Melita Kosanovic

Ph.D. analytical toxicology
Laboratory Consultant
Camel Research Centre · Department of President's Affairs

Publications

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    ABSTRACT: Visceral obesity is more common in the Arab population and more closely related to morbidity, including diabetes and related cardiovascular diseases (CVD). Possible mechanisms that link visceral fat/obesity to diabetes and CVD complications include inflammation and increased oxidative stress; however, few data are available from the Arab population. Our aim was to determine whether increased adiposity in obese diabetic United Arab Emirates citizens is associated with sub-clinical inflammation and/or increased oxidative stress. A hundred diabetic patients who were part of a randomized controlled trial of nutritional supplements had their baseline characteristics assessed from anthropometric and clinical data following informed written consent. We used WHO figures to classify general and central obesity. Fasting blood samples were collected for the measurement of antioxidants and markers of oxidative damage and inflammation. We found that increased adiposity measured by both body mass index and waist circumference was associated with increased C-reactive protein (CRP) and decreased vitamin C after adjusting for age, duration and treatment of diabetes (p < 0.05). Although there is a clear trend of increased inflammatory markers, notably CRP, and decreased antioxidants with increased BMI and waist circumference in both men and women, the results are statistically significant for women only. CRP were also inversely associated with HDL. Overall, we found that BMI underestimates the rates of obesity compared to waist circumference and that increased adiposity is associated with increased inflammation and decreased HDL and antioxidant status.
    Nutrients 01/2014; 6(11):4872-4880. · 3.15 Impact Factor
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    ABSTRACT: Children are frequently exposed to toxic metals in the environment, and their developing central nervous system is particularly vulnerable to their effects. This study examined the blood level of heavy metals in children with learning disorder (LD) as compared to children without LD in the United Arab Emirates (UAE). Significantly high blood concentrations of seven heavy metals were found in children with LD. Further analysis using forward stepwise logistic regression showed that molybdenum levels and family history of developmental problems were the best predictors of LD. Our findings suggest the need for monitoring for toxic metals in the environment.
    Asian journal of psychiatry. 10/2013; 6(5):394-400.
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    Melita Kosanovic, Milan Jokanovic
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    ABSTRACT: Over the last three decades, there has been an increasing awareness of environmental and occupational exposures to toxic or potentially toxic trace elements. The evolution of biological monitoring includes knowledge of kinetics of toxic and/or essential elements and adverse health effects related to their exposure. The debate whether a hair is a valid sample for biomonitoring or not is still attracting the attention of analysts, health care professionals, and environmentalists. Although researchers have found many correlations of essential elements to diseases, metabolic disorders, environmental exposures, and nutritional status, opponents of the concept of hair analysis object that hair samples are unreliable due to the influence of external factors. This review discusses validity of hair as a sample for biomonitoring of essential and toxic elements, with emphasis on pre-analytical, analytical, and post-analytical factors influencing results.
    Environmental Monitoring and Assessment 03/2011; 174(1-4):635-43. · 1.68 Impact Factor
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    ABSTRACT: No systematic studies have been carried out on the effects of toxic metals on childhood behavior in the Gulf Region including the UAE. The relationship between blood levels of heavy metals and Attention Deficit Hyperactivity disorder (ADHD) were explored in school-aged children of UAE and it was found that increased blood concentrations of lead (Pb), manganese (Mn) and zinc (Zn) were significantly associated with ADHD. The findings suggest that monitoring for exposure to heavy metal levels and education on potential child health hazards related to them are indicated.
    Journal of Tropical Pediatrics 02/2011; 57(6):457-60. · 1.01 Impact Factor
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    ABSTRACT: About 80 years have passed since the first cases of organophosphate induced delayed polyneuropathy (OPIDP), as the consequence of human poisoning with certain organophosphorus compounds, were described in the literature. OPIDP is a relatively rare neurodegenerative disorder in humans characterized by loss of function, ataxia and paralysis of distal parts of sensory and motor axons in peripheral nerves and ascending and descending tracts of spinal cord appearing 2-3 weeks after exposure or later. The molecular target for OPIDP is considered to be an enzyme in the nervous system known as neuropathy target esterase (NTE). This review discusses OPIDP in man with emphasis on clinical presentation, pathogenesis, molecular mechanisms, and possibilities for prevention/therapy.
    Clinical neurology and neurosurgery 09/2010; 113(1):7-10. · 1.30 Impact Factor
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    Milan Jokanović, Melita Kosanović
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    ABSTRACT: In this paper we review neurotoxic disorders appearing in patients poisoned with organophosphorus pesticides. These compounds cause four important neurotoxic effects in humans: the cholinergic syndrome, the intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP) and chronic organophosphate-induced neuropsychiatric disorder (COPIND). Compared to the cholinergic syndrome, that causes millions of cases of poisoning each year, other disorders involve much smaller numbers of patients. The review is focused on the neurotoxic effects appearing after acute and chronic exposure to organophosphates with emphasis on clinical presentation, pathogenesis, molecular mechanisms, and possibilities for prevention/therapy.
    Environmental toxicology and pharmacology. 05/2010; 29(3):195-201.
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    ABSTRACT: Streptozotocin (STZ) and alloxan (ALX) are widely used to induce diabetes mellitus in experimental animals. The direct effects of STZ and ALX on the amplitude and time course of ventricular myocyte shortening and on cardiac action potentials were investigated. STZ and ALX (10(-5)M) were dissolved in normal Tyrode (NT), maintained at pH 7.4 and 37 degrees C and stored for either 15 or 60-120min. Both compounds reduced the amplitude of myocyte shortening. Compared to NT the amplitude of shortening was 34.7+/-5.0% and 35.2+/-6.8% with STZ and 41.0+/-5.5% and 37.3+/-5.7% with ALX stored for 15 and 60-120min, respectively. During a 10min NT washout STZ myocytes recovered to 56.2+/-8.3% and 60.5+/-8.2% and ALX myocytes recovered to 88.9+/-10.0% and 83.7+/-9.9% after storage of compounds for 15 and 60-120min, respectively. Perfusion of the whole heart with ALX induced bradycardia but had no effects on the duration of action potential repolarization at 50% and 70% from peak action potential. The negative inotropic effects of STZ and ALX were not altered by storage. The results suggest that some of the effects on heart reported in STZ- and ALX-induced diabetes may be partly attributed to direct action of these compounds.
    Pharmacological Research 05/2009; 59(4):235-41. · 4.35 Impact Factor
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    ABSTRACT: In the United Arab Emirates (UAE), overall diabetes prevalence in adult population is around 20%. Along with, or instead of oral hypoglycemic drugs and insulin, some patients use bitter gourd (Momrodica charantia) because of its hypoglycemic properties. The aim of this study was to assess the essential (Ca, Mg, V, Cr, Mn, Co, Cu, Zn, and Mo) and toxic (As, Cd, Hg, and Pb) trace elements of bitter gourd using inductively coupled plasma-mass spectrometry (ICP-MS). Mean concentrations of each essential element were compared with literature data. Toxic As and Cd could not be detected, while Hg and Pb concentrations in our samples were much lower compared to values reported previously from contaminated areas. Results obtained in our study after ICP-MS/MW analysis, indicate that bitter gourd can be a good source of essential elements.
    International Journal of Food Properties - INT J FOOD PROP. 01/2009; 12(4):766-773.
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    ABSTRACT: A wide variation in the composition of breast milk has been reported from various countries. This study was undertaken to determine the trace element content of breast milk and plasma in lactating women. Mothers of children 4 weeks to 80 weeks in age, were studied. Blood and breast milk from the mothers were analysed for trace element content. Prepared samples were analysed using ICP-MS. 209 women agreed to take part in the study, 68 of whom were from the UAE and 124 were other nationalities (17 did not fill the this part of the questionnaire). Ninety-seven infants were male. The concentration of different trace elements in blood and breast milk were little different between women from the UAE and those from outside the UAE. Molybenum, chromium and arsenic significantly increased with increasing age of the infant, while manganese, copper and zinc significantly decreased with increasing age of the infant. The trace element concentrations of breast milk and maternal blood were comparable to published values. Normal values for plasma and breast milk trace metal concentrations have been obtained for UAE women.
    Journal of Environmental Science and Health Part A 03/2008; 43(3):329-34. · 1.25 Impact Factor
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    ABSTRACT: This article maybe used for research, teaching and private study purposes. Any substantial or systematic reproduction, re-distribution, re-selling, loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.
    01/2008;
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    ABSTRACT: We hypothesized that increased ambient concentrations of metals, as a consequence of escalating urbanization and industrialization of the Gulf region will respond in increased contamination of edible fish species. In this study, we report concentrations of chromium, manganese, cobalt, copper, zinc, arsenic, cadmium, mercury and lead in meat and liver of wild Red-spot emperor (Lethrinus lentjan) from three sampling points at the UAE coast. Analysis was performed by the ICP-MS/microwave digestion. Our study has shown that meat and liver metal content was significantly higher in areas with higher industrial activity, although metal values did not exceed permitted levels of fish for human consumption.
    Food and Chemical Toxicology 12/2007; 45(11):2261-6. · 3.01 Impact Factor
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    Melita Kosanovic, Milan Jokanovic
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    ABSTRACT: Oxidative stress has been postulated as major contributor to endothelial dysfunction and pregnancy-induced hypertension. We have examined the association of exposure to cadmium through cigarette smoke with hypertension disorders during pregnancy in the selenium deficient population. Markers of lipid peroxidation and antioxidative defense were measured and correlated with cadmium blood concentration in normotensive and hypertensive pregnant smokers and nonsmokers. We have observed significantly higher blood Cd in hypertensive smokers and significant differences in all other parameters. Se concentrations were lower in smokers, both in normotensive and hypertensive group as well as values of nonenzymatic (Zn, Cu, and glutathione) and enzymatic (superoxide dismutase, glutathione peroxidase, and glutathione reductase) parameters of antioxidative defense. Results of the study indicate that exposure to cadmium through cigarette smoke in pregnant women, living in Se deficient areas is associated with significantly higher cadmium concentrations and lower levels of enzymatic and nonenzymatic antioxidants and that it can be considered as a risk factor for pregnancy-induced hypertension. Selenium supplementation should be considered for recommendation in such condition.
    Environmental Toxicology and Pharmacology 07/2007; 24(1):72-8. · 2.01 Impact Factor
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    ABSTRACT: Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for approximately 16 weeks, resulting in a significant level of Pb in the blood (106.2+/-8.9 microg/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-gamma and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions.
    Toxicology and Applied Pharmacology 03/2007; 218(3):215-26. · 3.98 Impact Factor
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    ABSTRACT: Pollution has increased with industrialization and humans are subjected to exposure to heavy metals from different environmental sources. In oil-producing countries heavy metals are considered a major threat to the population. Metals such as lead, aluminum, manganese, nickel and cadmium may impact various organs of the body, and controlling their toxicity is crucial for individuals at risk. Previous studies utilized blood levels for monitoring metal toxicity. The current study was designed to investigate exposure to lead, aluminum, manganese, nickel and cadmium using scalp hair. Hair samples were randomly collected from 42 children (aged 6-18 y) representing rural and urban areas of the United Arab Emirates. The rural regions were defined as at least 50 km away from factories or traffic sites. Immediately after cutting, hairs were stored in plastic bags and attached to a questionnaire with the relevant background information. Samples were dried, weighed and sealed with polyethylene envelopes. Following extraction procedures with nitric acid, ICP-MS was utilized for metals determination. The analytical instrument showed a high degree of sensitivity and revealed significant differences between levels of some metals in hairs from rural and urban areas. Children from rural areas had mean hair lead levels (microg/g) of 0.79 + 0.10 whereas children from urban area had higher hair lead levels (3.47 + 0.47). Measuring metals concentration in scalp hair could be a useful method for studying exposure and assessing environmental pollution. Although the technique has the potential of being an effective tool for evaluating extent of pollution and identifying potentially toxic elements, it cannot yet replace the standard procedures of measuring air, water and soil metal content.
    Veterinary and human toxicology 07/2004; 46(3):119-21.
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    Jokanovic M, Kosanovic M, Stukalov P.V
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    ABSTRACT: This review discusses current understanding of organophosphate induced delayed polyneuropathy (OPIDP) with emphasis on molecular mechanisms, pathogenesis and possibilities for prevention / therapy. OPIDP is a rare toxicity caused by certain organophosphorus compounds (OP) characterized by degeneration of some long axons in the central and peripheral nervous system that appear about 2-3 weeks after exposure. The molecular target for OPIDP is considered to be an enzyme in the nervous system known as neuropathy target esterase (NTE). NTE can be inhibited by two types of inhibitors: a) phosphates, phosphonates, and phosphoramidates, which cause OPIDP when >70% of the enzyme is inhibited, and b) phosphinates, carbamates, and sulfonyl halides, which inhibit NTE and cause either protection from or promotion of OPIDP when given before or after a neuropathic OP, respectively. The ability of a NTE inhibitor to cause OPIDP, besides its affinity for the enzyme, is related to its chemical structure and residue left attached to NTE. If such residue can undergo the aging reaction i.e. the loss of alkyl group bound to the enzyme, those OPs usually have high potency to cause OPIDP. Protection from neuropathic doses of OP inhibitors is obtained when NTE is inhibited with nonageable inhibitors. Promotion of OPIDP involves another site besides NTE because it might occur when all NTE is affected. It is now known that this other site is similar to NTE in that it is also sensitive to mipafox but at much higher concentrations. Promotion affects either progression or expression of OPIDP after the initial biochemical effect on NTE. There were some recent observations that development of OPIDP in hens can be influenced by atropine, oximes and methylprednisolone when they are given before or soon after neuropathic OPs.
    Medicinal Chemistry Reviews - Online 03/2004; 1(2):123-131.
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    ABSTRACT: Introduction: OPE is monitored via cholinesterase (ChE) activity. No consensus exists as to which ChE to be measured: plasma or RBC. Purpose of the study was to determine the suitability of RBC-AChE determinations for OPE.Material & Methods: The number of rats per group (G) was 6. Substances were applied i.p.daily for 5 days, followed by a 2-day break. The cycle was repeated x10. After 8 week recovery the rats were sacrificed. Blood was collected at base line (t0), at the end of each cycle (t1 to t10) and after the recovery period (t11) and RBC-AChE activities determined. G1 received 10 nM paraoxon, G2 10 nM malathion & G3 saline. Statistics: Mann-Whitney test (α ≤ 0.05).Results- G1 vs G3: At t1-2 enzyme activity in G1 is significantly higher. From t3-6 no difference exists, while at t7 activities are higher in G3. At t 8-11 no difference between groups exists. (See Table I)RESULTS- G2 vs G3: At t1-2 enzyme activity in G1 is higher; thereafter no differences exist. (See Table II)CONCLUSIONS: After an initial drop in RBC-AChE activity, there is probably enzyme induction with a maximum arround week 7. RBC-AChE activity is not a reliable marker for OPE in rats.
    Clinical Pharmacology &#38 Therapeutics 01/2004; 75(2). · 6.85 Impact Factor
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    ABSTRACT: Green coconut water (GCW; liquid endosperm) is sterile and has been used in the past in remote locations and/or during armed conflicts as a short-term intravenous hydration fluid. It is also conceivable to use GCW for total parenteral nutrition (TPN) under similar circumstances. Patients on TPN need elemental supplementation. Although data on the major elements (calcium, magnesium, potassium, sodium, and phosphorus) found in GCW are abundant, very limited information concerning trace and minor element content in GCW is available. The purpose of this study was to determine trace and minor element content in GCW. Major elements were arbitrarily defined as those with a GCW concentration in the mM range, as opposed to minor ones in the μM range and trace elements in the nM range. The values determined show the great variability typical for samples of plant origin. Under TPN conditions, GCW (1,000 mL/day) would be able to provide adequate supplementation of manganese (12 ± 5 μmol/L) and possibly zinc (6 ± 1 μmol/L) but not chromium (not detected, i.e., less than 9 nM/L) and copper (105 ± 100 nM/L). With respect to elements usually considered nonessential or even toxic, GCW compares favorably with commonly used TPN solutions, most notably for aluminium content (740 ± 360 nM/L) and cadmium (7 ± 4 nM/L). The levels of lead (150 ± 67 nmol/L) and barium (600 ± 300 nmol/L) were similar to those typically found in commercial TPN solutions. Those of strontium (8 ± 4 μmol/L) are higher but unlikely to be harmful. In conclusion, although GCW is not completely equivalent to high-tech (and high-cost) TPN solutions with trace element supplements, it still may provide sufficient support of at least some of the trace elements if used as a substitute. The GCW investigated by us is, at least, not toxic. However, our results for several trace elements are much lower than values previously reported in the literature, especially in coconuts from “polluted” areas. GCW from polluted soil might be easily toxic if used intravenously. J. Trace Elem. Exp. Med. 17:273–282, 2004. © 2004 Wiley-Liss, Inc.
    The Journal of Trace Elements in Experimental Medicine 12/2003; 17(4):273 - 282.
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    ABSTRACT: Metoclopramide (MCP) is a dopamine receptor antagonist and serotonin receptor agonist widely used as an antiemetic and gastric prokinetic drug. In addition, MCP is a reversible inhibitor of cholinesterases from the human central nervous system and blood, and may have a red blood cell (RBC) acetylcholinesterase (AChE) protective effect against inhibition by organophosphates. The purpose of the study was to quantify 'in vitro', by means of the IC50 shift, the extent of MCP conferred protection, by using paraoxon (POX) and mipafox (MPFX) as inhibitors. Paraoxon is a widely used non-neuropathic organophospate responsible for a large number of accidental or suicidal exposures. Mipafox is a neuropathic organophospate. Red blood cell AChE activities in human plasma were measured photometrically in the presence of different POX, MPFX and MCP concentrations and the IC50 was calculated. Determinations were repeated in the presence of increasing MCP concentrations. It appears that the IC50 shift induced by the presence of MCP increases with the MCP concentration in a linear manner. The protective effect of MCP on cholinesterases could be of practical relevance in the treatment of POX and MPFX poisoning. We conclude that in vivo testing of MCP as an organophosphate protective agent is warranted.
    Journal of Applied Toxicology 11/2003; 23(6):447-51. · 2.60 Impact Factor

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