Effects of risperidone on dopamine receptor subtypes in developing rat brain.

The atypical antipsychotic risperidone is often prescribed to pediatric patients with neuropsychiatric disorders, though its effects on the developing brain remain unclear. Accordingly, we studied the effects of repeated treatment of risperidone on dopamine receptors in brain regions of juvenile rat. Levels of dopamine receptors (D(1), D(2), D(3), D(4)) in forebrain regions of juvenile rats were quantified after 3 weeks of treatment with three different doses of risperidone (0.3, 1.0 and 3.0 mg/kg) and compared findings to those in adult rats treated with risperidone (3.0 mg/kg/day) previously. Risperidone (at 1.0 and 3.0 mg/kg/day) increased levels of D(1) receptors in nucleus accumbens and caudate-putamen of juvenile, but not adult rats. Conversely, all three doses of risperidone dose-dependently increased D(2) labeling in medial prefrontal cortex and hippocampus, and D(4) receptor in nucleus accumbens, caudate-putamen and hippocampus of juvenile animals as well as in adults. Only the high dose of risperidone (3.0 mg/kg) increased D(2) receptors in caudate-putamen in both juvenile and adult brain. D(3) receptors were not altered by risperidone in any brain region at any dose or age. The findings indicate dose-dependent effects of risperidone on dopamine receptors in developing animals, and that juvenile animals are more sensitive than adults to the cerebral effects of risperidone.     

A dermal equivalent developed from fibroblast culture alone: Effect of EGF and insulin

We have recently developed a new dermal equivalent without exogenous materials by culturing dermal fibroblasts alone in serum-containing medium treated with several supplements. In this study, we investigated the effects of epidermal growth factor (EGF) and insulin on the formation of a dermal equivalent. After cultured dermal fibroblasts reached a confluence in serum-containing medium, they were treated with EGF or insulin. The combined effects of EGF and insulin were also studied. Macroscopically, in contrast to the culture without supplement, the addition of EGF or insulin produced a fibrous sheet. The combination of EGF and insulin showed a more marked effect than a single factor. Histologically, EGF or insulin alone induced a three-dimensional tissue containing several layers of fibroblasts. The combination of EGF and insulin produced a thicker tissue. It was composed of abundant extracellular matrix containing fibroblasts, suggesting a dermis-like tissue. It revealed collagen fibers by Masson-trichrome staining. Immunohistochemically, the components of dermal extracellular matrix such as type 1 collagen, elastin, and fibrillin-1 were diffusely expressed. Ultrastructurally, a large number of collagen fibrils with cross-striated patterns were found around the fibroblasts. These results showed that a dermal equivalent could be formed by culturing dermal fibroblasts alone postconfluently in serum-containing medium with EGF and insulin. They suggest that the two factors play an important role in the formation of a dermal equivalent.     

Structure-activity relationship (SAR) between some natural flavonoids and ocular blood flow in the rabbit.

PURPOSE: Flavonoids with two to five hydroxy groups, with or without sugar, and/or methoxy groups were studied on their effects to affect ocular blood flow. METHODS: Colored microsphere technique was used to determine the ocular blood flow in rabbit eyes. RESULTS: Flavonoids with three free hydroxy (OH) groups seemed to produce the optimal effects in increasing ocular blood flow (naringenin and hesperitin, Pfalts and Bauer, Waterbury, CT). Whether the OH groups are below three (naringenin, hesperitin, Pfalts and Bauer, Waterbury, CT) or above four (Quercetin, Pfalts and Bauer, Waterbury, CT), they produced no effects on the ocular blood flow. When OH groups are four (rutin, Aldrich, Milwaukee, WI), it produced mixed effects on ocular blood flow. The attachment of rutinose and/or methoxy group in the structure did not affect the ocular blood flow one way or the other. CONCLUSION: The ocular blood flow is increased significantly by the number of OH group in the molecule, with three the best to increase the ocular blood flow.     

Myocardial Depressant Effects of Desflurane: Mechanical and Electrophysiologic Actions In Vitro

Background: The authors determined whether desflurane altered myocardial excitation-contraction coupling and electrophysiologic behavior in the same manner as isoflurane and sevoflurane.

Methods: The effects of desflurane on isometric force in guinea pig ventricular papillary muscles were studied in modified standard and in 26 mm K+ Tyrode solution with 0.1 [mu]m isoproterenol. Desflurane effects on sarcoplasmic reticulum Ca2+ release were also determined by examining its actions on rat papillary muscles, guinea pig papillary muscles in low-Na+ Tyrode solution, and rapid cooling contractures. Normal and slow action potentials were recorded using a conventional microelectrode technique. Ca2+ and K+ currents of guinea pig ventricular myocytes were examined.

Results: Desflurane (5.3% and 11.6%) decreased peak force to approximately 70% and 40% of the baseline, respectively, similar to the effects of equianesthetic isoflurane concentrations. With isoproterenol in 26 mm K+ Tyrode solution, desflurane markedly depressed late peaking force and modestly depressed early peak force. The rested state contractions of rat myocardium or guinea pig myocardium in low-Na+ Tyrode solution were modestly depressed, whereas rapid cooling contractures were virtually abolished after desflurane administration. Desflurane significantly prolonged the action potential duration. Desflurane reduced L-type Ca2+ current and the delayed outward K+ current but did not alter the inward rectifier K+ current.     

Kidney Transplantation in Patients with Antibodies against Donor HLA Class II

The immunologic risk associated with donor-specific antibodies (DSA) against Class II human leukocyte antigens (HLA) in kidney transplant (KTx) recipients is unclear. The aim of this study was to determine the outcome of KTx when DSA was detected only against HLA Class II. To isolate the impact of anti-Class II DSA, we retrospectively analyzed 12 KTx recipients who at baseline had a positive B-cell flow cytometric crossmatch (FXM) and a negative T-cell FXM. Using alloantibody specification analysis, 58.3% (7/12) had DSA against donor Class II and 41.7% had no demonstrable DSA. Biopsy-proven AMR occurred in 57% (4/7) in the Class II(+) group and 0% in the Class II(-) group (p > 0.05). Peritubular capillaries stained positive for C4d in 86% (6/7) of the Class II(+) patients and in 40% (2/5) of the Class II(-) patients (p > 0.05). One patient in the Class II(+) group lost their graft at 3 months to accelerated transplant glomerulopathy, while all other grafts were functioning 3-37 months posttransplant despite the persistence of anti-Class II DSA. We conclude that KTx recipients with clearly defined anti-Class II DSA are at risk for humoral rejection suggesting that desensitization and/or close posttransplant monitoring may be needed to prevent AMR.     

Comparison of the effects of three different combinations of general anesthetics on the electroretinogram of dogs

The objective of this study is to compare the effects of three different anesthetic combinations on the electroretinogram in the same animals under similar laboratory conditions. Thiopental–isoflurane (TI), medetomidine–ketamine (MK), and xylazine–ketamine (XK) were used on each of 12 healthy miniature schnauzer dogs (MS) with a period of at least 3 weeks in between subsequent anesthesia protocols, using the Dog Standard Protocol. The scotopic ERGs consisted of scotopic low stimulus strength (S) responses designated S1, S2, S3, S4, and S5, at 1, 5, 10, 15, and 20 min after dark adaptation, respectively, and scotopic standard stimulus strength (S-ST) responses. The photopic ERGs consisted of a photopic single flash (P) response and 31 Hz flicker (P-FL) responses. For S-ST (2.5 cd s/m²), the amplitude of the a-wave using TI was significantly lower than that using MK (adjusted P = 0.05) and XK (adjusted P = 0.03), and the implicit time of the a-wave was significantly shorter than that using MK (adjusted P = 0.04). For P (2.5 cd s/m²), the amplitude of the b-wave using XK was significantly higher than that using MK (adjusted P = 0.01). The implicit times of the b-wave using TI was significantly longer and shorter than that of MK for S1, S2 and P-FL and for S4 and S-ST, respectively, and than that of XK for S2 and P-FL and for S5 and S-ST, respectively. The results of the present study showed that TI affected both the amplitude and the implicit time of the a-wave for S-ST and the implicit time of the b-wave relatively more so than was the case when using XK or MK. Therefore, it appears that either XK or MK could be advantageous to use rather than TI for clinical studies.     

Studies on in vitro S-methylation of naturally occurring thiol compounds with N-methyl-N-nitrosourea and methyl methanesulfonate

N-Methyl-N-nitrosourea (MNU) and methyl methanesulfonate (MMS) were found to rapidly methylate glutathione (GSH) in vitro yielding S-methyl glutathione, as verified and quantitated by high-performance liquid chromatography and thin-layer chromatography. Formation of S-methylcysteine in the acid-hydrolyzate of the methylated GSH further confirmed the formation of S-methyl glutathione. Other naturally occurring thiol compounds such as cysteine and homocysteine were also methylated by MNU. The observed pH dependency of GSH methylation by MNU suggests that the sulfide anion form of the thiol may represent the favored methyl acceptor. The high reactivity of GSH toward MNU and MMS may be of biological significance in that it could compete with macromolecular cellular components as a target for alkylation.     

Traumatic cervical Brown-Sequard and Brown-Sequard-plus syndromes: the spectrum of presentations and outcomes.

Brown-Sequard syndrome (BSS) and Brown-Sequard-plus syndrome (BSPS) are characterised by asymmetrical paresis with hypalgesia more marked on the less paretic side. This study examined the clinical features of 38 patients (30 males and 8 females; mean age = 32 years) with traumatic cervical BSS or BSPS who underwent comprehensive inpatient rehabilitation. Twenty two injuries were caused by road traffic accidents, 8 by penetrating injuries, 5 by diving injuries, and 3 by other causes. After an average of 35 days in acute care and 79 days in rehabilitation, 37 patients had increased muscle strength, all 38 patients improved functional abilities, 29 patients walked independently, 34 had spontaneous bladder emptying, 36 were discharged home, and 14 were employed. Statistically significant increases (p less than 0.001) were made in modified Barthel index functional scores between admission and discharge. Patients with BSPS had a better prognosis than did those with 'pure' BSS. Patients with predominant upper limb weakness had more favourable outcomes than did those with predominant lower limb weakness. Few other potentially predictive demographic, injury, or neurological factors were associated with functional outcome. Patients with BSS or BSPS generally have a good prognosis for neurological and functional improvement.     

Intraocular pressure and axial length in children

The intraocular pressure and the anteroposterior length of the eye are of great clinical importance for the diagnosis and management, before and after surgery, of congenital glaucoma. It is well-known that normal intraocular pressure in children is different from the normal levels in adults. We performed measurements of intraocular pressure and axial length in 141 children who had been admitted for eye problems other than glaucoma. The intraocular pressures were measured with the Perkins hand-held applanation tonometer at the beginning of general anesthesia. Simultaneously, A-scan ultra-sound measurements of the axial lengths of the eyes were made. In 10 children under the age of two years, the intraocular pressure was 11.85 +/- 1.35 mmHg. In 79 children from two to seven years, the intraocular pressure was 12.80 +/- 1.73 mmHg. In 52 children from seven to 15 years, the intraocular pressure was 13.31 +/- 1.79 mmHg. The axial lengths of the eyes in children under the age of two years, from two to seven years, and from seven to 15 years, were 21.31 +/- 0.97 mm, 22.04 +/- 0.92 mm, and 23.22 +/- 1.00 mm, respectively. These results were considered to be guidelines for measuring intraocular pressure and axial length in children suspected of having congenital glaucoma. The differences of intraocular pressures stated by other authors are due to early measurement of the intraocular pressure at the beginning of general anesthesia.