An enzymatic cow immunity-targeted approach to reducing milk somatic cell count. 1. A preliminary study using lysosubtilin

A cow experiment was conducted in order to give a preliminary evaluation for an enzymatic approach to reducing milk somatic cell count (SCC). Twenty second to third lactation Lithuanian black and white cows with a similar milk SCC [(800±150)×10³ cells ml^?1] and of a similar weight (550±50 kg) were randomly allocated into four groups (n=5) and were given lysosubtilin, a model enzyme preparation, once daily with feed at doses of 0, 5, 10 or 20 mg kg wt^?1 (each group of animals received a different dose) for ten successive days. Application of the highest lysosubtilin dose tested (20 mg kg wt^?1) resulted in a statistically significant (P<0.05) reduction of milk SCC. No significant changes in hematological indices of cows as well as in protein, fat ant lactose quantities in milk influenced by lysosubtilin application were observed. A possible mechanism of a beneficial action of lysosubtilin and prospects for future studies are discussed.     

An enzymatic cow immunity-targeted approach to reducing milk somatic cell count: 2. A study using lysozyme

The effects of the enzymatic approach to reducing the milk somatic cell count (SCC) have been examined. Bacterial lysozyme, a lytic carbohydrase, was used in this experiment as a model enzyme preparation. Twenty 2nd–3rd lactation Lithuanian black and white cows with a similar milk SCC [(600±150)×10³ cells ml^?1] and of a similar weight (550±50 kg) were involved in the study and were randomly allocated into three test groups (n=5) and one control group. The enzyme was given to the test groups once daily with feed (each group of animals received a different dose) for ten successive days. Application of any of lysozyme doses tested (50, 100 or 200 mg kg wt^?1) resulted in a reduction of milk SCC, the result obtained with the highest dose (200 mg kg wt^?1) was statistically significant (p<0.05). No significant changes in haematological indices of cows as well as in protein, fat and lactose quantities in milk influenced by lysozyme application were observed.     

The diagnostic value of determination of positive and negative acute phase proteins in milk from dairy cows with subclinical mastitis

Currently, somatic cell count (SCC) and bacterial culture are considered as the gold standard methods for the diagnosis of bovine subclinical mastitis. However, SCC has a low diagnostic accuracy. Therefore, for identification of infected animals, new biomarkers with high diagnostic accuracy are needed. Acute phase proteins (APPs) are proteins that are increased (positive APPs) or decreased (negative APPs) in response to inflammation. The objective of this study was to determine the diagnostic value of milk APPs for the diagnosis of subclinical mastitis in dairy cows. A total of 90 clinically healthy cows were randomly selected. Of these, 52 cows were considered subclinical mastitic based on a SCC higher than 130?×?1,000?cells/mL of milk and positive bacterial culture results of milk samples obtained from at least one of the quarters. Milk amyloid A (MAA) concentration was measured using a commercial ELISA kit and albumin, α-lactalbumin, β-lactoglobulin, and immunoglobulin (Ig) were measured in the whey samples by the use of cellulose acetate electrophoresis. Diagnostic sensitivity and specificity and cutoff points for each test were determined via receiver-operating characteristics analysis. Significant (P?<?0.001) increases in the mean and median concentration of MAA, albumin, α-lactalbumin, and Ig were found in the milk samples collected from cows with subclinical mastitis. MAA was the most accurate test with a diagnostic sensitivity of 92.3% and specificity of 92.1% at cutoff point of >1.6?mg/L. The results of this study showed that determination of MAA can be used as a reliable method for the diagnosis of bovine subclinical mastitis.     

Rapid response to and long-term effectiveness of anti-CD20 antibody in conventional therapy resistant Graves’ orbitopathy: A five-year follow-up study

Abstract

The aim of this investigations was to study the effectiveness of anti-CD20 antibody therapy in Graves’ orbitopathy (GO) resistant to glucocorticoids. Five patients were entered in the study. The protocol required no improvement of orbital status after a recent course of glucocorticoids. Activity of GO was confirmed by three independent techniques: clinical activity score (CAS), ^99mTc-labeled diethylene triamine pentaacetic acid (^99mTc DTPA) single photon emission computed tomography and magnetic resonance imaging. Rituximab (RTX) was given as weekly infusions of 375?mg/m² body surface area for four weeks. The mean follow-up period was 67 (range 58–81) months. Improvement of GO has been observed in all patients: CAS before therapy was 6.5?±?1.7 and decreased to 3.4?±?1.6 by one month (p?<?0.05) and remained unchanged (3.2?±?1.7) at 12 months. No further CAS change, in either direction, was detected during the yearly follow-up visits. The mean DTPA uptake before therapy was 16.52?±?4.51?MBq/cm³ and decreased to 11.97?±?2.36?MBq/cm³ at one year (p?<?0.002). The mean of T2 relaxation times before and one year after therapy were 96.91?±?17.61?ms and 84.29?±?9.41?ms, respectively (p?<?0.001). The mean serum TSH receptor antibody (TRAb) levels before therapy, at the one month and one year control visits were 7.4?±?3.4?U/L, 5.6?±?4.5?U/L and 1.7?±?1.5?U/L, respectively (p?<?0.004). No correlation between changes of TRAb and activity parameters has been found. Anti-CD20 treatment seems to influence positively the clinical course of GO, and this effect seems to be stable for five years. To our knowledge, this is the longest published follow-up of RTX treatment in GO.     

Haematological and acute-phase response of dogs with experimental skin <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> infection to treatment with antibiotic and parthenolide

Changes in white blood cells, leukogram patterns, the positive acute-phase protein (APP) fibrinogen and negative APPs (albumin and arylesterase) were monitored to evaluate their potential as sensitive indicators throughout the course of therapy in canine skin Pseudomonas aeruginosa infection. The study was performed on 15 male mixed-breed dogs, divided in three groups of 5 dogs each. Dogs from group A were injected subcutaneously with P. aeruginosa bacterial culture (1?×?10⁸ CFU/mL) at a dose of 0.3 mL/kg and treated with enrofloxacin (5 mg/kg, s.c.) on post infection hour 48 for 10 consecutive days. Dogs from group B were infected and treated with a combination of enrofloxacin (at above-mentioned dose and intervals) and parthenolide (feverfew extract 90 mg, 0.7 % parthenolide). The schedule consisted of daily oral intake of two capsules of feverfew beginning on post infection hour 4 and continued for 6 days. The control group C included healthy dogs, injected s.c. with 0.3 mL/kg physiological saline. The haematological indices and APPs were assayed before infection and on 4th, 24th, 48th and 72nd hours and on 7th, 10th and 14th days after infection. Infected and antibiotic-treated dogs responded with significant leukocytosis, left shift, eosinopaenia and lymphopaenia between hours 24 and 72. In this group, fibrinogen increased substantially by post infection hours 24 (p?<?0.01 vs 0 h; p?<?0.05 vs group C), 48 (p?<?0.001 vs 0 h; p?<?0.05 vs group C) and 72 (p?<?0.001 vs 0 h; p?<?0.01 vs group C) while albumin reduction was marked by hours 48 (p?<?0.05 vs 0 h) and 72 (p?<?0.05 vs 0 h; p?<?0.001 vs group C) and day 7 (p?<?0.01 vs 0 h; p?<?0.001 vs group C). The combination of enrofloxacin and parthenolide modified, at a significant extent, the deviations in studied parameters except for eosinophil percentage, which persisted low.     

Selected biologic markers of inflammation and activity of Crohn’s disease

Abstract

The study aimed to compare the accuracy of selected biologic markers in assessing the disease activity in patients with Crohn’s disease (CD). The analysis included serum IL-2, IL-6, IL-17, TNF-α, IFN-γ, hsCRP, peripheral CD4?+?CD25?+?FOXP3?+?regulatory T cells, as well as fecal calprotectin and lactoferrin. A group of 55 adults with CD was enrolled to the study. Disease activity was assessed using Crohn’s Disease Endoscopic Index of Severity (CDEIS), which currently represents the gold standard for the evaluation of endoscopic activity. For clinical activity scoring, the Crohn’s Disease Activity Index (CDAI) was used. Concentrations of investigated markers were estimated by means of flow cytometry and enzyme-linked immunosorbent assays, and the results were correlated with both indices. The study demonstrated that both fecal markers, i.e. calprotectin (r?=?0.827, p?<?0.001) and lactoferrin (r?=?0.704, p?<?0.001), correlate closely with CDEIS score, and might be used to evaluate the severity of CD in clinical setting. The correlation of those markers with CDAI was also significant, with r?=?0.742 for calprotectin (p?<?0.001) and r?=?0.675 for lactoferrin (p?<?0.05). As for the other investigated markers, only hsCRP (r?=?0.672, p?<?0.001) and IL-17 (r?=?0.296, p?<?0.005) correlated closely with CDEIS. The correlation of the markers with CDAI was also significant, though weaker, with r?=?0.518 for hsCRP (p?<?0.001) and r?=?0.296 for IL-17 (p?<?0.05). The study showed that IL-17, despite its vague role in the pathogenesis of CD, might be a useful marker, comparable with hsCRP, in assessing the activity of the disease.     

Obesity,hypertension, social determinants of health and the epidemiologic transition among traditional Amazonian populations

Abstract

Background: The health and nutritional situation of adults from three rural vulnerable Amazonian populations are investigated in relation to the Social Determinants of Health (SDH) and the epidemiologic transition.

Aim: To investigate the role of the environment and the SDH on the occurrence of chronic-degenerative diseases in these groups.

Subjects and methods: Anthropometric, blood pressure and demographic data were collected in adults from the RDS Mamirauá, AM (n?=?149), Flona Caxiuanã, PA (n?=?148) and quilombolas, PA (n?=?351), populations living in a variety of socio-ecological environments in the Brazilian Amazon.

Results: Adjusting for the effect of age, quilombola men are taller (F?=?9.85; p?<?0.001) and quilombola women present with higher adiposity (F?=?20.43; p?<?0.001) and are more overweight/obese. Men from Mamirauá present higher adiposity (F?=?9.58; p?<?0.001). Mamirauá women are taller (F?=?5.55; p?<?0.01) and have higher values of waist circumference and subscapular/triceps index. Quilombolas present higher prevalence of hypertension in both sexes and there are significant differences in rates of hypertension among the women (χ² = 17.45; p?<?0.01). The quilombolas are more dependent on government programmes, people from Mamirauá have more economic resources and the group from Caxiunã have the lowest SES.

Conclusion: In these populations, the SDH play a key role in the ontogeny of diseases and the ‘diseases of modernity’ occur simultaneously with the always present infectoparasitic pathologies, substantially increasing social vulnerability.     

Computerized acoustic cardiography correlates with echocardiography and invasive haemodynamics after percutaneous transvenous mitral commissurotomy

Background:?Rheumatic mitral stenosis severity has been assessed by the systolic time interval between the QRS onset and the first heart sound (QS1) by phonocardiography. We hypothesized that non-invasive computerized acoustic cardiography could evaluate mitral stenosis severity compared with echocardiography and invasive haemodynamics in patients undergoing percutaneous transvenous mitral commissurotomy (PTMC).

Methods:?27 patients underwent computerized acoustic cardiography, echocardiography, and invasive haemodynamic measurements prior to and after PTMC.

Results:?The mean age was 31?±?10 years, and 21 (78%) were female. By echocardiography, mitral valve area increased from 0.82?±?0.14 to 1.50?±?0.24 cm² (p?<?0.0001). The QS1 interval decreased from 101.7?±?12.9 to 93.2?±?9.2?ms (p?<?0.0001). The change in the QS1 interval correlated with the change in mitral valve area by echocardiography (p?=?0.037), right ventricular systolic pressure (p?<?0.0001), and the invasive mitral valve gradient (p?=?0.076).

Conclusions:?Acoustic cardiography may be used as an adjunctive non-invasive diagnostic tool to assess mitral stenosis severity.     

Body dimensions,exercise capacity and physical activity level of adolescent Nandi boys in western Kenya

The aim of this study was to characterize untrained Nandi boys (mean age 16.6 years) from a town (n = 11) and from a rural area (n = 19) in western Kenya (altitude ?2000 m.a.s.l.) in regard to their body dimensions, oxygen uptake and physical activity level. The town boys had a mean maximal oxygen uptake (VO_2max) of 50 (range: 45–60) mL?kg^?1?min^?1, whereas the village boys reached a value of 55 (37?63)?mL?kg^?1?min^?1 (?p<0.01) in VO_2max. The running economy, determined as the oxygen cost at a given running speed, was 221?mL?kg^?1?km^?1 (597?mL?kg^?0.75?km^?1) for town as well as for village boys. The body mass index (BMI) was very low for town as well as for village boys (18.6 vs 18.4?kg?m^?2). The daily mean time spent working in the field during secondary school and doing sports were significantly higher in village boys compared to town boys (working in the field: 44.2 (0–128) vs 1.3 (0–11)?min, p<0.01; sports: 32.0 (11–72) vs 12.8 (0–35)?min, p<0.01, respectively). A positive correlation between the daily time spent doing sports and VO_2max was found when pooling the data from the town and the village boys (R = 0.55, p<0.01). It is concluded that the body dimensions of adolescent Nandi town and village boys corresponds well with findings in Kenyan elite runners. They are very slender with relatively long legs. In addition, the VO_2max of the village boys was higher than that of the town boys, which is probably due to a higher physical activity level of the village boys during secondary school.     

Synthesis,toxicity study and anti-inflammatory effect of MHTP,a new tetrahydroisoquinoline alkaloid

Abstract

The alkaloid 2-methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)phenol (MHTP) was synthesized to prospect new compounds with therapeutic properties. Thus, the goal of this study was to evaluate the MHTP anti-inflammatory effect by in vivo and in vitro assays. The MHTP toxicity was analyzed. We found that MHTP pre-treatment (2.5–10?mg/kg) showed antiedematogenic effect (p?<?0.05) in carrageenan-induced paw edema by inhibiting the PGE2 action independently of mast cell degranulation or histamine activity. MHTP also diminished (p?<?0.01) total leukocyte migration in 41.5% into peritoneal cavity during carrageenan-induced peritonitis, reducing polymorphonuclear cells (PMNs) (59.6%) and proteins levels (29.4%). MHTP in an experimental model of acute lung injury inhibited (p?<?0.001) total inflammatory cell migration into the lungs and PMNs in 58% and 67.5%, respectively. Additionally, MHTP did not present cytotoxicity at concentrations of 10, 25 or 50?μM but decreased (p?<?0.001) the NO production in 24%, 47% and 39%, respectively. The alkaloid also reduced (p?<?0.001, in lipopolysaccharide (LPS)-stimulated macrophages (1?μg/mL), IL-1β, IL-6 and IL-10 levels in 35.7%, 31.0% and 33.4%, respectively. The results obtained in this study allow us to conclude that the inedited synthetic alkaloid, MHTP has anti-inflammatory effect by inhibiting PGE2 function as well as inhibiting inflammatory cell migration to the inflamed site and attenuated the acute lung injury disease by inhibiting the migration of neutrophil to the lung. However, further studies will be carried out to demonstrate the mechanisms of action of the molecule and explore its potential as a future drug to treat inflammatory processes.     

Maternal early second trimester pregnancy weight in relation to birth outcome among Bengalee Hindus of Kolkata,India

Objective: The study examined to what degree maternal early second trimester pregnancy weight is useful and efficient in predicting birth outcome of Bengalee women.

Subjects and methods: The cross-sectional retrospective study was conducted in a government general hospital in South Kolkata, India. This hospital serves the needs of people belonging to lower and lower middle class socio-economic groups. Data were collected by one-to-one interview for confirmation of age, history of last menstrual period (LMP) including medical disorders. Mother's weight was recorded at 14–18 weeks of pregnancy from the history of LMP. Birth weight was measured within 24?h of delivery and gestational age was assessed by Ballard's method using newborn physical and neurological maturity scoring. Of the 331 Bengalees, 295 mother–baby pairs met the recruitment criteria and were included in this study.

Result: Mean?±?SD maternal early second trimester pregnancy weight and birth weight were 45.9?±?7.0?kg and 2612?±?371?g, respectively. The difference in mean weight (3.74?kg) between mothers who delivered low birth weight (LBW) and normal birth weight (NBW) babies was statistically significant (t?=?4.497, p?<?0.001). Overall, the prevalence of LBW was nearly 34%. A higher incidence of LBW and lower mean birth weight was observed in first quartile or low weight (≤40?kg) mothers. The rate of LBW decreased (χ²?=?14.47, p?<?0.01) and mean birth weight increased significantly with increasing maternal weight (F?=?9.218, p?<?0.001). Risk ratio (RR) for LBW, intrauterine growth retardation (IUGR) and preterm birth in low weight (first quartile or <40.0?kg) mothers were 2.72 (95% confidence interval (CI): 1.45–5.10), 3.54 (95% CI: 1.17–10.74) and 1.97 (95% CI: 0.56–6.90), respectively, compared with heavier (>50.0?kg) mothers. Finally, the present data showed that the maternal weight of <46.0?kg is the best cut-off for detecting LBW with 66% sensitivity and 75% negative predictive power.

Conclusion: The findings suggest a positive association between maternal early second trimester pregnancy weight and birth outcome. The present study provided an efficient cut-off point for detecting LBW. Antenatal caregivers in health institutions and community health workers in the field can use this cut-off value for screening pregnant women at early second trimester.     

Effects of Oliviera decumbens and Satureja khuzestanica extract on some immunological and haematological parameters of Cyprinus carpio

Immunity stimulants are applied to improve the immune system of aquatic organisms. In this study, the effect of oral administration of Marze (Satureja khuzestanica) and mountainous Lael (Oliviera decumbens) extracts on haematological parameters and lysozyme activity stimulation in Common carp was investigated during a 5-week period. At the end of this period, blood samples were taken for haematological and immunological assays (lysozyme activity). The result showed that white blood cell count (p?>?0.05) and the ratio of white blood cells (p?>?0.05) were not significantly affected by plant extract administration. There were significant differences between the serum lysozyme activities in different treatments (p?<?0.05). Generally, it can be concluded that Marze extract, as an immune stimulant, has a positive effect on the immune system and increased the resistance of Common carp. The combination of Marze and Mountainous Lael extracts was also an effective immune stimulant, but Mountainous Lael extract on its own did not stimulate the immune system of Common carp.     

Gene polymorphisms of TNF-α−308 (G/A), IL-10−1082 (G/A), IL-6−174 (G/C) and IL-1Ra (VNTR) in Egyptian cases with type 1 diabetes mellitus

Background. Type 1 diabetes (T1D) is a genetically conditioned autoimmune disease in which cytokines play an important role.

Objectives. To check for the association of polymorphisms of cytokine genes with type 1 diabetes.

Subjects. This work included 50 cases with T1D and 98 healthy individuals from the Nile Delta region of Egypt. Cases included 20 males and 30 females with a median age of 25 and range of 15–50 years.

Methods. DNA was amplified using PCR with sequence-specific primers for detection of polymorphisms related to tumor necrosis factor (TNF)-α^{? 308} (G/A), interleukin (IL)-10^{? 1082} (G/A), IL-6^{? 174} (G/C), and IL-1Ra (VNTR).

Results. Cases with T1D showed significant higher frequency of genotypes of TNF-α^{? 308} AA (p < 0.001, odds ratio (OR) = 7.91), IL-6-17CC (p < 0.05, OR = 3.36) and IL-1Ra A1A1 (p < 0.05, OR = 3.68) with significant lower frequencies of TNF-α^{? 308} GA, and IL-1Ra A1A2 genotypes (p < 0.001 and < 0.05, respectively). They also showed significant higher frequency of TNF-α^{? 308} allele A (p < 0.05, OR = 2.0), IL-1Ra allele A1 (p < 0.05, OR = 2.98) with a significant lower frequency of TNF-α^{? 308} G allele and IL-1Ra A2 allele (p < 0.05). No significant difference was detected among cases in relation to IL-10^{? 1082} (G/A) genotypes or alleles nor in relation to age, sex, consanguinity or family history of the disease.

Conclusions. Polymorphisms related to TNF-α and IL-1Ra genes may be considered genetic markers for T1D among Egyptians with a potential impact on family counseling and management.     

The absence of physiological neonatal weight loss on the 1st–5th day is associated with decreased later physical indices

Abstract

Aim: To investigate associations between physiological neonatal weight loss on the 1st–5th day and physical indices from birth up to the age of 17 years.

Methods: Data were derived from the personal health records of healthy, full-term and breastfed children born in Vilnius in 1990 and 1996. Five hundred and thirty children (289 boys and 241 girls) who left a maternity unit on the 1st–5th day after birth were included in the analysis.

Results: Infants left the maternity unit on day 4.62?±?2.33. On the day of leaving a maternity unit, infants lost 105.06?±?130.48 g (2.85?±?3.65%) of birth weight. Girls who did not lose or gained weight after birth had already weighed less at birth (3163?±?547 and 3490?±?403 g, respectively, p?<?0.01) and remained lighter up to the age of 17 years (54.3?±?8.7 and 60.8?±?10.1?kg at the age of 17 years respectively, p?<?0.001). Girls who did not lose or gained weight after birth were also shorter than those who lost weight (164.3?±?5.7 and 168.6?±?5.4?cm at the age of 17 years, respectively, p?<?0.001).

Conclusion: Girls who did not lose or gained weight immediately after birth tended to remain shorter and lighter during childhood and adolescence. Only a few statistically significant differences were obtained in boys.     

Delphinidin diminishes in vitro interferon-γ and interleukin-17 producing cells in patients with psoriatic disease

The anthocyanidin delphinidin reduces psoriasiform lesions and inflammatory mediators in human cell culture systems. Its role in psoriatic disease has not yet been investigated. We assessed delphinidin’s in vitro immunomodulatory effect on ex vivo stimulated peripheral blood mononuclear cells (PBMCs) from 50 individuals [26 with psoriasis, 10 with psoriatic arthritis (PsA) and 14 healthy controls (HCs)]. Cells were either left untreated or stimulated with PMA plus ionomycin in the presence or absence of delphinidin. Intracellular production of interferon-γ (IFNγ), interleukin-17A (IL-17A), and interleukin-10 (IL-10) was measured flow cytometrically. Delphinidin dose-dependently reduced IFNγ⁺ T cells from patients and HCs. The mean IFNγ decrease in CD4⁺ T subpopulations was 42.5?±?28% for psoriasis patients, 51.8?±?21.5% for PsA patients and 49?±?17% for HCs (p?<?0.001 for all). Similarly, IFNγ reduction in CD8⁺ T cells was 34?±?21.6% for psoriasis patients, 47.1?±?22.8% for PsA and 44.8?±?14.3% for HCs (P <?0.001 for all). An inhibitory effect of delphinidin was also noted in IFNγ producing NKs and NKTs from psoriasis individuals. Delphinidin also significantly decreased IL-17⁺ CD4⁺ T cells in all tested subjects, with marginal effect on the increase of IL-10-producing T regulatory subsets. In conclusion, delphinidin exerts a profound in vitro anti-inflammatory effect in psoriasis and psoriatic arthritis by inhibiting IFNγ⁺ innate and adaptive cells and T helper (Th) 17 cells. If this effect is also exerted in vivo, delphinidin may be regarded as a nutraceutical with immunosuppressive potential.

     

Contributory Anti-Inflammatory Effects of Mesenchymal Stem Cells,Not Conditioned Media,On Ovalbumin-Induced Asthmatic Changes in Male Rats

Our aim in selecting an appropriate cell fraction and conditioned media (CM) was to achieve the suitable candidate for ameliorating long-term chronic asthmatic changes of respiratory tract. Thirty-six rats were classified into healthy and sensitized groups, which were further divided into three subgroups; rats received systemically 50 μl volume of PBS, CM, or 2?×?10⁶ rat bone marrow-derived mesenchymal stem cells (rBMMSCs). Tracheal responsiveness (TR), immunologic responses, and recruitment of rBMMSCs into the lungs were evaluated. A high degree of TR and total WBC and percentages of eosinophils and neutrophils was significantly recorded in all sensitized groups rather than of controls (p?<?0.001 to p?<?0.05). Concurrently, a significant improvement of TR and eosinophil and neutrophil return toward normal levels was evident in sensitized rats receiving cells as compared to parallel asthmatic animals. Flow cytometric monitoring of lymphocyte subpopulation revealed a decrease in the number of CD3⁺CD4⁺ and concurrent increase in CD3⁺CD8⁺ in all sensitized rats as compared to control (p?<?0.001 to p?<?0.05). Noticeably, no significant modulatory effects of either cell or CM administration were achieved on the CD3⁺CD4⁺ and CD3⁺CD8⁺ populations in non-asthmatic rats. Corroborating our results, the number of CD3⁺CD4⁺ tended to increase (p?<?0.05) which coincided with a decreased manner of CD3⁺CD8⁺ populations as compared to other asthmatic groups (p?<?0.01 to p?<?0.05). Moreover, stem cells could efficiently transmigrate to the lung parenchyma, albeit the dynamic of asthmatic changes stimulated the rate of recruited cells. Our study shed light on superior effects of mesenchymal stem cells, but not CM, in attenuating chronic asthmatic changes in the model of rat.     

Meta-Analysis of Associations Between Interleukin-10 Polymorphisms and Susceptibility to Vasculitis

Objective: This study determined whether interleukin-10 (IL-10) polymorphisms are associated with susceptibility to vasculitis.

Methods: A meta-analysis was conducted of the associations between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and the haplotype of the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and vasculitis.

Results: A total of 21 comparative studies involving 4121 patients and 5504 controls were considered in the meta-analysis. Meta-analysis revealed no association between the IL-10-1082 G allele and vasculitis in all study subjects (OR?=?0.927, 95% CI?=?0.780–1.102, p?=?0.389). However, disease-specific meta-analysis showed an association between Wegener’s granulomatosis (WG) and the IL-10-1082 G allele (OR?=?0.729, 95% CI?=?0.547–0.971, p?=?0.031). Meta-analysis revealed an association between vasculitis and the IL-10-819 C allele (OR?=?0.804, 95% CI?=?0.706–0.916, p?=?0.001) in all study subjects and Behcet’s disease (BD) (OR?=?0.724, 95% CI?=?0.679–0.781, p?<?1.0?×?10^?9). Meta-analysis of the IL-10-592 C allele showed an association with vasculitis in all study subjects (OR?=?0.805, 95% CI?=?0.619–0.938, p?=?0.005) and BD (OR?=?0.718, 95% CI?=?0.661–0.781, p?<?1.0?×?10^?9). Meta-analysis of the IL-10 haplotype revealed an association between the GCC haplotype and vasculitis in Europeans (OR?=?1.239, 95% CI?=?1.105–1.513, p?=?0.035).

Conclusions: This meta-analysis showed that IL-10 polymorphisms are associated with vasculitis susceptibility, especially in WG and BD.     

Serum Leptin Levels,Leptin Receptor Gene (LEPR) Polymorphism,and the Risk of Systemic Lupus Erythematosus in Kashmiri Population

The study is conducted to evaluate relationship between LEPRQ223R (Gln?>?Arg) polymorphism, serum leptin levels, soluble leptin receptor (SOb-R) levels and SLE risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE patients and equal number of healthy control subjects. Leptin and SOb-R levels were measured by ELISA assays. The present study showed higher frequency of variant genotype (AG?+?GG) in cases compared to controls [OR?=?2.52, CI?=?1.18–5.35, p?=?0.03]. Moreover the rare (G) allele was significantly more predominant in cases than controls [OR?=?1.49, p?=?0.04]. Interestingly a positive association between the variant genotype and the development of arthritis [OR?=?11.8, CI?=?1.6–85.1, p?=?0.002] and an inverse association with cardiac disorder [OR?=?0.09, CI?=?0.02–0.46, p?=?0.001] was observed in this study. Furthermore the study showed significant differences of leptin levels in SLE patients and controls (23.9?±?19.5 vs 14.8?±?10.4, p?<?0.001). SLE patients in the highest quartile leptin levels (≥32.5?ng/mL) were significantly more likely to have higher BMI (p?=?0.001) and increased risk of developing arthritis (p?=?0.02). Furthermore positive association was observed between the variant genotype(AG?+?GG) and leptin levels (p?=?0.001) in SLE patients. Thus, it is evident from our study that LEPRQ223R polymorphism and elevated leptin levels are associated with increased susceptibility of SLE in Kashmiri population.     

Short-term pharmacologically induced growth study of ontogenetic allometry of oxygen uptake in children

Background: A range of allometric coefficients have been proposed in describing the maximal oxygen uptake (VO_2max): body mass relation in children using weight-bearing ergometry. However, a wide deviation in the allometric coefficients for VO_2max may be apparent when selected pediatric cohorts are studied in conjunction with clinical intervention for growth abnormalities.

Aim: The purpose of this study was to determine the allometric coefficients for VO_2max after short-term pharmacologically induced growth in pre- and early pubescent children.

Subjects and methods: The treatment group consisted of nine subjects with non-growth hormone (GH)-deficient short stature and one with GH-deficient short stature (mean age: 13.7?±?1.7 years). Ten pre- and early pubescent children matched for age, height, weight, VO_2max and body mass index (BMI) were controls. The treatment group were evaluated before (Pre-GH) and after (Post-GH) 4 months of subcutaneous GH therapy (0.05?mg?kg^?1day^?1?×?6 days week^?1).

Results: The mean ontogenetic coefficient for the treatment group was 1.50?±?0.20 and for the control group was 0.77?±?0.34. The mean allometric coefficient for body mass relative to VO_2max was significantly higher in the treatment group compared with the control group (p<0.05). Height, weight, fat free mass (FFM), VO_2max indexed to body mass (mL?kg^?1?min^?1) and FFM (mL?kgFFM^?1?min^?1) increased (p<0.05) with GH therapy. GH therapy also increased insulin-like growth factor-I (IGF-I) and served as a biochemical marker of GH therapy (p<0.05). The control group had no significant differences in all the variables tested (p<0.05).

Conclusion: The scaling for oxygen uptake (VO₂) for body mass varies with GH treatment and the increase in VO_2max that commonly occurs in conjunction with physical growth in the pre-and early pubescent individual may be linked to an increase in FFM and linear size.

Résumé. Arrière plan: Une gamme de coefficients d’allométrie a été proposée pour décrire la relation entre consommation d’énergie maximum (VO_2max) et masse corporelle, chez des enfants examinés par ergométrie avec charge pondérale. On observe cependant qu’une large déviation des coefficients d’allométrie pour le VO_2max peut apparaître lorsque des cohortes pédiatriques sont étudiées pour les anomalies de la croissance, en conjonction avec une intervention clinique.

But: Le but de cette étude est de déterminer les coefficients d’allométrie pour le VO_2max à la suite d’une courte poussée de croissance induite par pharmacologie chez des enfants prépubères ou de puberté récente.

Sujets et méthodes: Le groupe sous traitement consiste en neuf sujets de stature courte sans déficience d’hormone de croissance (HC) et d’un sujet de stature courte suite suite à une déficience de l’hormone de croissance (âge moyen?: 13,7?±?1,7?ans). On a pris comme contrôles, dix enfants prépubères et de puberté récente appariés pour l’âge, la stature, le poids, le VO_2max et l’IMC. Le groupe en traitement a été évalué avant (Pré-HC) et après (post-HC) quatre mois d’injections d’HC sous cutanée (0,05?mg?kg^?1?jour^?1?×?6?jours semaine^?1).

Résultats: Le coefficient ontogénique moyen pour le groupe sous traitement est de 1,50?±?0,20 et pour le groupe de contrôle 0,77?±?0,34. Le coefficient allométrique moyen pour la masse corporelle en rapport avec VO_2max est significativement plus élevé dans le groupe traité que dans le groupe contrôle (p<0,05). La stature, le poids, la masse maigre, le VO_2max rapporté à la masse corporelle (mL?kg^?1?min^?1) et à la masse maigre (mL?kg^?1?min^?1) s’accroissent avec la thérapie par HC (p?<?0,05). La thérapie HC accroît également le facteur I de croissance insulino mimétique, lequel sert de marqueur biochimique de la thérapie HC (p?<?0,05). Le groupe de contrôle ne présente pas de différence significative pour toutes les variables examinées (p?<?0,05).

Conclusion: L’échelle de VO₂ en fonction de la masse corporelle, varie avec les traitement par HC et l’augmentation en VO_2max qui se produit en général en conjonction avec la croissance physique chez l’individu prépubère ou pubère récent, peut être liée à l’accroissement de la masse maigre et de la taille linéaire.

Zusammenfassung. Hintergrund: Eine Vielzahl allometrischer Koeffizienten ist vorgeschlagen worden, um die Relation von maximaler Sauerstoffaufnahme (VO_2max) zu Körpermasse im Kindesalter unter Verwendung von gewichtsbezogener Ergometrie zu beschreiben. Allerdings wird eine weite Abweichung allometrischer Koeffizienten für VO_2max offensichtlich, wenn ausgewählte pädiatrische Stichproben in Verbindung mit klinischen Interventionen bei Wachstumsstörungen untersucht werden.

Ziel: Sinn dieser Studie war die Bestimmung von allometrischen Koeffizienten für VO_2max nach kurzzeitigem medikamenteninduzierten Wachstum bei präpubertären Kindern und Kindern in der frühen Pubertät.

Probanden und Methoden: Die Behandlungsgruppe bestand aus neun Probanden mit nicht-wachstumshormonbedingtem Kleinwuchs und einem Patienten mit Kleinwuchs aufgrund eines Wachstumshormonmangels (mittleres Alter: 13,7?±?1,7?Jahre). Die Kontrollgruppe bestand aus zehn gleichaltrigen präpubertären Kindern und Kindern in der frühen Pubertät von vergleichbarer Körperhöhe und vergleichbarem Gewicht, VO_2max und BMI. Die Behandlungsgruppe wurde vor (prä-GH) und nach (post-GH) 4-monatiger subkutaner Wachstumshormontherapie (0,05?mg?kg^?1?Tage^–1?×?6?Tage Woche^?1) untersucht.

Ergebnisse: Der mittlere ontogenetische Koeffizient für die Behandlungsgruppe war 1,50?±?0,20 und für die Kontrollgrupp.,77?±?0,34. Der mittlere allometrische Koeffizient für Körpermasse relativ zu VO_2max war in der Behandlungsgruppe signifikant höher als in der Kontrollgruppe (p?<?0,05). Körperhöhe, Gewicht, fettfreie Masse (FFM), VO_2max in Bezug zu Körpermasse (mL?kg^?1?min^?1) und FFM (mL?kg?FFM^?1?min^?1) stiegen mit Wachstumshormontherapie (p?<?0,05). Die Wachstumshormontherapie führte auch zu einem Anstieg des Insulin-like Growth Factor-I (IGF-I) und diente als biochemischer Marker der Wachstumshormontherapie (p?<?0,05). Die Kontrollgruppe zeigte keine signifikanten Unterschiede bei den getesteten Variablen (p?<?0,05).

Zusammenfassung: Die Anpassung von VO₂ an Körpermasse variiert mit der Wachstumshormontherapie, und der Anstieg von VO_2max, der üblicherweise in Verbindung mit körperlichem Wachstum vor und zu Beginn der Pubertät auftritt, könnte mit einer Vermehrung von FFM und Körperlänge verknüpft sein.

Resumen. Antecedentes: Se ha propuesto un rango de coeficientes alométricos para describir la relación entre el consumo máximo de oxígeno (VO_2max) y la masa corporal en niños, utilizando la prueba de esfuerzo (ergometría “weight-bearing”). Sin embargo, puede ponerse de manifiesto una amplia desviación de los coeficientes alométricos para el VO_2max cuando se estudian las cohortes pediátricas seleccionadas junto con la intervención clínica para las anomalías del crecimiento.

Objetivo: El objetivo de este estudio fue determinar los coeficientes alométricos para el VO_2max tras un crecimiento a corto plazo inducido farmacológicamente en niños pre-puberales y con pubertad temprana.

Sujetos y métodos: El grupo de tratamiento consistió en nueve individuos con baja estatura no deficientes de hormona de crecimiento (GH) y uno con baja estatura y deficiente para la GH (edad media: 13,7?±?1,7 años). Diez niños pre-puberales y con pubertad temprana de la misma edad, estatura, peso, VO_2max e IMC fueron los controles. El grupo de tratamiento fue evaluado antes (Pre-GH) y después (Post-GH) de 4 meses de terapia subcutánea con GH (0,05?mg?kg^?1?día^–1?×?6?días por semana^?1).

Resultados: El coeficientes ontogénico medio para el grupo de tratamiento fue de 1,50?±?0,20 y para el grupo de control de 0,77?±?0,34. El coeficiente alométrico medio para la masa corporal respecto al VO_2max fue significativamente mayor en el grupo que recibía tratamiento que en el grupo control (p?<?0,05). La estatura, el peso, la masa libre de grasa (FFM), el VO_2max indexado para la masa corporal (mL?kg^?1?min^?1) y la FFM (mL?kg?FFM^?1?min^?1) aumentaban (p?<?0,05) con la terapia con GH. Esta terapia también incrementaba el factor de crecimiento semejante a la insulina tipo I (IGF-I) y sirvió como un marcador bioquímico de la terapia con GH (p?<?0,05). El grupo de control no mostró diferencias significativas en ninguna de las variables testadas (p?<?0,05).

Conclusión: la escala del VO_2max para la masa corporal varía con el tratamiento con GH; el incremento en el VO_2max que ocurre habitualmente junto con el crecimiento físico en los individuos pre-puberales y de pubertad temprana puede estar asociado con un incremento de la FFM y del tamaño lineal.     

Association of FTO and IRX3 genetic variants to obesity risk in north India

Abstract

Objective: Validation of body adiposity index (BAI) in a paediatrics sample; and to develop, if necessary, a valid BAI for paediatrics (i.e. BAI_p).

Methods: A total of 1615 children (52% boys) aged 5–12 years underwent anthropometry. Their body composition was assessed using a foot-to-foot bioimpedance. The validity of BAI?=?(Hip circumference/Height^1.5)???18 was tested by combining correlation and agreement statistics. Then, the sample was split into two sub-samples for the construction of BAI_p. A regression was used to compute the prediction equation for BAI_p-based percentage of body fat (%BF).

Results: The initial BAI over-estimated the %BF of children by 49% (29.6?±?4.2% versus 19.8?±?6.8%; p?<?0.0001). The original methodology led to a BAI_p?=?(Hip circumference/Height^0.8) ? 38 in children. When compared to BAI, BAI_p showed both better correlation (r?=?0.57; p?<?0.01 versus r?=?0.74; p?<?0.0001) and agreement (ICC?=?0.34; [95% CI?=??0.19–0.65] versus ICC?=?0.83; [95% CI?=?0.81–0.84]). However, there were some systematic biases between the two values of %BF as exemplified by the large 95% limit of agreement [?9.1%; 8.8%] obtained.

Conclusion: BAI over-estimates the %BF in children. In contrast, BAI_p appears as a new index for children’s body fatness, with acceptable accuracy. In its current form, this index is valid only for large-scale studies.