Elevated plasma vasopressin in cardiomyopathic hamsters

Hamsters of the BIO 14.6 strain characteristically develop cardiomyopathy as they age, and hamsters of this strain have overt signs of heart failure by 11 months of age. Plasma levels of the posterior pituitary hormone arginine-vasopressin (AVP) were found to be elevated (approximately 2-fold) in 11 month old BIO 14.6 hamsters, compared to age-matched hamsters of a control strain. AVP appeared inappropriately elevated in these animals, since they were neither hyperosmotic nor markedly hypotensive. The elevated levels of AVP observed in these animals appears to contribute to vasomotor tone, since intravenous adminstration of a specific antagonist of the vasoconstrictor action of AVP [d(CH₂)₅Ome(TYR)AVP] elicited a fall in arterial pressure (9±2 mm Hg, n=6, p<0.05). The AVP antagonist had no effect on arterial pressure in hamsters of a control strain, and vehicle administration had no effect on arterial pressure in either strain. These data indicate that inappropriately elevated levels of AVP contribute to the cardiovascular state of myopathic hamsters. Since elevated plasma AVP has been noted in human congestive heart failure, these results suggest that AVP may contribute to the cardiovascular status during congestive heart failure.     

Effect of different anesthetics on immunoreactive atrial natriuretic factor concentrations in rat plasma

The effect of different conditions of blood withdrawal and use of different anesthetics on immunoreactive atrial natriuretic factor (IR-ANF) concentrations in plasma was studied in rats. The concentration of IR-ANF in plasma from jugular vein of non-anesthetized conscious rats, cannulated either 24 hr before blood withdrawal was 93.9 +/- 17.1 pg/ml (n = 30); and 48 hr: 81.9 +/- 11.5 pg/ml (n = 29). Immobilization stress (4 hr) increased IR-ANF concentration: 248.0 +/- 80.2 pg/ml (n = 5). Anesthesia by morphine, diethyl-ether, chloral hydrate and ketamine chlorhydrate increased IR-ANF concentrations to 2,443.0 +/- 281.2 pg/ml (n = 24), 806.1 +/- 74.6 pg/ml (n = 64), 224.0 +/- 81.4 pg/ml (n = 20), and 195.0 +/- 20.3 pg/ml (n = 51), respectively. IR-ANF in plasma of sodium-pentobarbital and urethane anesthetized rats was 59.2 +/- 6.7 pg/ml (n = 10) and 42.6 +/- 8.1 pg/ml (n = 8), respectively. These changes in IR-ANF evoked by different types of anesthetics and different conditions of blood withdrawal have to be taken into consideration during studies on the physiopathological role of atrial natriuretic factor.     

Immuno-electron microscopy of atrial natriuretic factor secretory pathways in atria and ventricles of control and cardiomyopathic hamsters with heart failure

Summary The secretory pathways of atrial natriuretic factor have been investigated in atrial and ventricular cardiocytes of control and cardiomyopathic Syrian hamsters in severe congestive heart failure with four antibodies: a monoclonal antibody (2H2) against rat synthetic atrial natriuretic factor (101–126), which is directed against region 101–103 of rat atrial natriuretic factor (99–126), and polyclonal, affinity-purified antibodies produced in rabbits against synthetic C-terminal atrial natriuretic factor (101–126), synthetic N-terminal atrial natriuretic factor (11–37) or the putative cleavage site of atrial natriuretic factor (98–99): atrial natriuretic factor (94–103). Application of the immunogold technique on thin frozen sections (immunocryoultramicrotomy) revealed an identical picture with the four antibodies. In atria of both control and cardiomyopathic hamsters where atrial natriuretic factor secretion is regulated, the atrial natriuretic factor propeptide travels, uncleaved, from the Golgi complex to immature and mature secretory granules. In ventricles of control hamsters, where secretion is constitutive, the atrial natriuretic factor propeptide travels from the Golgi complex to secretory vesicles. In the ventricles of hamsters with severe congestive heart failure, the Golgi complex is larger, secretory vesicles more abundant and a few secretory granules are present in 20% of cardiocytes. Here again, the peptide travels uncleaved in all these pathways. These results reveal the pathways of secretion of atrial natriuretic factor in atrial and ventricular cardiocytes and indicate that the propeptide is not cleaved intracellularly.Supported by a grant from the Medical Research Council of Canada to the Multidisciplinary Research Group on Hypertension, by the Canadian Heart Foundation and the Pfizer Company (England)     

Immunoreactive atrial natriuretic factor (IR-ANF) in human plasma

A direct radioimmunoassay for ANF in human plasma was developed. A synthetic alpha-human atrial peptide (Ser 99-Tyr 126) was used for preparation of the iodinated tracer and the standards. The sensitivity of the method is 1.9 pg/ml. Concentration of immunoreactive ANF (IR-ANF) in plasma of 59 clinically normal subjects was 65.3 +/- 2.5 pg/ml (mean +/- SE). In two patients who underwent atrial pacing an increase of about 100 percent in circulating IR-ANF was observed. IR-ANF was extracted from human plasma by Vycor glass and purified by HPLC. The main immunoreactive isolated peak contained a low molecular weight peptide.     

Elevated plasma atrial natriuretic peptide in rats with myocardial infarcts

We measured atrial natriuretic peptide (ANP) plasma levels in rats with experimental heart failure caused by left coronary artery ligation. ANP levels were clearly higher in infarcted rats (409 +/- 59 pg/ml; mean +/- S.E.M.) than in sham-operated controls (39 +/- 6 pg/ml). Moreover, plasma ANP levels increased progressively with the severity of cardiac dysfunction and size of infarct. Increased release of ANP in post-infarction heart failure appears to be a meaningful compensatory response to control rising preload. Our results are in keeping with evidence from human studies showing increased plasma concentration of ANP in patients with congestive heart failure. This model is a useful tool to further explore the role of ANP in heart failure.     

Effect of supplementation with Se-enriched yeast and factors influencing Se concentration in plasma of transplant recipients

The aim of this study was to assess the bioavailability of selenium (Se) in Se-enriched yeast and the possible impact of age, sex and area of residence on the Se concentration in plasma in 179 transplant recipients, as Se clinical effects in the prevention of cutaneous epithelial lesions in organ transplant recipients has been reported elsewhere. Subjects were randomized to receive either 200 μg Se/day (group 1:91 patients) or placebo (group 2: 88 patients) for 3 years. Plasma Se levels were measured at the beginning of the study and after 4, 12, 24 and 36 months of Se or placebo supplementation. Initial plasma Se levels were 90.9±26.1 μg/L for placebo and 94.0±25.3 μg/L for Se-supplemented groups. At baseline, the Se level was not linked to sex and age but to area of residence, although the number of subjects in each area was insufficient to draw any conclusions. Plasma Se levels were statistically lower in cases of liver transplant compared to kidney and heart transplant (p=0.03). Over the 3-year period of supplementation, plasma Se in the supplemented subjects was significantly higher than in the placebo group (p<0.01) and there was an interaction (p<0.01) between supplementation and time for plasma Se. Supplementation with Se-enriched yeast significantly increased the Se concentration in plasma of the patients to a plateau: the mean plasma Se of the Se-supplemented patients increased to 164.7±35.8 μg/L at 4 months and then remained similar at 12 (176.1±48.3 μg/L), 24 (176.1±54.2 μg/L) and 36 (182.2±46.4 μg/L) months.     

The Association Between Severity of Vitamin D Deficiency and Hashimoto's Thyroiditis

ObjectiveThe relation between vitamin D and autoimmune disorders has long been investigated regarding the important roles of this hormone in immune regulation. We evaluated 25-hydroxyvitamin D (25OHD) status in subjects with Hashimoto’s thyroiditis (HT) and healthy controls.MethodsGroup-1 included 180 euthyroid patients (123 females/57 males) with HT who were on a stable dose of L-thyroxine (LT). A total of 180 sex-, age-, and body mass index (BMI)-matched euthyroid subjects with newly diagnosed HT were considered as Group-2, and 180 healthy volunteers were enrolled as controls (Group-3). All 540 subjects underwent thyroid ultrasound and were evaluated for serum 25OHD, anti-thyroid peroxidase (anti- TPO), and anti-thyroglobulin (anti-TG) levels.ResultsGroup-1 had the lowest 25OHD levels (11.4 ± 5.2 ng/mL) compared to newly diagnosed HT subjects (Group-2) (13.1 ± 5.9 ng/mL, P = .002) and to control subjects (15.4 ± 6.8 ng/mL, P<.001). Serum 25OHD levels directly correlated with thyroid volume (r = 0.145, P<.001) and inversely correlated with anti-TPO (r = -0.361, P<.001) and anti-TG levels (r = -0.335, P<.001). We determined that 48.3% of Group-1, 35% of Group-2, and 20.5% of controls had severe 25OHD deficiency (<10 ng/mL). Female chronic HT patients had the lowest serum 25OHD levels (10.3 ± 4.58 ng/mL), and male control subjects had the highest (19.3 ± 5.9 ng/mL, P<.001).ConclusionsWe demonstrated that serum 25OHD levels of HT patients were significantly lower than controls, and 25OHD deficiency severity correlated with duration of HT, thyroid volume, and antibody levels. These findings may suggest a potential role of 25OHD in development of HT and/or its progression to hypothyroidism. (Endocr Pract. 2013;19:479-484)     

Plasma Urotensin II Act as a Diagnostic Biomarker for Acute Coronary Syndromes

Urotensin II (U-II), one of powerful vasoconstrictor peptides, is involved in the pathogenesis of hypertension, diabetes, myocardial infarction and heart failure. However, its role in patients with acute coronary syndromes (ACS) is still unknown. We performed the present study to measure plasma U-II level in patients with ACS and the healthy subjects in the Chinese Han population. Plasma U-II level in patients with unstable angina (UA 313 ± 286 pg/dl) and acute myocardial infarction (AMI 333 ± 269 pg/dl) was higher than in healthy controls (183 ± 154 pg/dl). Plasma U-II level is positively correlated with the Gensini score (r = 0.285, P = 0.003) and Apo B level (r = 0.239, P = 0.015). Moreover, the area under the receiver operating characteristic curve for the combination of CRP and U-II was significantly higher than it for CRP (P = 0.024). We conclude that U-II, which is elevated in ACS patients, may act as a clinical non-invasive biomarker for ACS diagnosis.     

The effects of Δ9-tetrahydrocannabinol Δ9-THC) on the regional concentrations of spermidine in the rat brain

The effects of intravenous administration of Δ⁹-tetrahydrocannabinol (Δ⁹-THC, 2 mg/kg, i.v.) on the regional brain spermidine concentrations of the rat were examined. Thirty minutes after vehicle treatment, the spermidine concentrations were: for the medulla oblongata/pons, 68.2 ± 7.7 μg/g; the hypothalamus, 67.7 ± 2.6 μg/g; the midbrain, 59.1 ± 4.4 μg/g; the cerebellum, 47.3 ± 5.9 μg/g and for the cortex, 13.8 ± 0.8 μg/g. Thirty minutes after Δ⁹-THC, these concentrations were reduced in the midbrain (47.0 ± 8.0% of control, P < 0.0001) and cortex (69.4 ± 7.4% of control, P < 0.009). The spermidine concentrations were not significantly altered in the medulla oblongata/pons (86.5 ± 13.3%, P > 0.36), hypothalamus (107.2 ± 11.8, P > 0.36) or cerebellum (89.0 ± 14.4%, P < 0.48). These results suggest that spermidine within the midbrain and cortex may be involved in the expression of some of the actions of Δ⁹-THC.     

The effect of isoproterenol on right and left atrial dynamics and plasma atrial natriuretic factor in anesthetized rabbits.

The effect of isoproterenol on mean right and left atrial pressures (RAP, LAP) and dimensions (RAD, LAD), and plasma immunoreactive atrial natriuretic factor (IR-ANF) was investigated in anesthetized rabbits. Infusion of isoproterenol (10 micrograms.kg-1.min-1 for 10 min) significantly increased plasma IR-ANF and heart rate. There were no significant changes in mean RAP or LAP following isoproterenol. Neither mean RAD, systolic RAD and diastolic RAD nor mean LAD, systolic LAD or diastolic LAD changed significantly. Systolic right and left atrial wall stress and diastolic right and left atrial wall stress did not change significantly during the infusion of isoproterenol. Since atrial dimensions did not increase, it is unlikely that the release of IR-ANF in response to isoproterenol is mediated by atrial stretch. These results suggest that the release of IR-ANF in response to this dose of isoproterenol is mediated by factors other than stretch or changes in atrial dynamics.     

Cholesterol lowering action of HOE 402 in the normolipidemic and hypercholesterolemic Golden Syrian hamster

The potent hypolipidemic activity of HOE 402 (4-amino-2-(4,4-dimethyl-2-oxo-l-imidazolidinyl)pyrimidine-5-N-(trifluoromethylphenyl)carboxamide monohydrochloride), which was previously demonstrated in rat and rabbit, was investigated in noncholesterol and cholesterol fed male hamsters. In normolipidemic hamsters fed a low cholesterol chow diet containing 0.10% or 0.15% HOE 402 for 3 weeks, the plasma total cholesterol level fell by 13% and 20% respectively, but no effect on hepatic total cholesterol content was detected. Hepatic sterol synthesis was increased 3-fold in hamsters fed 0.15% HOE 402. In hamsters fed a chow diet containing 0.25% cholesterol for 3 weeks, the plasma cholesterol level increased to 226 mg/dl (compared to 123 mg/dl in their chow fed controls) and the liver cholesterol content was 26.2 mg/g compared to 2.3 mg/g in the control group. However, 0.15% HOE 402 led to a 48% reduction and 0.20% HOE 402 to a 80% reduction, in total hepatic cholesterol concentration. There was a 43% fall in plasma cholesterol level being observed with the higher HOE 402 dose. Using the dual isotope plasma ratio method, no inhibition of intestinal cholesterol absorption by HOE 402 was found, either in the noncholesterol fed or in the cholesterol fed hamsters. Cholesterol feeding diminished the whole LDL animal clearance to 393 ± 17 μl/h per 100 g animal (control 666 ± 81 μl/h per 100 g). When treated with 0.20% HOE 402, the whole animal LDL clearance rate was enhanced 2.3-fold to 824 ± 66 μl/h per 100 g. In the hamsters fed 0.25% cholesterol alone whole liver LDL receptor activity was suppressed to 63 ± 5%, compared to that in the untreated controls (100%). The addition of 0.20% HOE 402 to the cholesterol enriched diet not only reversed this suppression, but resulted in a marked stimulation of liver receptor activity to 165 ± 15% (whole body LDL receptor activity 141 ± 10%). These results indicate that HOE 402 exerts its lipid lowering effect by a more direct activation on hepatic LDL receptor activity rather than by an indirect intestinal effect on cholesterol absorption.     

Endocrinology of oviposition in the tuatara (Sphenodon punctatus)—II. Plasma arginine vasotocin concentrations during natural nesting

• 1.1. Plasma concentrations of the neurohypophysial arginine vasotocin (AVT) were measured during three stages of natural nesting [nest digging (N = 16), oviposition (N = 6), nest guarding (N = 6)] in the rare New Zealand reptile, the tuatara (Sphenodon punctatus).
• 2.2. Nest digging females (X ± 1 SE: 134.9 ± 15.0 pg/ml) exhibited elevated but significantly lower concentrations of plasma AVT compared to those observed during oviposition (216.0 ± 28.1 pg/ml). Nest guarding females (54.6 ± 29.8 pg/μl) had plasma AVT concentrations significantly lower than other stages.
• 3.3. These data are similar to those reporting elevated plasma AVT concentrations during oviposition in sea turtles but tuatara exhibit significantly lower plasma AVT values (10-fold difference). Plasma AVT concentrations reported for tuatara and birds are comparable.

     

Evaluation of Mineral Concentrations in Maternal Serum Before and After Birth and in Newborn Cord Blood Postpartum—Preliminary Study

The mineral levels in maternal serum change during pregnancy and may be correlated with those of newborn cord blood. The aim of this study was to evaluate the concentrations of calcium (Ca), magnesium (Mg), zinc (Zn), iron (Fe), and copper (Cu) in maternal blood before and after delivery and in umbilical cord vein and artery serum. The study was carried out in 64 Caucasian pregnant women who delivered in a district hospital in Greater Poland region, aged 28.1 ± 5.4 years, with a mean gestational age of 39.2 ± 1.3 weeks. Blood samples were taken from women 2–8 h before delivery and immediately after childbirth. The umbilical cord artery and vein blood of newborns was obtained immediately after childbirth. The levels of minerals in serum were determined by flame atomic absorption spectrometry. A significant drop in the concentrations of Mg (17.71 ± 1.51 vs 17.07 ± 1.61 μg/ml; p < 0.007), Fe (1.08 ± 0.46 vs 0.82 ± 0.35 μg/ml; p < 0.0004), and Zn (0.63 ± 0.17 vs 0.46 ± 0.16; p < 0.0001) in maternal serum was found after delivery. Moreover, higher levels of Ca, Fe, and Zn and lower levels of Cu were observed in the umbilical vein (Ca: 102.80 ± 7.80 μg/ml; p < 0.0001, Fe: 1.96 ± 0.43 μg/ml; p < 0.0001, Zn: 0.65 ± 0.16 μg/ml; p < 0.0001, Cu: 0.36 ± 0.09 μg/ml; p < 0.0001) and in the umbilical artery cord blood (Ca: 98.07 ± 8.18 μg/ml; p < 0.0001, Fe: 1.63 ± 0.30 μg/ml; p < 0.0001, Zn: 0.65 ± 0.15 μg/ml; p < 0.0001, and Cu: 0.36 ± 0.10 μg/ml; p < 0.0001) compared to the maternal serum (Ca: 85.05 ± 10.76 μg/ml, Fe: 0.82 ± 0.35 μg/ml, Zn: 0.46 ± 0.16 μg/ml, and Cu: 1.90 ± 0.35 μg/ml). Fe levels in the cord artery serum negatively correlated with blood loss during delivery (R = ?0.48; p = 0.01), while the Ca concentration in the maternal serum after birth decreased with the age of the women (R = ?0.25; p = 0.03). In conclusion, it seems that the process of birth alters the mineral levels in pregnant women’s blood. Moreover, it was found that blood loss and the age of the mother are associated with mineral concentrations in the maternal serum and cord artery blood.     

Evaluation of the effects of pharmacological zinc oxide and phosphorus source on weaned piglet growth performance,plasma minerals and mineral digestibility

Crossbred pigs (n=720; average age=28±3 days and weight=9.5±0.3 kg) were used in a 20-day trial in order to determine the influence of phosphorus (P) source and various doses of pharmacological zinc (Zn) on growth performance, plasma minerals and mineral digestibility. Pigs (five intact males and five females per pen) were randomly allotted to treatments in a 3×3 factorial arrangement with three sources of dietary P (4.5 g/kg digestible P, 4.5 g/kg digestible P plus 2500 phytase units (FTU)/kg, or 5.5 g/kg digestible P) and three dietary levels of supplemental Zn (0, 1750 or 3500 mg/kg) from ZnO (82% Zn) with eight pens per treatment. Diets were formulated to exceed all nutrient requirements, including calcium (Ca), P and Zn from day 0 to 20. Zn supplementation increased (quadratic P<0.05) average daily feed intake. There was a significant Zn level×P source interaction on average daily gain and feed conversion ratio (FCR). Pigs fed 4.5 g/kg digestible P without or with 2500 FTU/kg phytase gained more per day (quadratic P<0.05) and had better FCR (quadratic P<0.05) when they were fed 1750 mg/kg supplemental Zn. However, pigs fed 5.5 g/kg digestible P gained more per day (linear P<0.05) and were more efficient (linear P<0.05) when they were fed 3500 mg/kg supplemental Zn. Plasma Zn and Zn digestibility increased (linear P<0.05) as pharmacological Zn supplementation increased from 0 to 3500 mg/kg, irrespective of P source. However, Ca, P, sodium (Na), potassium (K) and copper (Cu) digestibility were reduced (P<0.05) as pharmacological Zn supplementation increased, and this was mitigated or exacerbated by the supplementation of 5.5 g/kg digestible P or phytase. In conclusion, increasing the dietary inclusion of pharmacological Zn may impact growth performance in young pigs through the interaction with minerals such as Ca, P, Na and K. Pharmacological Zn may reduce Na or K digestibility and indirectly reduce water secretion into the lumen, resulting in an increase in faecal dry matter as pharmacological Zn supplementation in the diet increased.     

Role of diagnostic factors associated with antioxidative status and expression of matrix metalloproteinases (MMPs) in patients with cancer therapy induced ocular disorders

Background

Cancer patients when treated with different chemotherapeutic drugs often develop mild to severe sight threatening diseases during or after chemotherapy. The mechanism involved in the pathogenesis of ocular toxicities is poorly understood. Oxidative stress, inflammation and MMPs (angiogenic factor) are involved in the progression of chemotherapy related ocular disorders.

Regulation of basal and norepinephrine-induced cAMP and ICa in hiPSC-cardiomyocytes: Effects of culture conditions and comparison to adult human atrial cardiomyocytes

BackgroundThere is ongoing interest in generating cardiomyocytes derived from human induced pluripotent stem cells (hiPSC) to study human cardiac physiology and pathophysiology. Recently we found that norepinephrine-stimulated calcium currents (I_Ca) in hiPSC-cardiomyocytes were smaller in conventional monolayers (ML) than in engineered heart tissue (EHT). In order to elucidate culture specific regulation of β₁-adrenoceptor (β₁-AR) responses we investigated whether action of phosphodiesterases (PDEs) may limit norepinephrine effects on I_Ca and on cytosolic cAMP in hiPSC-cardiomyocytes. Results were compared to adult human atrial cardiomyocytes.MethodsAdult human atrial cardiomyocytes were isolated from tissue samples obtained during open heart surgery. All patients were in sinus rhythm. HiPSC-cardiomyocytes were dissociated from ML and EHT. Förster-resonance energy transfer (FRET) was used to monitor cytosolic cAMP (Epac1-camps sensor, transfected by adenovirus). I_Ca was recorded by whole-cell patch clamp technique. Cilostamide (300 nM) and rolipram (10 μM) were used to inhibit PDE3 and PDE4, respectively. β₁-AR were stimulated with the physiological agonist norepinephrine (100 μM).ResultsIn adult human atrial cardiomyocytes, norepinephrine increased cytosolic cAMP FRET ratio by +13.7 ± 1.5% (n = 10/9, mean ± SEM, number of cells/number patients) and I_Ca by +10.4 ± 1.5 pA/pF (n = 15/10). This effect was not further increased in the concomitant presence of rolipram, cilostamide and norepinephrine, indicating saturation by norepinephrine alone. In ML hiPSC-cardiomyocytes, norepinephrine exerted smaller increases in cytosolic cAMP and I_Ca (FRET +9.6 ± 0.5% n = 52/21, number of cells/number of ML or EHT, and I_Ca + 1.4 ± 0.2 pA/pF n = 34/7, p < 0.05 each) and both were augmented in the presence of the PDE4 inhibitor rolipram (FRET +16.7 ± 0.8% n = 94/26 and I_Ca + 5.6 ± 1.4 pA/pF n = 11/5, p < 0.05 each). Cilostamide increased the response to norepinephrine on FRET (+12.7 ± 0.5% n = 91/19, p < 0.05), but not on I_Ca. In EHT hiPSC-cardiomyocytes, norepinephrine responses on both, FRET and I_Ca, were larger than in ML (FRET +12.1 ± 0.3% n = 87/32 and I_Ca + 3.3 ± 0.2 pA/pF n = 13/5, p < 0.05 each). Rolipram augmented the norepinephrine effect on I_Ca (+6.2 ± 1.6 pA/pF; p < 0.05 vs. norepinephrine alone, n = 10/4), but not on FRET.ConclusionOur results show culture-dependent differences in hiPSC-cardiomyocytes. In conventional ML but not in EHT, maximum norepinephrine effects on cytosolic cAMP depend on PDE3 and PDE4, suggesting immaturity when compared to the situation in adult human atrial cardiomyocytes. The smaller I_Ca responses to norepinephrine in ML and EHT vs. adult human atrial cardiomyocytes depend at least partially on a non-physiological large impact of PDE4 in hiPSC-cardiomyocytes.     

Effect of Zinc Supplementation on Thyroid Hormone Metabolism of Adolescents with Down Syndrome

Studies have evidenced that zinc metabolism is altered in the presence of Down syndrome, and zinc seems to have a relationship with the metabolic alterations usually present in this syndrome. In this work, the effect of zinc supplementation on thyroid hormone metabolism was evaluated in adolescents with Down syndrome. A prospective study was carried out on 16 adolescents with Down syndrome (age: 10–19 years) who were randomized for treatment with 30 mg zinc daily for 4 weeks. Diet evaluation was accomplished y using a 3-day dietary record, and the analysis was performed by the NutWin program, version 1.5. Anthropometric measurements were performed for evaluation of body composition. The Zn-related nutritional status of the groups was evaluated by means of zinc concentration determinations in plasma and erythrocytes using the method of atomic absorption spectroscopy, and the thyroid hormone was obtained by radioimmunoassay. The diet of patients with Down syndrome, before and after the intervention presented reduced energy level and adequate zinc concentrations. Mean plasma zinc values were 59.2?±?13.2 and 71.0?±?21.9 μg/dL before and after the intervention, respectively. Erythrocyte concentrations of the mineral before supplementation, instead, were 51.5 μg/dL?±?11.1 μg Zn/gHb, and at the end of the experiment, they were 42.9?±?8/5 μg Zn/gHb, with a significant statistical difference (p?<?0.05). Serum concentrations of T₄ hormone before and after zinc supplementation were 1.26?±?0.20 and 1.54?±?0.63 pg/mL, respectively. Mean T₃ values before intervention were 2.47?±?037 pg/mL and, after supplementation, 2.25?±?0.67 pg/mL, without significant statistical difference (p?>?0.05). Intervention with zinc showed to be effective in the stabilization of the concentrations of this mineral in plasma and erythrocytes, but had no influence on the metabolism of thyroid hormones.     

In vivo and in vitro evaluation of pharmacological activities of Adenia trilobata (Roxb.)

Adenia trilobata, locally known as akandaphal in Bangladesh, has some traditional uses. Leaves and stems extracted with pure methanol (MEATL, MEATS) and fractioned by n-hexane (NFATL, NFATS), which was subjected to qualitative phytochemical analysis. The qualitative phytochemical analysis of four extracts showed the presence of secondary metabolites such as alkaloid, carbohydrate, glycosides, flavonoids, phenols, flavonol, and saponins. All four extracts of A. trilobata, exhibited a strong antioxidant activity while a moderately (MEATS = 328 μg/mL) to weakly toxic (NFATL = 616.85 μg/mL) LC₅₀ observed in brine shrimp lethality bioassay. In thrombolytic test, MEATL (18.54 ± 2.18%; P < 0.01) and MEATS (25.58 ± 4.76%; P < 0.0001) showed significant percentage of clot lysis in human blood. The in vivo analgesic activity carried by acetic acid test and formalin test, while the antidiarrheal activity assayed by two standard methods e.g., castor oil-induced diarrhea and castor oil-induced gastrointestinal motility. Both, in vivo model, showed an extremely significant (P < 0.0001) dose-dependent manner percentage of inhibition in comparison to the control group. Present results suggested, A. trilobata could be a potential source for antioxidative, cytotoxic, thrombolytic, analgesic, antidiarrheal agents which require further study to identify the mechanism of A. trilobata.