Effects of vitamin D3 and cyclosporin A on HgCl2-induced autoimmunity in Brown Norway rats

BACKGROUND.: Mercuric chloride (HgCl₂ induces a lymphoproliferative disorderand autoimmune glomerulonephritis in Brown Norway (BN) rats.This syndrome is the consequence of T cell-dependent polyclonalB cell activation and autoantibody production. We have previouslyshown that HgCl₂-induced autoimmune perturbations can be preventedin BN rats by the administration of cyclosporin A (CsA). Themost potent vitamin D₃ metabolite 1,25(OH)₂ D₃ (Vit D₃) sharescertain immunomodulatory properties with CsA. We therefore choseto compare the effects of Vit D₃ to those of CsA in BN ratstreated with HgCl₂ in order to establish whether Vit D₃ eitheralone or in combination with CsA can attenuate an autoimmunesyndrome in vivo. METHODS.: BN rats were treated with HgCl₂ according to a standard protocol.Subgroups of rats were also given CsA alone, Vit D₃ or syntheticanalogues of Vit D₃ alone, or combinations of both agents. Differentdoses and routes of administration were compared. The followingmarkers of disease activity were evaluated: mortality, peakproteinuria, serum IgE concentrations, and renal immunoglobulindeposition. RESULTS.: Disease activity was markedly attenuated in all rats treatedwith CsA alone. Vit D₃ and certain of its synthetic analoguesadministered alone also tempered the autoimmune process, butto a lesser extent than did CsA. The effect of CsA alone wasso potent, that no additive or synergistic effects could bedemonstrated when CsA was administered in combination with VitD₃. CONCLUSIONS.: Despite similar described immunomodulatory effects in vitro,CsA is clearly more effective than Vit D₃ in preventing HgCl₂autoimmune disease in BN rats. This suggests that there is adifference in the cellular targets of these two agents in vivo,and/or a difference in the potency with which HgCl2-triggeredimmune activation is suppressed.     

Multiple brown tumors in a patient with nutritional secondary hyperparathyroidism

Summary For years, brown tumors have been considered to be a characteristic of primary hyperparathyroidism. However, since 1963 several reports indicate the incidence of brown tumors in patients with renal secondary hyperparathyroidism to be 1.5%–1.7%. The appearance of multiple brown tumor lesions is rather uncommon in secondary hyperparathyroidism which is also true for malabsorption as its cause. We report on a 56-year-old man presenting with pain in the bones and multiple osteolyses. A bone biopsy specimen and the laboratory examinations were indicative of secondary hyperparathyroidism caused by malabsorption most likely due to Billroth's II/I gastric resection. Thus, the patient's osteolyses represent brown tumors which have been induced by nutritional secondary hyperparathyroidism.     

Reproduction and thermoregulation in Peromyscus: Effects of chronic short days

Seven groups of laboratory reared Connecticut P. leucopus were exposed to a 9L:15D photoperiod for either 6, 9, 12, 20, 25, 32, or 36 weeks. An eighth group was maintained on 16L:8D. During the final 6 weeks all mice were cold exposed (13°C). Substantial reproductive regression occurred in females following 6 weeks exposure to 9L:15D relative to 16L:8D animals. In males, a slight decrease in testicular weight occurred following 6 weeks on 9L:15D; this effect was pronounced by 9 weeks, along with a decrease in seminal vesicle weight. Reproductive recrudescence occurred in females by week 32 and in males by week 36. Between 10 and 12 weeks on 9L:15D mice exhibited increases in nesting, incidence of daily torpor, and presence of the winter molt. These increases persisted through 36 weeks on 9L:15D. An increase in the interscapular brown fat pad occurred between 12 and 25 weeks. Reproductive and thermoregulatory characters respond differently to prolonged exposure to a short day photoperiod in this species.     

Small effect of brown adipose tissue and major effect of photoperiod on body weight in hamsters (Mesocricetus auratus)

It has been suggested that brown adipose tissue plays a special role in the control of body weight. This hypothesis was investigated by measuring the body weight of female hamsters over a two month period following removal of interscapular brown adipose tissue. Two groups of animals were used, one maintained on a short day (10:14 light: dark ratio) and the other on a long day (16:8 light: dark ratio) photoperiod. Under both photoperiod conditions hamsters with interscapular brown adipose tissue removed gained somewhat more weight than their corresponding sham operated controls. Photoperiod, however, had a much larger effect on body weight. Hamsters maintained on short days increased their body weight by about 60 percent during the two months of the experiment whereas the hamsters maintained on long days increased their body weight by only about 17 percent. It was concluded that brown adipose tissue plays a small non special role in the control of body weight in the female hamster, but that the light-dark ratio is quantitatively much more important under these experimental conditions.     

Impaired diet-induced thermogenesis in brown adipose tissue from rats made obese with parasagittal hypothalamic knife-cuts

Two experiments were performed to determine if bilateral parasagittal hypothalamic knife-cuts (KCs), which produce long-term overeating and obesity, after biochemical indices of brown adipose tissue (BAT) reactivity to thermogenic stimuli. In the first study, responses to environmental cold were tested. Four weeks after surgery, KC rats had gained 4-5 times more weight than controls and were obese (increased Lee Obesity Index and weight of gonadal white fat). Before being sacrificed, groups of KC and control rats were exposed to 4 degrees C for 21 hr or remained at 28 degrees C. Interscapular BAT weighed 300% more in KC rats, due largely to increased white fat content. Functional indices of BAT thermogenic capacity (protein content, DNA content, cytochrome oxidase activity and mitochondrial guanosine diphosphate (GDP) binding) were normal at 28 degrees C. Exposure to 4 degrees C produced greatly enhanced responses but these were equivalent for both groups. This suggested an intact capacity for non-shivering thermogenesis in obese KC rats. In the second study, the same BAT responses were examined in other rats fed a palatable "cafeteria" diet (CAFE). One week after surgery, KC and control rats were subdivided into groups that received chow alone or chow plus four different palatable foods daily. Before sacrificing 4-5 weeks later, KC rats had gained 3-4 times more weight than controls and were obese. Interscapular BAT weighed 200-300% more in KC rats. CAFE feeding produced larger increments in all variables for KC vs. control rats. Most importantly, GDP binding was reduced in both KC groups, and significantly more so after CAFE feeding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term effects of lateral hypothalamic lesions on brown adipose tissue in rats

A classic feature of animals with lateral hypothalamic (LH) lesions is their regulation of body weight at sub-normal levels. The present studies were done to determine whether this is associated with enhanced thermogenic activity of their brown adipose tissue (BAT). Three groups of young chow-fed male Holtzman rats were formed: (1) animals receiving bilateral radiofrequency heat lesions of the dorsal LH and then permitted free access to chow (LH rats); (2) non-lesioned animals that were pair-fed (PF) to the lesioned rats during a 2 week post-operative recovery period (Phase 1); (3) non-lesioned, ad lib fed (NORM) controls. After Phase 1, each group was divided and permitted free access to chow alone or an additional selection of palatable, novel food items (a "cafeteria" diet) for 2-3 weeks (Phase 2) to stimulate diet-induced thermogenesis in BAT. Finally, half of each sub-group was exposed to 4 degrees C for 15 hr to stimulate nonshivering thermogenesis in BAT. During Phase 1 LHs and PFs ate 50% less than NORMs. This resulted in a weight deficit of 16% for LHs and 12% for PFs. After the additional period of feeding palatable foods (Phase 2) LHs collectively weighed 14% less than NORMs whereas previously PFs had a weight deficit of only 4%. They gained less weight than NORMs or PFs despite a similar energy intake. LHs had small deposits of gonadal white adipose tissue [both total amount and expressed per metabolic body mass (kg 0.75)]. The weight of interscapular BAT was less in the LHs but its concentration of protein (mg/g) was higher.(ABSTRACT TRUNCATED AT 250 WORDS)     

中药紫株的化学成分研究

目的：研究紫株Callicarpa pedunculata R.Brown的化学成分。方法：利用各种色谱技术进行分离纯化,通过各种理化方法及光谱（IR,MS,^1HNMR,^13CNMR)分析鉴定其化学结构。结果：从紫株全草的氯仿提取物中分离得到10种化合物,分别鉴定为：4个二萜类化合物：14α－羟基－7,15－异松烷二烯－18烷酸（14α－hydroxy-7,15-isopimaradien-18-oic acid,Ⅰ）;16α,17-二羟基－3－氧－扁枝杉烷（16α,17-dihydroxy-3-oxo-phyllocladane,Ⅱ）;8,11,13,15-四烯松香烷－18－烷酸（8,11,13,15-abietatraen-18-oic acid,Ⅲ）;6α-羟基尼刀瑞尔醇（6α-hydroxy nidorellol,Ⅳ）;2个黄酮类化合物5－羟基－3,4‘,7-三甲氧基黄酮（5－hydroxy-3,4‘,7-trimethoxyflavone,Ⅴ）;3,5-二甲基莰非醇（3,5－dimethylkaempherol,Ⅵ）;其余的分别为：熊果酸（ursolic acid,Ⅶ）,肌醇（myoinositol, Ⅷ）,β-谷甾醇（β-sitosterol,Ⅸ）,β-香树素（β－amyrin, Ⅹ）。结论：化合物Ⅰ-Ⅵ为首次从该种植物中分离得到,且化合物Ⅰ-Ⅳ分别为4种不同类型的二萜。熊果酸的含量高达1％,本植物可作为其资源植物。     

Interleukin-1 receptor antagonist in newborn babies and pregnant women

We have used patch-clamp techniques to study the effect of the sulfhydryl group oxidizing agents mercury and thimerosal on calcium-activated nonselective cation channels from brown adipose tissue. 100 nmol/l mercury and 50 mol/l thimerosal induced a complete block. Blockade could be reversed by reduction of the mercaptide by dithiotreitol (DTT). Mercury was found to be the most potent blocker (IC₅₀-value 21×10^–9 mol/l), whereas thimerosal (IC₅₀-value 1.5×10^–6 mol/l) was as effective as 3,5-dichlorodiphenylamine-2-carboxylic acid (DCDPC). The DCDPC effect, however, could not be reversed by DTT, indicating different blocking mechanisms. It is concluded that SH-groups are involved in gating of the calcium-activated nonselective channel.     

Neutropenia, fever, and infection

With the advances in the management of various neoplastic diseases and subsequent improvement in "disease-free" states, complications of therapy--particularly, infectious complications--have evolved as stumbling blocks to survival. Among neutropenic (absolute neutrophil count below 1,000/mm3) patients with cancer, infection is the major autopsy-determined cause of death. With expected "cure rates" of childhood leukemia approaching 60 to 70 percent, it seems unreasonable to lose such patients to an infectious cause of death, yet this, indeed, happens. The purpose of this review is to (1) define the magnitude of the problem; (2) describe the various agents responsible for infections in neutropenic patients; (3) attempt to more sharply define degrees of neutropenia and mechanical defenses; and (4) consider various approaches to studying and treating these infections.