Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: A systematic review and meta-analysis.

Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying the aging process. Some biological and pharmaceutical compounds may reduce systemic inflammation and potentially avert functional decline occurring with aging. The aim of the present meta-analysis was to examine the association of pre-selected interventions on two established biomarkers of inflammation, interleukin-6 (IL-6), and C-reactive protein (CRP) in middle-age and older adults with chronic LGI. We reviewed the literature on potential anti-inflammatory compounds, selecting them based on safety, tolerability, acceptability, innovation, affordability, and evidence from randomized controlled trials. Six compounds met all five inclusion criteria for our systematic review and meta-analysis: angiotensin II receptor blockers (ARBs), metformin, omega-3, probiotics, resveratrol and vitamin D. We searched in MEDLINE, PubMed and EMBASE database until January 2017. A total of 49 articles fulfilled the selection criteria. Effect size of each study and pooled effect size for each compound were measured by the standardized mean difference. I2 was computed to measure heterogeneity of effects across studies. The following compounds showed a significant small to large effect in reducing IL-6 levels: probiotics (-0.68 pg/ml), ARBs (-0.37 pg/ml) and omega-3 (-0.19 pg/ml). For CRP, a significant small to medium effect was observed with probiotics (-0.43 mg/L), ARBs (-0.2 mg/L), omega-3 (-0.17 mg/L) and metformin (-0.16 mg/L). Resveratrol and vitamin D were not associated with any significant reductions in either biomarker. These results suggest that nutritional and pharmaceutical compounds can significantly reduce established biomarkers of systemic inflammation in middle-age and older adults. The findings should be interpreted with caution, however, due to the evidence of heterogeneity across the studies.

Cognitive Performance Does not Limit Physical Activity Participation in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P).

OBJECTIVES: We examined whether multiple domains of baseline cognitive performance were associated with prospective physical activity (PA) adherence in the Lifestyle Interventions and Independence for Elders Pilot study (LIFE-P). DESIGN, SETTING, PARTICIPANTS: The LIFE-P study was a single-blind, multicenter, randomized controlled trial of a PA intervention compared to a successful aging educational intervention in sedentary, mobility-limited older adults. INTERVENTION: A 12-month structured, moderate-intensity, multi-modal PA program that included walking, resistance training, and flexibility exercises. For the first 2 months (adoption), 3 center-based exercise sessions (40-60 min) / week were conducted. During the next 4 months (transition), center-based sessions were conducted 2 times / week. The subsequent maintenance phase consisted of optional once-to-twice-per-week center-based sessions and home-based PA. MEASUREMENTS: Tests of executive and global cognitive functioning, working memory and psychomotor speed were administered at baseline. Median test scores were used to dichotomize participants into low or high cognitive performance groups. RESULTS: 52 mobility-limited older adults (age: 76.9 ±5 yrs) were randomized to the PA arm of LIFE-P. Compared to participants with high cognitive performance, participants with low performance had similar PA adherence rates (all P ≥ 0.34). Furthermore, weak and non-significant univariate relationships were elicited between all measures of cognition and overall PA adherence levels (r values ranged: -0.20 to 0.12, P ≥ 0.12). CONCLUSION: These data suggest that cognitive performance does not limit long-term PA adherence in mobility-limited older adults. Additional studies in larger cohorts are warranted to verify these findings.

Biomarkers associated with severe hypoglycaemia and death in ACCORD.

AIMS AND HYPOTHESIS: In patients with Type 2 diabetes, intensive glycaemic control is associated with hypoglycaemia and possibly increased mortality. However, no blood biomarkers exist to predict these outcomes. Using participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, we hypothesized that insulin deficiency and islet autoantibodies in patients with clinically diagnosed Type 2 diabetes would be associated with severe hypoglycaemia and death. METHODS: A nested case-control study design was used. A case (n = 86) was a participant who died with at least one episode of severe hypoglycaemia, defined as hypoglycaemia requiring assistance, at any point during ACCORD follow-up. A control (n = 344) was a participant who did not die and did not have severe hypoglycaemia during follow-up. Each case was matched to four controls (glycaemic intervention arm, race, age and BMI). Baseline insulin deficiency (fasting C-peptide ≤ 0.15 nmol/l) and islet autoantibodies [glutamic acid decarboxylase (GAD), tyrosine phosphatase-related islet antigen 2 (IA2), insulin (IAA) and zinc transporter (ZnT8)] were measured. Conditional logistic regression with and without adjustment for age, BMI and diabetes duration was used. RESULTS: Death during ACCORD in those who experienced at least one episode of severe hypoglycaemia was associated with insulin deficiency [OR 4.8 (2.1, 11.1): P < 0.0001], GAD antibodies [OR 2.3 (1.1, 5.1): P = 0.04], the presence of IAA or baseline insulin use [OR 6.1 (3.5,10.7): P < 0.0001], which remained significant after adjusting for age, BMI, and diabetes duration. There was no significant association with IA2 or ZnT8 antibodies. CONCLUSIONS: In patients with Type 2 diabetes, C-peptide or GAD antibodies may serve as blood biomarkers predicting higher odds of subsequent severe hypoglycaemia and death. (Clinical Trial Registry No: NCT00000620, www.clinicaltrials.gov for original ACCORD study).

Neutron flux assessment of a neutron irradiation facility based on inertial electrostatic confinement fusion.

Neutron generators based on inertial electrostatic confinement fusion were considered for the design of a neutron irradiation facility for explanted organ Boron Neutron Capture Therapy (BNCT) that could be installed in a health care center as well as in research areas. The chosen facility configuration is "irradiation chamber", a ~20×20×40 cm(3) cavity near or in the center of the facility geometry where samples to be irradiated can be placed. Neutron flux calculations were performed to study different manners for improving scattering processes and, consequently, optimize neutron flux in the irradiation position. Flux distributions were assessed through numerical simulations of several models implemented in MCNP5 particle transport code. Simulation results provided a wide spectrum of combinations of net fluxes and energy spectrum distributions. Among them one can find a group that can provide thermal neutron fluxes per unit of production rate in a range from 4.1·10(-4) cm(-2) to 1.6·10(-3) cm(-2) with epithermal-to-thermal ratios between 0.3% and 13% and fast-to-thermal ratios between 0.01% to 8%. Neutron generators could be built to provide more than 10(10) n s(-1) and, consequently, with an arrangement of several generators appropriate enough neutron fluxes could be obtained that would be useful for several BNCT-related irradiations and, eventually, for clinical practice.

Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina.

PURPOSE: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA-3 reactor in the province of Buenos Aires, Argentina. (l)-4p-dihydroxy-borylphenylalanine fructose complex (BPA-F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. METHODS: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA-3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. RESULTS: Concentration-time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung-to-blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA-F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect quantification of the estimated value in the explanted healthy lung. The proposed preclinical animal model allowed for the study of the explanted lung. As expected, the boron concentration values fell as a result of the application of the preservation protocol required to preserve the lung function. The distribution of the boron concentration retention factor was obtained for healthy lung, with a mean value of 0.46 ± 0.14 consistent with that reported for metastatic colon carcinoma model in rat perfused lung. Considering the human lung model and suitable tumor control probability for lung cancer, a promising average fraction of controlled lesions higher than 85% was obtained even for a low tumor-to-normal boron concentration ratio of 2. CONCLUSIONS: This work reports for the first time data supporting the validity of the ovine model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Collectively, the results and analysis presented would strongly suggest that ex situ whole lung BNCT irradiation is a feasible and highly promising technique that could greatly contribute to the treatment of metastatic lung disease in those patients without extrapulmonary spread, increasing not only the expected overall survival but also the resulting quality of life.

Identifying information needs among children and teens living with haemophilia.

Transitioning from one life stage to the next can be difficult, but for those living with a chronic condition, it can be even more challenging. Children and adolescents with haemophilia need help to manage transitions while dealing with the complications of their disorder. The National Haemophilia Foundation (NHF), headquartered in New York City, has an extensive information centre on bleeding disorders, but it was not clear how much material existed on the topic of transition. The objectives of this project were to (i) assess the availability of literature about transition for children and adolescents living with haemophilia, (ii) determine which transition issues were the most relevant and (iii) develop and test information products that would address those transition issues. An inventory of NHF's resources and an environmental scan over the Internet was performed. Focus groups were conducted to determine messaging. Video prototypes containing messages were created, tested by focus groups and revised. The literature search yielded limited information available on transition for children and adolescents with haemophilia. Results of the formative research indicated that adolescents wanted more information on sports participation and disclosure of their condition (e.g. to peers, teachers, coaches, health care providers). Video was found to be the preferred delivery format. Children and adolescents living with haemophilia need information to help them transition through life. As a result of this study, two educational products were produced, but several more are recommended to guide these individuals in making healthy transitions into adulthood.

Intracochlear schwannoma presenting as diffuse cochlear enhancement: diagnostic challenges of a rare cause of deafness.

Intracochlear schwannoma is a rare, treatable, cause of unilateral hearing loss. Due to the small size, position, and variable clinical and imaging features, diagnosis presents a significant challenge and is often delayed. We present a case of a patient with an intracochlear schwannoma presenting as a diffuse enhancement of the cochlea, mimicking an infectious or inflammatory process. The absence of focal nodularity in this lesion on multiple high-resolution MRI examinations led to a delay of over 3 years from the patient's initial presentation to surgical diagnosis. Clinical history and examination, imaging features, pathologic findings, and surgical management options are described.

Expression and characterization of a multivalent human respiratory syncytial virus protein.

Respiratory syncytial virus (RSV) has been recognized as one of the most common causes of severe respiratory tract infection in infants worldwide. As yet, a safe and effective vaccine has not been developed to protect humans from RSV. The F and G surface proteins have been widely investigated due to their potential to induce protective immunity. In addition, the M2 protein has been shown to be important in inducing a T-cell response. Our project involved the cloning of the immunodominant regions of the RSV F, M2 and G proteins into a bacterial vector, pET-32a (+). The recombinant RFM2G protein was expressed in Escherichia coli and purified using His Bind columns. The purified rRFM2G protein was analyzed by polyacrylamide gel electrophoresis and Western blotting. The predicted structure of the recombinant protein built by the Swiss PDB Viewer program suggested a rod shape with a distinct swollen head and neck which was confirmed by transmission electron microscopy and atomic force microscopy. BALB/c female mice were immunized with either RSV, rRFM2G alone, or rRFM2G in combination with flagellin as a mucosal adjuvant. Serum was collected on days 0, 14, 28 and 49 to assess the immune response by Enzyme-linked immunosorbent assay. Intranasal immunization of mice with the rRFM2G protein yielded significantly high serum IgG titers. Co-administration of the rRFM2G protein with flagellin did not augment the serum antibody response.

Chronic renal failure in Jamaican children--an update (2001-2006).

OBJECTIVE: This study evaluated the incidence, epidemiology, aetiology and outcome of chronic renal failure (CRF) in Jamaican children < 12 years old between 2001 and 2006. METHODS: The required data on all children who fulfilled inclusion criteria were obtained from their medical records at the University Hospital of the West Indies, Bustamante Hospital for Children and from practitioners in hospitals serving children islandwide. RESULTS: Eighteen new children (72.2% male) presented with CRF. The cumulative annual incidence was 4.61/million child population under age 12 years or 1.14/million total population. Congenital urological disease (44.5%) was the commonest cause of CRF, followed by glomerulonephritis (33.3%). Half of the cases of glomerulonephritis were secondary to HIV-associated nephropathy. Although all children with posterior urethral valves were diagnosed before age 6 months and promptly treated, renal failure present at birth proved irreversible. The mean age at diagnosis of CRF was 6.72 years. Ten children (55.6%) were already in CRF at first presentation with renal disease. Of these, the five with non-urological disease were already in End Stage Renal Disease (ESRD). Mortality was 44.4%. Five children died in ESRD without the benefit of dialysis. CONCLUSION: The incidence of CRF has increased from the 1985-2000 local study and is mainly due to urological pathology which progresses despite early diagnosis and treatment. Non-urological renal disease is presenting too late for therapeutic intervention. Greater public awareness of symptoms of renal disease is needed. Children's access to dialysis is unpredictable. A paediatric dialysis and transplantation programme is needed.

Estimation of bone strength from pediatric radiographs of the forearm.

OBJECTIVE: Bone strength is a function of both material and architectural properties. However, bone geometry or architecture, which determines the distribution of bone, is an underappreciated determinant of bone strength. The aim of the study was to evaluate the contribution of only architecture to bone strength. METHODS: We used 2-D (planar) geometric information from radiographs of human radii to construct 3-D finite-element models. To transition from 2-D to 3-D (volume) space, we assumed that all bone cross-sections were elliptical in shape. The finite-element models were subjected to cantilever loading to determine the locations in the bone with the highest propensity to fracture (points of maximum stress). The finite-element-analysis results of the models generated from radiographs of both normal (18) and temporary-brittle-bone-disease (11) infants were subjected to a receiver operating curve analysis. The area under the receiver operating curve was used to evaluate the power of a given bone-strength indicator in segregating the two populations. The actual choice of the material properties (Young's modulus or Poisson's ratio) was not critical for this study, since the finite element analyses were designed to capture the difference in the bone strength of the two populations only based on their architecture. Therefore, the material properties were assumed to be the same in both the normal and TBBD populations. RESULTS: The area under the curve of the bending load required to cause fracture among the two populations was 0.82. Other bone-strength indicators, such as average section modulus, cortical thickness and bone length, were associated with an area under the curve of 0.75, 0.73 and 0.63, respectively. CONCLUSION: The results of the finite-element-analysis suggest that the temporary-brittle-bone-disease population has an altered bone geometry, which increases susceptibility to fracture under normal bending loads.

First Report of Iris yellow spot virus on Onion (Allium cepa) in Texas.

Iris yellow spot virus (IYSV; family Bunyaviridae, genus Tospovirus) has emerged as a potentially devastating and widespread virus of onion. IYSV was first reported in the United States from Idaho in 1993 and has since spread to many of the onion-producing areas (1). In South America, the most recent reports of the virus on onion were from Peru and Chile (2,4). In 2005, onion plants in Uvalde County, Texas exhibited necrotic lesions on leaves typical of IYSV and disease incidence approached 100% in some fields with yield loss and quality problems. Five of six plants tested were positive for IYSV with double antibody sandwich-enzyme linked immunosorbent assay (DAS-ELISA; Agdia Inc., Elkhart, IN). In 2006, similar lesions were observed on onion plants in Uvalde County and approximately 400 km south in Hidalgo and Cameron counties. Infection points generally started as a single plant near the edge of fields and spread to plants in a 3- to 4-m area after 1 to 2 weeks. Early-season disease incidence was low in onions grown for bulbs and transplants, <10% in 2006. Disease incidence increased in some fields until the crop was harvested. Leaves of symptomatic plants were tested for IYSV and Tomato spotted wilt virus (TSWV) using DAS-ELISA, and 18 of 23 samples from the Hidalgo County area and 12 of 21 samples from the Uvalde County area were positive for IYSV. All samples tested for TSWV from these counties were negative. Virus infection in some ELISA-positive plants was verified by reverse transcription-polymerase chain reaction (RT-PCR) using primers derived from the small RNA of IYSV. The primers flanked the IYSV nucleocapsid (N) gene (5'-TAA AAC AAA CAT TCA AAC AA-3' and 5'-CTC TTA AAC ACA TTT AAC AAG CAC-3' (3). RT-PCR gave a PCR product of expected size (approximately 1.2 kb). The DNA amplicon was cloned and sequenced (GenBank Accession No. DQ658242). Nucleotide sequence analysis confirmed the identity of the amplicon as that of IYSV N gene and sequence comparisons with known IYSV N gene sequences showed 95 to 98% sequence identity. The primary vector of IYSV, onion thrips (Thrips tabaci), is a widespread and destructive pest of onion in south Texas. The year-to-year incidence of IYSV and the severity of the disease will probably depend on the onion thrips population levels. Bulb yield reduction could be severe during years with high thrips populations. More research is needed to determine the impact of IYSV on bulb yield in Texas, the relationship between IYSV incidence and T. tabaci population levels, and oversummering hosts. To our knowledge, this is the first known report of IYSV in Texas. References: (1) D. H. Gent et al. Plant Dis. 88:446, 2004, (2) S. W. Mullis et al. Plant Dis. 90:377, 2006, (3) H. Pappu et al. Arch. Virol. 151:1015, 2006. (4) M. Rosales et al. Plant Dis. 89:1245, 2005.

First Report of Rust Caused by Phakopsora pachyrhizi on Soybean and Kudzu in Texas.

The Asian soybean rust fungus, Phakopsora pachyrhizi H. Sydow & Sydow, was found on a 0.4-ha patch of kudzu (Pueraria lobata) near Dayton (Liberty County) in East Texas on November 2, 2005. Nearly 100% of the 300 leaflets examined were diseased with severity ranging from 5 to >100 lesions per leaflet. Eleven soybean fields as much as 20 km away were scouted and no infected plants were found. Asian soybean rust was also found on a 0.4-ha field of soybean (Glycine max cv. Vernal) on February 14, 2006 at the Texas A&M Agricultural Experiment Station in Weslaco (Hidalgo County) in the Lower Rio Grande Valley (LRGV) of Texas. Disease incidence was 100% (severity ranging from 5 to >100 lesions per leaflet) on 50 younger plants with green leaves along the edges of the field, whereas most of the plants in this field had senesced. These plants were not symptomatic and were at the R6 stage (full seed) when this field was previously scouted on December 19, 2005. Lesions on leaflets of kudzu and soybean were small and angular with erumpent uredinia typical of P. pachyrhizi. Urediniospores were ovoid or globose, hyaline, and measured 25 to 30 × 14 to 21 µm. Leaf samples with pustules were positive for P. pachyrhizi using enzyme-linked immunosorbent assay (ELISA) (Envirologix, Portland, ME). Morphological and polymerase chain reaction (PCR) identification of P. pachyrhizi from kudzu and soybean samples were confirmed by the USDA-APHIS-PPQ NIS and CPHST laboratories in Beltsville, MD as previously described (2). The kudzu in East Texas is not likely to support overwintering of the pathogen because it usually dies back during the winter. Leaves at this site were dead by January 17, 2006. This is the southernmost infestation of kudzu in Texas known to us. In contrast, the LRGV has a subtropical climate that would favor year-round survival of the fungus (3). This area, where 120 to 160 ha of soybeans are grown, may be a source of inoculum for soybean rust epidemics in the Midwest. Spore movement would follow the same pattern as seen with cereal rusts (1). However, soybeans are typically absent from the LRGV between late December and early March, so survival of the fungus during this interval would require other hosts. Regardless of whether the fungus overwinters here, or moves in from elsewhere, the LRGV spring crop could serve as an early indicator of a potential rust epidemic. References: (1) M. G. Eversmeyer and C. L. Kramer. Annu. Rev. Phytopathol. 38:491, 2000. (2) J. M. Mullen et al. Plant Dis. 90:112, 2006. (3) S. Pivonia et al. Plant Dis. 89:678, 2005.

Benzo-[a]-pyrene increases invasion in MDA-MB-231 breast cancer cells via increased COX-II expression and prostaglandin E2 (PGE2) output.

Benzo-[a]-pyrene (B[a]P), a carcinogenic component of cigarette smoke, has been shown to increase both COX-II expression and prostaglandin output in vascular smooth muscle and oral epithelial cells. In addition, invasive breast cancer cells have been reported to over express COX-II and PGE(2). Therefore, the objective of this study was to quantify the effect of increasing B[a]P concentrations on COX-II expression, PGE(2) output, and invasion using MDA-MB-231 cells, an invasive estrogen unresponsive breast cancer cell line. B[a]P significantly increased invasion in MDA-MB-231 cells at concentrations greater than 4 x 10(-8) M. Treatment of MDA-MB-231 cells with Vomitoxin (a selective COX-II inducer) enhanced invasion whereas co-treatment with NS398 (a selective COX-II inhibitor) attenuated B[a]P-induced invasion in MDA-MB-231 cells. Immunohistochemical staining and Western blots demonstrated a significant B[a]P treatment-induced increase in both the number of COX-II immunopositive MDA-MB-231 cells and COX-II protein levels. Moreover, B[a]P-treatment induced a profound (46 fold) increase in PGE(2) production by MDA-MB-231 cells. The aryl hydrocarbon receptor (AhR) antagonists resveratrol (RES) and alpha-naphthaflavone (alpha-NF) had no effect on their own, whereas B[a]P-induced invasion was significantly inhibited by co-treatment with RES and alpha-NF. Our data demonstrate that B[a]P-induced changes in invasion are mediated through augmented COX-II expression and PGE(2) production involving an AhR regulated pathway. Moreover, these results suggest a potential role for the AhR signalling pathway in breast cancer invasion.

Cellular basis of diabetic nephropathy: III. In vitro GLUT1 mRNA expression and risk of diabetic nephropathy in type 1 diabetic patients.

AIMS/HYPOTHESIS: Altered glucose transporter expression has been implicated in the pathogenesis of diabetic nephropathy. There is increasing evidence that genetic factors convey risk of, or protection from, diabetic nephropathy and that the behaviour of cultured skin fibroblasts from type 1 diabetic patients may reflect these genetic influences. This study aimed to compare GLUT1 mRNA expression levels in skin fibroblasts from type 1 diabetic patients with either rapid ("fast-track", n=25) or slow ("slow-track", n=25) development of diabetic nephropathy and from non-diabetic normal control subjects (controls, n=25). METHODS: Skin fibroblasts were cultured in Dulbecco's Modified Eagle's Medium with 25 mmol/l glucose for 36 h. Total RNA was isolated, and GLUT1 mRNA levels were estimated by microarray analysis and RT-PCR. RESULTS: Levels of GLUT1 mRNA expression in skin fibroblasts from "slow-track" patients were greater than those from "fast-track" patients (p=0.02), as initially detected by microarray. GLUT1 mRNA expression levels were confirmed by RT-PCR to be higher in skin fibroblasts from "slow-track" patients (4.59+/-2.04) than in those from "fast-track" patients (3.34+/-1.2, p=0.02), and were also higher than in skin fibroblasts from control subjects (3.52+/-1.66, p=0.03). There was no statistically significant difference between levels of expression in the "fast-track" patients and the control subjects. CONCLUSIONS/INTERPRETATION: This finding is consistent with the presence of cellular protection factors against diabetic nephropathy in the "slow-track" patients. These factors could be associated with the regulation of the GLUT1 pathway and may be genetically determined.

Implantable self-powered detector for on-line determination of neutron flux in patients during NCT treatment.

A novel system to determine thermal neutron flux in real time during NCT treatments was developed in the National Atomic Energy Commission of Argentina. The system is based on a special self-powered detector that can be implanted in patients owing to its small size and biocompatibility. High voltage is not required to operate this kind of detectors, which is a considerable advantage in terms of medical uses. By choosing the appropriate materials, it was possible to obtain a prototype with thermal neutron sensitivity providing for an adequate signal level in typical NCT thermal fluxes. It was also possible to minimize gamma response in order to neglect its contribution.

Improving the insecticidal activity of Bacillus thuringiensis subsp. aizawai against Spodoptera exigua by chromosomal expression of a chitinase gene.

A transcriptionally fused gene comprising the P19 gene from Bacillus thuringiensis subsp. israelensis fused with a chitinase gene (chiBlA) from B. licheniformis was integrated into the B. thuringiensis subsp. aizawai BTA1 genome by homologous recombination. The resulting B. thuringiensis subsp. aizawai strain (INT1) showed growth and sporulation comparable with that of the wild-type strain. INT1 produced four chitinases of different molecular masses (i.e., 66, 55, 39, 36 kDa). Three of these (66, 55, 36 kDa) were derived from the cloned chiBlA gene, whereas the 39-kDa chitinase originated from BTA1. Using surface contamination bioassays, the 50% lethal concentration of lyophilized whole culture broth of INT1 against Spodoptera exigua neonate larvae was 12.2 microg/cm2, compared with 30.8 microg/cm2 for BTA1. Bioassays using filtered culture supernatant of INT1 (110 microg/cm2) together with trypsin-activated purified Cry1C protein of B. thuringiensis (1,280 ng/cm2) showed 75.0% mortality, compared with 56.7% mortality for Cry1C combined with BTA1 at the same concentration. Using scanning electron microscopy, clear perforations were observed in S. exigua fifth instar peritrophic membranes incubated with either crude or purified chitinase, or isolated from fifth instar S. exigua fed purified chitinase since the first instar. These results show that chitinase can increase the activity of B. thuringiensis subsp. aizawai against S. exigua. This is the first documentation of expressing a chimeric chitinase gene on the chromosome of B. thuringiensis; and chromosomal integration might be used as a potential technique for strain improvement.

Chronic renal failure in Jamaican children

In order to document the incidence, aetiology and outcome of chronic renal failure in Jamaican children, paediatric surgeons and hospital based paediatricians island-wide were contacted, and the nephrology records at the island's paediatric nephrology centres searched for data on children < 12-year-old with chronic renal failure diagnosed for the first time between January 1985 and December 2000. Thirty-four children were identified, 21 were male. The cumulative annual incidence of chronic renal failure was 3.2 per million children aged < 12 years. The incidence is likely underestimated, as some children may have been undiagnosed and/or not referred. Glomerulonephritis was the commonest cause of chronic renal failure (50) followed by obstructive uropathy, reflux nephropathy, renal dysplasia and chronic pyelonephritis (41.2). Five children (14.7) had reflux nephropathy (post obstructive in four). Half the children were already in chronic renal failure at time of presentation. Mortality was 65. In Jamaica, childhood chronic renal failure is due mainly to potentially treatable diseases. Local physicians should be more aware of potentially progressive renal diseases and their prevention. Earlier referral of difficult cases for nephrological consultation is recommended. A paediatric dialysis/transplant programme is needed

Hepatitis B-associated nephrotic syndrome in Jamaican children.

Between December 1984 and November 1996, 171 children under 12 years old presented to the University Hospital of the West Indies with nephrotic syndrome. Hepatitis B surface antigen (HBsAg) was found in ten (6%) of these children, eight of whom had membranous nephropathy (MN), and one each had mesangial proliferative glomerulonephritis (MesN) and minimal change nephrotic syndrome (MCNS). Only those children with MesN and MCNS were steroid-sensitive. The HBsAg-positive status was identified incidentally on screening. At a mean follow-up of 34 months, seven of ten children had experienced complete or partial remission and three had persistent nephrotic syndrome, although none was in renal failure. Six of the ten had biochemical hepatitis. All the children were still HBsAg-positive. Hepatitis B virus (HBV) is a factor contributory to nephrotic syndrome in Jamaican children. As diagnostic clinical markers for HBV-associated nephropathy are usually absent, all children presenting with nephrotic syndrome should be screened for HBsAg. A policy should be implemented in Jamaica for screening pregnant women and at-risk groups for HBsAg, as well as for immunising susceptible neonates, in order to reduce the incidence of HBV-associated pathology.

Oxytocin does not directly affect vascular tone in vessels from nonpregnant and pregnant rats.

Recent evidence suggests oxytocin (OT) may regulate vascular tone. OT and its receptor (OTR) have been identified in the rat heart and great vessels. Expression of OT and OTR is increased in some tissues during pregnancy. We hypothesized that the OT/OTR system may be a physiological regulator of vascular tone and mediate the decreased vascular resistance noted during pregnancy. Using a wire myograph system, we measured changes in vascular tone in response to OT in small mesenteric arteries, uterine arcuate arteries, and thoracic aorta from nonpregnant and pregnant rats. Additionally, we used reverse transcriptase-polymerase chain reaction (RT-PCR) to measure mRNA for OTR in these vascular tissues. Although OTR mRNA was identified by RT-PCR, OT did not elicit a vasodilatory effect in any of the vessels studied. High concentrations of OT (>10(-8) M) caused vasoconstriction that was eliminated by a specific vasopressin V(1a) receptor antagonist. Although it may have an indirect effect in regulation of peripheral resistance, we conclude that OT is unlikely to play a direct role in the physiological regulation of vascular tone.

Chronic renal failure in Jamaican children.

In order to document the incidence, aetiology and outcome of chronic renal failure in Jamaican children, paediatric surgeons and hospital based paediatricians island-wide were contacted, and the nephrology records at the island's paediatric nephrology centres searched for data on children < 12-year-old with chronic renal failure diagnosed for the first time between January 1985 and December 2000. Thirty-four children were identified, 21 were male. The cumulative annual incidence of chronic renal failure was 3.2 per million children aged < 12 years. The incidence is likely underestimated, as some children may have been undiagnosed and/or not referred. Glomerulonephritis was the commonest cause of chronic renal failure (50%) followed by obstructive uropathy, reflux nephropathy, renal dysplasia and chronic pyelonephritis (41.2%). Five children (14.7%) had reflux nephropathy (post obstructive in four). Half the children were already in chronic renal failure at time of presentation. Mortality was 65%. In Jamaica, childhood chronic renal failure is due mainly to potentially treatable diseases. Local physicians should be more aware of potentially progressive renal diseases and their prevention. Earlier referral of difficult cases for nephrological consultation is recommended. A paediatric dialysis/transplant programme is needed.