Statins and the kidney

In this paper an attempt is described to estimate the incidence and frequency of neurologic and otologic symptoms among patients two years after TBE. We examined 43 persons of both sexes aged 17-58. The most frequent complaints were: headache--34.9%, equilibrium problems--37.2%, buzzing in the ears--27.9%, hearing problems--23.3%, memory problems--25.6%. Decrease of throat reflexes was stated in 3 (7%) and pseudobulbaris symptoms in 2 (4.6%), weakness of muscles in 4 (9.3%). In audiometric examination decrease of hearing was stated in 8 persons (18.5%). We registered nystagmus: spontaneous--4.6-7%, gaze--13.9-18.6%, positional-T, mainly Nylen I and III type-18.6-25.6%. Pathologic recording in the eye-tracking pattern test was shown in 7 (16.3%) persons. Asymmetry of optokinetic nystagmus was stated in 6 (13.9%) examined persons. Asymmetry in caloric test was proved in 25.5% of examined persons.     

Effect of the callipyge phenotype and cooking method on tenderness of several major lamb muscles

We conducted three experiments to determine the effects of the callipyge phenotype on the tenderness of several major lamb muscles and to determine the effect of method of cookery on the tenderness of callipyge lamb at 7 d postmortem. In Exp. 1, chops from normal (n = 23) and callipyge (n = 16) carcasses were open-hearth-broiled. Warner-Bratzler shear force values of longissimus, gluteus medius, semimembranosus, biceps femoris, semitendinosus, adductor, and quadriceps femoris were 123, 44, 28, 26, 19, 16, and 13% greater, respectively, for callipyge (P < .05). In Exp. 2, muscles from normal (n = 18) and callipyge (n = 18) carcasses were oven-roasted. Shear force of triceps brachii was 11% greater for callipyge (P < .001); however, phenotype did not affect shear force of supraspinatus (P = .87) or psoas major (P = .64). In Exp. 3, a trained sensory panel evaluated leg roasts and open-hearth-broiled leg chops from normal (n = 60) and callipyge lamb carcasses (n = 60). Callipyge chops were less tender than normal chops (P < .05). Regardless of callipyge phenotype, muscles were more (P < .05) tender when roasted; however, the effect of method of cookery on tenderness scores was greater for callipyge muscles than for normal muscles. Callipyge roasts and normal roasts had similar tenderness (P = .58), and callipyge roasts were more tender than normal chops (P < .05). Regardless of cooking method, callipyge samples were less juicy than normal samples (P < .05). These data demonstrate that the callipyge phenotype will likely reduce consumer satisfaction due to reduced tenderness and juiciness; however, reduced tenderness in callipyge leg muscles could be prevented by ovenroasting.     

Reactivity of gemfibrozil 1-o-beta-acyl glucuronide. Pharmacokinetics of covalently bound gemfibrozil-protein adducts in rats

Acyl glucuronides are electrophilic metabolites that are readily hydrolyzed, undergo intramolecular rearrangement, and mediate the covalent binding of many acidic drugs to endogenous proteins. Gemfibrozil is extensively metabolized to gemfibrozil acyl glucuronide in humans and rats. The aims of this study were to demonstrate the reactivity of gemfibrozil glucuronide, determine whether gemfibrozil formed covalently bound protein adducts in vivo, describe the pharmacokinetics of adduct formation, and examine the role of gemfibrozil glucuronide in adduct formation. Rats were administered 150 mg/kg gemfibrozil daily for up to 37 days and killed 1, 2, 5, 10, 19, and 37 days after commencement of dosing, and 1, 2, 3, 8, 17, and 30 days after cessation of dosing. Plasma, liver, kidney, and heart were examined for adduct formation. Plasma was quantitatively the most important site for formation of gemfibrozil-protein adducts with mean (SE) steady-state concentrations of 31.40 (2.40) ng/mg protein attained by approximately the 10th day of dosing. Adduct half-life in plasma was 3.1 days, consistent with the elimination half-life of albumin. Mean (SE) kidney, liver, and heart steady-state adduct concentrations were 2.13 (0.11), 0.89 (0.35), and 0.95 (0.07) ng/mg protein, respectively. The rate of gemfibrozil-protein adduct accumulation seemed greatest in liver, but was similar in kidney and plasma, with approximately 2x, 16x, and 30x accumulation, respectively, over the dosing interval. In all tissues, adduct half-lives were significantly greater than those of the noncovalently bound gemfibrozil or gemfibrozil glucuronide.(ABSTRACT TRUNCATED AT 250 WORDS)     

A conundrum in molecular toxicology: molecular and biological changes during neoplastic transformation of human cells

The process of multistage carcinogenesis lends itself to the concept that the effects of carcinogens are mediated through dose-related, multi-hit, linear changes. Multiple in vitro model systems have been developed that are designed to examine the cellular changes associated with the progression of cells through the different stages in the process; however, these systems may have inherent limitations due to the cell lines used for these studies, the manner of assessing the effects of the carcinogens, and the subsequent growth and differentiation of the exposed cells. Each of these variables results in increasing levels of uncertainty relative to the correlation of the events with the actual process of human tumor development. Therefore, the prediction of the ultimate effect of any carcinogen is difficult. Moreover, relationships between individual biological endpoints resulting from carcinogen treatment appear at best to be approximations. The presence of an activated carcinogen inside the cell can give rise to multiple outcomes, only some of which may be critical events. For example, site-specific modification of the 12th and 13th codons of H-ras is different than that in the adjacent 14th and 15th codons. It is interesting to speculate what effect these differences might have on a biological outcome, e.g., transformation to anchorage-independent growth. The use of different model systems to examine the effects of activated carcinogens also creates additional problems. Comparisons of in vitro transformed cells with similar cells isolated from human tumors indicate that the culture environment appears to influence the expression of a particular phenotype, in that human tumor cells in culture express many of the same parameters as those found in cells transformed with carcinogens in vitro. If the process of transformation is linear, then less aggressive phenotypes should progress to a more aggressive transformed stage. However, in carcinogen-transformed human cells, the populations exhibit phenotypic diversity in that many of the transformed cells differentiate and fail to continue to divide in culture. Historically, we have assumed only a limited role for epigenetic modulation of molecular changes that occur during progression; however, our data suggest quite strongly that nonmalignant tumor populations can be converted to a more malignant phenotype without additional mutations taking place and, conversely, malignant populations can be downregulated to a nontumorigenic phenotype. Tumor cell plasticity is not only a fundamental characteristic of diverse types of human tumors, but also appears as an integral characteristic of carcinogen-transformed cells in vitro.     

Crop classification with landsat multispectral scanner data II

The Landsat multispectral scanner data have been analyzed with a view toward crop identification and inventory. The notion of spectral-temporal trajectory as crop signature, introduced in an earlier paper, has been further developed leading to a formulation of the problem similar to one of recognition of hand-written characters. A simple classification rule based on angular features of the trajectory is discussed and classification results are given for Landsat images from several sites.     

Dimer acid structures: Cyclic structures of clay catalyzed dimers of normal linoleic acid, 9-cis, 12-cis-Octadecadienoic acid

The clay catalyzed dimer of linoleic acid has been examined by mass spectrometry of the unhydrogenated, the partially hydrogenated and completely hydrogenated dimer. The results show that monocyclic, bicyclic and tricyclic structures are present. Monocyclic structures predominate, bicyclic structures are also prominent, and tricyclic structures are relatively minor. The monocyclic structure is believed to arise from a Diels-Alder type addition reaction. The bicyclic structure may result from a free radical coupling followed by intramolecular ring closure. The monocyclic structure in the unhydrogenated dimer appears to be mostly a benzene ring with saturated and unsaturated side-chains. It probably is formed by hydrogen transfer from the Diels-Alder cyclohexene structure first formed. Little, if any, of the Diels-Alder dimer structure as such is present. The catalytic linoleate dimer has a higher ratio of monocyclic to bicyclic dimer than does the noncatalytic (thermal) dimer made from normal (nonconjugated) linoleate, while the thermal dimer of a conjugatedtrans-trans linoleate is exclusively monocyclic. It is suggested that the clay catalyzes conjugation and hence favors the Diels-Alder reaction, and then catalyzes hydrogen transfer to aromatize the cyclohexene ring.     

Calcareous deposits formed on IUDs in human exposures

Characteristics of the calcareous deposits on several hundred IUDs of various designs and materials following in vivo exposures were examined, and an in vitro method of study was devised. There were 650 copper-wound IUDs and 18 plastic IUDs. The copper-wound IUDs had been in the uteri for 6-27 months; the plastic IUDs for 3 months to over 8 years. Microscopic examinations, X-ray diffraction, weight changes, and chemical analyses were used. X-ray diffraction showed that calcite (CaCO3) was the major crystalline constituent of the calcareous deposits. A large fraction of the deposited material was organic. Surfaces in contact with the uterine wall were essentially free of depos its. Microscopic inspection of copper-wound IUDs revealed the amount of deposit. Length of exposure increased the amount of deposit, but there were marked variations in amount. Accumulation of deposits was mostly at the fundal end. More marked local erosion of copper was noted where there was little or no carbonate deposit. Deposits occurred in patches on Lippes loops and Margulies spirals. The in vitro carbonate deposits did not reproduce the rates or morphology of the in vivo deposits. Variations in uterine carbonate formation are attributed to differences in uterine chemistry of individuals.