Analysis of bone loss with aging and menopause--using digital image processing

To study bone loss relationships to aging and menopause, cross-sectional bone mass measurements by digital image processing (DIP method), and menopause information collected by questionnaire, were analyzed on 291 women who live in Tsukude village. The results are as follows. 1) The mean DIP values (sigma GS/D, MCI) by age-stratified groups decrease with age after menopause. The rate of bone loss in sigma GS/D is almost constant, but in MCI it increases with aging. 2) In 30-year old and 40-year old age groups, the frequency distribution of DIP values is symmetrical and bell-shaped. But after the fifties the distribution is asymmetrical, with the mode of distribution deviated toward low bone mass. The change of mode with aging is larger than that of mean. This fact suggests that change of mean bone mass substantially underestimates actual bone loss from aging. 3) The change of the mean DIP values stratified by years elapsed since menopause is not especially large at start of menopause but becomes almost constant after menopause. DIP values reflect the bone loss from the aging rather than from menopause, and are beneficial to the study of bone loss in elderly women.     

Effect of prepartum bovine somatotropin in primigravid ewes on mammogenesis, milk production, and hormone concentrations

Twenty-five primigravid ewes were used to investigate the effect of bST, between 97 and 124 d of gestation, on mammogenesis and subsequent milk production. Five ewes (reference group) were slaughtered at 96 d of gestation, and the remaining ewes were injected daily with saline (control group: n = 10) or .1 mg/kg of BW of bST (bST group: n = 10). Following bST treatment, 5 control and 5 bST group ewes were slaughtered (slaughter group). The remaining ewes were slaughtered after lambing and being milked for 8 wk (production group). Weekly blood samples were obtained from both slaughter and production group ewes. Slaughter group ewes were also subjected to 8-h serial blood sampling at 98 d (period 1) and 123 d (period 2) of gestation. Milk production was 42% higher in ewes treated prepartum with bST than in those treated with saline. Results suggest that the increase in milk was due to an increase in mammary parenchymal cell number rather than to an increase in cellular activity. The high rate of [3H]thymidine incorporation into parenchymal tissue in reference group ewes suggests that the increase in parenchyma during the second trimester of gestation is due to cellular hyperplasia but that cellular hypertrophy may be more important during the last trimester. Plasma IGF-I concentrations were significantly higher during bST treatment and remained elevated between daily injections; the increase was greatest in period 2.     

Diagnosis of childhood BK virus cystitis by electron microscopy and PCR

A case of BK virus cystitis in a 5 year old boy is reported. This patient, who was not immunocompromised, had had acute cystitis for two weeks. Many intracytoplasmic inclusions were observed in urinary sediment smears stained by the Papanicolaou method. Electron microscopic examination showed virus particles, presumed to be human polyomavirus, in the nuclei of the degenerated urothelial cells. A DNA sequence of the BK virus was detected in 200-300 urothelial cells in Papanicolaou stained smears by the polymerase chain reaction. BK virus is an unusual cause of symptomatic cystitis in a healthy child.     

The levels of integrin alpha v beta 5 may predict the susceptibility to adenovirus-mediated gene transfer in human lung cancer cells

Adenovirus mediated transfer of growth-inhibiting molecules, such as p53 shows promise as an effective method of suppressing the growth of cancer cells. As the basis for in vivo studies, we examined transfection efficiency using 15 human lung cancer cell lines that differ in their endogenous p53 status. When infected with an adenovirus expressing bacterial beta-galactosidase, the different cell lines showed different levels of beta-galactosidase activity. We found a correlation between the level of integrin alpha v beta 5, which is thought to be an adherence receptor for adenoviruses, and the expression level of the transferred gene, suggesting that gene expression is largely dependent on the infection efficiency. Growth inhibition was induced in all cell lines tested following infection with an adenovirus containing p53, regardless of the genetic status of their endogenous p53 provided a sufficient amount of p53 protein was expressed. Our results (1) confirm that the examination of the susceptibility of target cancer cells to an adenovirus is important when considering performing adenovirus-mediated gene transfer and for evaluating its therapeutic effects; and (2) suggest that the quantification of integrin alpha v beta 5 may be a good way of predicting the susceptibility of cells to adenoviral vectors.     

Biotransformation and toxicity of the lipoxygenase inhibitor 2-hydroxy-5-methyllaurophenone oxime (FLM 5011) on Hep G2 cells

2-Hydroxy-5-methyllaurophenone oxime (FLM 5011) is an inhibitor of lipoxygenase with antiinflammatory and antiallergic actions. We incubated FLM 5011 on the human immortal cell line Hep G2 and found a similar metabolite spectrum as in rat urine and faeces. We also measured the cytotoxicity of FLM 5011 on Hep G2 monolayers by the amido black assay and found that the influence of cell proliferation is partly due to apoptotic activities. Although the metabolic activity of Hep G2 cells is lower compared to rat hepatocyte cultures they are a suitable test system for biotransformation studies. Their higher proliferation rate allows toxicity to be characterised more exactly.     

Familial idiopathic intracranial hypertension with spinal and radicular pain

OBJECTIVE: To describe a mother and her 2 sons affected by idiopathic intracranial hypertension (IIH), associated in the sons with root irritation symptom. Unlike the other 4 families reported previously, obesity was not present in our patients. DESIGN: Case reports. SETTING: Department of pediatrics in a university school of Medicine, Naples, Italy. PATIENTS: A mother (aged 36 years) and her 2 sons (aged 14 and 9 years) developed IIH at different times. Neuroimaging showed an empty sella in the mother, while IIH was associated with spinal and radicular pain in her 2 sons. The mother and the younger son developed permanent visual loss. CONCLUSIONS: Ophthalmologic follow-up in our patients indicates that IIH is a chronic disease. Surgical treatment should be considered an option.     

Increase of striatal dopamine release by cadmium in nursing rats and its prevention by dexamethasone-induced metallothionein

Repeated daily intraperitoneal (i.p.) administrations of cadmium (CdCl2, 1 mg/kg per day for 5 days) increased striatal dopamine (DA) release (180% of controls) and turnover (150% of controls) in 13-day-old rats. Cd treatment also increased striatal metallothionein (MT) content (161%), Cd (127%) and lipid peroxidation (LPO, 190%). In addition, Cd treatment decreased striatal tyrosine hydroxylase (TH) activity (-28%), and such an effect may result from D-2 receptor blockade as a consequence of excessive dopamine release, since sulpiride (a specific D-2 receptor antagonist) administration to Cd-treated rats abolished the effect of Cd on TH. No effect was observed on striatal monoamine oxidase (MAO) activity. Dexamethasone (Dx) treatment increased striatal MT content and caused no effect on either DA release or turnover. However, Dx administration prevented the effects caused by Cd, including the increased DA release and enhanced striatal lipid peroxidation. These results indicate that toxic effects on the brain are to be expected as a result of Cd exposure and that Dx administration can attenuate them.     

Percutaneous transluminal angioplasty of an innominate artery occlusion

A middle-aged woman presented with recent-onset left hemiparesis and right subclavian steal syndrome. She was found to have an obstructed innominate artery. We successfully performed balloon angioplasty of the occluded innominate artery and encountered no complications during follow-up of currently 8 months.     

Heterochromatin effects on the frequency and duration of LCR-mediated gene transcription

Organ transplantation is associated with an early bone loss that subsequently increases the risk of osteopenia and bone fractures. It is not known whether bone loss continues in long-term survivors, but persistent bone demineralization could further jeopardize an already diminished bone mass. To better define long-term bone status of kidney transplant recipients (KTR), we conducted cross-sectional and longitudinal evaluations of bone mineral density (BMD) in 70 KTR with a mean posttransplantation time of 8.1 years. BMD was determined by dual-energy X-ray absorptiometry and was repeated in 55 of the patients after a mean follow-up period of 22 +/- 5 months. Lumbar and femoral osteopenia, defined as a BMD lower than 2 standard deviations from mean value of sex- and age-matched controls, was present in 28.6% and 10.5% of patients, respectively. There was a significant negative correlation between cumulative prednisone dose and adjusted lumbar as well as femoral BMD (R = 0.45, P < 0.001 and R = 0.29, P < 0.05, respectively). Five patients had a vertebral BMD below a fracture threshold of 0.777 g/cm2. Vertebral fractures (VF) were found in four men and were associated with higher prednisone dosage (P < 0.05), larger cumulative prednisone dose (P < 0.05), and significantly lower BMD values. According to World Health Organization recent criteria for women, prevalences of lumbar and femoral osteopenia and lumbar and femoral osteoporosis in female patients reach 75%, 65%, 33%, and 10%, respectively. The longitudinal part of the study showed a persistent pathological lumbar demineralization process. Over the study period, BMD, expressed as a percentage of that of controls, decreased from 89 +/- 14% to 86 +/- 14% (P < 0.001). Annual change of bone mass was -1.7 +/- 2.8% per year. Accelerated vertebral bone loss (defined as a decrease of BMD, expressed as a percentage of that of controls, of more than 1% per year) was present in 56% of patients and was associated with higher prednisone dosage (P < 0.01). In conclusion, although VF are relatively infrequent in long-term survivors of renal transplantation, osteopenia is a frequent finding, and a substantial proportion of women present lumbar osteoporosis. An ongoing demineralization process of the spine is also demonstrated and probably contributes to long-term spinal osteoporosis incidence. Prednisone dosage remains the most constantly isolated risk factor.     

Systemic aluminum toxicity: effects on bone, hematopoietic tissue, and kidney

Although the full mechanisms are not yet elucidated, research into the mechanism of toxicity of aluminum (Al) on bone formation and remodeling and on hematopoietic tissue is ongoing. In contrast little information exists on the interactive effects of systemic Al and the kidney. In bone, both clinically and experimentally, high doses of Al inhibit remodeling, slowing both osteoblast and osteoclast activities and producing osteomalacia and adynamic bone disease. In contrast, while very low levels of Al are mitogenic in bones of experimental animals, the effect of low levels of Al in humans is unknown. Aluminum has been shown to have its mitogenic action at the osteoblast, but whether the effect on resorption is viz osteoblast-directed changes in osteoclast activity has not yet been determined. Parathyroid hormone (PTH) levels are disrupted by Al in humans and animals. Whether altered PTH levels play a major or even a minor role in Al-dependent osteotoxicity requires clarification. In hematopoietic tissue, Al causes a microcytic anemia, not reversible by iron. Friend leukemia cells treated with Al have been reported to accumulate excess iron, without incorporating it into ferritin or heme. It is not yet known which steps in iron metabolism are disrupted by Al, if they involve a single mechanism of action, or even if this disruption in iron metabolism accounts for the anemia seen in Al toxicosis. In kidney, research is needed to evaluate Al nephrotoxicity; there are almost no studies in this area. Furthermore, research is needed to evaluate mechanisms of renal Al excretion, presently shown by one study to occur at the distal tubule. Such studies might well throw light on whether Al plays a role in aggravating renal insufficiency, or whether the role of the kidney in Al toxicosis is limited to the causative effect of renal compromise on Al accumulation. In summary, while a number of mechanisms have been proposed for the toxic action of Al, no single mechanism emerges to explain these diverse effects of systemic Al. Recommendations for future research are presented and summarized in Table 1.