Anabolic effect of genistein and genistin on bone metabolism in the femoral-metaphyseal tissues of elderly rats: the genistein effect is enhanced by zinc

The effect of genistein and genistin on bone components in the femoral-metaphyseal tissues obtained from elderly female rats was investigated in vitro. The metaphyseal tissues were cultured for 24 h in a medium containing either vehicle, genistein (10(-8)-10(-5) M) or genistin (10(-7)-10(-5) M). The presence of genistein or genistin caused a significant increase in alkaline phosphatase activity, deoxyribonucleic acid (DNA) and calcium contents in the metaphyseal tissues. The effect of genistein was greater than that of genistin. The bone components increased by genistein (10(-5) M) or genistin (10(-5) M) were completely blocked by the presence of cycloheximide (10(-6) M). The presence of zinc sulfate (10(-5) M) caused a significant increase in the genistein (10(-5) M)-elevated alkaline phosphatase activity, DNA and calcium contents. The enhancement with zinc was not seen by genistin (10(-5) M). The stimulatory effect of zinc on the genistein-induced increase in bone components of the metaphyseal tissues was completely blocked by the presence of cycloheximide (10(-6) M). The present results suggest that genistein and genistin have an anabolic effect on bone metabolism in the femoral-metaphyseal tissues of elderly rats, and that the genistein effect is enhanced by zinc, an essential trace element.     

Epidemiology and detection of HIV-1 among pregnant women in the United Kingdom: results from national surveillance 1988-96

OBJECTIVE: To describe the epidemiology of HIV-1 infection in pregnant women in the United Kingdom. DESIGN: Serial unlinked serosurveillance for HIV-1 in neonatal specimens and surveillance through registers of diagnosed maternal and paediatric infections from reporting by obstetricians, paediatricians, and microbiologists. SETTING: United Kingdom, 1988-96. SUBJECTS: Pregnant women proceeding to live births and their children. MAIN OUTCOME MEASURES: Time trends in prevalence of HIV-1 seropositivity in newborn infants (as a proxy for infection in mothers); the proportions of mothers with diagnosed HIV-1 infections, and their characteristics. RESULTS: HIV-1 prevalence among mothers in London rose sixfold between 1988 and 1996 (0.19% of women tested; 1 in 520 in 1996). Apart from in Edinburgh and Dundee, levels remained low in Scotland (0.025%; 1 in 3970) and elsewhere in the United Kingdom (0.016%; 1 in 1930). Over a third of births to infected mothers in 1996 occurred outside London. In London the reported infections were predominantly among black African women, whereas in Scotland most were associated with drug injecting. The contribution of reported infection among African women increased over time as that of drug injecting declined. In Scotland 51% of mothers' infections were diagnosed before the birth. In England, despite a national policy initiative in 1992 to increase the antenatal detection rate of HIV, no improvement in detection was observed, and in 1996 only 15% of previously unrecognised HIV infections were diagnosed during pregnancy. CONCLUSIONS: HIV-1 infection affects mothers throughout the United Kingdom but is most common in London. Levels of diagnosis in pregnant women have not improved. Surveillance data can monitor effectively the impact of initiatives to reduce preventable HIV-1 infections in children.     

Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a double-blind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2.4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2.39 +/- 0.02 vs 2.32 +/- 0.02 mmol/l, P = 0.037) and phosphate (0.97 +/- 0.06 vs 0.75 +/- 0.05 mmol/l, P = 0.011) increased and the index of phosphate excretion (0.03 +/- 0.03 vs 0.19 +/- 0.02, P < 0.001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64.8 +/- 11.8 vs 17.4 +/- 1.8 ng/ml, P < 0.001; procollagen type I carboxyterminal propeptide (PICP), 195.3 +/- 26.4 vs 124.0 +/- 15.5 ng/ml, P = 0.026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8.9 +/- 1.2 vs 3.3 +/- 0.5 ng/ml, P < 0.001; urinary hydroxyproline, 0.035 +/- 0.006 vs 0.018 +/- 0.002 mg/100 ml glomerular filtration rate, P = 0.009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306 +/- 45.3 vs 88.7 +/- 22.5 ng/ml, P < 0.001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1.194 +/- 0.058 vs 1.133 +/- 0.046 g/cm2, P = 0.015), femoral neck (1.009 +/- 0.051 vs 0.936 +/- 0.034 g/cm2, P = 0.004), Ward's triangle (0.881 +/- 0.055 vs 0.816 +/- 0.04 g/cm2, P = 0.019) and the trochanteric region (0.869 +/- 0.046 vs 0.801 +/- 0.033 g/cm2, P = 0.005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < -1.0 S.D.) increased more than in those with normal bone mass (lumbar spine 11.5 vs 2.1%, P = 0.030, and femoral neck 9.7 vs 4.2%, P = 0.055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk.     

Physiologic and clinical significance of myocardial blood flow quantitation: what is expected from these measurements in the clinical ward and in the physiology laboratory?

In this essay we review data on absolute quantitation of myocardial blood flow (MBF) in humans. Earlier work established that coronary heart disease (CAD) can be detected by coronary angiography and that this disease has characteristic features at rest and during stress, which indicate the linkage between regional metabolic needs and myocardial perfusion. In the 1970s myocardial perfusion was mapped in patients with radioxenon, but this method had significant technical limitations. About the same time, radioactive microspheres were introduced for cardiovascular research and investigations; these particles provided insights on MBF in acute infarction and ischemia, myocardial reperfusion, collateral circulation, myocardial blood flow during exercise, coronary flow reserve (CFR), and layer-to-layer distribution of MBF. Studies with microspheres also permitted investigators to establish the presence in the heart of MBF heterogeneity. Currently, there are several techniques that aim at extending these concepts into clinical investigation. Two of these techniques, i.e. Doppler coronary flow velocity and fast magnetic resonance imaging assess epicardial flow dynamics and CFR. Contrast myocardial echocardiography is another novel technique which has been useful in mapping the area at risk, reperfusion, myocardial viability and collateral circulation. This essay also considers the emerging technique of intracoronary ultrasound which has shown evidence of disease underestimation by conventional contrast angiography. Positron emission tomography (PET) is a noninvasive technique that uniquely and quantitatively maps myocardial perfusion and CFR. The latter can be computed before and after angioplasty. PET studies have further demonstrated that chronic myocardial ischemia does not exist as a distinct state in patients with CAD. From the above investigations the concept has arisen that not only is CAD an entity involving epicardial vessels but also, in a significant portion of patients, an abnormal microcirculation plays an important role in the pathogenesis of ischemic syndromes. PET studies have relatively low spatial resolution since they cannot resolve layer-to-layer absolute MBF.     

Acquisition of conditional discriminations in hippocampal lesioned and decorticated rats: Evidence for learning that is separate from both simple classical conditioning and configural learning.

This study examined whether hippocampal or neocortical lesions would impair acquisition of a discrimination task using taste aversions. Male rats were injected with a drug 15 min before a flavored solution–LiCl pairing. On alternate days, vehicle injections preceded and followed access to the same flavored solution. Ss learned to consume significantly more of the flavored solution after vehicle injections than after drug injections. Ss with hippocampal lesions or neonatal decortication performed as well as controls. Ss with hippocampal lesions also learned a similar task in which visual and textural cues predicted whether access to a flavored solution would be followed by an injection of LiCl or vehicle. However, these hippocampal lesions did impair performance in the Morris water task. Occasion setting may involve a type of learning dissociated from both simple classical conditioning and configural learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral discrimination between quinine and KCl is dependent on input from the seventh cranial nerve: implications for the functional roles of the gustatory nerves in rats

The rat glossopharyngeal nerve (GL), which innervates posterior tongue taste buds, contains several physiologically defined taste fiber types; at least one type is primarily responsive to certain alkaloids (such as quinine), and another is primarily responsive to acids and salts. In contrast, the chorda tympani (CT), which innervates anterior tongue taste buds, does not appear to contain fibers that differentially respond to quinine relative to salts and acids. It was therefore predicted that GL transection should disrupt behavioral discriminations between quinine and either acids or salts. Water-restricted rats were trained to press one of two levers if a sampled taste stimulus was quinine (0.1-1.0 mM) and the second lever if the sampled stimulus was KCl (0.1-1.0 M). Sham surgery, GL transection, and sublingual and submaxillary salivary gland extirpation were found to have no effect relative to presurgical performance. Both CT transection and combined GL and CT transection caused a substantial and approximately equal decrement in discrimination performance. Removal of the gustatory branches of the seventh cranial nerve [CT and greater superficial petrosal (GSP)] nearly eliminated the discrimination of the taste stimuli, and combined transection of the CT, GL, and GSP unequivocally reduced performance to chance levels. Although these findings were not presaged by the known electrophysiology, they nonetheless compare favorably with other studies reporting little effect of GL transection on behavioral responses to quinine. These results, in the context of other discrimination studies reported in the literature, suggest that, in rats, the neural coding of taste quality depends primarily on the input of the facial nerve.