Compatibility of an organically based insect control program with honey bee (Hymenoptera: Apidae) pollination in cantaloupes.

The application of azadirachtin to foliage of cantaloupes did not significantly reduce successful pollination by commercially managed honey bees, Apis mellifera L., as measured by numbers of foraging honey bees and yield. Similar results were obtained when the synthetic insecticide imidacloprid (used as a standard by cantaloupe growers) was applied to the soil. Fruit yield and quality, as a function of bee pollination, were statistically equal between the two treatments, and equal to that of the untreated control. The standard treatment of imidacloprid gave significantly better control than azadirachtin of one pest (cucumber beetle) early in the season. Fruit maturity was delayed in untreated plots, consistent with light insect pressure observed. These results indicate that an organically based insect control approach will not alter bloom acceptance and bee forager activity in cantaloupes.

Short-term calcitriol administration improves calcium homeostasis in adults with cystic fibrosis.

Osteoporosis is a well-defined health risk in cystic fibrosis (CF) patients due to many factors. Vitamin D insufficiency, despite routine cholecalciferol supplementation in CF patients, may contribute to a relative secondary hyperparathyroidism and possibly deficient bone mineralization. An alternate form of vitamin D, calcitriol, was studied to determine short-term effects on fractional calcium absorption and other calciotropic markers in 10 adult CF subjects and in 10 age-, sex- and body mass index (BMI)-matched controls. Serum fractional absorption of (45)Ca was determined after a calcium-containing meal prior to calcitriol intervention. Other measurements included serum parathyroid hormone (PTH), ionized calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and urinary calcium:creatinine and N-telopeptide (NTx) concentrations. Both groups were then given calcitriol (0.5 micro g p.o. b.i.d. for 14 days) and restudied following the same protocol. Both groups increased their fractional absorption of (45)Ca after calcitriol ( p=0.015 CF subjects, p=0.001 controls), although calcitriol tended to be less effective in the CF group compared with the controls ( p=0.055). Post-prandial serum PTH concentrations were suppressed compared with baseline in both groups ( p=0.03 CF subjects, p=0.006 controls). Urinary NTx concentrations, a marker for bone resorption, decreased significantly in CF subjects after calcitriol (96.0+/-16.0 vs 63.9+/-12.7 nmol BCE/mmol Cr, p=0.01) and remained unchanged in the control group. The controls had an increase in serum 1,25(OH)(2)D concentrations (69.9+/-4.2 vs 90.7+/-9.6 pmol/l, p=0.02) while there was no significant change in the CF group. Oral calcitriol administration appears to improve markers of calcium balance in adults with CF by increasing fractional absorption of (45)Ca and lowering PTH concentrations, similar to its known effects in healthy subjects, while also suppressing urinary NTx, a marker of bone turnover.

Calcium homeostasis and bone surface proteins, a postulated vital process for plasma calcium control.

This report is a more in-depth explanation of a recently reported hypothesis for controlling the ionic calcium content of plasma and extracellular fluids (ECF). The hypothesis proposes a two-step process for returning calcium to the ECF against the established gradient continuously moving calcium from plasma to bone surfaces. The first step in this process is the predicted transfer of calcium directly from bone surfaces to the non-collagenous proteins, which are in contact with bone mineral. This calcium would be complexed to existing proteins and a portion would automatically become available for equilibration with ionic calcium in the ECF. The basis of the hypothesis is that the equilibration level helps to set the ionic calcium concentration of plasma. The gradient toward bone and the proposed two-step return occur in the ECF of bone and would be considered normal physiochemical processes. Thus, these processes are critical for mineral ion homeostasis in mammals. In this hypothesis, parathyroid hormone (PTH) is not required for the basic process. However, PTH works within the process to raise and set a precise plasma calcium concentration. The report to follow describes the process and discusses its relationship to normal and pathological conditions affecting human health.

Abnormal bone turnover in cystic fibrosis adults.

Cystic fibrosis (CF) patients often have low bone mineral density (BMD) and may suffer from fractures and kyphosis. The pathogenesis of low BMD in CF is multifactorial. To study bone metabolism, we collected fasting serum and urine from 50 clinically stable CF adults (mean age 28 years) and 53 matched controls to measure markers of bone formation and bone resorption. The CF subjects had moderate lung disease (FEV1: 46.1 +/- 18.6% predicted) and malnutrition (BMI: 20.0 +/- 3.3 kg/m2). Only 3 subjects had normal BMD. CF subjects had higher urinary N-telopeptides of type I collagen (81.0 +/- 60.0 vs 49.0 +/- 24.2 nm BCE/mmol creatinine, p = 0.0006) and free deoxypyridinoline (7.3 +/- 5.0 vs 5.3 +/- 1.9 nM/mM, p = 0.004) levels than controls. Serum osteocalcin levels were similar in the two groups, a result confirmed by two immunoassays that recognize different epitopes on osteocalcin. Serum bone-specific alkaline phosphatase levels were elevated in CF patients (32.0 +/- 11.3 vs 21.8 +/- 7.0 U/l, p < 0.0001), but were much more closely associated with serum total alkaline phosphatase levels (r = 0.51, p = 0.001) than with age or gender. Parathyroid hormone levels were elevated (p = 0.007) and 25-hydroxyvitamin D levels were depressed (p = 0.0002) in the CF patients in comparison with controls. These results indicate that adults with CF have increased bone resorption with little change in bone formation. Medications that decrease bone resorption or improve calcium homeostasis may be effective therapies for CF bone disease.

The effect of NKISK on tendon in an in vivo model.

The mechanism through which ligaments and tendons change length during growth and contracture is unclear. It has been hypothesized that there is a reversible "interfibrillar bond" that, when broken, allows the sliding of collagen fibrils past one another during length changes. The pentapeptide NKISK has been reported to inhibit the binding of decorin to fibronectin. This study was designed to evaluate the effect of NKISK in an in vivo model. Male Sprague-Dawley rats were divided into three groups (n = 9, 9 and 14, respectively). The left patellar tendon was injected with 1.0 ml of NKISK (Group 1 = 1.0 mM, Groups 2 and 3 = 5.0 mM). The contralateral/control limb was injected with carrier. Group 1 was sacrificed after three, Group 2 after four and Group 3 after seven daily injections. The patellar tendon lengths were measured in all groups with comparisons made to the contralateral control limb. NKISK injection resulted in a significant increase in length in Group 2 (3.14% +/- 2.04, P = 0.002) and in Group 3 (6.12% +/- 3.84, P < 0.001). Biomechanical testing of Group 3 showed no differences in maximum load, ultimate strength, structural stiffness, or elastic modulus of the treated tendons but did demonstrate a statistically significant decrease in the displacement and strain at maximum load in the NKISK-treated tendons. This study demonstrates that inhibition of decorin/fibronectin binding by NKISK results in tendon lengthening in an in vivo setting as noted by a progressive increase in the length of the patellar tendon.

Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis patients.

BACKGROUND: Osteoporosis diminishes the quality of life in adults with cystic fibrosis (CF). Vitamin D deficiency resulting from malabsorption may be a factor in the etiology of low bone mineral density (BMD) in patients with CF. OBJECTIVE: Absorption of oral ergocalciferol (vitamin D2) and the consequent response of 25-hydroxyvitamin D in 10 adults with CF and exocrine pancreatic insufficiency was compared with that of 10 healthy control subjects. DESIGN: In this pharmacokinetic study, CF patients and control subjects were pair-matched on age, sex, and race. Each subject consumed 2500 microg oral vitamin D2 with a meal. The CF group also took pancreatic enzymes that provided > or = 80000 U lipase. Blood samples were obtained at baseline and at 5, 10, 24, 30, and 36 h after vitamin D2 consumption to measure serum vitamin D2 and 25-hydroxyvitamin D concentrations. RESULTS: Vitamin D2 concentrations in all subjects were near zero at baseline. CF patients absorbed less than one-half the amount of oral vitamin D2 that was absorbed by control subjects (P < 0.001). Absorption by the CF patients varied greatly; 2 patients absorbed virtually no vitamin D2. The rise in 25-hydroxyvitamin D in response to vitamin D2 absorption was significantly lower over time in the CF group than in the control group (P = 0.0012). CONCLUSIONS: Vitamin D2 absorption was significantly lower in CF patients than in control subjects. These results may help explain the etiology of vitamin D deficiency in CF patients, which may contribute to their low BMD.

Selective drug resistant human osteosarcoma cell lines.

Chemotherapy in combination with surgery has been shown to be effective for the control of osteosarcoma. Development of resistance to chemotherapeutic agents is a recurring clinical problem. To investigate this phenomena, human osteosarcoma cells, TE-85, were exposed to increasing doses of Taxol or Taxotere during a 9-month period. Highly resistant subclones (TE-85TXL; TE-85TXR, respectively) were developed. Chemosensitivities are presented for TE-85 cell line and these new lines to Taxol, Taxotere, doxorubicin, cisplatin, and topotecan. Drug concentrations that inhibited cell growth by 50% compared with untreated cells were determined. The TE-85TXL cells showed resistance greater than 1,000-fold to Taxol and Taxotere and 60-fold to doxorubicin. The TE-85TXR cells showed resistance greater than 1,000-fold to Taxol, 800-fold to Taxotere, and 90-fold to doxorubicin. There was little cross resistance to topotecan and enhanced sensitivity to cisplatin. The role of P-170 glycoprotein in Taxol and Taxotere resistance was explored. Coincubation with verapamil, to block the actions of P-170 glycoprotein, partly reversed resistance to Taxol, Taxotere, and doxorubicin in both cell lines. Anti-P-170 glycoprotein antibodies revealed positive staining in TE-85TXL and TE-85TXR cell lines. Flow cytometry revealed reduced accumulation of doxorubicin in resistant cells. These data indicate that a human osteosarcoma cell line will develop resistance to Taxol and Taxotere, which is mediated in part by the P-170 glycoprotein.

Cartilaginous extracellular matrix of failed massive osteoarticular allografts.

Osteoarticular defects present a reparative challenge to orthopaedic surgeons. Osteoarticular allografts provided a promising solution. Unfortunately, many of these allografts failed secondary to articular cartilage degeneration. To determine the role of the extracellular matrix in graft failure, the authors have characterized the proteoglycan content of cartilage from grafts that failed early (2-4 years) and grafts that failed late (approximately 8 years) and compared this with normal cartilage. Cartilage was removed from all specimens. Proteoglycans were extracted and characterized based on molecular size and reactivity with antibodies. Protein and proteoglycan contents of early and late failure grafts were significantly lower per gram of tissue than normal cartilage. Patterns of distribution of associated proteoglycans and dissociated proteoglycans differed between early and later failure grafts and both were different from normal cartilage. Early failure cartilage contained less keratan sulfate proteoglycan with a different distribution of molecular sizes. Chondroitin sulfate epitopes showed discordance between early failure and normal cartilage and concordance between normal and late failure cartilage. These data show distinct differences in proteoglycan content between failed graft and normal cartilage and also between cartilage from grafts that failed early and late. Proteoglycan content and glycosaminoglycan substitution were altered in all specimens. Maintenance of a more normal extracellular matrix will be required to preserve function in these grafts for longer periods.

Calcitonin, an enigmatic hormone: does it have a function?

This editorial presents our view of the status of thyroidal calcitonin (TCT) in mammalian physiology. The discovery of calcitonin (CT) enabled the development of a valuable therapeutic agent but the early experiments most likely misled us with regard to its physiological significance. These early purported roles for TCT, first as an agent important in blood calcium regulation and later as an agent to prevent hypercalcemia, are no longer considered as physiological functions. While large supraphysiological doses of CT have an effect on the morphology and function of osteoclasts, it is unlikely that these effects of CT are important in the normal physiology of osteoclasts or bone remodeling. It is surprising that 38 years after the discovery of TCT there is no consensus as to its role in normal mammalian physiology. This editorial concerns three possibilities with respect to TCT: 1) the hormone is vestigial; 2) the hormone plays a role in water metabolism, ionic concentrations, and/or acid-base balance, actions that may not involve calcium metabolism at all; and 3) TCT acts to store phosphate postprandially on bone surfaces as a labile calcium-phosphate colloid, an action that may provide calcium needed for use in non-feeding periods or to reduce postprandial loss of phosphate when dietary phosphate is limited. Also discussed are recent publications indicating that CT synthesized in non-thyroidal tissues (NTCT) may have paracrine actions.

Adverse alterations in bone metabolism are associated with lung infection in adults with cystic fibrosis.

Low bone density, fractures, and kyphosis complicate the lives of adults with cystic fibrosis (CF), and inflammatory cytokines (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha) that may alter bone metabolism have been previously found to be increased in the lungs and serum of CF patients. The objective of this prospective study was to determine the impact of lung infection on bone physiology in 17 adult CF patients. Serum osteocalcin, a marker of bone formation; urine N-telopeptides of type I collagen and free deoxypyridinoline, both of which are markers of bone breakdown; serum cytokines (TNF-alpha, IL-1beta, and IL-6); and general inflammatory markers (serum C-reactive protein [CRP] and chondrex) were measured at the beginning and end of treatment for an acute exacerbation of lung infection and again 3 wk later. After treatment with conventional antibiotics, decreases in N-telopeptides (147.3 +/- 77.5 [mean +/- SEM] versus 95.5 +/- 57.3 bone collagen equivalents (BCE)/mmol creatinine, p = 0.0014), deoxypyridinoline (8.42 +/- 2.8 versus 6.8 +/- 3.0 mmol/mmol creatinine, p = 0.08), IL-1beta (1.43 +/- 1.13 versus 0.65 +/- 0.63 pg/ml, p = 0.03), IL-6 (9.5 +/- 6.5 versus 4.7 +/- 3.2 pg/ml, p = 0. 012), CRP (43.1 +/- 29.3 versus 23.4 +/- 25.3 mg/ml, p = 0.04), and chondrex (151.7 +/- 111.7 versus 101.4 +/- 67.3 ng/ml, p = 0.014), and increases in osteocalcin levels (14.5 +/- 5.4 versus 22.5 +/- 8. 7 ng/ml, p = 0.010) were observed. Three weeks later, the changes in N-telopeptides and osteocalcin persisted. These data indicate that pulmonary infection, through the elaboration of inflammatory cytokines, may be linked to increased bone resorption and diminished bone formation. These results provide insights into the impact of systemic inflammation on bone health, and suggest novel mechanisms for bone disease in CF.

Relation between empathy and aggression and behavior compliance among abused group home youth.

Physically abused youth are often described as more aggressive and noncompliant in comparison with normal children, despite inconclusive findings regarding the nature of behavior problems among these youth. The present study investigated whether empathy would be differentially related to aggression and behavior compliance of abused youth within the natural living context of a group home environment. As predicted, results suggest a strong, positive relationship between empathy and lower rates of interpersonal aggression and a strong positive relationship between empathy and higher rates of behavior compliance. In contrast to previous studies which support the intergenerational cycle theory of abuse, the results of this study do not support the belief that abuse results in stabilized aggression and suggests that the empathetic abused child is less likely to be aggressive and noncompliant than his/her non-empathic counterpart. The implications of these results for understanding and helping abused youth are discussed.

The pentapeptide NKISK affects collagen fibril interactions in a vertebrate tissue.

The pentapeptide NKISK has been reported to inhibit the binding of decorin, a proteoglycan on the surface of collagen fibrils, to fibronectin, a tissue adhesion molecule. Because of our interest in fibril-fibril binding as it relates to changes in length of ligament or tendon (during growth or contracture), we investigated the potential of this peptide to dissociate fibrils. The peptide permitted the release of intact fibrils into suspension for examination under the electron microscope (which has not previously been possible in mature vertebrate tissues).

Efficacy of pamidronate for osteoporosis in patients with cystic fibrosis following lung transplantation.

Lung transplantation with its attendant life-long immunosuppression contributes to bone loss and its sequelae, fractures and kyphosis, in patients with lung disease, many of whom already suffer from severe osteoporosis. Patients with cystic fibrosis (CF) are one of the most severely affected groups. We conducted a controlled, randomized, nonblinded trial of pamidronate (30 mg intravenously every 3 mo) with vitamin D (800 IU/d) and calcium (1 g/d) (n = 16) compared with vitamin D and calcium alone (n = 18, the control subjects) for 2 yr in 34 patients after lung transplant to improve bone mineral density (BMD). The treatment groups were similar in age, sex, baseline T-scores, renal function, hospitalization rates, immunosuppressant levels, change in lung function, and body mass index (BMI) over the study period. The patients treated with pamidronate gained 8.8 +/- 2.5% and 8.2 +/- 3.8% in spine and femur BMD after 2 yr in comparison to control subjects, who gained, on average (+/- SD), 2.6 +/- 3.2 and 0.3 +/- 2.2%, respectively (p 0.2). Measures of bone resorption were highest immediately after lung transplant and improved with both pamidronate and time. Measures of bone formation were very poor after lung transplant, but recovered in the first post-lung transplant year irrespective of therapy. We conclude that pamidronate was more effective than control in improving bone mineral density after lung transplantation in patients with CF and appears to be one of the most promising agents studied to date for posttransplant osteoporosis.

Polyamines and their cellular anti-senescence properties in honey dew muskmelon fruit.

Activated oxygen free radicals cause peroxidative damage to all membranes and hasten senescence. Polyamines (PAs) are effective scavengers of these free radicals produced by lipoxygenase (LOX) and phospholipase-D (PL-D). Five days prior to abscission (harvest), 'Honey Brew' (Cucumis melo L. (Inodorus group)) fruit have a change in the ratio of endogenous spermidine (SPD) to putrescine (PUT), from SPD>PUT to SPD

Parathyroid hormone and plasma calcium control: an editorial.

The purpose of this report is to examine the various processes by which parathyroid hormone might control the ionic calcium concentration of plasma and extracellular fluid, and to emphasize the need for study of the maintenance of plasma calcium in the absence of the parathyroid glands. The report discusses mechanisms to explain the control of extracellular calcium and proposes new approaches to the study of calcium homeostasis.

Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk.

OBJECTIVE: To determine if blood levels of 25-hydroxyvitamin D (25-D) or its active metabolite, 1,25-dihydroxyvitamin D (1,25-D), are lower in women at the time of first diagnosis of breast cancer than in comparable women without breast cancer. DESIGN: This was a clinic-based case-control study with controls frequency-matched to cases on race, age, clinic and month of blood drawing. SETTING: University-based breast referral clinics. SUBJECTS: One hundred and fifty-six women with histologically documented adenocarcinoma of the breast and 184 breast clinic controls. RESULTS: There were significant mean differences in 1,25-D levels (pmol ml(-1)) between breast cancer cases and controls; white cases had lower 1,25-D levels than white controls (mean difference +/-SE: -11.08+/-0.76), and black cases had higher 1.25-D levels than black controls (mean difference +/-SE: 4.54+/-2.14), although the number of black women in the study was small. After adjustment for age, assay batch, month of blood draw, clinic and sample storage time, the odds ratio (95% confidence interval, CI) for lowest relative to highest quartile was 5.2 (95% CI 2.1, 12.8) for white cases and controls. The association in white women was stronger in women above the median age of 54 than in younger women, 4.7 (95% CI 2.1, 10.2) vs. 1.5 (95% CI 0.7, 3.0). There were no case-control differences in 25-D levels in either group. CONCLUSIONS: These data are consistent with a protective effect of 1,25-D for breast cancer in white women.

Altered calcium homeostasis in adults with cystic fibrosis.

Bone mineral density (BMD) in cystic fibrosis (CF) patients falls progressively below normal with advancing age, in part due to steroid administration, low levels of sex hormones, chronic inflammatory disease, physical inactivity, and chronic malabsorption of calcium and/or vitamin D. The purpose of this study was to compare the fractional absorption of (45)Ca and urinary excretion of calcium in CF subjects and normal controls following a high-calcium breakfast containing (45)Ca. Seven young men and 5 young women with CF with pancreatic insufficiency were studied on two separate occasions, with and without administration of pancreatic enzymes. Eleven healthy young adults with normal BMD measurements served as controls. Mean T-scores at the lumbar spine and femur were significantly lower in the CF subjects (p<0.002). Following baseline, fasting collections, timed serum and urine samples were obtained for 5 h after the meal. Fractional absorption (FA) of (45)Ca was estimated by the method of Marshall and Nordin. At baseline, CF subjects had lower mean serum 25-hydroxyvitamin D, calcium and albumin values (p<0.03 for each), slightly, but not significantly (p = 0.12), lower albumin-corrected calcium values, equivalent serum 1, 25-dihydroxyvitamin D values and a trend toward a higher mean serum parathyroid hormone (PTH) value (p = 0.10). Without pancreatic enzymes, CF subjects showed significantly impaired calcium absorption (5 h FA: 11.8 +/- 0.5 for controls vs 8.9 +/- 0.2 for CF subjects, p = 0.02) and excretion (4 h excretion: 0.20 +/- 0.08 mg Ca/mg creatinine for controls vs 0.16 +/- 0.09 mg Ca/mg for CF subjects, p = 0.025). Addition of pancreatic enzymes did not fully compensate for this deficiency. In addition, CF patients had higher serum PTH values after a high-calcium meal (p = 0.03), suggesting mild secondary hyperparathyroidism. Altered calcium homeostasis is likely to be a factor in the development of bone disease in CF patients.

Collagen fiber sliding during ligament growth and contracture.

It is hypothesized that the sliding of collagen fibers past one another plays an important role in changes of ligament length during growth or contracture. To explore this possibility, we used the fluorescent dye dichlorotriazinyl fluorescein to stain collagen fibers perpendicular to their orientation in a rat medial collateral ligament model. Growth, contracture, and control models (with rats weighing 50-75 g in the first and 500-600 g in the latter two groups) were studied. In the contracture model, the medial collateral ligament was transected distally. Marking sutures were used to verify the presence of growth or contracture in each medial collateral ligament. Fluorescence photomicrography after 2 weeks demonstrated stained collagen fibers protruding from either side of the original mark as one would expect, in either growth or contracture, if the fibers slid past one another and away from their initial location during changes in length. By measuring the initial and final widths of the growth and contracture model marks and correlating them to controls that had minimal growth (rats grow throughout their life) and were free of contracture, we have provided evidence that collagen sliding plays a significant role in changes in ligament length.

Effect of ciprofloxacin on the proliferation of osteoblast-like MG-63 human osteosarcoma cells in vitro.

Locally applied antibiotic therapy is gaining popularity for the treatment of infections associated with open fractures and posttraumatic osteomyelitis. With use of local techniques, ciprofloxacin levels as high as 1,300 microg/ml, or over 200 times the bone levels achieved with intravenous administration, have been reported. To study the possible effects of ciprofloxacin on bone, osteoblast-like cells from the MG-63 human osteosarcoma cell line were studied. The cells were grown in antibiotic-free media and exposed to concentrations of ciprofloxacin at 0, 10, 100, 200, and 1,000 microg/ml to establish an initial dose-response curve. Media containing the appropriate dose of ciprofloxacin were changed every 24 hours. Cell number and [3H]thymidine incorporation per cell were determined at 0, 24, and 72 hours. A second dose-response curve was performed at concentrations of 0, 10, 20, 40, and 80 microg/ml. Three experiments, each with four observations, were performed. The results of this study demonstrated that ciprofloxacin caused significant decreases (p < 0.05) in cell number at 40 microg/ml at 24 hours and 20 microg/ml at 72 hours. [3H]thymidine incorporation per cell decreased significantly at levels of 80 microg/ml at 24 hours and 20 microg/ml at 72 hours. The authors conclude that reported local levels of ciprofloxacin seen in vivo inhibit the proliferation of human osteoblast-like cells in vitro.