Ultrastructural studies on prolactin and growth hormone cells in Anguilla pituitaries in long term cultures

Eel hemi-pituitaries were cultured in vitro on high or low sodium media, previously shown to affect differentially prolactin and growth hormone release. After 6 days culture, there were marked differences in the ultrastructure or both prolactin and growth hormone cells from the two groups. Morphometric data on the prolactin cells from SW-adapted eels showed a greater abundance of RER and paucity of secretory granules in cells from the low sodium medium. The size of the Golgi apparatus and the number of exocytosed secretory granules did not differ markedly between experimental groups, in contrast to previous findings on short-term cultures. Differences in the profile diameters of secretory granules are recorded between the experimental groups and the pattern differs markedly from that previously recorded for short-term cultures. The growth hormone cells from low sodium media were characterised by abundant, vesiculated RER, a prominent Golgi apparatus (in SW-adapted animals) and relatively few secretory granules. The activity of these growth hormone cells is in marked contrast to previous findings relating to short-term cultures. The shape and size of the non-granulated (stellate) cells of the RPD was again affected by the osmotic pressure of the medium.     

Time course of vinblastine-induced autophagocytosis and changes in the endoplasmic reticulum in murine pancreatic acinar cells: a morphometric and biochemical study

The time course of the vinblastine(-sulfate; 10 mg/kg body weight, single injection)-induced enlargement and subsequent regression of the autolysosomal compartment was studied by electron microscopic morphometrical and cell biochemical methods in order to gain information concerning some key problems of this major route of intralysosomal degradation of the cell's endogenous macromolecules and structures. Detailed analysis of the dynamics of the total autophagic vacuole (AV) compartment and its different subcompartments (early, advanced, late, and fused AVs), as well as of changes of rough-surfaced endoplasmic reticulum (RER) showed: 1. Pancreatic acinar cells react to vinblastine biphasically, i.e. two expansion phases of the AV compartment, the first in the 0 to 90 min and the second in the 2 to 8 h post-injectional periods, were detected. 2. Fusions of AVs are not inhibited by vinblastine, at least during the second expansion phase when cytoplasmic volume fraction (CVF) of fused AVs steadily increased until the 12th h. Fusion of early, advanced and late AVs or composition of fused complex vacuoles (AVc) are somehow regulated, as the proportion of the three AV stages from the CVF of AVc, was maintained constant throughout the second expansion phase. 3. Stimulation of autophagosome formation and resulting substrate overload seems to be the primary mode of action by which vinblastine causes the enormous expansion of the autolysosomal compartment. 4. Degranulation of the rough-surfaced endoplasmic reticulum (RER) membranes occurs in a biphasic fashion, similarly to the volume and surface changes of the AV compartment, thus supporting our previous hypothesis, that labilization or change of RER may have a role in the formation of autophagosomes. 5. Vinblastine-induced autophagocytosis is a selective process, as mitochondria, Golgi elements and zymogen granules are very much underrepresented, whereas RER is more than twice overrepresented in the volume of early AVs, when compared to their volume fraction in the whole cytoplasm. 6. Immunogold electron microscopy revealed the presence of ubiquitinylated proteins in advanced and late, but not in early AVs.     

Afferent influences on the development of the brain stem auditory nuclei of the chicken: otocyst ablation

The effects of embryonic deafferentation on the morphological development of the avian cochlear nuclei, n. angularis (NA) and n. magnocellularis (NM), were investigated. The right otocyst was surgically removed from chick embryos at 55 to 60 hours of incubation and the subsequent development of total volume, neuron number, and neuron cross-sectional area were studied with quantitative methods in animals sacrificed at 2-day intervals between embryonic days 9 and 19 and at 28 days posthatching. The development of NA and NM is severely affected by otocyst ablation. Between embryonic days 9 and 19, a large group of NA neurons in the medioventral portion of the nucleus on the operated side moves to an ectopic ventromedial position, while the remainder of this nucleus stays in its normal dorsolateral position. Beginning about day 13 of incubation, the normal increase in the volume of NA and the size of its neurons becomes progressively retarded and 40% of its neurons are lost. The growth of NM is also retarded after day 11 of incubation and the growth of mean neuron size is retarded after day 15. There is a 30% loss of neurons in NM which begins after embryonic day 11. The results indicate the primary cochlear fibers make a critical contribution to the growth and maintenance of their target neurons. The absence of this facilitative influence following otocyst ablation becomes apparent just at the time synapses would normally be formed between the the primary auditory afferents and the brain stem auditory neurons. The abnormal movement of neurons in nucleus angularis to an ectopic position after otocyst ablation suggests that primary auditory afferents may serve to stabilize the position of their target cells within the developing brain.     

Localisation of insulin-like growth factor receptors in skin follicles of sheep (Ovis aries) and changes during an induced growth cycle

Pelage growth cycles are regulated by circulating prolactin in many mammals, but the intercellular mediators of this signaling are unknown. Binding sites for insulin-like growth factors (IGFs) were examined in sheep skin to show changes in distribution and abundance of IGF receptors associated with a prolactin stimulus and the subsequent hair follicle growth cycle. Follicle cycles were induced in New Zealand Wiltshire ewes by a surge in plasma prolactin following a 4-month period of prolactin suppression with bromocriptine. Eight treated and three control sheep were slaughtered at intervals over 43 days during the follicle growth cycle. At 12-20 days after the elevation of prolactin, wool follicles passed through brief catagen and telogen phases, followed by a return to anagen. IGF binding sites were localized in skin sections by incubation with 125I-IGF-I or 125I-IGF-II. Displacement with competitive binding inhibitors (unlabeled IGF-I, IGF-II, des(1-3)IGF-I, des(1-6)IGF-II, or insulin) and affinity cross-linking showed that these binding sites were predominantly IGF type 1 and type 2 (mannose-6-phosphate) receptors. The radioligands bound especially to follicle germinal cells and prekeratinocytes. Increases in specific binding of both radioligands were observed after the rise in prolactin, but prior to anatomical changes in follicles associated with cessation of growth. For IGF-I, highest binding density was observed during catagen in the germinal matrix and dermal papilla cells. For IGF-II, peak density occurred during late anagen/early catagen in the germinal matrix and during telogen in the dermal papilla. These cycle associated changes in receptor availability suggest that IGF receptors are involved in control of the wool growth.     

Alpha-pompilidotoxin (alpha-PMTX), a novel neurotoxin from the venom of a solitary wasp, facilitates transmission in the crustacean neuromuscular synapse

The volume of cochlear nucleus and nucleolus, neural populations were determined in rats of three groups aged (1, 2-3, 22-28 months). The study data indicated that there is no difference between the volume of cochlear nucleus in the aged and adult animals (P > 0.05). Compared with the other two groups, the aged animals show a reduction of volume of necleolus of cochlear nucleus neurons (P < 0.01), a loss of neurons (spherical cell and multipolar cell) (P < 0.01). On the other hand, it shows an increase in number for the glial cells in the aged animals (48.48%, P < 0.01). Quantitative results of the cell of cochlear nucleus were analysed. We suggest that central changes also play an important role in presbycusis.     

Effects of reserpine on ECL-cell ultrastructure and histamine compartmentalization in the rat stomach

The histamine-storing ECL cells in the stomach play a key role in the control of acid secretion. They contain granules, secretory vesicles and microvesicles, and sustained gastrin stimulation results in the additional formation of vacuoles and lipofuscin bodies. The cells are rich in the vesicle monoamine transporter type-2 (VMAT-2), which can be inhibited by reserpine. The present study examines the effect of reserpine on ECL-cell ultrastructure and histamine compartmentalization. Rats received reserpine and/or gastrin. Reserpine was given twice by the intraperitoneal route (25 mg/kg once daily). Gastrin-17 was given by subcutaneous infusion (5 nmol/kg/h), starting at the time of the first reserpine injection and continuing for 4 days when the rats were killed. At this stage, histamine in the oxyntic mucosa was unaffected by reserpine but elevated by gastrin. Immunocytochemical analysis (confocal microscopy) showed ECL-cell histamine in control and gastrin-treated rats to be localized in cytoplasmic organelles (e.g., secretory vesicles). After treatment with reserpine alone or reserpine+gastrin, ECL-cell histamine occurred mainly in the cytosol. Planimetric analysis (electron microscopy) of ECL cells showed reserpine to increase the number, size and volume density of the granules and to reduce the size and volume density of the secretory vesicles. Gastrin reduced the number and volume density of granules and secretory vesicles, increased the number and volume density of microvesicles and caused vacuoles and lipofuscin bodies to appear. Reserpine+gastrin increased the number, volume density and size of the granules. Reserpine prevented the effects of gastrin on secretory vesicles, vacuoles and microvesicles, but did not prevent the development of lipofuscin. Our findings are in line with the views: (1) that preformed cytosolic histamine is taken up by granules/secretory vesicles via VMAT-2, that histamine is instrumental in the transformation of granules into secretory vesicles and in their consequent enlargement and (2) that vacuoles are formed by the fusion of large secretory vesicles.     

Changes in plasma levels of the two prolactins and growth hormone during adaptation to different salinities in the euryhaline tilapia, Oreochromis mossambicus

Studies were undertaken to determine whether the adaptation of the tilapia, Oreochromis mossambicus, to different salinities was accompanied by changes in plasma levels of growth hormone (GH) and its two prolactins (tPRL177 and tPRL188). Transfer from fresh water to 70% seawater (22 ppt) produced significant increases in plasma GH levels in males, but not in females. Both tPRLs decreased by the first sampling interval (6 hr) after transfer to seawater in both sexes. A second group of tilapia were adapted gradually to seawater (32 ppt) and were maintained in seawater for an additional 2 weeks. The fish were then transferred from seawater to fresh water. The transfer to fresh water induced a significant decline in plasma GH levels in both males and females. Both tPRLs increased within 6 hr after transfer to fresh water in both sexes. Then, plasma tPRL177 levels decreased gradually. By contrast, tPRL188 continued to increase and attained its highest levels 3 days after transfer to fresh water. These findings show that blood levels of the two tPRLs change rapidly during freshwater and seawater adaptation. The fact that tPRL177 and tPRL188 levels followed distinctly dissimilar patterns as freshwater acclimation proceeded suggests that the secretion and/or metabolic clearance of the two PRLs may be differentially regulated. The changes in GH which occurred when tilapia were moved between fresh water and seawater are compatible with the idea proposed by others for salmonids that GH may have an important role for seawater adaptation.     

Prolactin in the circulation of chronically catheterised piglet foetuses and pregnant sows, and the effect of thyrotrophin-releasing hormone

We chronically catheterised 12 piglet foetuses and 11 sows to determine the changes in circulating concentrations of prolactin during the last 2 weeks of gestation. Prolactin levels were measured by homologous radioimmunoassay and were found to average 2.12 +/- 0.23 ng . ml-1 in the foetuses and 4.19 +/- 0.84 ng . ml-1 in the sows. Foetal concentrations of prolactin increased significantly during the time period of the study. There was no change in maternal concentrations over the corresponding time. Injection of 5 micrograms TRH into 7 foetuses increased the plasma concentrations of prolactin in 6 animals, produced no apparent change in the seventh foetus and did not affect maternal concentrations of prolactin. The magnitude of the maximum response of TRH of the younger foetuses (less than 107 days delta = 0.7, 1.3, 4.2 ng . ml-1) was substantially less than that of the foetuses prior to term (greater than 107 days delta = 6.4, 21.7, 27.5 ng . ml-1). Injection of saline and the haemorrhage of blood sampling produced no significant change in the initial concentration of prolactin. We conclude that prolactin is present in the circulation of the pig foetus, that it is produced endogenously in lower concentrations than in the pregnant sow and that the foetal responsiveness to TRH stimulation increases towards the end of gestation.     

Sampling methods for potential epidemic vectors of eastern equine encephalomyelitis virus in Massachusetts

The neurotoxic effect of monosodium L-glutamate (MSG) on the morphologies in the darkly stained sexually dimorphic nucleus of the preoptic area (SDN-POA) and the lighter-staining surrounding area (non-SDN-POA) within the medial preoptic nucleus (MPN) was evaluated. Male and female Long-Evans rats were used. MSG (4 mg/g of body weight) was administered subcutaneously to pups on days 1 and 3 postnatally. Normal saline was used as the vehicle. At the age of 6 months, the rats were sacrificed and the brain tissues were fixed for histological examination. The morphological changes, i.e., total volume, density, total neuron number, neuronal nuclear volume (NNV) and ratio of pyknosis, of the SDN-POA and non-SDN-POA within the MPN, were estimated using the AMS VIDS III semiautomatic image-analytic system. The results indicate that neonatal MSG treatment caused significant neuronal loss and decreases in total volume of the SDN-POA and non-SDN-POA of male and female rats. However, only the SDN-POA of MSG-treated male rats showed a significant increase of pyknosis and decrease of neuronal density. A significant enlargement of NNV in the SDN-POA and non-SDN-POA was observed in the MSG-treated male rats. These results indicate that the MPN shows sex-specific and area-specific changes after neonatal neurotoxicity due to MSG.     

The effect of prolactin on kidney structure of the euryhaline teleost Gasterosteus aculeatus during adaptation to fresh water

The effect of injections of ovine prolactin on kidney structure was examined in the first 10 days following transfer of seawater sticklebacks to fresh water. In hormone injected animals as well as in controls the glomeruli increase slightly in size after transfer. The podocytes intensify the secretion of mucopolysaccharides, which is indicative of increased turnover of the components of the glomerular basal lamina. The nuclei of the podocytes become enlarged, while those of the juxtaglomerular cells decrease in size. These changes are related to the well known rise of the glomerular filtration rate following transfer to fresh water. Structural indications that prolactin is involved in the control of glomerular filtration were not found. The epithelial cells of the three nephronic segments and of the ureter become considerably better developed after transfer to fresh water. Cell height, nuclear and mitochondrial volume, and surface of the membranes of the basal labyrinth increase in all tubular epithelia, although not to the same extent. Increases are moderate in the first proximal segment, but increasingly higher for the second proximal segment, collecting duct and the ureter. Especially the growth of membrane surface of the basal labyrinth, site of ion transport mechanisms, is impressive. In controls, values characteristic for freshwater fishes are reached in 6 to 9 days for all parameters for cellular development. Prolactin injections greatly stimulate growth rates in all tubular epithelia: freshwater values are reached within 3 days. No further increase was found, however.     

Ultrastructural evidence for bouton proliferation in the partially deafferented dentate gyrus of the adult rat

A quantitative morphological study of the changes in the dentate gyrus molecular layer in response to the removal of perforant path afferents was made utilizing electron microscopic techniques. Alterations in 1. the population of remaining afferents, 2. glial cells, and 3. granule cell dendrites are reported. The major observation was an increase in intact bouton density in the region of denervation which began at 5 days post-lesion and continued through 11 days post-lesion, the longest post-lesion survival time studied.     

Cultures of normal human mammary cells

This paper describes a method of obtaining epithelial cells from large quantities of normal human breast tissue and the response of these cells in culture to lactogenic hormones. Suspensions of single cells and clusters of cells resembling normal ductal and alveolar structures were obtained by mechanical disaggregation and subsequent (3h) incubation of tissue fragments in 0.5 mg/ml collagenase. Cells rapidly attached to glass or plastic surfaces within 48 h and grew to form large colonies which maintained their epithelial appearance throughout 2 months of observation. Cell cycling as monitored by DNA synthesis was enhanced by insulin, hydrocortisone, or ovine prolactin (in concentrations of 5.0mug/ml each) at respectively 2,3 and 5 days of incubation. These results were observed in cultures derived from 3 premenopause samples of mammary tissue maintained in medium with 1% fetal calf serum. Prolactin at a concentration of 5 mug/ml induced phosphoprotein synthesis 8-fold over control values. In addition, prolactin induced morphological changes in cells including the development of distended endoplasmic reticulum, large microvilli, and the deposition of glycogen granules. These initial results led to the tentative conclusion that prolactin was sufficient to initiate some of the characteristics in cultured cells normally associated with lactating tissues.     

HVAF喷涂La2O3改性WC-20Cr3C2-11NiMo涂层的耐磨耐蚀性能

为进一步提升高质量WC涂层的耐磨性、耐海水腐蚀性和耐海水气蚀性。采用大气超音速火焰喷涂(HVAF)在0Cr13Ni5Mo基体上制备稀土La₂O₃改性WC-20Cr₃C₂-11NiMo涂层。通过显微硬度测试、平面孔隙测试、摩擦磨损实验、电化学实验和模拟海水超声波气蚀实验,测试涂层的显微硬度、孔隙率、摩擦因数、摩擦磨损性能、耐海水腐蚀性能和耐海水气蚀性能,分析La₂O₃对WC-20Cr₃C₂-11NiMo涂层耐磨耐蚀性能的影响。结果表明,改性后的涂层显微硬度提升到1400 HV0.2左右,平均孔隙率降低约48.6%;涂层磨损质量降低约33%,摩擦因数降低约30%,摩擦磨损表面微凹坑和微裂纹明显减少;电化学自腐蚀电位明显右移,电化学自腐蚀电流密度明显减小;涂层的气蚀质量损失减少约20%,气蚀坑洞明显减少和变小。HVAF喷涂La₂O₃改性后的WC-20Cr₃C₂-11NiMo涂层硬度略微提升,致密性、耐磨性、耐海水腐蚀性和耐海水气蚀性得到明显提升,除表面疲劳磨损外,表面摩擦磨损机理从严重磨粒磨损转变为轻微磨粒磨损,气蚀机理主要为流体冲击波侵蚀。     

Heterogeneity of growth hormone (GH)-producing cells in aging male rats: ultrastructure and GH gene expression in somatotrope subpopulations

Mammalian aging is characterized by a decline in the content and release of pituitary growth hormone (GH). However, few studies on the age-related changes in the population of GH-producing cells (somatotropes) have been carried out. We have investigated whether changes in number, ultrastructure and GH gene expression in subpopulations of somatotropes could explain the reduced GH release in aged rats. Three representative ages were studied: adult (5-month-old), old (19-month-old), and senescent (26-month-old) male rats. The total number of immunoreactive-GH cells per pituitary gland remained invariable to age. The separation of dispersed pituitary cells on a density gradient yielded two somatotrope subpopulations, of low density (LD) and high density (HD). Both subpopulations were equally represented in adults, whereas in old and senescent rats a predominance of LD-somatotropes was observed. Morphometric analysis showed that subpopulations exhibited storage and biosynthetic features inversely related. In LD-somatotropes, rough endoplasmic reticulum (RER) was more prominent but secretory granules (SG) were less abundant than in HD somatotropes. Concurrently, in situ hybridization for GH mRNA showed that GH gene expression was higher in LD-cells. Differences between subpopulations were essentially retained through the animals' lifespan, but small-sized SG, reduced RER, and low GH mRNA levels were inherent to aging both in LD- and in HD-somatotropes. The present findings demonstrate that the reduced content of pituitary GH in aged male rats is not due to a diminished number of GH-producing cells, but to the numerical predominance of scarcely granulated LD-somatotropes, combined with the decline in GH biosynthetic capacity observed in both subpopulations. In addition, age-related changes in ultrastructure and GH gene expression suggest a chronic inhibition of GH release and/or a weak stimulation of GH biosynthesis affecting both subpopulations.     

Histological observations on some of the endocrine glands in the ironfish, with special regard to the hypophysis

Endocrine glands of the ironfish were studied light microscopically to elucidate the relationship between the races of the genus Carassius. The rostral pars distalis of the adenohypophysis consists mainly of acidophils corresponding to prolactin cells and lead-hematoxylin positive cells corresponding to corticotrophs (ACTH cells). The prolactin cells are obviously arranged in the form of follicles. The proximal pars distalis contains orangenophils (STH cells) and two types of basophils (TSH and GTH cells). In the pars intermedia, three types of cells are identified: periodic acid Schiff positive cells, lead-hematoxylin stainable cells and orangenophils containing PAS positive coarse granules. In addition, small agranular cells are seldom demonstrated in the entire adenohypophysis. A considerable amount of aldehyde fuchsin positive neurosecretory material is laden in the cells of the nucleus preopticus and in the pars nervosa. The nucleus lateralis tuberis is composed of three portions: pars anterior, pars posterior, and pars lateralis. The thyroid follicles found in the pharyngeal region and head kidney show a mild state of activity. The interrenal cells intermingled with the chromaffin cells have a considerable amount of eosinophil cytoplasm. Judging from the gonadal condition, the breeding season of the ironfish may extend to the end of July.     

Interaction of progesterone and adrenocorticoids in ultrastructural development of the mammary gland of the cat

Comparative development of rough endoplasmic reticulum (RER) in mammary glands of rats was studied in relation to levels of progesterone and adrenocorticosteroids. The tranquilizer perphenazine was administered to stimulate secretion of prolactin; serum glucocorticoids also increased. When perphenazine was administered after ovulation, serum progesterone was increased 18-fold, but when treatment was begun on proestrus, ovulation was inhibited and serum progesterone increased only 4-fold. Concentrations of progesterone in the breast were approximately 10-fold greater than, but parallel to, serum concentrations. In ovulating rats the RER was poorly developed. In nonovulating rats extensive development of RER occurred. Cortisol acetate given to ovulating, perphenazine-treated rats did not alter levels of serum progesterone, but tissue progesterone was reduced by 50 per cent and development of RER approached that in nonovulating rats. The development of secretory capacity (formation of RER) in the breast appears to depend on the relation between stimulation by glucocorticoid and inhibition by progesterone.     

Relationship between the Golgi apparatus, GERL, and secretory granules in acinar cells of the rat exorbital lacrimal gland

The method of secretory granuleformation in the acinar cells of the rat exorbital lacrimal gland was studied by electron microscope morphological and cytochemical techniques. Immature secretory granules at the inner face of the Golgi apparatus were frequently attached to a narrow cisternal structure similar to GERL as described in neurons by Novikoff et al. (Novikoff, P. M., A. B. Novikoff, N. Quintana, and J.-J. Hauw. 1971. J. Cell Bio. 50:859-886). In the lacrimal gland. GERL was located adjacent to the inner Golgi saccule, or separated from it by a variable distance. Portions of GERL were often closely paralleled by modified cisternae of rough endoplasmic reticulum (RER), which lacked ribosomes on the surface adjacent to GERL. Diaminobenzidine reaction product of the secretory enzyme peroxidase was localized in the cisternae of the nuclear envelope, RER, peripheral Golgi vesicles, Golgi saccules, and immature and mature secretory granules. GERL was usually free of peroxidase reaction product or contained only a small amount. Thiamine pyrophosphatase reaction product was present in two to four inner Golgi saccules; occasionally, the innermost saccule was dilated and fenestrated, and contained less reaction product than the next adjacent saccule. Acid phosphatase (AcPase) reaction product was present in GERL, immature granules, and, rarely, in the innermost saccule, but not in the rest of the Golgi saccules. Thick sections of AcPase preparations viewed at 100 kV revealed that GERL consisted of cisternal, and fenestrated or tublular portions. The immature granules were attached to GERL by multiple connections to the tublular portions. These results suggest that, in the rat exorbital lacrimal gland, the Golgi saccules participate in the transport of secretory proteins, and that GERL is involved in the formation of secretory granules.     

The effect of neocortical lesions on the number of cells in neonatal or adult feline caudate nucleus: comparison to fetal lesions

After a unilateral resection of the frontal cortex in fetal cats the volume of the caudate nucleus increases while the packing density of neuronal and glial cells does not change. In the present report we address the questions of whether a similar lesion sustained neonatally or a more extensive neodecortication sustained neonatally or in adulthood may have the same unusual effect. Stereological methods were used to determine bilaterally the volume of the caudate nucleus as well as to estimate the total number and packing density of neurons and glial cells in the caudate nucleus ipsilateral to the lesion. Comparisons between each of three experimental groups and intact animals were made at a time when all animals were young adults. In cats with a unilateral frontal cortical lesion performed between postnatal days 8 and 14, none of the measured parameters changed significantly compared to intact controls. In cats with removal of the entire left neocortex in adulthood, the ipsilateral caudate nucleus volume decreased by 18.1% and by 21.5% relative to intact and to neonatal hemidecorticated cats respectively (P < 0.05), with no change in the contralateral caudate. In the ipsilateral caudate the total number of neurons decreased by 21.8% (P < 0.05) compared to controls while the number of glial cells did not change significantly. In the same caudate the packing density of neurons did not change significantly (except for a 17.1% decrease, P < 0.05, relative to frontal-lesioned cats) while that of glial cells increased by 19.9% and by 24.7% compared to intact and neonatal neodecorticated cats respectively (P < 0.05). In adult cats in which a similar hemineodecortication was performed between postnatal days 8 and 13, the only significant changes were a 25.8% (P < 0.05) and a 30.6% (P < 0.05) decrease in neuron packing density compared to intact and frontal-lesioned cats, respectively. In summary, a restricted unilateral neocortical resection in neonatal cats did not induce any morphological changes in the caudate nucleus that we could detect with the methods employed. In contrast, an extensive neodecortication sustained in adulthood produced ipsilateral caudate shrinkage with substantial neuron loss and increase in packing density of glial cells, while a similar lesion but sustained neonatally only altered substantially the packing density of glial cells (decreased). Therefore, we concluded that (i) the caudate nucleus hypertrophy which we reported after a unilateral discrete cortical removal during the prenatal period is a unique phenomenon which is peculiar to the cat brain during the last third of gestation; (ii) the caudate nucleus changes seen in the cats with hemineodecortication in adulthood are degenerative in nature and closely resemble those which we reported for other subcortical nuclei following a similar lesion; and (iii) the animals with neonatal hemidecortication are relatively spared from these degenerative effects. Overall, these results indicate that, as for other structures, the morphological changes of the caudate nucleus following neocortical damage depend on the maturational state of the brain at the time of the injury and on the size of the lesion, and support the notion that the consequences of cerebral cortex lesions upon subcortical brain nuclei are of a different nature when sustained in prenatal as compared to postnatal cats.     

Bacteriological, pharmacokinetic and clinical evaluation of azithromycin in the pediatric field]

Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules was studied for pharmacokinetic and clinical evaluation in the pediatric patients. Antibacterial activity of AZM against 43 clinical isolates: AZM exhibited slightly lower activity against Gram-positive bacteria and 2-8-fold higher activity against Gram-negative bacteria than erythromycin or clarithromycin. Plasma or urine samples were collected from eight patients receiving the drug in fine granular form, and two patients receiving it in capsules for the determination of drug levels. The elimination half-lives of AZM after administration at dose of 10 mg/kg/day for 3 days were 50.0 and 51.2 hours for fine granules, and 41.5 hours for capsules. AUC0-infinity was 11.7 and 24.3 micrograms.hr/ml for fine granules, and 8.3 micrograms.hr/ml for capsules. The cumulative excretion rates up to 120 hours after the start of treatment were 8.24 and 13.84% for fine granules, and 3.83% for capsules. AZM was administered to 123 patients once daily at 3.7-20.0 mg/kg body weight over 3 to 5 days with reference to the standard dose of 10 mg/kg. The drug was used to treat patients with pharyngitis, tonsillitis, scarlet fever, pneumonia, mycoplasmal pneumonia, chlamydial pneumonia, otitis media, pertussis, intestinal infection, and SSTI. The effectiveness of AZM was evaluated in 109 cases. The drug was rated "excellent" in 65.1% of the patients and "good" in 29.4%, resulting in an efficacy rate of 94.5%. Furthermore, AZM eradicated 43 of 46 (93.5%) bacteria that had been identified before the treatment. Three patients complained of side effects of urticaria (1 case) and diarrhea (2 cases). Abnormal laboratory changes were reported as follows: decreased leukocyte (3 cases), increased eosinophil (5), increased platelet (2), increased eosinophil and platelet, elevated GPT (1), and elevated GOT and GPT (1). The abnormalities, however, were mild enough to raise no clinically significant problems. In conclusion, AZM in once daily regimen was effective and safe in treatment of pediatric infections.