Peptide growth factors in normal and hypertrophied bladder

The pharmacokinetics of oral zidovudine in HIV-infected children and adults are reported. Fourty-six patients were investigated. For data analysis three groups of similar size were formed: young children 4 months-4 years, n = 15 (group 1), older children up to 13 years, n = 16 (group 2) and young adults, n = 15 (group 3). After a single oral dose repeated blood samples were taken 1/2 hourly during a period of 4 hours and zidovudine concentrations in plasma were determined by high performance liquid chromatography. For better comparison of dose dependent parameters peak concentrations (Cmax) and the area under the time-concentration curves (AUC) were normalized either to the dose/body weight (bw) or the dose/body surface area (bs), respectively. Time to reach peak concentrations and mean terminal elimination half-life times (t1/2 beta = 63.4 +/- 47.6, 74.9 +/- 54.9 and 56.9 +/- 16.4 min in group 1, 2 and 3, respectively, mean +/- SD) were not significantly different between the three groups. With normalization to dose/bw young children in comparison to adults had significantly lower Cmax (2.7 +/- 1.3 vs. 4.6 +/- 2.4 mumol/l, p = 0.016) and AUC (226 +/- 108 vs. 373 +/- 224 mumol.min/l, p = 0.038). Group 2 gave intermediate values. However, with normalization to dose/bs differences in Cmax (6.5 +/- 3.3, 7.3 +/- 4.2 and 6.8 +/- 3.6 mumol/l, in group 1, 2, and 3, respectively) and AUC (563 +/- 313, 691 +/- 351 and 555 +/- 342 mumol.min/l, in group 1, 2 and 3) were not significant between the three groups. It is likely that changes in body water content with age may account for most of these differences observed. In conclusion, a similar pharmacokinetic profile was found in children older than 3 months as compared to older children or adults.     

Cardiac MRI of the normal and hypertrophied mouse heart

With the development of recent transgenic techniques, studies involving mice offer opportunities to increase understanding of cardiac disease. This provides motivation for the current study to perform noninvasive evaluation of the normal and hypertrophied mouse heart with MRI. By acquiring ECG and respiratory signals, the MR image acquisition was gated to both the cardiac and respiratory cycles. Combining a spin-warp imaging sequence with an RF surface coil resulted in short-axis images that allowed quantification of in vivo cardiac mass. Excellent agreement between MRI-determined (y) and postmortem heart weight (x) was obtained: y = 0.991x + 1.43 (r = 0.996). Isoproterenol, at 282 micromol/kg body weight (BW) and 573 micromol/kg BW, induced a dose-dependent increase in the ratio of heart weight to BW of 16.8 +/- 1.09% and 24.1 +/- 1.71%, respectively, which was accurately measured by MRI. These results demonstrate the ability of MRI to noninvasively monitor cardiac anatomy in the mouse.     

Doppler studies in normal kidneys of healthy children

Oral malodor (halitosis) is a common concern in Western society. As with other human perceptions, emotional as well as cognitive variables play a major role in one's sensation and complaint. To study factors potentially associated with the complaint of oral malodor, periodontal and psychological evaluations were carried out on 38 subjects (66% female, mean age 43 years) with a complaint of oral malodor. Subjects underwent evaluation of their periodontal status, odor evaluation by an odor judge, and psychopathological symptom survey by means of the SCL-90 questionnaire. The patient's self-rating of oral odor was significantly higher than the evaluation of an objective odor judge and was not associated with their periodontal status. The SCL-90 profile of subjects was relatively higher than that of an age- and gender-matched reference group of dental patients. The results suggest that the complaint of oral malodor may be related to psychopathological symptoms as recorded by the SCL-90 questionnaire.     

Serial light and electron microscopic changes in renal glomeruli in mice fed griseofulvin

The acclimation of the clawed toad Xenopus laevis to hyperosmotic solutions of NaCl (balanced solution of sea salt), urea or mannitol was studied. The animals could not be acclimated to salt solutions more concentrated than 400 mosm.1-1. Urea was tolerated till 500 mmol.1-1. Plasma osmolality was always hyperosmotic to the environmental solution, but with diminished osmotic gradient at the highest tolerated solutions. Plasma urea concentration approached 90 mmol.1-1, similar in the three solutions of acclimation. Urine volume was very small under all conditions. Serum aldosterone and corticosterone did not differ significantly, although there was a slight tendency towards lower aldosterone in the NaCl solution. In vivo water uptake in tap water acclimated animals was very small, and was higher in the other groups. Only the salt- and urea-acclimated, but not the tap water and mannitol-acclimated groups responded with a clear increase following injection of oxytocin or theophylline. In vitro urea fluxes were similar and invariable in both directions under all conditions. No significant effect of theophylline was observed. Sodium transport measured by the short-circuit technique in vitro was lower in salt- and mannitol-acclimation conditions, and was stimulated significantly under all conditions in response to serosal oxytocin or theophylline. It is concluded that Xenopus laevis can osmoregulate at a limited range of external solutions. It is limited in the increase of its plasma urea concentration; the transport properties of the skin do not change very much upon acclimation, except for the hydroosmotic response to oxytocin.     

Effects of angiotensin II on inotropy and intracellular Ca2+ handling in normal and hypertrophied rat myocardium

The direct inotropic effect of angiotensin II on the myocardium is still controversial and little information exists as to its potential modification by heart disorders. Therefore, this study performed simultaneous measurements of isometric force and intracellular Ca2+ concentrations ([Ca2+]i) in left ventricular papillary muscles from sham-operated and aortic-banded rats at 10 weeks post-surgery. Angiotensin II (10(-6) M) induced a reduction of peak systolic [Ca2+]i (0.56 +/- 0.03 to 0.48 +/- 0.04 microM; P<0.05) and a parallel but insignificant diminution of developed tension (10.5 +/- 1.3 to 9.6 +/- 0.8 mN/mm2) in normal papillary muscles from sham-operated animals. Hypertrophied papillary muscles from aortic-banded rats demonstrated a significant decline in both peak systolic [Ca2+]i (0.51 +/- 0.02 to 0.44 +/- 0.01 microM; P<0.05) and developed tension (8.4 +/- 1.1 to 6.8 +/- 1.7 mN/mm2; P<0.05) after addition of angiotensin II. The time courses of the mechanical contraction and the intracellular Ca2+ signal were prolonged by angiotension II in both groups. Isoproterenol dose-dependently increased developed tension and peak systolic [Ca2+]i in papillary muscles from sham-operated rats. In contrast, the positive inotropic response to isoproterenol was markedly reduced in hypertrophied muscles despite a seemingly unimpaired increase in peak systolic [Ca2+]i. Pretreatment with angiotensin II (10(-6) M) resulted in a significant attenuation of the systolic [Ca2+]i response to isoproterenol stimulation in both normal and hypertrophied papillary muscles. Neither the bradykinin B2 antagonist icatibent (10(-6) M) nor the nitric oxide (NO) inhibitor L-NMMA (10(-6) M) abolished the depressant effects of angiotension II. Thus, ANG II induces a parallel decline of the mechanical performance and Ca2+ availability in rat myocardium. These effects are more distinct in hypertrophied than in normal muscle and become accentuated during beta-adrenergic stimulation. The underlying mechanism is not associated with the NO pathway but might involve a negative functional coupling between the angiotensin and beta-adrenergic-receptor complex.     

Effects of noise stress on EFS-mediated cholinergic and inhibitory NANC responses in tracheae from normal and sensitized guinea-pigs

1 The aim of the present research was to study the cholinergic and inhibitory non-adrenergic-non-cholinergic (NANC) responses obtained with electrical field stimulation (EFS) of tracheal tissues from sham- and noise-exposed guinea-pigs. A comparison was also made between normal and ovalbumin (OA)-sensitized animals. 2 In proximal tracheae pretreated with indomethacin (3 microM), propranolol (1 microM), alpha-chymotrypsin (2 U ml-1) and L-NAME (0.1 mM), frequency-dependent responses to EFS (0.1 ms width; 20 V, 0.1-100 Hz, 15 s train duration) were obtained, both contractile and relaxing in nature. The contractile responses were abolished by atropine (1 microM), and did not vary significantly between sham- and noise-exposed guinea-pigs, or between normal and sensitized animals. The NANC relaxing responses, present in spite of the pre-treatment of the tissues with L-NAME and alpha-chymotrypsin, and almost completely abolished by tetrodotoxin (TTX) treatment (10 microM), appeared to be enhanced in noise-exposed guinea-pigs, with respect to sham-exposed animals, but only when the animals were not OA-sensitized. 3 In distal tracheae contracted with histamine (10 microM), the study of the whole inhibitory NANC response (pre-treatment with propranolol, but not with alpha-chymotrypsin and L-NAME), which was mainly TTX-sensitive, revealed a statistically non-significant difference between sham- and noise-exposed guinea-pigs, both normal and OA-sensitized. When distal tracheae were preincubated with alpha-chymotrypsin (2 U ml-1) and L-NAME (0.1 mM), in addition to propranolol, a significant residual inhibitory NANC response to EFS was observed. Surprisingly, in this case, similarly to the evidence obtained in proximal tracheae, a significantly enhanced response was revealed in noise-exposed guinea-pigs with respect to sham-exposed animals. 4 The noise-induced enhancement of the relaxant response disappeared when the tissues were pretreated with the A2 purinergic antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 1 microM), while it persisted in the presence of the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 nM). 5 The above data indicate that, while not modifying the cholinergic and the whole inhibitory NANC response to EFS, noise stress selectively influences an inhibitory component of the NANC system in guinea-pig trachea with a mechanism probably involving an enhanced neurally mediated release of adenosine, which relaxes the smooth muscle via A2 receptors. This effect appears to be lacking or masked in sensitized guinea-pigs.     

Protein level in testes, kidneys and liver after AET or MEA treatment of mice

The nucleotide sequence of the genomic RNA of a Polish isolate of a potato leafroll virus was determined. Some variations between the determined sequences were observed. A comparison of the frequency of sequence variants in particular regions of the genome is presented.     

Plasma hormone levels in normal and lead-treated pregnant mice

Dietary lead (0.5%) was given to mice which, after mating, exhibited a vaginal plug. Estradiol, progesterone and prostaglandins E and F 2 alpha were determined in the plasma by radioimmuno assay at different times thereafter. The increase in estradiol and decrease in prostaglandins prior implantation are not greatly altered by lead treatment, whereas the subsequent increase in progesterone and later in estradiol is abolished. It is concluded that the lower number of pregnancies seen in lead-treated mothers is due to a maternal hormonal imbalance caused by lead.     

Distribution of gallium-67 in normal and hypotransferrinemic tumor-bearing mice

The mechanism by which 67Ga accumulates in tumors is controversial. The most popular theory is that 67Ga binds to transferrin and gains access to cells by the transferrin receptor. However, substantial evidence suggests that uptake of 67Ga may not be universally mediated by transferrin in tumors. To determine whether transferrin is required for uptake of 67Ga in vivo, we compared the uptake of 67Ga by two types of implanted tumors and by normal tissues in normal and severely hypotransferrinemic strains of Balb/C mice. One type of tumor was strongly gallium-avid in normal mice; the other was not. Uptake of 67Ga by normal soft tissues was markedly less in hypotransferrinemic than in normal mice. Uptake of 67Ga by bone was equivalent in the two types of mice. For the more gallium-avid tumor, uptake of 67Ga was similar and the ratio of tumor-to-background activity was substantially higher in the hypotransferrinemic than in the normal mice. For the less gallium-avid tumor, uptake was significantly less in hypotransferrinemic than in normal mice. These data suggest that uptake of 67Ga by bone and by some tumors may be a transferrin-independent process.     

A study of microtubules in hypertrophied cardiomyocytes

Microtubules, components of the cytoskeleton, play an important role in the maintenance of cellular shape, in intracellular transport of organelles and membrane vesicles, and in signal transduction in the cell. Studies on the role of microtubules in hypertrophied myocardial cells have been carried out using an acute pressure overloading model in which stenosis was produced in the aorta. Clinically, however cardiac hypertrophy is most frequently caused by a gradual increase in blood pressure due to essential hypertension. We evaluated the role of microtubulas by observing their serial changes in cells from spontaneously hypertensive rats (SHR), which are used as a model of essential hypertension. Blood pressure, body weight, left ventricular weight, and the cell cross-sectional area were measured in SHR and Wistar-Kyoto (WKY) rats aged 4, 6, 10, and 16 weeks (5 rats each). Microtubules in cardiocytes were observed using confocal laser scanning microscopy by the immunofluorescence method against beta-tubulin. Microtubules in cardiocytes run primarily in a longitudinal direction, thinly through the intermyofibrillar spaces and densely around the nuclei. The numbers of microtubules were measured separately in the perinuclear region and the nonperinuclear region, and their total was calculated. The cross-sectional area of a whole cell and nucleus was measured at the level of the nucleus, and microtubule density was calculated by the number of nonperinuclear microtubules in the cytosolic area. Five myocardial cells were randomly selected in each rat, and the mean density (/micron2) was observed. For comparison, similar analysis was done in an acute pressure loading model. This study showed that: 1) In the acute pressure overload model, hypertrophy was immediately observed, and microtubules were increased in 16% of cardiocytes. In SHR, an increase in blood pressure and hypertrophy of hearts were observed at the age of 6 weeks and after. The density of microtubules at the age of 4, 6, 10, and 16 weeks was 0.69 +/- 0.03 (/micron2), 0.73 +/- 0.05 (/micron2), 0.64 +/- 0.02 (/micron2), respectively, in WKY rats, and 0.54 +/- 0.03 (/micron2), 0.54 +/- 0.02 (/micron2), and 0.51 +/- 0.02 (/micron2), respectively, in the SHR, showing a relatively stability in the latter. This suggested that a gradual increase of blood pressure could not be a stimulus that changes the density and distribution of microtubules. 2) The immunofluorescence method against beta-tubulin using confocal laser scanning microscopy seems to be good method for quantitative analysis of microtubules in cardiocytes.     

The response of transplants of cultured fetal mouse ovaries in kidneys of ovariectomized adult mice

Whole ovaries from 16-day fetal mice were cultured for 6 to 20 days and then transplanted to the kidneys of ovariectomized adult mice where they remained for one to four weeks. After three weeks in the host's kidneys, many follicles developed within the transplants and became vesiculated. Many of the oocytes within these follicles had formed the first metaphase spindle of meiosis and several had completed the first polar body. Host mice bearing transplants that contained vesiculated follicles showed uterine stimulation and keratinization of their vaginae. However, ovaries that had been in culture for more than ten days before transplantation showed a limited response to the gonadotropins and never matured sufficiently to stimulate the host's reproductive tract. No ovulations occurred in any of the transplants.     

Segregated distribution of TH-immunoreactivity in olfactory glomeruli

Atypical and typical olfactory glomeruli differ in their primary afferents, centrifugal control and in some chemically identified subpopulations of interneurones. The distribution of tyrosine hydroxylase (TH)-immunopositive neurones in the periglomerular region of both typical and atypical glomeruli has been studied using a double histochemical-immunohistochemical method. A segregated distribution of TH-immunopositive cells was found among both types of glomeruli. TH-immunolabelled cells were more abundant (p < 0.05) in the atypical glomeruli. These data suggest that some neuronal subpopulations are related to specific properties of the glomerular physiology and they have a segregated distribution in different subsets of glomeruli. Thus, catecholamines might be involved in the processing of specific olfactory cues in atypical glomeruli. This study presents new differences in the cellular composition of typical and atypical glomeruli.     

Effect of furosemide and intravenous normal saline fluid load upon the renal resistive index in nonobstructed kidneys in children

Recent literature has shown that relative to baseline the renal resistive index remains unchanged in nonobstructed kidneys and increases in obstructed kidneys after administration of furosemide. To our knowledge the effect upon the renal resistive index of furosemide administered in conjunction with intravenous normal saline fluid load has not been reported. We evaluated the renal resistive index in 13 nonobstructed kidneys in 8 children 6 to 18 years old before and after furosemide and intravenous normal saline fluid load. The mean resistive index decreased from baseline (mean decrease was 0.06 +/- 0.06 standard deviation), with the observation of a resistive index decrease significant to p < 0.005). It appears likely that the combination of an intravenous normal saline fluid load and furosemide caused the resistive index decrease, since a decrease was not observed with furosemide alone; however, these results cannot exclude the possibility that the resistive index decrease was due to the intravenous normal saline fluid load alone. Nonetheless, these data are important since they may provide the foundation for the development of a pharmacologically challenged Doppler sonographic examination using furosemide and intravenous normal saline fluid load to evaluate better potentially obstructed kidneys.     

Beta-adrenergic signal transduction in the failing and hypertrophied myocardium

A strong sympathetic activation has been observed in heart failure and is the cause of beta-adrenergic desensitization in this condition. On the receptor level there is downregulation of beta1-adrenergic receptors and uncoupling of beta2-adrenoceptors. The latter mechanism has been related to an increased activity and gene expression of beta-adrenoceptor kinase in failing myocardium, leading to phosphorylation and uncoupling of receptors. beta3-Adrenoceptors mediate negative inotropic effects, but alterations in these receptors are not known. In addition, an increase in inhibitory G protein alpha subunits (Gi alpha) has been suggested to be causally linked to adenylyl cyclase desensitization in heart failure. In contrast, the catalytic subunit of adenylyl cyclase, stimulatory G protein alpha and betagamma subunits, have been observed to be unchanged. Recent evidence shows that increases in Gi alpha also depress adenylyl cyclase in compensated cardiac hypertrophy both in monogenic and polygenic and in secondary hypertension. These increases of Gi alpha can suppress adenylyl cyclase in the absence of beta-adrenergic receptor downregulation. Since cardiac hypertrophy in pressure overload is a strong predictor of cardiac failure, these observations indicate that adenylyl cyclase desensitization by Gi alpha may be a pathophysiologically relevant mechanism contributing to the progression from compensated cardiac hypertrophy to heart failure.     

Effect of guarana on exercise in normal and epinephrine-induced glycogenolytic mice

For cells irradiated by alpha particles in suspension, there is presently no simple test to show that the cell killing can be attributed to alpha-particle passages through the nuclei. In this communication, for a uniform distribution of alpha-particle sources and spherical nuclei, a D0 is calculated such that at least 63% of the cell nuclei have at least one alpha-particle passage. For a uniform distribution of alpha-particle sources and spherical nuclei, it is shown that the average dose for 63% of the cell nuclei to be hit (37% not hit) is equal to the average dose per hit. For this condition an energy deposition of any size would result in cell death and the average dose is the minimum D0 possible. Minimum D0 values are calculated using a Monte Carlo treatment for nuclear diameters from 4 to 10 microm and initial alpha-particle energies between 3.18 and 8.38 MeV.     

Glycine receptors in the retinas of normal and spastic mutant mice

PURPOSE: Spastic mutant mice have abnormal gait and righting behavior, and the responses of their retinal ganglion cells have recently been shown to be abnormal. The former defects have been linked to a reduction of glycine-receptor density in the spinal cord of spastic mutants, but the cause of the retinal defects has not yet been determined. The authors thus tested for reduced glycine-receptor density in the mutant retina by comparing the levels of glycine receptors in the retinas of spastic mutant mice with those found in normal mice. METHODS: Indirect immunofluorescence histochemistry was employed, using monoclonal antibodies directed against the alpha- and beta-subunits of the receptor and against the 93-kd cytoplasmic receptor-associated protein, gephyrin. RESULTS: In normal mice, all glycine-receptor antibodies labeled two laminae of the inner plexiform layer (IPL): a broad band in the distal third of the IPL and a narrow band in the middle of the IPL. Lighter labeling was also seen in the outer plexiform layer with these antibodies. In spastic mutant mice, the glycine-receptor labeling of the IPL was reduced markedly. However, the overall structure of the spastic mutant retina was not disrupted because the distribution and intensity of both a presynaptic marker (synaptophysin) and a marker for the rod bipolar cell (protein kinase C) in the mutant retina were indistinguishable from those in normal retinas. CONCLUSIONS: The glycine-receptor distribution in normal mice was consistent with that previously reported for the rat and with the distribution of glycine responsiveness of dissociated rodent bipolar cells. The reduced levels of glycine receptors in spastic mice help explain the abnormal ganglion cell responses in the spastic mutant.     

Antitussive activity of moguisteine enantiomers in guinea-pigs and rats

PURPOSE: We studied a case of Vogt-Koyanagi-Harada syndrome in a patient with a shallow anterior chamber. METHODS: High-resolution, anterior segment ultrasound biomicroscopy was performed to analyze the mechanism of a shallow anterior chamber. RESULTS: Ultrasound biomicroscopy disclosed a slit-like narrow angle and circumferential supraciliary fluid. The ciliary body was rotated anteriorly, and the iris showed anterior bowing consistent with pupillary block. With systemic corticosteroid treatment, the supraciliary fluid disappeared, and the ciliary body reverted to its normal position. CONCLUSION: Ultrasound biomicroscopy was useful in diagnosis and evaluation of the response to corticosteroid treatment in a patient with Vogt-Koyanagi-Harada syndrome accompanied by shallow anterior chamber.