Disk hypodensity and disk herniation

The authors report the case of a patient with a herniated lumbar disk and bacterial meningitis. CT scan showed central disk hypodensity at the hernia level, whilst full cytological and bacteriological study of the disk following surgery revealed no evidence of spondylodiscitis. The problem was thus that of consequences of "degenerative" events related to the herniation. Central or peripheral disk hypodensity must in no case be considered as specific of discitis when there is a concomitant disk herniation.     

Antihypertensive effect of canrenone in a model where endogenous ouabain-like factors are present

The effect of canrenone, an antialdosterone and partial ouabain-agonist drug, was studied in rats that developed volume expansion and hypertension after renal mass reduction and excess Na+ intake (RRM-salt). The RRM-salt was characterized by: (1) increased endogenous "digitalis-like" compounds in plasma [cross reactivity with digoxin-antibodies (57.5 +/- 5.0 vs. 42.1 +/- 3.8 pg/ml, p less than 0.02); inhibition of kidney Na+, K+-ATPase activity (135 +/- 5 vs. 154 +/- 5 mumol/mg/h, p less than 0.01); and inhibition of Na+ extrusion from normal erythrocytes (5.96 +/- 0.40 vs. 7.68 +/- 0.34 mmol/L cells/h, p less than 0.01)]; (2) reduced Na+, K+-pump activity (7.34 +/- 0.29 vs. 10.88 +/- 0.41 mmol/L cells/h, p less than 0.001) and increased Na+ content (4.66 +/- .08 vs. 4.16 +/- 0.11 mmol/L cells, p less than 0.01) in erythrocytes; and (3) low plasma renin activity (2.1 +/- 0.9 vs. 12.6 +/- 1.6 ng/ml/h). Ninety minutes after the administration to RRM-salt of a single oral dose of 60 mg/kg of canrenone, the systolic blood pressure decreased by 36 +/- 4 mm Hg (mean +/- SEM). Chronic canrenone administration (60 mg/kg/day) resulted in a marked antihypertensive effect associated to a correction of volume expansion, a decrease in endogenous "digitalis-like" compounds, and a partial recovery of Na+, K+-pump activity and Na+ content in erythrocytes. Our results suggest that the antihypertensive effect in RRM-salt rats results, at least in part, from antagonism with endogenous "digitalis-like" compounds.     

Enzymatic synthesis of penicillins

Different penicillins (phenylacetyl, 2-hydroxyphenylacetyl, 4-hydroxyphenylacetyl, phenoxyacetyl and 2-thiopheneacetylpenicillin) have been synthesized "in vitro" by direct N-acylation of 6-aminopenicillanic acid (6-APA) with the acyl group of several acyl-CoA derivatives. The enzyme that catalyzes these reactions, acyl-CoA: 6-APA acyltransferase of Penicillium chrysogenum, was purified to homogeneity (374-fold) and its amino acid composition is given. This protein accepts as substrates several aliphatic acids and different aromatic acids with the only requirement that an acetyl-CoA moiety must be present in the substrate molecule. Shortening or lengthening of the acyl moiety prevents the 6-APA-N-acylation reaction. The presence of an amino group in the alpha-position of the acetyl group does not allow this molecule to be used as substrate. However, different substitutions in the phenyl group (hydroxylation of the carbons 2 and 4) or its replacement by another aromatic ring (thiophene) were accepted with varying reactions rates in the acylation reaction when a 176-fold purified acyltransferase was employed. The homogeneity pure enzyme accepts as substrate thiophene acetyl-CoA but it did not 2-hydroxyphenyl and 4-hydroxyphenylacetyl-CoA. The presence of an oxygen atom between the aromatic and the acetyl moieties did not affect the catalysis.     

The effect of isoluminant and isochromatic stimuli on latency and amplitude of saccades

When two stimuli are presented in different positions successively at short time intervals saccadic eye movements are usually directed at intermediate positions. This phenomenon of "averaging" of saccadic eye movements has been studied in responses to double-step target displacements in different stimulus conditions. In these conditions isoluminant and isochromatic stimuli were used with variable contrast and at different background luminances. Although the critical duration of temporal summation differed considerably in these stimulus conditions the duration of the phenomenon of "averaging" remained the same in all conditions. This indicates that temporal properties of the sensory system are not the prime cause of "averaging". Moreover, the onset time of "averaging" relative to the second target displacement turned out to be highly correlated with the mean latency of saccades in the different conditions. The implications of the results for models of oculomotor control are discussed.     

Chemical derivatization as a strategy to enhance detectability of agents used in cancer management

The bioanalysis of drugs used in the management of cancer is often complicated by the lack of selectivity and sensitivity. Chemical derivatization of these drugs prior to their chromatographic analysis represents a viable strategy to improve chromatographic resolution and to enhance detectability. This review provides examples of how this approach can meet these objectives. Derivatization of racemic cyclophosphamide with a chiral acylating agent, following hydroxyalkylation to introduce a reactive centre into the molecule, provides the basis for its stereospecific analysis. The analysis of dianhydrogalactitol is described, in which diethyldithiocarbamate is used as a nucleophilic derivatizing agent that improves chromatographic behaviour and analytical sensitivity. The final example that is described is the design and preparation of improved fluorogenic reagents (o-phthalaldehyde analogues) for the derivatization of peptides and application of these reagents to the trace analysis of leu-enkephalin in plasma.     

国外新冠医疗防疫体系建设策略研究及启示：以新加坡、英国为例

目的 通过案例研究总结国外新冠医疗防疫体系建设策略。方法 选取新加坡和英国作为研究案例,采用深度访谈和资料研究相结合的方式,访谈对象包括政府卫生署官员、传染病学专家以及基层全科医师等各类别专业人员,访谈内容涉及受访对象所在国家的医疗防疫体系设置情况和设计逻辑等。结果 两国的新冠防疫体系以分级诊疗为重要特征,其中新加坡通过"Hot Clinic"分流患者,英国通过远程诊疗分流患者。两国的门急诊设施改建以利用现有设施为主。两国全科诊所医护基本配置都相对简单,应对新冠疫情时常通过借用全院医护、统筹安排、适当延长工作时间等方式来扩充医护数量。两国在医疗防疫体系建设中均积极采取了信息化方式,疫情数据采集和信息公开较为及时。两国坚持"平战结合"策略,在逐步放开过程中灵活调整防疫政策和资源配置方案。结论 两国案例的优势及劣势可为我国医疗防疫体系实行分级建设、规范诊疗流程、细化基础设施、完善人员配置、推进信息化建设、贯彻"平战结合"策略并落实转化方案提供参考。     

Heterogeneity of human basophils and mast cells in response to muscle relaxants

We investigated thein vitro effects of increasing concentrations (10^–5–10^–3 M) of four muscle relaxants (succinylcholine, d-tubocurarine, vecuronium and atracurium) on histamine release (HR) from human peripheral blood basophils and mast cells isolated from lung parenchyma (HLMC) and skin tissues (HSMC). Basophils released less than 5% of their histamine content when incubated with any one of the muscle relaxants. In contrast, mast cells showed a marked heterogeneity in their response. Succinylcholine did not induce HR from any type of mast cell, and only high concentrations of d-tubocurarine (10^–3 M) caused HR from HSMC and HLMC. Vecuronium concentration-dependently induced HR from HLMC and HSMC. Atracurium concentration-dependently caused marked HR from HLMC and HSMC up to a maximum of 46.2±15.1% and 30.6±6.0%, respectively. From both HLMC and HSMC HR caused by atracurium and vecuronium was extremely rapid (t_1/2<1 min).=" the=" releasing=" activity=" of=" atracurium=" and=" vecuronium=" on=" hlmc=" and=" hsmc=" was=" reduced,=" but=" not=" abolished,=" by=" lowering=" the=" temperature=" of=" the=" incubation=" buffer=" to=" 22°c=" and=" 4°c.=" these=" results=" confirm=" that=" there=" are=" functional=" differences=" between=" human=" basophils=" and=" mast=" cells=" and=" among=" mast=" cells=" isolated=" from=" different=" anatomical=" sites=" in=" response=" to=" the=" muscle=" relaxants=">     

Relative sensitivity of four noninvasive methods in assessing systolic cardiovascular effects of isoproterenol in healthy volunteers.

STUDY OBJECTIVE: The study was performed to evaluate the relative sensitivity of various noninvasive methods to detect and describe the systolic cardiovascular effects of stepwise increasing doses of isoproterenol: two-dimensional left ventricular echocardiography (main variable, ejection fraction), ACVF (attenuation compensated volume flow)--dual-beam Doppler echoaortography (time-averaged mean velocity), electrical impedance cardiography [(dZ/dtmax)/RZ index], and systolic time intervals from mechanocardiography (PEP and QS2c). METHODS: Isoproterenol was administered by constant rate intravenous infusion in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 minutes). Saline control infusions were given in analog fashion. The treatments (isoproterenol and saline solution) were administered in a period-balanced two-way crossover design with randomly allocated sequences. The subjects, observers, and analysts were blinded to the treatment protocol. Study subjects were 10 healthy male volunteers (age range, 23 to 31 years; mean age, 26.6 years). RESULTS: Compared with saline solution, isoproterenol caused a dose-related increase in ejection fraction, (dz/dt)/RZ index, and time-averaged mean velocity and a dose-related shortening of PEP and QS2c. The responses are congruent with an enhancement of cardiac systolic performance caused by a positive inotropic stimulation and an afterload reduction ("inodilatory" response). The effects on systolic time intervals reached statistical significance (alpha = 0.05) at the first isoproterenol dose step, the effects on the impedance cardiography and the Doppler echoaortography variables reached statistical significance at the second dose step, and the effects on the two-dimensional echocardiography reached statistical significance at the third dose step. CONCLUSIONS: All methods allowed to detect isoproterenol-related changes. Systolic time intervals were the most sensitive, followed by impedance cardiography, ACVF--dual-beam Doppler echoaortography, and two-dimensional echocardiography. The practical convenience and high sensitivity of the systolic time intervals makes them suitable to evaluate investigational systolic inodilatory changes in humans.     

Thyroid albumin originates from blood.

Iodoalbumin has been found in the goiter of Dutch goats with a thyroglobulin synthesis defect. Immunohistochemical studies showed that in the goiter the percentage of follicles containing albumin was higher than that in normal thyroid glands. In the albumin-containing follicles of normal and goitrous glands, transferrin and immunoglobulin G could be found. Also, between the epithelial cells, serum proteins were detected. These results indicate intercellular passage of serum proteins. After in vivo labeling with 125I, goiter slices were incubated with [3H] leucine. Purified 125I-containing albumin did not contain [3H]leucine, while thyroglobulin antigens were double labeled. Cyanogen bromide treatment of albumin out of the goiter and of serum albumin gave comparable cleavage patterns, indicating that no great differences in amino acid composition, especially methionine, exist. In total RNA from goiter, no albumin mRNA could be detected after blotting and hybridization with goat albumin cDNA. Also, the polymerase chain reaction method with albumin DNA primers was unable to detect any albumin mRNA in normal and goitrous glands of goats. From these results we conclude that "thyralbumin" originates from blood and is not synthesized by the thyroid gland.     

Naevus follicularis keratosus: clinical aspects, histology and histogenesis]

The clinical, histological and histogenetic aspects of naevus follicularis keratosus (NFK) ("naevus comedonicus") are reported. Clinically, NFK appears mostly as linear and unilateral groups of dark comedo-like plugs. Clinical forms include variants with minimal and distinctive deviations from the basic form. Recurrent inflammation is not mandatory. Histological examination reveals keratin-filled infundibula, with granular layers that are always present but though not always equally obvious. This finding corresponds to the mode of keratinization in the follicular infundibulum. Overall, the findings are indicative of a harmartoma of the follicular infundibulum with additional rudimentary sebaceous glands.