted infections in confirmed HIV cases at a referral clinic in Jamaica.

  Authors: Nellian Hutton-Rose, Charmaine Blythe, Chinedu Ogbonna, Donovan McGrowder

  Journal of the Royal Society of Health. 10/2008; 128(5):242-7.

  Jamaica has the second highest number of acquired immunodeficiency syndrome (AIDS) cases and deaths in the Caribbean and a significant number of human immunodeficiency virus (HIV) infectedJamaica has the second highest number of acquired immunodeficiency syndrome (AIDS) cases and deaths in the Caribbean and a significant number of human immunodeficiency virus (HIV) infected individuals have a concomitant sexually transmitted infection (STI). The study determined the prevalence of non-ulcerative and ulcerative STIs and their association with sexual risky behaviour in a sample of HIV seropositive men and women. This study was conducted at the Comprehensive Health Centre in Jamaica, a sexually transmitted infection referral centre. The sample comprised 138 men and 132 women age 15-49 years, of average 29.5 years. The study was retrospective, from 2000 to 2002, and sample collection was randomized. The sexual behaviours of the subjects were assessed from the case records. In the 270 HIV diagnosed cases examined, the prevalence of STIs was 51.1% in men and 48.9% in women, with 85.4% having one or more STIs with an average of four STIs per patient. There was a total occurrence of 744 STIs with non-gonococcal urethritis (19.4%), gonorrhoea (17.2%), candidiasis (13.4%), trichomonas (12.4%), genital ulcer (10.4%) and syphilis (7.3%) the most common in HIV infected men and women. The presence of STI was associated with continued practice of risky sexual behaviour. The age group most implicated was the 30-34 year old, and 73.1% of the HIV infected patients had multiple sexual partners with only 16.4% reporting frequent condom use. The study demonstrates that there is a high prevalence of non-ulcerative and to a lesser extent ulcerative STIs in HIV infected patients in Jamaica. There are significant associations between STIs and continued high risk sexual practices in HIV infected men and women. The findings support the need for implementation of effective diagnosis and treatment strategies coupled with education about safe-sex practices in HIV prevention and STI control programmes.

• Effect of exercise therapy on lipid profile and oxidative stress indicators in patients with type 2 diabetes

  Authors: Lorenzo Gordon, Errol Morrison, Donovan McGrowder, Ronald Young, Yeiny Fraser, Eslaen Zamora, Ruby Alexander-Lindo, Rachael Irving

  BMC Complementary and Alternative Medicine. 01/2008;

  Abstract Background Yoga has been shown to be a simple and economical therapeutic modality that may be considered as a beneficial adjuvant for type 2 diabetes mellitus. This study investigated theAbstract Background Yoga has been shown to be a simple and economical therapeutic modality that may be considered as a beneficial adjuvant for type 2 diabetes mellitus. This study investigated the impact of Hatha yoga and conventional physical training (PT) exercise regimens on biochemical, oxidative stress indicators and oxidant status in patients with type 2 diabetes. Methods This prospective randomized study consisted of 77 type 2 diabetic patients in the Hatha yoga exercise group that were matched with a similar number of type 2 diabetic patients in the conventional PT exercise and control groups. Biochemical parameters such as fasting blood glucose (FBG), serum total cholesterol (TC), triglycerides, low-density lipoprotein (LDL), very low-density lipoproteins (VLDL) and high-density lipoprotein (HDL) were determined at baseline and at two consecutive three monthly intervals. The oxidative stress indicators (malondialdehyde – MDA, protein oxidation – POX, phospholipase A2 – PLA2 activity) and oxidative status [superoxide dismutase (SOD) and catalase activities] were measured. Results The concentrations of FBG in the Hatha yoga and conventional PT exercise groups after six months decreased by 29.48% and 27.43% respectively (P < 0.0001) and there was a significant reduction in serum TC in both groups (P < 0.0001). The concentrations of VLDL in the managed groups after six months differed significantly from baseline values (P = 0.036). Lipid peroxidation as indicated by MDA significantly decreased by 19.9% and 18.1% in the Hatha yoga and conventional PT exercise groups respectively (P < 0.0001); whilst the activity of SOD significantly increased by 24.08% and 20.18% respectively (P = 0.031). There was no significant difference in the baseline and 6 months activities of PLA2 and catalase after six months although the latter increased by 13.68% and 13.19% in the Hatha yoga and conventional PT exercise groups respectively (P = 0.144). Conclusion The study demonstrate the efficacy of Hatha yoga exercise on fasting blood glucose, lipid profile, oxidative stress markers and antioxidant status in patients with type 2 diabetes and suggest that Hatha yoga exercise and conventional PT exercise may have therapeutic preventative and protective effects on diabetes mellitus by decreasing oxidative stress and improving antioxidant status. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12608000217303

• The use of soluble transferrin receptor to assess iron deficiency in adults with cystic fibrosis.

  Authors: Sabiha Khalid, Donovan McGrowder, Mike Kemp, Pauline Johnson

  Clinica chimica acta; international journal of clinical chemistry. 04/2007; 378(1-2):194-200.

  BACKGROUND: Iron deficiency (ID) is common in cystic fibrosis (CF) and the soluble transferrin receptor (sTfR) is a sensitive, quantitative measurement of tissue iron deficiency. The studyBACKGROUND: Iron deficiency (ID) is common in cystic fibrosis (CF) and the soluble transferrin receptor (sTfR) is a sensitive, quantitative measurement of tissue iron deficiency. The study investigated the use of sTfR together with serum iron, transferrin saturation (TS) and serum ferritin, in assessing iron status in adult CF patients. METHODS: The patient population consisted of 127 CF patients which consisted of 51 inpatients with infected exacerbation (IE) and 76 outpatients at the time of their annual review (AR). Serum sTfR was measured using a particle-enhanced immunoturbidimetric assay on the Beckman Coulter LX20. RESULTS: Sixty five percent (65%) of CF patients in the IE group and 28% in the AR group had ID as determined TS, but only 18% (IE group) and 20% (AR group) as determined by ferritin. Serum sTfR detected 20% in the IE group and 12% in the AR group. We found significant correlation between C-reactive protein and TS (r=-0.56; P<0.01) but not with ferritin (r=0.22; P=0.380) in the IE group. CONCLUSION: Iron status of patients with CF can be accurately assessed by sTfR which is unaffected by the acute phase response and can be used in conjunction with serum ferritin.

• Increased PC-1 phosphodiesterase activity and inhibition of glucose uptake in adipocytes of type 2 diabetic rats.

  Authors: Karlene Barrett, Donovan McGrowder, Paul Brown, Dalip Ragoobirsingh

  Molecular and cellular biochemistry. 12/2006; 293(1-2):9-14.

  This study was designed to understand the cellular mechanisms responsible for defects in the insulin-stimulated signal transduction pathway in a type 2 diabetic animal model. We examined the in vitroThis study was designed to understand the cellular mechanisms responsible for defects in the insulin-stimulated signal transduction pathway in a type 2 diabetic animal model. We examined the in vitro PC-1 phosphodiesterase activity and glucose uptake in adipose tissue of streptozotocin (STZ)-induced type 2 diabetic rats. The PC-1 activity was significantly increased in adipose tissue of diabetic rats (0.54 +/- 0.08 nmol PNTP hydrolyzed/mg protein/min) compared with controls (0.29 +/- 0.05 nmol PNTP hydrolyzed/mg protein/min, p < 0.05). Upon insulin stimulation (100 nM), glucose uptake in the adipose tissue of the controls (4.17 +/- 1.28 x 10(-8) micromol/mg/min) was significantly higher than that in the diabetic rats (1.26 +/- 0.35 x 10(-8); p < 0.05). These results suggest that elevated PC-1 phosphodiesterase activity and decreased glucose uptake in adipose tissues may be acquired characteristics contributing to the development of type 2 diabetes mellitus.

• Modulation of glucose uptake in adipose tissue by nitric oxide-generating compounds.

  Authors: Donovan McGrowder, Dalip Ragoobirsingh, Paul Brown

  Journal of biosciences. 10/2006; 31(3):347-54.

  There is increasing evidence that endogenous nitric oxide (NO) influences adipogenesis, lipolysis and insulin-stimulated glucose uptake. We investigated the effect of NO released fromThere is increasing evidence that endogenous nitric oxide (NO) influences adipogenesis, lipolysis and insulin-stimulated glucose uptake. We investigated the effect of NO released from S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) on basal and insulin-stimulated glucose uptake in adipocytes of normoglycaemic and streptozotocin (STZ)-induced diabetic rats. GSNO and SNAP at 0.2,0.5, and 1 mM brought about a concentration-dependent increase in basal and insulin-stimulated 2-deoxyglucose uptake in adipocytes of normoglycaemic and STZ-induced diabetic rats. SNAP at 1.0 mM significantly elevated basal 2-deoxyglucose uptake (115.8+/-10.4% compared with GSNO at the same concentration (116.1+/-9.4%; P less than 0.05) in STZ-induced diabetic rats. Conversely, SNAP at concentrations of 10 mM and 20 mM significantly decreased basal 2-deoxyglucose uptake by 50.0+/-4.5% and 61.5+/-7.2% respectively in adipocytes of STZ-induced diabetic rats (P less than 0.05). GSNO at concentrations of 10 mM and 20 mM also significantly decreased basal 2-deoxyglucose uptake by 50.8+/-6.4% and 55.2+/-7.8% respectively in adipocytes of STZ-induced diabetic rats (P less than 0.05). These observations indicate that NO released from GSNO and SNAP at 1 mM or less stimulates basal and insulin-stimulated glucose uptake,and at concentrations of 10 mM and 20 mM inhibits basal glucose uptake. The additive effect of GSNO or SNAP, and insulin observed in this study could be due to different mechanisms and warrants further investigation.

• Acute effects of exogenous nitric oxide on glucose uptake in skeletal muscle of normoglycaemic and diabetic rats.

  Authors: Donovan McGrowder, Dalip Ragoobirsingh, Paul Brown

  Medical science monitor : international medical journal of experimental and clinical research. 02/2006; 12(1):BR28-35.

  BACKGROUND: The role of nitric oxide (NO) in the modulation of basal and insulin-stimulated glucose uptake remains controversial. The aim of this study was to investigate the role of NO released fromBACKGROUND: The role of nitric oxide (NO) in the modulation of basal and insulin-stimulated glucose uptake remains controversial. The aim of this study was to investigate the role of NO released from its donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), on glucose uptake in skeletal muscle of normoglyceamic and type 2 diabetic rats. MATERIAL/METHODS: Skeletal muscle strips of type 2 diabetic and normoglycaemic Sprague-Dawley rats were incubated with or without various concentrations (200 microM, 500 microM, 1000 microM, 10 mM & 20 mM) of SNAP or GSNO in the presence or absence of insulin (100 nM or 10 microM). The associated radioactivity was determined by liquid scintillation counting in a Beckman LS6000 scintillation counter programmed for dual-channel counting. RESULTS: SNAP and GSNO at 1000 microM significantly elevated basal and insulin-stimulated 2-deoxyglucose uptake (P<0.05) in normoglycaemic and diabetic rats. Millimolar concentrations (10 & 20 mM) of GSNO and SNAP significantly decreased basal and insulin-stimulated glucose uptake in skeletal muscle strips of normoglycaemic and type 2 diabetic rats in a concentration-dependent manner (P<0.05). The inhibition of insulin-stimulated glucose uptake was greater in the diabetic rats using both NO donors compared with normoglycaemic rats (P<0.05). CONCLUSIONS: The stimulatory effect of micromolar concentrations of GSNO and SNAP enhances basal and insulin-stimulated glucose uptake in normoglycaemic and type 2 diabetic rats, however higher concentrations elicited an inhibitory effect in normoglycaemic and diabetic rats. This highlights the NO-glucose uptake mechanism as a possible potential therapeutic target in the treatment of type 2 diabetes.

• The effect of nitric oxide on glucose metabolism.

  Authors: Dalip Ragoobirsingh, Donovan McGrowder, Tara Dasgupta, Paul Brown

  Molecular and cellular biochemistry. 08/2004; 263(1-2):29-34.

  Nitric oxide (NO) is an important bioactive signaling molecule that mediates a variety of normal physiological functions, which, if altered, could contribute to the genesis of many pathologicalNitric oxide (NO) is an important bioactive signaling molecule that mediates a variety of normal physiological functions, which, if altered, could contribute to the genesis of many pathological conditions, including diabetes. In this study, we examined the possible diabetogenicity of NO by noting differences in the cellular binding of insulin in dogs treated with the NO donor, S-nitrosoglutathione (GSNO) compared to captopril-treated controls. GSNO administration resulted in an abnormality in glucose metabolism which was attributed to decreased binding of insulin to its receptor on the cell membrane of mononuclear leucocytes, 11.60 +/- 0.60% in GSNO-treated dogs compared with 18.10 +/- 1.90% in captopril-treated control (p < 0.05). The decreased insulin binding was attributed to decreased insulin receptor sites per cell, 21.43 +/- 2.51 x 10(4) in GSNO-treated dogs compared with 26.60 +/- 1.57 x 10(4) in captopril-treated controls (p < 0.05). Average affinity analysis of the binding data demonstrated that this decrease in insulin binding was also due to a decrease in average affinity of the receptor on mononuclear leucocytes for insulin. This was evident by a decrease in empty and filled site affinities in GSNO-treated dogs compared with that of captopril-treated dogs (p < 0.05). It appears that GSNO is exerting its effect by decreasing the number of insulin receptor sites and/or decreasing the average receptor affinity. These results provide evidence for a novel role of NO as a modulator of insulin binding and the involvement of NO in the aetiology of diabetes mellitus.

• The enhancement of the hyperglycemic effect of S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine by vitamin C in an animal model.

  Authors: Donovan McGrowder, Dalip Ragoobirsingh, Tara Dasgupta

  BMC pharmacology. 09/2002; 2:18.

  BACKGROUND: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetlypenicillamine (SNAP) are two of the most common sources of nitric oxide (NO) in the biomedical field. Vitamin C has been known toBACKGROUND: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetlypenicillamine (SNAP) are two of the most common sources of nitric oxide (NO) in the biomedical field. Vitamin C has been known to accelerate the decomposition of GSNO and SNAP increasing the release and availability of NO which is cytotoxic at non-physiological concentrations. The study investigates any potential detrimental effect of vitamin C and GSNO, vitamin C and SNAP on glucose metabolism in normotensive and normoglycemic dogs. RESULTS: The results showed that administration of vitamin C (50 mg/kg) and GSNO (35 mg/kg & 50 mg/kg), or vitamin C (50 mg/kg) and SNAP (10 mg/kg) to overnight fasted dogs resulted in significant elevation of the blood glucose levels, attaining maximum level at the 2.0 or 2.5 h time point postprandially. The elevated blood glucose levels were due to significant reduction in plasma insulin levels in the dogs treated with vitamin C and GSNO, or vitamin C and SNAP (P < 0.05). The decreased insulin response was associated with significant elevation of nitric oxide produced from GSNO and SNAP co-administered with vitamin C, as assessed by plasma nitrate/nitrite levels. CONCLUSIONS: The results indicate that enhanced NO release by vitamin C affects postprandial blood glucose and plasma insulin levels and the reduced glucose tolerance is mainly due to impaired insulin release. The clinical relevance of the findings of this study suggest that hypertensive diabetic patients treated with GSNO or SNAP, who are on vitamin C supplements may be more predisposed to further decrease in their glycemic control.

• The Jamaican hypertension prevalence study.

  Authors: Dalip Ragoobirsingh, Donovan McGrowder, Errol Y Morrison, Pauline Johnson, Eva Lewis Fuller, John Fray

  Journal of the National Medical Association. 08/2002; 94(7):561-5.

  This study was designed to investigate the prevalence of hypertension in Jamaica. Jamaica has an area of 4,411 square miles and is divided into 14 parishes. The visited districts were randomlyThis study was designed to investigate the prevalence of hypertension in Jamaica. Jamaica has an area of 4,411 square miles and is divided into 14 parishes. The visited districts were randomly selected. The sample population was selected based upon a two-stage stratified random sampling design. Each dwelling in the "Sampling Universe" had an equal probability of being selected. The survey team spent a week in the districts in each parish selected. Employing the Statistical Institute of Jamaica's (STATIN) two-stage stratified random sampling design, preselected house-holds were visited. Non-response was documented and considered in the final analysis. Only individuals 15 years and older were allowed to participate in the study. The 2,064 subjects who participated were the basis for estimates of hypertension. Following logistic regression analysis, the main risk factors for hypertension are being female, advancing age, obesity, having diabetes and having a family history of hypertension. Jamaica has a point prevalence of hypertension of 30.8% in the 15-and-over age group. These findings would greatly assist in formulating policies to deal with this scourge of society.

• Decreased insulin binding to mononuclear leucocytes and erythrocytes from dogs after S-nitroso-N-acetypenicillamine administration.

  Authors: Donovan McGrowder, Dalip Ragoobirsingh, Tara Dasgupta

  BMC biochemistry. 01/2002; 3:1.

  BACKGROUND: Nitric oxide (NO) and oxygen free-radicals play an important part in the destruction of beta-cells in auto- immune diabetes although the precise mechanism of interaction is still notBACKGROUND: Nitric oxide (NO) and oxygen free-radicals play an important part in the destruction of beta-cells in auto- immune diabetes although the precise mechanism of interaction is still not known. This study was designed to examine any possible diabetogenic effect of NO by investigating any differences in cellular binding of insulin to its receptor on the cell membranes of erythrocytes and mononuclear leucocytes of dogs treated with the NO donor, S-nitroso-N-acetylpenicillamine (SNAP) and controls treated with captopril. RESULTS: The result obtained showed decreased binding of insulin to its receptor on the cell membranes of erythrocytes and mononuclear leucocytes. Mononuclear leucocytes from SNAP-treated dogs had decreased ability to bind insulin (16.30 +/- 1.24 %) when compared to mononuclear leucocytes from captopril-treated controls (20.30 +/- 1.93 %). Similar results were obtained for erythrocytes from dogs treated with SNAP (27.20 +/- 1.33 %) compared with dogs treated with captopril (34.70 +/- 3.58 %). Scatchard analysis demonstrated that this decrease in insulin binding was accounted for by a decrease in insulin receptor sites per cell, with mononuclear leucocytes of SNAP-treated dogs having 55 % less insulin receptor sites per cell compared with those of captopril-treated controls (P < 0.05). Average affinity and kinetic analysis revealed a 35 % decrease in the average receptor affinity, with mononuclear leucocytes from captopril-treated controls having an empty site affinity of 12.36 +/- 1.12 x 10(-8) M(-1) compared with 9.64 +/- 0.11 x 10(-8) M(-1) in SNAP-treated dogs (P < 0.05). CONCLUSION: These results suggest that acute alteration of the insulin receptor on the membranes of mononuclear leucocytes and erythrocytes occurred in dogs treated with S-nitroso-N-acetylpenicillamine. These findings suggest the first evidence of the novel role of NO as a modulator of insulin binding and the involvement of NO in the aetiology of diabetes mellitus.

• Effects of S-Nitroso-N-acetyl-penicillamine Administration on Glucose Tolerance and Plasma Levels of Insulin and Glucagon in the Dog

  Authors: Donovan McGrowder, Dalip Ragoobirsingh, Tara Dasgupta

  Nitric Oxide.

  It has been suggested that nitric oxide (NO, nitrogen monoxide) is a regulator of carbohydrate metabolism in skeletal muscle. The present study was undertaken to investigate the acute effects of theIt has been suggested that nitric oxide (NO, nitrogen monoxide) is a regulator of carbohydrate metabolism in skeletal muscle. The present study was undertaken to investigate the acute effects of the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) on blood glucose levels and on the gluco-regulatory hormones insulin and glucagon in healthy dogs. The acute effects of SNAP on mean arterial pressure and heart rate were also investigated. The drug was administered intravenously and the pre- and postprandial blood glucose, plasma insulin, and glucagon concentrations were determined at half-hour time intervals postadministration after a glucose challenge. The plasma nitrate and nitrite concentrations were measured and taken as the biochemical markers of in vivo NO formation. The oral glucose tolerance test revealed an impaired glucose tolerance in SNAP-treated dogs as reflected by the area under the glucose curve, 1150.50 ± 63.00 mmol × 150 min and 1355.25 ± 102.01 mmol/L × 150 min in dogs treated with 10 and 20 mg/kg of SNAP, respectively, compared with 860.25 ± 60.68 mmol/L × 150 min in captopril-treated controls (P < 0.05). The 2-h blood glucose concentration in dogs treated with 20 mg/kg body wt of SNAP was 9.17 ± 1.10 mmol/L compared with 5.59 ± 0.26 mmol/L for captopril-treated controls (P = 0.015). The oral glucose tolerance test also confirmed an impaired insulin secretion in the SNAP-treated dogs. While the plasma insulin concentration increased gradually in the captopril-treated controls to a peak value of 39.50 ± 2.55 μIU/ml, 1.5 h after a glucose challenge there was a decrease in the plasma insulin concentration in SNAP-treated dogs to a low value of 20.67 ± 0.88 μIU/ml (P = 0.006). In contrast, there were no significant differences in plasma glucagon concentration in SNAP-treated dogs and captopril-treated dogs at any time points. Using the Griess reaction, we found that there was a 27–95% increase in plasma nitrate/nitrite concentration on administration of SNAP. The sustained hyperglycemic effect observed in SNAP-treated dogs was accompanied by a marginal decrease in the mean arterial blood pressure and a significant increase in heart rate (P < 0.05). We conclude that acute administration of SNAP in the oral glucose tolerance test releases NO that modulates the parameters of carbohydrate metabolism.

• The use of soluble transferin receptor to assess iron deficiency in adults with cystic fibrosis

  Authors: Sabiha Khalid, Donovan McGrowder, Mike Kemp, Pauline Johnson

  Clinica Chimica Acta.

  BackgroundIron deficiency (ID) is common in cystic fibrosis (CF) and the soluble transferrin receptor (sTfR) is a sensitive, quantitative measurement of tissue iron deficiency. The study investigatedBackgroundIron deficiency (ID) is common in cystic fibrosis (CF) and the soluble transferrin receptor (sTfR) is a sensitive, quantitative measurement of tissue iron deficiency. The study investigated the use of sTfR together with serum iron, transferrin saturation (TS) and serum ferritin, in assessing iron status in adult CF patients.MethodsThe patient population consisted of 127 CF patients which consisted of 51 inpatients with infected exacerbation (IE) and 76 outpatients at the time of their annual review (AR). Serum sTfR was measured using a particle-enhanced immunoturbidimetric assay on the Beckman Coulter LX20.ResultsSixty five percent (65%) of CF patients in the IE group and 28% in the AR group had ID as determined TS, but only 18% (IE group) and 20% (AR group) as determined by ferritin. Serum sTfR detected 20% in the IE group and 12% in the AR group. We found significant correlation between C-reactive protein and TS (r = − 0.56; P < 0.01) but not with ferritin (r = 0.22; P = 0.380) in the IE group.ConclusionIron status of patients with CF can be accurately assessed by sTfR which is unaffected by the acute phase response and can be used in conjunction with serum ferritin.