Treatment of established osteoporosis with 1α (OH) vitamin D3 and low dose intermittent elcatonin (eel calcitonin derivative)

In addition to estrogen widely used all over the world for the prevention of postmenopausal osteoporosis, calcitonin and vitamin D derivatives are commonly employed to treat established osteoporosis at higher age in Japan. In order to critically assess the usefulness of vitamin D derivatives and calcitonin alone or in combination on the advancement of vertebral deformity at higher age, 32 osteoporotic patients with vertebral deformity with the mean age of 79 were randomly divided into 4 groups with indistinguishable age and severity of the vertebral deformity. Group 1 served as the control without specific medications for osteoporosis. Group 2 was treated with 10 units elcatonin (eel calcitonin derivative) injected intramuscularly twice a week. Group 3 was given 0.75 to 1.5μg/day 1α (OH) vitamin D₃ orally. Group 4 was given a combination of treatments used in Groups 2 and 3. In the lateral X-ray film of the spine taken prior to the test and every 6 months thereafter, the shape of the vertebral body T₈ through L₄ was monitored by measuring the anterior, central and posterior heights. Decrease of the vertebral height ratio; anterior or middle height/posterior or adjacent intact posterior height, by more than 20% of the original value or from above to below 0.80 both appeared to be inhibited during administration of 1α (OH) vitamin D₃. Such effect seems to be augmented by simultaneous administration of elcatonin. Actual decrease of vertebral height ratio values and the per cent fall from the original value significantly less in Groups 3 and 4 than in Group 1. Development of vertebral deformity assessed by the changes of the vertebral height thus appears to decrease during treatment with 1α (OH) vitamin D₃ especially together with calcitonin in established osteoporosis.     

亚硝酸钠与AFB1相互作用对遗传物质影响的实验研究

以正常人外周血淋巴细胞的ＳＣＥ率作为细胞遗传学指标，研究了Ｎａ＿２ＳｅＯ＿３与ＡＦＢ＿１相互作用对细胞遗传物质的影响。结果表明，一定浓度的Ｎａ＿２ＳｅＯ＿３（１０￣（－５）ｍｏｌ）对ＡＦＢ＿１所诱发的ＳＣＥ有明显的抑制作用，但当浓度达到１０￣（－２）ｍｏｌ时，细胞增殖受到抑制，到１０￣（－１）ｍｏｌ时细胞出现毒性现象。提示Ｎａ＿２ＳｅＯ＿３具有抑变和细胞毒性双相作用。所以在Ｎａ＿２ＳｅＯ＿３与ＡＦＢ＿１相互作用的ＳＣＥ实验中应避免Ｎａ＿２ＳｅＯ＿３的浓度过高而损伤培养的细胞。     

Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.

Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.     

Breast Cancer Genes

Abstract: The identification of familial breast cancer genes heralds an era of directed breast cancer treatment. Currently, two hereditary breast cancer genes have been identified, BRCA-1 and BRCA-2 . Although accounting for only approximately 5% of all breast cancers, they are being used to identify women with germ-line alterations that are at high risk of developing breast or ovarian cancer. With the identification of such genes comes a need for consideration of the ethical issues associated with testing. These genes are also being examined from a biochemical standpoint encompassing both their biological roles and biochemical pathways in which they reside. Such studies are likely to lead to novel breast cancer therapies.     

Human chronic kidney allograft rejection is accompanied by increased intraglomerular cathepsin B and L activity

Abstract The major reason for late graft losses is chronic rejection. Recently, a large number of studies have indicated that proteolytic enzymes play an important role as mediators of glomerular injury. The cysteine proteinases cathepsins B and L degrade structural matrix proteins such as type I collagen and laminin. We investigated intraglomerular protease activities in 12 patients after kidney graftectomy because of end-tage renal disease following chronic rejection. A group of 12 patients undergoing nephrectomy because of cancer served as controls using only non-involved parts of the kidney. The activities of cathepsins B and L in homogenates of isolated glomeruli were measured fluorometrically methylcoumarylamidc substrates and related to DNA content. In rejected kidney allografts we observed significantly enhanced intraglomerular cathepsin B activity and cathepsin B + L activity.     

E1 Tor霍乱弧菌SM_6和江苏1d菌株

ＳＭ６是我国检测Ｅ１Ｔｏｒ霍乱弧菌是否带有溶源性噬菌体的指示菌株。江苏的６株Ｅ１Ｔｏｒ霍乱弧菌和ＳＭ６都属于噬菌体－生物分型的１ｄ型，而在噬菌体分型中ＳＭ６为１／２型，江苏的６株菌株则为１／２／３型；霍乱毒素（ＣＴ）基因测定也表明两者的不同，ＳＭ６不含ＣＴ基因，江苏的６株都含有ＣＴ基因，显示噬菌体分型可将噬菌体－生物分型的型别进一步划分，ＳＭ６的特性也为霍乱的进一步研究提供了资料。     

Evidence for differential effects of 8-OH-DPAT on male and female rats in the Anxiety/Defense Test Battery

The Proxemics/Activity test and the Eat/Drink test, two components of the Anxiety/Defense Test Battery, were developed to measure defensive reactions to situations associated with a natural predator (cat). In the present studies the behavioral effects of 8-OH-DPAT treatment (0.01–1.0 mg/kg, SC) were entirely consistent with anxiety/fear reduction. These effects included an increase in time spent near the cat compartment, and a complimentary decrease in time spent farthest from this compartment, together with an increase in transits and locomote behavior. 8-OH-DPAT (1.0 mg/kg) also increased eat frequencies and durations (highly preferred food) both during and following cat presentation, without influencing drinking. This finding is discussed with reference to previous findings with 8-OH-DPAT in studies assessing both food intake and anxiolysis. Interestingly, 8-OH-DPAT was more potent in a majority of its effects in female subjects, a finding consistent with recent neurochemical data. These findings provide important behavioral evidence for a sexual differentiation in 5-HT function, and support the case for greater emphasis on female subjects in animal models of anxiety.Supported by NIH MH42803 and RCMI Grants RR03061 and RR01825     

Localization and characterization of epidermal growth-factor receptors in the developing rat medial septal area in culture

The presence and binding properties of epidermal growth-factor receptors (EGF-Rs) in different cell types purified from the rat medial septal area in culture were investigated. We report that astrocytes, oligodendrocytes and neurons from this area possess EGF-Rs while microglia do not. EGF-binding sites are detectable on astrocytes derived from the medial septum of both embryonic and neonatal rats. Scatchard analysis of the data for astrocytes from the fetal rats show that EGF specifically binds to both high- (K_d = 7.21 × 10⁻¹⁰ M, B_max = 3602 receptors/cell) and low-affinity (K_d = 3.99 × 10⁻⁸ 10⁻⁸ M, B_max = 6,265 receptors/cell) receptors on these cells. On the other hand, astrocytes purified from neonatal tissue possess a greater number of high-affinity receptors (B_max = 10,938 receptors/cell) when compared with the embryonic astroglia. With time in culture, the number of both types of receptors on neonatal astrocytes decreases. Oligodendrocytes also possess high- and low-affinity EGF-Rs with dissociation constants of 3.25 × 10⁻¹⁰ M and 3.85 × 10⁻⁸ M, respectively. The number of receptors on oligodendrocytes is significantly lower than those on neonatal astrocytes (B_max = 1185 and 25,081 receptors/cell for high- and low-affinity binding sites, respectively). Finally, neurons from this area also exhibit two different EGF-R types with dissociation constants similar to those described for astrocytes. As the number of receptors/neuron (B_max = 136 and 1159 receptors/cell for high- and low-affinity binding sites, respectively) appears to be extremely low, it is possible that EGF specifically binds only to a subpopulation of neurons from this area. These studies demonstrate which cell types in the developing medial sepal area posses EGF-Rs and provide a detailed characterization of these binding sites. These EGF-R-bearing cells may be potential targets for this growth factor or for transforming growth factor α in this brain area.     

5-Hydroxytryptamine increases excitability of CA1 hippocampal pyramidal cells.

In the presence of spiperone to block the 5-HT1A-mediated inhibition of pyramidal cell activity, 5-hydroxytryptamine (serotonin, 5-HT) produces a rapid transient increase in amplitude of the extracellularly recorded population spike from area CA1 of the hippocampus. Intracellular recording techniques in area CA1 of rat hippocampal slices were used to identify the ionic mechanism and to characterize the 5-HT receptor mediating this excitatory response to 5-HT. Most of the experiments were conducted in the presence of spiperone to block the 5HT1A hyperpolarization. Since spiperone also has high affinity for 5-HT2 receptors, any response mediated by 5-HT2 receptors would also be blocked. Bath perfusion of the slice with 5-HT increased the rectification of pyramidal cells in the subthreshold region, increased the resistance, and increased the amplitude of subthreshold excitatory postsynaptic potentials (EPSPs) to initiate spike firing. The 5-HT2,1C-selective agonist DOI mimicked this effect of 5-HT, and the 5-HT2,1C antagonist ketanserin (1 microM) blocked the effect of DOI. There was no change in the amplitude of the slow afterhyperpolarization (sAHP) or the amplitude of evoked inhibitory postsynaptic potentials (IPSPs). The increase in rectification and EPSP amplitude by 5-HT occurred even in the presence of the 5-HT4-selective antagonist BRL 24924 to prevent the decrease in amplitude of the sAHP by 5-HT. We conclude that 5-HT produces a fast excitatory response by increasing subthreshold conductance in CA1 hippocampal pyramidal cells. The identity of the receptor mediating this response was not conclusively identified, but resembled the 5-HT1C receptor.