Interaction of clozapine with metformin in a schizophrenia rat model.

The low efficacy of antipsychotic drugs (e.g., clozapine) for negative symptoms and cognitive impairment has led to the introduction of adjuvant therapies. Because previous data suggest the procognitive potential of the antidiabetic drug metformin, this study aimed to assess the effects of chronic clozapine and metformin oral administration (alone and in combination) on locomotor and exploratory activities and cognitive function in a reward-based test in control and a schizophrenia-like animal model (Wisket rats). As impaired dopamine D1 receptor (D1R) function might play a role in the cognitive dysfunctions observed in patients with schizophrenia, the second goal of this study was to determine the brain-region-specific D1R-mediated signaling, ligand binding, and mRNA expression. None of the treatments affected the behavior of the control animals significantly; however, the combination treatment enhanced D1R binding and activation in the cerebral cortex. The Wisket rats exhibited impaired motivation, attention, and cognitive function, as well as a lower level of cortical D1R binding, signaling, and gene expression. Clozapine caused further deterioration of the behavioral parameters, without a significant effect on the D1R system. Metformin blunted the clozapine-induced impairments, and, similarly to that observed in the control animals, increased the functional activity of D1R. This study highlights the beneficial effects of metformin (at the behavioral and cellular levels) in blunting clozapine-induced adverse effects.

Perineural capsaicin induces the uptake and transganglionic transport of choleratoxin B subunit by nociceptive C-fiber primary afferent neurons.

The distribution of spinal primary afferent terminals labeled transganglionically with the choleratoxin B subunit (CTB) or its conjugates changes profoundly after perineural treatment with capsaicin. Injection of CTB conjugated with horseradish peroxidase (HRP) into an intact nerve labels somatotopically related areas in the ipsilateral dorsal horn with the exceptions of the marginal zone and the substantia gelatinosa, whereas injection of this tracer into a capsaicin-pretreated nerve also results in massive labeling of these most superficial layers of the dorsal horn. The present study was initiated to clarify the role of C-fiber primary afferent neurons in this phenomenon. In L5 dorsal root ganglia, analysis of the size frequency distribution of neurons labeled after injection of CTB-HRP into the ipsilateral sciatic nerve treated previously with capsaicin or resiniferatoxin revealed a significant increase in the proportion of small neurons. In the spinal dorsal horn, capsaicin or resiniferatoxin pretreatment resulted in intense CTB-HRP labeling of the marginal zone and the substantia gelatinosa. Electron microscopic histochemistry disclosed a dramatic, ∼10-fold increase in the proportion of CTB-HRP-labeled unmyelinated dorsal root axons following perineural capsaicin or resiniferatoxin. The present results indicate that CTB-HRP labeling of C-fiber dorsal root ganglion neurons and their central terminals after perineural treatment with vanilloid compounds may be explained by their phenotypic switch rather than a sprouting response of thick myelinated spinal afferents which, in an intact nerve, can be labeled selectively with CTB-HRP. The findings also suggest a role for GM1 ganglioside in the modulation of nociceptor function and pain.

Ultrastructural changes in the receptor parts of retinal rods in experimental alloxan-induced diabetes in rabbits.

Mature rabbits were administered a single dose of alloxan at the dose 100 mg/kg b.m. After 3 and 6 weeks and after 3 and 6 months, the samples of the retina were taken from the areas immediate to the papilla of the optic nerve. Ultrathin sections were dyed according to the Reynold's method, and the receptive parts of the rods were examined under electron microscope BS-500 Tesla. After 6 weeks following alloxan administration, distinct morphological changes in the form of enlargement of certain discs in the receptive parts of rod cells were observed. After 3 months the majority of the discs was damaged, and after 6 months only single, quite well preserved rod cells were found to be present in the retina.

Histological changes in the retina in experimental alloxan-induced diabetes in rabbits.

Mature rabbits were given a single dose of alloxan at the dose of 100 mg/kg of b.m. After 3 and 6 weeks and after 3 and 6 months the retina samples were taken from the areas immediate to the papilla of the optic nerve. Half-thin sections were stained with Swiss blue and azure, and the changes in the particular layers were evaluated under the light microscope. Morphological changes in the form of decreased number of neurones (especially ganglionic) and narrowed layer of rods and cones occurred after 6 weeks. After 3 months even further increase in the number of neurones and atrophy of the pigmented epithelium cells were observed. After 6 weeks nearly total atrophy of ganglionic neurones and distinct narrowing of all the layers were found.

Embryofetotoxicity of acetaminophen (paracetamol) in experimental in vivo model.

The aim of the study was to evaluate the toxic effect of acetaminophen on rat fetuses. Acetaminophen, suspended in Tween 80 solution, was administered once a day, orally by a stomach tube to pregnant Wistar rats from day 8th to 14th of pregnancy at the dose: 3.5 (P1), 35.0 (P2), 350.0 mg/kg (P3). The pregnant females were terminated on day 21st of pregnancy and the number of corpora lutea, implants, resorptions, and fetuses was counted. The fetuses and the placentas were weighed and the length of the fetuses and their tails were checked. The slides of the fetal liver were examined via light microscopy in four stains: hematoxylin and eosin, silver Gomorii, van Giesson, and periodic acid-Schiff. There was a statistical (p < 0.05) difference in fetal body length in group P3 without any macroscopic malformation, except for the non-statistical number of subcutaneous ecchymoses. Histological adaptive changes of the fetal liver were observed occasionally in all the studied groups. In conclusion, the oral administration of acetaminophen caused an embryotoxic effect in the highest doses without any macroscopic malformation, and only slightly impaired morphology of the rat fetal liver.

Branches of posterior cerebral artery vascularising visual cortex in man.

In 180 brains it was found that the calcarine artery was the main branch supplying the medial surface of the occipital lobe. Also the accessory calcarine artery contributed to vascularization of the occipital lobe. This artery originated from the medial occipital, lateral occipital, parietooccipital, and occipitotemporal arteries.

Activity of cathepsins in rat's spleen due to experimentally induced pancreatitis.

The aim of this study was to establish and quantify the changes of the level of cathepsin B, D and L in the spleen during experimental pancreatitis. The experiment was carried out in 115 male Wistar rats, randomly divided into three groups: intact (n = 15), injected with 0.9% NaCl solution into the common bile pancreatic duct (n = 50) and injected with 5% sodium taurocholate into this duct to induce acute pancreatitis (n = 50). After 2, 6, 12, 24 and 48 hours rats were anaesthetised, and blood was taken for amylase determination from the heart, and the spleen was removed. Alpha-amylase level in the blood serum samples was measured by enzymatic method. Cathepsin activity was established by spectrophotometric methods using substrates which form coloured complexes when they react with these proteases. The specific free fraction activity of cathepsin B, D and L in the spleen changed during the course of experiment, but there was no correlation between their activity and the intensity of pancreatitis established by serum amylase level.

The activity of lysosomal enzymes in visual cortex of rabbits during experimental diabetes.

The activity of all principal groups of lysosomal enzymes (acid phosphatase, lipase, beta-galactosidase, sulphatase and cathepsin B) was measured in the visual cortex of rabbits with experimental diabetes. In the first stage of diabetes (21 days), it was observed that enzyme activities in the free fraction and in the membrane-bound fraction are decreased as compared to the initial values determined in healthy animals. In the later stages of diabetes (90-180 days), all lysosomal enzyme activities increased except for sulphatase. This indicated a superiority of catabolic processes in visual cortex cells in the course of experimental diabetes.

Cost management information improves financial performance.

Cost management information creates flexible and effective solutions to a hospital's most pressing challenges. A cost management approach recognizes that all strategic, operational, and financial issues are interrelated. Thus, cost management information enables executives to improve strategic planning, cost controls, and financial performance.

The posterior portion of the cerebral arterial circle in postnatal life.

The posterior cerebral arteries and posterior communicating arteries were dissected in 180 human brains. The origin and diameter of vessels were determined with consideration to age, sex and body side. In 30 brains of humans aged 0 to 60 years microscopic structure of arteries was described. There is no histological difference in the structure of arterial wall in different age periods.

[The basilar artery of humans]. / Tetnica podstawna u czlowieka.

The basilar artery in 44.4% of the cases came into being by joint of two vertebral arteries on the height of the inferior margin of the pont. However, in 40.4%--below, and in 15.1%--above of this margin. In 78.7% of the human the course of basilar artery was rectilinear. In 20.5% of the cases the bulge of this artery was observed on the right or left side, whereas in 0.8%--the S-shaped forms. In 56% of the persons the segmentation of the basilar artery on the posterior cerebral arteries takes place on the height of the superior margin of the pont, in 32.9%--above, and in 11.1%--below this one. The results of the investigations concerning the place of genesis, the height of segmentation and the direction of course of the particular artery, were permitted on separation of nine types of these blood vessels. The diameter of the initial and terminal section of the basilar artery at the new-born children was--respectively--1.9 and 1.8 mm, whereas at the adult persons it exceeded 4 mm. The length of this vessel ranged from 17.2 mm in the above-mentioned children to approximately 33 mm in persons over 20 years old. In all the examined cases the basilar artery was passing the arteries of the pont: medial and lateral and almost always the superior and the inferior anterior cerebellar arteries. In 12.4% of the persons the inferior posterior cerebellar arteries and, moreover, in 22.2%--the labyrinth arteries were beginning from this blood vessel.

Product-line performance reporting: a key to cost management.

For many hospitals, performance reporting is the most important and valuable function of a cost management system. Performance reporting provides hospitals--or any organization, for that matter--with an enhanced ability to reduce and control costs and monitor profitability. By periodically comparing strategic and operational plans with actual results, managers are provided with measurements of their performance for the aspects of the organization they control. The following is an excerpt from the book, Cost Management for Hospitals. This section deals with product-line performance reporting and the variances that measure the effects different factors have on performance.