Renal urate transport during variations in urate synthesis in the rat

Summary In order to determine the effect of intrarenal synthesis of urate upon the urinary urate excretion in the rat, we effected large changes in urate synthesis by increasing it with hypoxanthine and decreasing it with allopurinol. Hypoxanthine infusion increased plasma urate rapidly and also increased the urinary urate excretion and its renal clearance. However, when the plasma urate was maintained constant, hypoxanthine had no effect upon renal urate transport. Conversely, allopurinol infusion rapidly diminished the plasma urate, urinary urate excretion and its renal clearance. Again, the maintenance of a constant plasma urate concentration prevented any change in urate transport during allopurinol. The urinary degradative purine metabolite pattern was altered pre-dictably by hypoxanthine and allopurinol. Assuming that any putative intrarenal component of urate synthesis would be affected predictably and consistently by hypoxanthine and allopurinol, these results suggest that changes in intrarenal urate synthesis are not an important determinant of urate excretion in the rat.Reported in abstract form in Clinical Research23, 508 A (1975)     

Correlates of low dietary energy reporting in free-living elderly: the MEDIS study

Objectives

To evaluate the prevalence of low energy reporting (LER) and associations between LER and lifestyle, psychological and clinical parameters, in elderly people living in eastern Mediterranean islands.

Methods

1190 men and women, aged 65–100 years, participated in this cross-sectional study. Socio-demographic, clinical and lifestyle characteristics were recorded for the study participants. Among others, the ratio of energy intake to estimated basal metabolic rate (EI/BMR) was calculated and was used for the assessment of LER.

Results

Prevalence of LER was 47.7%. Lower EI/BMR (i.e., higher risk for LER) was associated with older age (p = 0.001), male sex (p < 0.001), higher body mass index (BMI; p = 0.04), lower adherence to the Mediterranean diet (p < 0.001) and non-current smoking (p = 0.007). The sex-specific analysis revealed that, lower EI/BMR values were associated with lower adherence to the Mediterranean diet and being non-current smoker in both men and women (p ≤ 0.05), as well as with older age (p = 0.01), higher BMI (p = 0.02) and hypercholesterolemia (p = 0.02), only in women.

Conclusion

In elderly, several clinical and lifestyle factors seem to be related to LER, and they should be taken into account in their nutritional assessment.     

Genetic analysis of the relationships between behavioral and neuroendocrine traits in roman high and low avoidance rat lines

In order to determine whether the coselection observed between the selection trait (active avoidance behavior) of the Roman High Avoidance (RHA) and Roman Low Avoidance (RLA) rat lines and their neuroendocrine characteristics were genetically determined, we analyzed, in nonsegregating (RHA, RLA, and F₁) and segregating (F₂ and the two backcrosses) crosses, the inheritance pattern and the phenotypic correlations among behavioral (shuttle-box behavior), physiological (body, adrenal, and thymus weights), and neuroendocrine (corticosterone and prolactin reactivity, catecholamine enzyme activities) variables. Physiological characteristics and enzyme activities have acrucial role in sex dissociation. Avoidance behavior and prolactin reactivity to novel environment remained associated in segregating crosses despite gene rearrangement. They represented the most important variables to differentiate the Roman lines, perhaps sharing a common regulatory mechanism under genetic control.     

A randomized double-blind comparison of fluoxetine augmentation by high and low dosage folic acid in patients with depressive episodes

Background

Though encouraging evidence exists for the use of folic acid as an augmenting agent to antidepressants, evidence regarding its optimal dosage is lacking.

Methods

Forty-two female out-patients with moderate (with or without somatic syndrome) or severe depressive episodes (without psychotic symptoms) diagnosed as per ICD-10 criteria, were randomized in a double-blind fashion to receive either 20 mg fluoxetine and a relatively low dose folic acid (1.5 mg/day; n=23; Group I) or 20 mg fluoxetine and high dose folic acid (5 mg/day; n=19; Group II). Primary outcome measures were weekly changes of scores on Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) for 6 weeks.

Results

Group II patients showed greater improvement in both HDRS [Mean (SD) baseline HDRS score=21 (2.3) for group I and 20.0 (1.4) for group-II; time X group interaction effect: p=0.01] and BDI [Mean (SD) baseline BDI score=25.1 (5.2) for group-1 and 23.1 (2.7) for group-II; time X group interaction effect: p=0.01]. With regard to HDRS, 7 (36.8%) group II patients remitted compared to 2 (8.7%) group I patients (p=0.03); 9 (47.4%) patients of group II responded when compared to 6 (26.1%) from group I (p=0.15). When BDI was considered, 5 (26.3%) group II patients remitted when compared to 2 (8.7%) from group I (p=0.13); 10 patients (52.6%) from group II responded when compared to 5 (21.7%) from group I (p=0.04). No adverse effects were noted in either group.

Limitations

Lack of a placebo arm and small sample size.

Conclusion

Compared to folic acid 1.5 mg/day, augmentation with 5 mg/day may be more beneficial in female patients with depressive episodes taking fluoxetine 20 mg/day.     

Genetic control of eosinophilia in guinea pig strains inbred for high or low bronchial allergic reactivity 2. A genetic study of spontaneous and immunization-induced eosinophilia

Ploug Winthereik M, Spärck JV, Lundberg L, Sompolinsky D. Genetic control of eosinophilia in guinea pig strains inbred for high or low bronchial allergic reactivity. 2. A genetic study of spontaneous and immunization-induced eosinophilia.
In 4 inbred strains of guinea pig the tendency to develop peripheral high-eosinophilia was shown to be genetically controlled. The development of eosinophilia with age and following immunization was examined in high- and low-eosinophilic parental strains, in F₁-hybrids and in backcross offspring. The results show that probably only one or a very few segregating genes control eosinophilia, and they also indicate that different genes are involved in the determination of spontaneous (age-related) and immunization-induced eosinophilia.     

Perceptions of risk in adults with a low or high risk profile of developing type 2 diabetes; a cross-sectional population-based study

Objective

To compare the perceived seriousness and risk of type 2 diabetes among low risk with high risk profile non-diabetic subjects and examine the relationship of perceived risk with multiple self-reported risk indicators.

Methods

A cross-sectional population-based study among 4435 low risk profile and 2607 high risk profile non-diabetic residents of the Hoorn region, participating in a stepwise type 2 diabetes screening study. Main outcome measures were perceived seriousness and risk of diabetes in subjects categorized (low vs. high risk profile) using the Symptom Risk Questionnaire.

Results

85.0% of the low risk and 81.2% of the high risk profile subjects perceived diabetes as a moderate to very serious disease. About half (43.0%) of all 7042 subjects reported that they do not know their risk of having diabetes. The mean perceived risk of having diabetes was slightly lower for the low risk compared with the high risk profile subjects (difference = 2.8%; 95% confidence interval [CI] = 1.8% to 3.8%; P < 0.001). This difference was mostly explained by having a parent or sibling with diabetes, frequent thirst and claudication (difference = 0.6%; 95% CI = −0.7% to 1.9%). Interestingly, perceived risk decreased with increasing age within both groups (P for trend < 0.001).

Conclusions

Both low risk and high risk profile subjects perceive diabetes as a serious disease. Even among those at high risk profile for type 2 diabetes, almost half appeared not to know their risk. Perceived risk of having diabetes was slightly lower for the low risk compared with the high risk profile subjects. Furthermore, perceived risk decreases with increasing age.

Practice implications

This study points to a greater need to effectively address people's (mis)perceptions, and how to raise the awareness and understanding of type 2 diabetes and its risk factors in the general population in order to influence early detection and healthy lifestyle changes.     

A comparative study of cholinergic systems of the neocortex and hippocampus in rats with low and high resistance to hypoxia

Synaptic structures in the neocortex and hippocampus of the intact brain were compared between rats with low and high resistance to hypobaric hypoxia. Activities of choline acetyltransferase, acetylcholinesterase, Na,K-ATPase, and the portion of protein in the light and heavy synaptosome fractions and subfractions were measured. A discrepancy in cholinergic metabolism molecular mechanisms between high and low resistance animals have been found in the heavy somatosoma fraction from the neocortex. Activities of choline acetyltransferase, acetylcholinesterase, and Na,K-ATPase in the synaptolemmal subfraction of low resistant rats were much lower than in high resistant rats. This implies a less effective synaptic transmission in proper cholinergic neurons in the low resistance animals and, therefore, specifically changed neuron functioning in the circulation control. No differences in the cholinergic components of either neocortical light synaptosome fraction or hippocampal light and heavy synaptosome fractions were found between low and high resistance rats. Translated fromByulleten' Eksperimental'noi Biologii I Meditsiny, Vol. 125, No. 5, pp. 521–525, May, 1998     

高中生心理防御机制研究

不少研究表明 ,防御机制的动用与心理健康水平密切相关[1- 3] 。在过去数年中 ,国外对心理防御机制研究方面做了大量的工作[4 ] ,早在 90年代初 ,即有研究表明 ,在青少年精神病患者这类人群中 ,防御机制的成熟度是与心理功能紧密相连的[5] 。近年来 ,国内也有了一些在正常青少年中的拓展性研究 ,如对大学生群体的研究发现不成熟防御机制与心理健康水平显著相关[6 ] ,对初三学生的相关分析显示 ,初中生对成熟型防御机制运用较好[7] 。那么 ,对于处于人生花季雨季的高中生 ,他们的心理防御机制又有什么特点 ?为此 ,我们进行了调查研究 ,为高中…     

Plasma procalcitonin levels remain low at the onset of gram-positive bacteremia regardless of severity or the presence of shock: A retrospective analysis of patients with detailed clinical characteristics

ObjectivesProcalcitonin (PCT) is an early diagnosis marker of sepsis/bacteremia. However, some reports refer to its lower responsiveness to gram-positive bacteremia. We retrospectively evaluated the PCT values at the onset of bacteremia in relation to severity index.MethodsPatients with bacteremia caused by two gram-negative bacteria (46 E. coli and 50 Klebsiella pneumoniae) and three gram-positive bacteria (45 S. aureus, 56 S. epidermidis, and 10 S. mitis) were studied. The plasma PCT and C-reactive protein (CRP) levels were compared between species and different Sequential Organ Failure Assessment (SOFA) score groups.ResultsThe median PCT level was higher in gram-negative than in gram-positive bacteremia in overall (13.09 vs. 0.50 ng/mL, p < 0.0001), in SOFA score≥4 group (28.85 vs.1.72 ng/mL, p < 0.0001) and in SOFA<4 group (2.64 vs. 0.42 ng/mL, p < 0.0001). Only 46%, and 11% of patients showed PCT ≥0.5 ng/mL in S. epidermidis, and S. mitis bacteremia, respectively. PCT was significantly better than CRP in discriminating gram-negative from gram-positive bacteremia (AUCROC; 0.828 and 0.634, p < 0.001), but it was low in Staphylococcus epidermidis bacteremia regardless of SOFA scores.ConclusionsPCT levels are lower in gram-positive bacteremia regardless of SOFA scores or the presence of shock. The conventional sepsis cutoff of 0.5 ng/mL may overlook certain proportions of gram-positive bacteremia.     

Risk factors for the development of bronchiolitis obliterans in children with severe adenovirus pneumonia: A retrospective study with dose-response analysis

To investigate and analyze the relevant risk factors for bronchiolitis obliterans (BO) in children with severe adenovirus pneumonia, a retrospective study of children with severe adenovirus pneumonia was performed in 34 cases that developing BO and 105 cases not developing BO in Children's hospital of Chongqing Medical University from January 2015 to February 2019. The multivariate logistic regression analysis was used to identify factors which were significantly associated with development of BO after the univariate analysis, and receiver operating characteristic (ROC) curve analysis was performed to find out the cut-off value for the significant relevant factors. A nonlinear dose-response relationship between risk factors and the risk of BO was assessed by restricted cubic spline model. Three factors were independently associated with development of BO, which were length of fever (OR 1.129, 95% CI 1.033-1.234), dyspnea (OR 3.922, 95% CI 1.060-14.514) and invasive mechanical ventilation (OR 6.861, 95% CI 1.854-25.387). The cut-off value of length of fever were 10.5 days. A linear dose-response relationship between length of fever and occurrence of BO was observed (P = .57 for nonlinearity). Children with severe adenovirus pneumonia who have a longer duration of fever (especially more than 10.5 days), have dyspnea or require invasive mechanical ventilation in the acute phase are more likely to develop BO.     

Atrial sympathetic nerves after perfusion of the rabbit heart with low sodium solutions containing potassium chloride or urea—a biochemical,histochemical and fine structural study

Rabbit hearts were perfused in vitro with Tyrode's solution or low sodium media (17mm Na⁺) substituted with either KCl (low Na-high K) or urea (low Na-urea). Samples of right atrial tissues were removed for fluorescence and electron microscopy after 5, 15 and 120 min. In separate experiments, the noradrenaline concentrations in the right and left atria and ventricles were estimated at these times, and the amine overflow into the perfusion fluid determined. The cardiac noradrenaline concentrations and ultrastructural appearance of adrenergic axon terminals were not significantly affected by perfusion with Tyrode's solution for 120 min.Low Na-urea caused a progressive loss of noradrenaline from all parts of the heart which resulted in a 86–88% decrease of amine concentrations. Similar changes were observed after low Na-high K and also if the noradrenaline concentrations were expressed in terms of protein content of tissue. The amounts lost from the hearts were almost quantitatively recovered from the perfusates. There was greater tissue edema in hearts perfused with low Na-urea than after perfusion with the other media.After 5 min perfusion with either of the low Na solutions, little change was apparent in the ultrastructure of nerve terminals; there was no obvious alteration in histofluorescence, but after 15min it was reduced and at 120 min nearly abolished. Low Na-high K reduced the size of dense cores within the vesicles at 15 min. At 120 min the vesicles were agranular and their number per unit axon profile had dropped by 50%. In contrast, low Na-urea did not significantly alter the number of small dense-cored vesicles per profile despite causing myocardial cell damage from 5 min onwards which intensified with prolonged perfusion.The concomitant loss of histofluorescence, dense-cored vesicles and noradrenaline after low Na-high K is compatible with the view that the amine was released by exocytosis, as reported by others. However, despite myocardial tissue damage by low Na-urea, the noradrenaline overflow in this case is not due to disruption of vesicles and axon membranes. The preservation of electron-dense material in the vesicles is consistent both with previous reports that macromolecules rather than amines are responsible for the electron opaque cores and that amine release by low Na-urea is probably not by exocytosis.     

人生精细胞内酶性磷酸酶活性与膜结构关系的研究

目的　研究人生精细胞内酸性磷酸酶 (ACP)活性与细胞膜结构之间的关系。方法　选取 5例抗精抗体 (AsAb)阳性 (不育A组 ) ,9例生殖系统有过炎症中 (不育B组 )及 6例原因不明 (不育C组 )共 2 0例男性不育患者新鲜精液 ,同时取 8例正常生育男性新鲜精液作对照 ,用Gomori s铅法对标本进行孵育后 ,在透射电镜下观察。结果　AsAb阳性和有炎症史男性不育患者标本中 ,见较多的脱落生精细胞 ,有大量与铅结合的ACP显现于溶酶体 ,ACP活性明显升高。ACP阳性反应数在生育组和不生育A、B、C组分别为 4、16、19和 5 ,生育组与不育组A、B组间的差异均有显著性 (P <0 .0 5或 0 .0 1)。结论　ACP活性大小与精子和膜的损伤密切相关 ,检测ACP活性可推断生精细胞和膜受损程度 ,提高诊断水平     

A study of intercellular relationships between trabecular bone and marrow stromal cells in the murine femoral metaphysis

The cellular relationship between the substantia spongiosa of bone (cancellous or trabecular bone) and the haematopoietic bone marrow in the femoral metaphysis of C57BL/6NJCL mice was studied by transmission electron microscopy (TEM). Special attention was directed to intercellular junctions between osteocytes, osteoblasts, and bone marrow reticular cells. These were gap junctions and adhesive devices of simple architecture referred to as primitive junctions or zonula adherens-like junctions. Gap junctions were observed between osteocytes (within the trabeculae) and osteoblasts (at the trabecular surface) and between osteoblasts and marrow reticular cells. Gap junctions were also observed between the same cell type within each of these categories. These junctions involved the plasmalemmal membranes of adjacent cell bodies and of processes. Primitive cell junctions had a similar cellular distribution. Quantitative analysis of the cell types covering or positioned around the trabecular bones and of gap junctions between these and other cells was carried out by TEM. It was found that osteoblasts were the most numerous cell type, occupying 31% of the total of each cell type positively identified around the trabeculae (31%), while pre-osteoblasts, (flattened bone marrow reticular cells) took up 26%. These data emphasise the intimate relationship of the various mesenchymal cells based on processes and intercellular junctions, and point to an anatomical and probably functional integration of trabeculae and marrow. The functional significance and putative regulatory activity of this unit are discussed.     

A study on the renal synthesis of dopamine in aged rats

The present study has examined the synthesis of dopamine from l -DOPA in kidney slices and in kidney homogenates of 3- and 24-month-old rats. The deamination of newly-formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) was also studied. The assay of l -DOPA, dopamine, noradrenaline and DOPAC was performed by high pressure liquid chromatography with electrochemical detection. Incubation of renal slices and homogenates of whole kidney with exogenous l -DOPA (0.1–100 μm) resulted in a concentration-dependent formation of both dopamine and DOPAC. At 50 and 100 μm l -DOPA, but not at lower concentrations (10 and 25 μM), the total amounts of dopamine and DOPAC formed were significantly greater in kidney slices obtained from 3-month-old rats. By contrast, the total amount of dopamine and DOPAC formed was greater in homogenates of renal tissues from aged rats than from young animals; this was particularly evident at 5.0 and 10.0 μm l -DOPA in the incubation medium. However, the DOPAC/dopamine ratios, both in kidney slices and kidney homogenates, were found to be higher in young rats than in old rats. The present results suggest an impairment in the formation of dopamine and of its deamination into DOPAC in renal tissues of aged rats; however, the reduced synthesis of dopamine does not appear to be the result of a decreased activity of the enzyme aromatic l -amino acid decarboxylase.     

Adjuvant effects of mannose-binding lectin ligands on the immune response to infectious bronchitis vaccine in chickens with high or low serum mannose-binding lectin concentrations

Mannose-binding lectin (MBL) plays a major role in the immune response as a soluble pattern-recognition receptor. MBL deficiency and susceptibility to different types of infections have been subject to extensive studies over the last decades. In humans and chickens, several studies have shown that MBL participates in the protection of hosts against virus infections. Infectious bronchitis (IB) is a highly contagious disease of economic importance in the poultry industry caused by the coronavirus infectious bronchitis virus (IBV). MBL has earlier been described to play a potential role in the pathogenesis of IBV infection and the production of IBV-specific antibodies, which may be exploited in optimising IBV vaccine strategies. The present study shows that MBL has the capability to bind to IBV in vitro. Chickens from two inbred lines (L10H and L10L) selected for high or low MBL serum concentrations, respectively, were vaccinated against IBV with or without the addition of the MBL ligands mannan, chitosan and fructooligosaccharide (FOS). The addition of MBL ligands to the IBV vaccine, especially FOS, enhanced the production of IBV-specific IgG antibody production in L10H chickens, but not L10L chickens after the second vaccination. The addition of FOS to the vaccine also increased the number of circulating CD4+ cells in L10H chickens compared to L10L chickens. The L10H chickens as well as the L10L chickens also showed an increased number of CD4−CD8α−γδ T-cells when an MBL ligand was added to the vaccine, most pronouncedly after the first vaccination. As MBL ligands co-administered with IBV vaccine induced differences between the two chicken lines, these results indirectly suggest that MBL is involved in the immune response to IBV vaccination. Furthermore, the higher antibody response in L10H chickens receiving vaccine and FOS makes FOS a potential adjuvant candidate in an IBV vaccine.