Resetting of the arterial baroreflex increases orthostatic sympathetic activation and prevents postural hypotension in rabbits

Since humans are under ceaseless orthostatic stress, the mechanism to maintain arterial pressure (AP) under orthostatic stress against gravitational fluid shift is of great importance. We hypothesized that (1) orthostatic stress resets the arterial baroreflex control of sympathetic nerve activity (SNA) to a higher SNA, and (2) resetting of the arterial baroreflex contributes to preventing postural hypotension. Renal SNA and AP were recorded in eight anaesthetized, vagotomized and aortic-denervated rabbits. Isolated intracarotid sinus pressure (CSP) was increased stepwise from 40 to 160 mmHg with increments of 20 mmHg (60 s for each CSP level) while the animal was placed supine and at 60 deg upright tilt. Upright tilt shifted the CSP–SNA relationship (the baroreflex neural arc) to a higher SNA, shifted the SNA–AP relationship (the baroreflex peripheral arc) to a lower AP, and consequently moved the operating point to marked high SNA while maintaining AP. A simulation study suggests that resetting in the neural arc would double the orthostatic activation of SNA and increase the operating AP in upright tilt by 10 mmHg, compared with the absence of resetting. In addition, upright tilt did not change the CSP–AP relationship (the baroreflex total arc). A simulation study suggests that although a downward shift of the peripheral arc could shift the total arc downward, resetting in the neural arc would compensate this fall and prevent the total arc from shifting downward to a lower AP. In conclusion, upright tilt increases SNA by resetting the baroreflex neural arc. This resetting may compensate for the reduced pressor responses to SNA in the peripheral cardiovascular system and contribute to preventing postural hypotension.     

Long-term outcomes of 600 living donor liver transplants for pediatric patients at a single center.

This report concerns the long-term outcome of living donor liver transplantation (LDLT) for pediatric patients at a single center. Between June 1990 and December 2003, a total of 600 LDLTs, including 568 primary transplantations and 32 retransplantations, were performed for pediatric patients, who were immunosuppressed with FK506 and low-dose corticosteroids. Patient survival at 1, 5, and 10 years were 84.6%, 82.4%, and 77.2%, respectively, and the corresponding findings for graft survivals were 84.1%, 80.9%, and 74.5%. Multivariate analysis demonstrated that fulminant hepatic failure (FHF), a graft vs. body weight (GBWR) ratio of <0.8, and ABO-incompatible transplants were independently associated with both patient and graft survival. The retransplantation rate was 6%, and 55 patients (9.7%) have been completely weaned off immunosuppressants. Long-term patient and graft survival after pediatric LDLT for a large cohort of children at our hospital were found to be as good as those for cadaveric liver transplantation, although this series includes 13% liver transplantations with ABO-incompatible donors, which are obviously inferior in patient and graft survival. To obtain better outcomes for patients with FHF and for patients with ABO-incompatible transplants, immunosuppressive therapy needs to be improved.     

Pharmacodynamic Modeling for Change of Locomotor Activity by Methylphenidate in Rats

Purpose. The locomotive activity changes after intravenous (i.v.) administration of methylphenidate (MPD) in rats were pharmacodynamically analyzed. Methods. MPD concentration in plasma, MPD concentration and dopamine (DA) level in striatal dialysate collected by microdialysis method, and the locomotor activity after i.v. administration of MPD (2, 5 and 10 mg/kg doses) were used for the analysis. Results. The transport of MPD from plasma to the interstitial fluid in the brain could be expressed by the linear two-compartment model. The clockwise hysteresis between the MPD concentration and the DA level in the dialysate could be explained by the pharmacodynamic model considering Michaelis-Menten type reuptake process of the extracellular DA into the terminal of the dopaminergic nerve and its competitive inhibition by the extracellular MPD. The inhibition constant (K_i) of MPD for DA reuptake was estimated to be 41.3 ± 73.8 nM (mean ± SE), which was closely consistent with the in vitro value after correction with dialysis recovery. The relationship between DA level in dialysate and locomotor activity was expressed by the Emax model considering two contrary effects, hyperkinesia and stereotypy. The bi-phasic locomotor activity-time profiles after high dose of MPD could be represented by this model. Conclusions. The developed model made it possible to explain the tolerance in DA increase and the complicated locomotive change induced by MPD, and may be useful for other DA reuptake inhibitors, such as amphetamine and methamphetamine.     

Synthesis,characterization and photoreaction of side-chain liquid-crystalline polymers and copolymers comprising alkenyloxy-biphenyl mesogen

Photoreactive (meth)acrylate monomers having mesogenic groups based on 4-hexyloxy-4′-(3-methyl-2-butenyloxy)biphenyl and 4-hexyloxy-4′-(2-butenyloxy)biphenyl were synthesized. Methacrylate monomers ( 3c, d ) and acrylate monomer having 3-methyl-2-butenyloxy group ( 3b ) were polymerized by free radical mechanism; the acrylate monomer having 2-butenyloxy group ( 3a ) caused gelation during the polymerization. To obtain photoreactivity, 4-benzoylphenyl (meth)acrylates were radically copolymerized with monomers 3b and 3d . Thermal behavior of (co)polymers was determined by differential scanning calorimetry, polarized optical microscopy and temperature-controlled X-ray analysis. (Co)polymers showed liquid-crystalline behaviour with nematic and smectic phases. UV-irradiation was used to photochemically crosslink copolymer films, and the resultant films were insoluble in organic solvents. The uniaxially oriented copolymer thin film was photo-crosslinked and showed thermally stable orientation.     

Micro- and macro-consequences of ooplasmic injections of early haploid male gametes

This review refers to the evolution of ooplasmic injectionsof round spermatid nuclei ROSNI) or intact round spermatidsROSI). Conclusions from their preliminary application in thehamster, rabbit, mouse and human are discussed. Criteria foridentification of round spermatids and guidelines/quality controlfor application of ROSNI/ROSI techniques are emphasized. Althoughall the animal offspring and the human newborns delivered afterROSNI/ROSI are healthy additional research efforts are necessaryto confirm the safety of these procedures and improve theiroutcome     

Cutaneous eruption with or without ocular complications in patients with herpes zoster involving the trigeminal nerve

We examined 62 patients with acute herpes zoster involving the trigeminal nerve; 13 had eruptions only and 49 (51 eyes) had eruptions with ocular complications. Bilateral involvement was found in two patients. The frequency of the disease appeared to increase with age, and the disease was least active in November. Patients with eruptions only demonstrated affected areas along the first, second, and/or third divisions of the trigeminal nerve. Ocular complications occurred in patients who had eruptions along the first and/or second divisions of the nerve, and they were usually noted in patients with eruptions on the tip and one side of the node. The ocular complications and associated systemic conditions varied.     

Expression of human epidermal growth factor and its receptor in esophageal cancer

The expression of human epidermal growth factor (hEGF) was examined immunohistochemically in 86 esophageal cancer lesions, comprising 67 primary tumors and 19 metastatic lymph nodes. In the normal esophagus, the parabasal and intermediate cell layers showed a weak expression of hEGF, however, hEGF-positive tumor cells were detected in 62 (92.5 per cent) of the 67 primary esophageal carcinomas and in 18 (94.7 per cent) of the 19 metastatic lymph nodes. In this study, the immunoreactivity of hEGF was classified into 4 grades according to the number of stained tumor cells. A significant correlation was observed between the histologic type and the grade of hEGF immunoreactivity (Chi-square test, p less than 0.01). hEGF immunoreactivity in well differentiated squamous cell carcinomas was significantly higher than in other squamous cell carcinomas, although there were no correlations between other pathological findings and hEGF immunoreactivity. Patients with hEGF immunoreactivities of grades II or III had much worse prognoses than those with grades 0 or I (p less than 0.05). In 22 esophageal carcinomas and 10 normal esophageal mucosae, EGF receptor (EGFR) contents were measured by the competitive binding assay. The average EGFR content (101.3 +/- 35.7 fmol/mg protein, mean +/- SE) of the esophageal carcinomas was significantly higher than that (5.3 +/- 1.2) of the normal esophageal mucosae (p less than 0.05). Moreover, in hEGF negative tumors, EGFR contents were lower than in hEGF positive tumors. These results suggest that hEGF and EGFR show increased production in squamous cell carcinomas and could to be useful prognostic factors in patients with esophageal cancer.     

Rapidly growing calcified cerebellar astrocytoma in infants

We report the case of an infant with a cerebellar astrocytoma that showed marked calcification within only 6 months. In general, only slow-growing tumors tend to calcify. To our knowledge, no other case of such rapid calcification in cerebellar astrocytoma has been reported.     

Detection of nephritogenic antigen from the Lewis rat renal tubular basement membrane

Immunopathogenicity of trypsin-solubilized or non-solubilized renal tubular basement membrane (TBM) of the Lewis (LEW) rat was investigated. Autoimmune tubulointerstitial nephritis (TIN) was induced in BALB/c mice by immunization with trypsin-solubilized LEW rat TBM, while immunization with non-solubilized TBM did not produce the disease. Based on this preliminary experiment we studied the characterization of immunogenic and nephritogenic TBM antigen of the LEW rat. TIN was characterized by severe mononuclear cell infiltrates with multi-nucleated giant cells in the interstitium, tubular destruction and intensive IgG and C3 deposits along the TBM. Anti-TBM antisera and eluate from the nephritic mouse kidneys reacted with the TBM of normal LEW rat kidney by immunofluorescence. LEW rat TBM was also detected immunofluorescently by using antisera from BALB/c mice immunized with autologous trypsin-solubilized TBM. A competitive inhibition test revealed a higher titer of anti-TBM antibody in the eluate than in the adsorption-treated antisera per microgram IgG. Immunoblotting showed one reactive band with a molecular weight of 45,000 daltons, and the blotting patterns in tryptic TBM of the Brown Norway (BN) and LEW rats appeared similar. Amino acid analysis of nephritogenic LEW rat tryptic TBM showed that it contained no hydroxyproline and hydroxylysine, suggesting that this TBM preparation was not collagenous. These findings suggest that tryptic digestion contributes to the release of nephritogenic antigen from the LEW rat TBM and that this antigen system might participate in the immune system involved in the anti-TBM associated TIN that is well known to be induced by non-digested TBM of TBM antigen positive animals.