Paresh Dandona - Academia.edu (original) (raw)

Papers by Paresh Dandona

Critical Care Medicine, Sep 1, 1995

To determine whether reactive oxygen metabolite production by alveolar macrophages is affected by... more To determine whether reactive oxygen metabolite production by alveolar macrophages is affected by liquid perfluorochemical exposure. Controlled, animal laboratory investigation of alveolar macrophage function in vitro. Animal research facility of a health sciences university. Six adult male New Zealand white rabbits and six young piglets. Alveolar macrophages were obtained after sacrifice from both species by total lung lavage. Macrophages were divided into control and experimental groups. Macrophages in the experimental groups were exposed to perfluorooctylbromide. To determine production of reactive oxygen metabolites, hydrogen peroxide production and chemiluminescence were measured in both experimental and control groups after chemical stimulation. Perfluorooctylbromide-exposed alveolar macrophages produced significantly less hydrogen peroxide (1.4 +/- 1.5 vs. 2.4 +/- 1.6 nmol/10(6) cells; p = .002). Perfluorooctylbromide-exposed alveolar macrophages demonstrated significantly less chemiluminescence activity compared with nonexposed cells (0.70 +/- 0.2 vs. 1.5 +/- 0.2 mV of relative activity per 3.5 x 10(5) cells; p = .005). Exposure of alveolar macrophages to perfluorooctylbromide in vitro decreases the responsiveness of macrophages to potent stimuli. This finding may partially explain the decrease in pulmonary inflammation seen in animals treated with partial liquid ventilation during experimentally induced lung injury.

Diabetologia, Dec 16, 2006

Circulation, Jan 18, 2000

Androgens: Clinical Research and Therapeutics, 2020

The Journal of Clinical Endocrinology & Metabolism, 2020

Context Dapagliflozin and other SGLT2 inhibitors are known to increase hematocrit, possibly due t... more Context Dapagliflozin and other SGLT2 inhibitors are known to increase hematocrit, possibly due to its diuretic effects and hemoconcentration. Objective Since type 2 diabetes is a proinflammatory state and since hepcidin, a known suppressor of erythropoiesis, is increased in proinflammatory states, we investigated the possibility that dapagliflozin suppresses hepcidin concentrations and thus increases erythropoiesis. Design Prospective, randomized, and placebo-controlled study. Setting Single endocrinology center. Patients Fifty-two obese type 2 diabetes patients. Intervention Patients were randomized (1:1) to either dapagliflozin (10 mg daily) or placebo for 12 weeks. Blood samples were collected before and after treatments and serum, plasma, and mononuclear cells (MNC) were prepared. Main Outcome Measure Hepcidin and other hematopoietic factors. Results Following dapagliflozin treatment, there was a significant fall in HbA1c and a significant increase in hemoglobin concentration a...

Journal of the Endocrine Society, 2019

Context and ObjectiveHypertriglyceridemia is implicated in ~5% of cases of acute pancreatitis. It... more Context and ObjectiveHypertriglyceridemia is implicated in ~5% of cases of acute pancreatitis. It is assumed that intravenous insulin is effective in lowering triglyceride (TG) concentrations in hypertriglyceridemia-associated acute pancreatitis (HAAP). However, the efficacy of intravenous insulin versus conservative management alone is not known.Design and SettingCharts of 106 patients who were admitted with HAAP and had TG concentrations >1000 mg/dL at admission were reviewed. Patients who received intravenous insulin for at least 8 hours were included in the intravenous insulin group, while the rest were considered to have received conservative management. We compared the change in TG concentrations from baseline in the 2 groups.ResultsFifty-one patients received intravenous insulin while 55 patients were managed conservatively. Baseline TG concentrations were higher in the intravenous insulin group (median [25th, 75th percentile] 3307 [2106, 4425] mg/dL vs 2304 [1416, 2720] m...

International Journal of Endocrinology, 2018

A quarter of men with obesity or type 2 diabetes have hypogonadotropic hypogonadism. Animal studi... more A quarter of men with obesity or type 2 diabetes have hypogonadotropic hypogonadism. Animal studies and in vitro data have shown that insulin action and insulin responsiveness in the brain are necessary for the maintenance of the functional integrity of the hypothalamo-hypophyseal-gonadal axis. We conducted a randomized, placebo-controlled trial to evaluate the effect of one dose of intranasal insulin (40 IU of regular insulin) or saline on LH concentrations in 14 men (8 with type 2 diabetes and 6 healthy lean men). Insulin or saline was administered intranasally on two different occasions, at least one week apart. Blood samples were collected to measure LH concentrations every 15 minutes for 5 hours. Study drug was administered intranasally after a 2-hour baseline sampling period. Patients remained fasting throughout the procedure. The primary endpoint of the study was to compare the change in LH concentrations after intranasal insulin as compared to placebo (intranasal saline). Ch...

AACE Clinical Case Reports, 2016

Clinical Endocrinology, 2016

SummaryContextAs the syndrome of hypogonadotropic hypogonadism (HH) is associated with anaemia an... more SummaryContextAs the syndrome of hypogonadotropic hypogonadism (HH) is associated with anaemia and the administration of testosterone restores haematocrit to normal, we investigated the potential underlying mechanisms.DesignRandomized, double‐blind, placebo‐controlled trial.MethodsWe measured basal serum concentrations of erythropoietin, iron, iron binding capacity, transferrin (saturated and unsaturated), ferritin and hepcidin and the expression of ferroportin and transferrin receptor (TR) in peripheral blood mononuclear cells (MNC) of 94 men with type 2 diabetes. Forty‐four men had HH (defined as subnormal free testosterone along with low or normal LH concentrations) while 50 were eugonadal. Men with HH were randomized to testosterone or placebo treatment every 2 weeks for 15 weeks. Blood samples were collected at baseline, 3 and 15 weeks after starting treatment. Twenty men in testosterone group and 14 men in placebo group completed the study.ResultsHaematocrit levels were lower ...

The Journal of Clinical Endocrinology & Metabolism, 2012

The Journal of Clinical Endocrinology & Metabolism, 1998

In view of the recent demonstration that obesity in animals and humans is associated with an incr... more In view of the recent demonstration that obesity in animals and humans is associated with an increase in tumor necrosis factor-α (TNFα) expression, that this expression falls with weight loss, and that TNFα may specifically inhibit insulin action, the possibility that TNFα may be a mediator of insulin resistance has been raised. We have undertaken this study to investigate whether serum TNFα concentrations are elevated in obese subjects, whether they fall after weight loss, and whether this fall parallels the fall in insulin release after glucose challenge. Obese patients (age range: 25–54, weight mean ± sd: 96.4 ± 13.8 kg, body mass index: 35.7 ± 5.6 kg/m2) were started on a diet program. The mean weight fell to 84.5 ± 11.3 (P < 0.0001) and body mass index to 31.3 ± 4.9 (P < 0.0001). Plasma TNFα concentrations were markedly elevated in the obese (3.45 ± 0.16 pg/mL), when compared with controls (0.72 ± 0.28 pg/mL), and fell significantly (2.63 ± 1.40 pg/mL) after weight loss (...

Hypertension, 1995

To directly assess insulin-related venomotor changes objectively and quantitatively, we used a mo... more To directly assess insulin-related venomotor changes objectively and quantitatively, we used a modified ultrasonographic technique to measure venous diameter. Ten healthy men and women were studied by use of an Acuson 128 XP ultrasonograph with a linear 7.5-MHz ultrasonographic transducer (sensitivity, ±0.1 mm). Venous diameter was measured with the arm kept at 30° elevation and with a pneumatic cuff above the elbow inflated at 40 mm Hg for the last 2 minutes of each 5-minute observation period. Norepinephrine was infused at incremental concentrations of 12.5, 25, 50, and 100 ng/min (75, 150, 300, and 600 pmol/min, respectively) for 5 minutes each. Maximal venoconstriction was achieved by the dose of 100 ng/min norepinephrine, which was then combined with insulin doses of 8, 16, 24, and 32 μU/min (60, 120, 180, and 230 fmol/min, respectively) for 5 minutes each. In six different subjects, methylene blue, an inhibitor of guanylate cyclase, was infused simultaneously with 32 μU/min in...

Journal of Hypertension, 1999

An exaggerated blood pressure response to mental stress in postmenopausal women has been reported... more An exaggerated blood pressure response to mental stress in postmenopausal women has been reported but the underlying mechanism is not clear. In the present study, we examined the role of estrogen in the blood pressure response to mental stress. Hemodynamic responses to mental stress and constrictor responses to norepinephrine were compared in 18 premenopausal (mean +/- SD age 33 +/- 5 years), 22 postmenopausal women (62 +/- 7 years) and 13 postmenopausal women with estrogen replacement therapy (58 +/- 8 years). Premarin was infused in 10 postmenopausal women to determine whether estrogen attenuates norepinephrine-induced vasoconstriction. The hemodynamic responses to a standard mental arithmetic test were measured. Norepinephrine (12.5, 25, 50, 100 ng/min) was infused at 0.5 ml/min for 5 min via the dorsal hand vein. Norepinephrine (100 ng/min) combined with premarin (200 microg/min) was infused into the dorsal hand vein of postmenopausal women. Changes in venous diameter were measured by ultrasonography using a 7.5 MHz transducer. All study subjects were healthy, normotensive and had normal lipid profiles. The postmenopausal women showed a significantly greater blood pressure response to the mental arithmetic test than the premenopausal women or those taking estrogen replacement therapy (P < 0.01). Norepinephrine induced significant dose-dependent vasoconstriction in all three groups (P < 0.001). The postmenopausal women showed significantly greater constriction in response to norepinephrine than the premenopausal women and those taking estrogen replacement therapy (P = 0.02). Premarin significantly attenuated the norepinephrine-induced vasoconstriction in the postmenopausal women (P< 0.001). Healthy, normotensive postmenopausal women showed an exaggerated blood pressure response to mental stress. An increased vasoconstriction in response to norepinephrine and loss of estrogen-mediated vasodilation may contribute to the increased blood pressure response to stress in postmenopausal women without estrogen replacement therapy.

Nature Clinical Practice Cardiovascular Medicine, 2008

European Journal of Endocrinology, 2018

Aims One-third of males with type 2 diabetes (T2DM) have hypogonadism, characterized by low total... more Aims One-third of males with type 2 diabetes (T2DM) have hypogonadism, characterized by low total and free testosterone concentrations. We hypothesized that this condition is associated with a compensatory increase in the expression of androgen receptors (AR) and that testosterone replacement reverses these changes. We also measured estrogen receptor and aromatase expression. Materials and methods This is a randomized double-blind placebo-controlled trial. Thirty-two hypogonadal and 32 eugonadal men with T2DM were recruited. Hypogonadal men were randomized to receive intramuscular testosterone or saline every 2 weeks for 22 weeks. We measured AR, ERα and aromatase expression in peripheral blood mononuclear cells (MNC), adipose tissue and skeletal muscle in hypogonadal and eugonadal males with T2DM at baseline and after 22 weeks of treatment in those with hypogonadism. Results The mRNA expression of AR, ERα (ESR1) and aromatase in adipose tissue from hypogonadal men was significantly...

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Archives of Neurology, 2012