Optic Nerve Sheath Diameter Remains Constant during Robot Assisted Laparoscopic Radical Prostatectomy

Background

During robot assisted laparoscopic radical prostatectomy (RALRP), a CO₂ pneumoperitoneum (CO₂PP) is applied and the patient is placed in a head-down position. Intracranial pressure (ICP) is expected to acutely increase under these conditions. A non-invasive method, the optic nerve sheath diameter (ONSD) measurement, may warn us that the mechanism of protective cerebrospinal fluid (CSF) shifts becomes exhausted.

Methods

After obtaining IRB approval and written informed consent, ONSD was measured by ocular ultrasound in 20 ASA I–II patients at various stages of the RALRP procedure: baseline awake, after induction, after applying the CO₂PP, during head-down position, after resuming the supine position, in the postoperative anaesthesia care unit, and on day one postoperatively. Cerebral perfusion pressure (CPP) was calculated as the mean arterial (MAP) minus central venous pressure (CVP).

Results

The ONSD did not change during head-down position, although the CVP increased from 4.2(2.5) mm Hg to 27.6(3.8) mm Hg. The CPP was decreased 70 min after assuming the head-down position until 15 min after resuming the supine position, but remained above 60 mm Hg at all times.

Conclusion

Even though ICP has been documented to increase during CO₂PP and head-down positioning, we did not find any changes in ONSD during head-down position. These results indicate that intracranial blood volume does not increase up to a point that CSF migration as a compensation mechanism becomes exhausted, suggesting any increases in ICP are likely to be small.     

Optimal Optic Nerve Sheath Diameter Threshold for the Identification of Elevated Opening Pressure on Lumbar Puncture in a Chinese Population

Ultrasonography of the optic nerve sheath diameter (ONSD) is a non-invasive and rapid method that might be helpful in the identification of increased intracranial pressure (ICP). The use of an ONSD greater than 5 mm on ultrasound as an indicator of increased ICP in a Caucasian population has been studied. However, the cut-off point of this predictor in Chinese patients has not been established. Thus, we conducted this study to identify the ONSD criterion for the detection of elevated opening pressure on lumbar puncture (LP) in a Chinese population and to investigate the influencing factors. This study was a blind cross-sectional study. Patients who presented with suspected increased ICP were included. The opening pressure on LP of each participant was confirmed. We analyzed the clinical differences between the groups of patients with abnormal and normal opening pressures on LP. A receiver operating characteristic curve was constructed to determine the ONSD cut-off point for the identification of abnormal opening pressure on LP. In total, 279 patients were recruited, and 101 patients presented with elevated opening pressure on LP. ONSD was a significant independent predictor of elevated opening pressure on LP (p<0.001). However, no statistical significance was observed regarding the factors that might have affected this relationship including gender, age, body mass index, waistline, head circumference, hypertension and pathological subtype. The ONSD cut-off point for the identification of elevated opening pressure on LP was 4.1 mm; this cut-off yielded a sensitivity of 95% and a specificity of 92%. ONSD is a strong and accurate predictor of elevated opening pressure on LP. The cut-off point of this predictor in a Chinese population was remarkably lower than that found in a Caucasian population. Thus, ethnic differences should be noted when using the ONSD as an indicator of increased ICP.     

Phosphorylation of Proteins in Normal and Regenerating Goldfish Optic Nerve

Within 6 h after radiolabeled phosphate was injected into the eye of goldfish, labeled acid-soluble and acid-precipitable material began to appear in the optic nerve and subsequently also in the lobe of the optic tectum, to which the optic axons project. From the rate of appearance of the acid-precipitable material, a maximal velocity of axonal transport of 13-21 mm/day could be calculated, consistent with fast axonal transport group II. Examination of individual proteins by two-dimensional gel electrophoresis revealed that approximately 20 proteins were phosphorylated in normal and regenerating nerves. These ranged in molecular weight from approximately 18,000 to 180,000 and in pI from 4.4 to 6.9. Among them were several fast transported proteins, including protein 4, which is the equivalent of the growth-associated protein GAP-43. In addition, there was phosphorylation of some recognizable constituents of slow axonal transport, including alpha-tubulin, a neurofilament constituent (NF), and another intermediate filament protein characteristic of goldfish optic axons (ON2). At least some axonal proteins, therefore, may become phosphorylated as a result of the axonal transport of a phosphate carrier. Some of the proteins labeled by intraocular injection of 32P showed changes in phosphorylation during regeneration of the optic axons. By 3-4 weeks after an optic tract lesion, five proteins, including protein 4, showed a significant increase in labeling in the intact segment of nerve between the eye and the lesion, whereas at least four others (including ON2) showed a significant decrease. When local incorporation of radiolabeled phosphate into the nerve was examined by incubating nerve segments in 32P-containing medium, there was little or no labeling of the proteins that showed changes in phosphorylation during regeneration. Segments of either normal or regenerating nerves showed strong labeling of several other proteins, particularly a group ranging in molecular weight from 46,000 to 58,000 and in pI from 4.9 to 6.4. These proteins were presumably primarily of nonneuronal origin. Nevertheless, if degeneration of the axons had been caused by removal of the eye 1 week earlier, most of the labeling of these proteins was abolished. This suggests that phosphorylation of these proteins depends on the integrity of the optic axons.     

Does Immunohistochemistry Allow Easy Detection of Lymphatics in the Optic Nerve Sheath?

We evaluated the validity of anti-D2-40 and anti-LYVE-1 (antibodies against lymphatic endothelium) for IHC diagnosis and semiquantification of lymphatic vessels in the dura mater of the intraorbital portion of the human optic nerve (ON). Fourteen specimens were analyzed using light microscopy within 12 hr postmortem. We found in all specimens that both D2-40 and LYVE-1 stained lymphatic vessels as well as venules and arterioles. Our findings show lymphatic vessels in the meninges of the intraorbital portion of the human ON. Anti-D2-40 and anti-LYVE-1 antibodies, however, are not found to be exclusively specific to the endothelial layer of lymphatics because they also stain the endothelial layer of venules and arterioles. For the unequivocal identification of lymphatics, additional morphological criteria are necessary. Nevertheless, D2-40 and LYVE-1 staining allows rapid identification of endothelial layers. (J Histochem Cytochem 56:1087–1092, 2008)     

Optic Nerve Head Blood Flow Autoregulation during Changes in Arterial Blood Pressure in Healthy Young Subjects

Aim

In the present study the response of optic nerve head blood flow to an increase in ocular perfusion pressure during isometric exercise was studied. Based on our previous studies we hypothesized that subjects with an abnormal blood flow response, defined as a decrease in blood flow of more than 10% during or after isometric exercise, could be identified.

Methods

A total of 40 healthy subjects were included in this study. Three periods of isometric exercise were scheduled, each consisting of 2 minutes of handgripping. Optic nerve head blood flow was measured continuously before, during and after handgripping using laser Doppler flowmetry. Blood pressure was measured non-invasively in one-minute intervals. Intraocular pressure was measured at the beginning and the end of the measurements and ocular perfusion pressure was calculated as 2/3*mean arterial pressure –intraocular pressure.

Results

Isometric exercise was associated with an increase in ocular perfusion pressure during all handgripping periods (p < 0.001). By contrast no change in optic nerve head blood flow was seen. However, in a subgroup of three subjects blood flow showed a consistent decrease of more than 10% during isometric exercise although their blood pressure values increased. In addition, three other subjects showed a consistent decline of blood flow of more than 10% during the recovery periods.

Conclusion

Our data confirm previous results indicating that optic nerve head blood flow is autoregulated during an increase in perfusion pressure. In addition, we observed a subgroup of 6 subjects (15%) that showed an abnormal response, which is in keeping with our previous data. The mechanisms underlying this abnormal response remain to be shown.     

Clinical Evaluation of the Bioavailability of Zinc-enriched Yeast and Zinc Gluconate in Healthy Volunteers

Zinc (Zn)-enriched yeast and gluconate are considered two of the more biologically available supplements. However, there have been few reports comparing the bioavailability of these supplements. The objective of this study was to demonstrate whether Zn was absorbed better by healthy male volunteers when given supplements where the mineral is found organically bound in yeast or as a salt gluconate form. The trial used a randomized, two-way crossover design. Urine, blood, and fecal samples were collected and analyzed over a 48-h period after a single dose of supplement. The net Zn balance and the relative bioavailability were calculated. No differences were observed in urine excretion of the two supplements. Zinc gluconate gave higher Zn concentrations in the blood in the first 6 h but also showed greater losses in the feces. Zinc yeast also increased in blood with time but showed significantly less loss in the feces. Thus, the net Zn balance after 48 h for Zn yeast was 9.46 but for Zn gluconate it was −2.00, indicating that Zn gluconate supplementation contributed to a net loss of Zn. It was concluded that organic Zn yeast supplements are more biologically available than Zn gluconate salts.     

Carpal Tunnel Syndrome Assessment with Ultrasonography: Value of Inlet-to-Outlet Median Nerve Area Ratio in Patients versus Healthy Volunteers

Objective

To evaluate the diagnostic value of the Inlet-to-outlet median nerve area ratio (IOR) in patients with clinically and electrophysiologically confirmed carpal tunnel syndrome (CTS).

Methods

Forty-six wrists in 46 consecutive patients with clinical and electrodiagnostic evidence of CTS and forty-four wrists in 44 healthy volunteers were examined with ultrasonography. The cross-sectional area (CSA) of the median nerve was measured at the carpal tunnel inlet (the level of scaphoid-pisiform) and outlet (the level of the hook of the hamate), and the IOR was calculated for each wrist. Ultrasonography and electrodiagnostic tests were performed under blinded conditions. Electrodiagnostic testing combined with clinical symptoms were considered to be the gold standard test. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value between the inlet CSA and IOR.

Results

The study population included 16 men and 30 women (mean age, 45.3 years; range, 18–83 years). The control population included 18 men and 26 women (mean age, 50.4 years; range, 18–79 years). The mean inlet CSA was 8.7 mm² in healthy controls and 14.6mm² in CTS group (P<0.001). The mean IOR in healthy volunteers (1.0) was smaller than that in patients (1.6, P<0.001). Receiver operating characteristic analysis revealed a diagnostic advantage to using the IOR rather than the inlet CSA (P<0.01). An IOR cutoff value of ≥ 1.3 would yield 93% specificity and 91% sensitivity in the diagnosis of CTS.

Conclusion

The IOR of median nerve area promises to be an effective means in the diagnosis of CTS. A large-scale, randomized controlled trial is required to determine how and when this parameter will be used.     

Ral Overactivation in Malignant Peripheral Nerve Sheath Tumors

Ras leads an important signaling pathway that is deregulated in neurofibromatosis type 1 and malignant peripheral nerve sheath tumor (MPNST). In this study, we show that overactivation of Ras and many of its downstream effectors occurred in only a fraction of MPNST cell lines. RalA, however, was overactivated in all MPNST cells and tumor samples compared to nontransformed Schwann cells. Silencing Ral or inhibiting it with a dominant-negative Ral (Ral S28N) caused a significant reduction in proliferation, invasiveness, and in vivo tumorigenicity of MPNST cells. Silencing Ral also reduced the expression of epithelial mesenchymal transition markers. Expression of the NF1-GTPase-related domain (NF1-GRD) diminished the levels of Ral activation, implicating a role for neurofibromin in regulating RalA activation. NF1-GRD treatment caused a significant decrease in proliferation, invasiveness, and cell cycle progression, but cell death increased. We propose Ral overactivation as a novel cell signaling abnormality in MPNST that leads to important biological outcomes with translational ramifications.The Ras family of guanine-nucleotide bound proteins exerts a fundamental role in cell biology and constitutes an important area of cancer research due to its significant involvement in the development and progression of malignancies (8, 10, 17, 18, 32). Ras-like (Ral) proteins are crucial members of this family and have been shown to play a pivotal role in human tumors (7, 28, 41, 66, 70). Because Ral guanine nucleotide exchange factors (Ral-GEFs) are direct effectors of Ras, the Ral signaling pathway has been traditionally considered a Ras-effector pathway. Activation of Ras (in resemblance to Ral) is regulated by two classes of proteins: Ras-GEFs (e.g., SOS) and Ras- GTPase activating proteins (Ras-GAPs such as neurofibromin). The latter induces hydrolysis of Ras from the active (GTP) form to the inactive (GDP) form (13). Ral-GEFs include two main groups: the proteins that are stimulated by Ras because of their carboxy-terminal Ras binding domain (RalGDS, RGL1, and RGL2) and the proteins that are activated by substrates of PI3K through a pleckstrin homology domain on their C-terminal (RALGPS1 and RALGPS2) (19). Although highly similar to Ras, Ral proteins (RalA and RalB) involve a series of distinctly different effectors that influence gene expression and translation through interaction with ZO-1-associated nucleic acid binding protein (ZONAB) and RalA binding protein 1 (RalBP1) (11, 23, 33). RalB directly interacts with the SEC5 subunit of exocyst to facilitate the host defense response (48, 58).In addition to overactivation of GEFs, inactivation of GAPs is another mechanism for overactivation of GTP-bound proteins. The lack of neurofibromin (encoded by NF1 on human chromosome 17q11.2), a Ras-GAP protein, is the main molecular event in neurofibromatosis type 1 (NF-1), an autosomal-dominant human genetic disease occurring in approximately 1 in 2,500 to 3,500 births (22, 27, 42). One of the main tumor-causing effects of inactivating mutations in the tumor suppressor NF1 gene is postulated to be the subsequent activation of Ras (3, 29, 53, 57, 69). With two main functional domains, SEC14 and Ras-GAP, neurofibromin is best known for its Ras-GAP function. Although the yeast SEC14p is shown to be involved in regulating intracellular proteins and lipid trafficking, the function of its homologous domain in neurofibromin is unknown (49, 62). Although neurofibromas are the most common tumors in NF-1, 10% of patients with plexiform develop malignant peripheral nerve sheath tumors (MPNSTs), which are typically high grade and often fatal (21, 34, 65).The molecular events involved in the malignant transformation of benign neurofibromas to MPNST are poorly defined. Usually arising in the third through sixth decades of life, these tumors are composed of tightly packed hyperchromatic spindle-shaped cells with frequent mitotic figures. Inactivation of both copies of the NF1 gene has been demonstrated in benign human neurofibromas and shown to cause tumors in murine models (56). Loss of heterozygosity of NF1 and p53 has frequently been observed in human MPNST (35, 47, 54). Recombinant mouse strains (NP mice), which harbor inactivated Nf1 and p53 alleles (cis-Nf1^+/−:p53^+/−), demonstrate the cumulative effects of loss of both Nf1 and p53 genes in the etiology of MPNST (14, 68).In the present study, we show that while both Ras activation and activation of a series of its downstream effector pathways are observed in a fraction of MPNST cells, RalA is activated globally in all studied mouse and human MPNST cells and tumor samples. Our results also explain the involvement of this signaling molecule in a series of key biological functions of MPNST cells, as shown in a variety of in vitro assays and an in vivo model of MPNST. Such information may play a role in designing novel therapies for treatment of MPNST or other tumors with overactivation of the Ral pathway.     

Increased Set Shifting Costs in Fasted Healthy Volunteers

We investigated the impact of temporary food restriction on a set shifting task requiring participants to judge clusters of pictures against a frequently changing rule. 60 healthy female participants underwent two testing sessions: once after fasting for 16 hours and once in a satiated state. Participants also completed a battery of questionnaires (Hospital Anxiety and Depression Scale [HADS]; Persistence, Perseveration and Perfectionism Questionnaire [PPPQ-22]; and Eating Disorders Examination Questionnaire [EDE-Q6]). Set shifting costs were significantly increased after fasting; this effect was independent of self-reported mood and perseveration. Furthermore, higher levels of weight concern predicted a general performance decrement under conditions of fasting. We conclude that relatively short periods of fasting can lead to set shifting impairments. This finding may have relevance to studies of development, individual differences, and the interpretation of psychometric tests. It also could have implications for understanding the etiology and maintenance of eating disorders, in which impaired set shifting has been implicated.     

Comparison of Optic Disc Morphology of Optic Nerve Atrophy between Compressive Optic Neuropathy and Glaucomatous Optic Neuropathy

Objectives

To compare the optic nerve head (ONH) structure between compressive optic neuropathy (CON) and glaucomatous optic neuropathy (GON), and to determine whether selected ONH quantitative parameters effectively discriminate between GON and CON, especially CON cases presenting with a glaucoma-like disc.

Methods

We prospectively assessed 34 patients with CON, 34 age-matched patients with moderate or severe GON, and 34 age-matched healthy control subjects. The quantitative parameters of ONH structure were compared using the Heidelberg Retina Tomograph 2 (HRT2) and Spectralis optical coherence tomography with an enhanced depth imaging method.

Results

The mean and maximum cup depths of CON were significantly smaller than those with GON (P<0.001 and P<0.001, respectively). The distance between Bruch''s membrane opening and anterior surface of the lamina cribrosa (BMO-anterior LC) of CON was also significantly smaller than that of glaucoma but was similar to that of the healthy group (P<0.001 and P = 0.47, respectively). Based on Moorfields regression analysis of the glaucoma classification of HRT2, 15 eyes with CON were classified with a glaucoma-like disc. The cup/disc area ratio did not differ between cases of CON with a glaucoma-like disc and cases of GON (P = 0.16), but the BMO-anterior LC and mean and maximum cup depths of CON cases with a glaucoma-like disc were smaller than those in GON (P = 0.005, P = 0.003, and P = 0.001, respectively).

Conclusions

Measurements of the cup depths and the LC depth had good ability to differentiate between CON with a glaucoma-like disc and glaucoma. There was no laminar remodeling detected by laminar surface position in the patients with CON compared to those with GON.     

Assessment of Olfactory Nerve by SPECT-MRI Image with Nasal Thallium-201 Administration in Patients with Olfactory Impairments in Comparison to Healthy Volunteers

Purpose

The aim of this study was to assess whether migration of thallium-201 (²⁰¹Tl) to the olfactory bulb were reduced in patients with olfactory impairments in comparison to healthy volunteers after nasal administration of ²⁰¹Tl.

Procedures

10 healthy volunteers and 21 patients enrolled in the study (19 males and 12 females; 26–71 years old). The causes of olfactory dysfunction in the patients were head trauma (n = 7), upper respiratory tract infection (n = 7), and chronic rhinosinusitis (n = 7). ²⁰¹TlCl was administered unilaterally to the olfactory cleft, and SPECT-CT was conducted 24 h later. Separate MRI images were merged with the SPECT images. ²⁰¹Tl olfactory migration was also correlated with the volume of the olfactory bulb determined from MRI images, as well as with odor recognition thresholds measured by using T&T olfactometry.

Results

Nasal ²⁰¹Tl migration to the olfactory bulb was significantly lower in the olfactory-impaired patients than in healthy volunteers. The migration of ²⁰¹Tl to the olfactory bulb was significantly correlated with odor recognition thresholds obtained with T&T olfactometry and correlated with the volume of the olfactory bulb determined from MRI images when all subjects were included.

Conclusions

Assessment of the ²⁰¹Tl migration to the olfactory bulb was the new method for the evaluation of the olfactory nerve connectivity in patients with impaired olfaction.     

Parallel Changes in Structural and Functional Measures of Optic Nerve Myelination after Optic Neuritis

IntroductionVisual evoked potential (VEP) latency prolongation and optic nerve lesion length after acute optic neuritis (ON) corresponds to the degree of demyelination, while subsequent recovery of latency may represent optic nerve remyelination. We aimed to investigate the relationship between multifocal VEP (mfVEP) latency and optic nerve lesion length after acute ON.MethodsThirty acute ON patients were studied at 1,3,6 and 12 months using mfVEP and at 1 and 12 months with optic nerve MRI. LogMAR and low contrast visual acuity were documented. By one month, the mfVEP amplitude had recovered sufficiently for latency to be measured in 23 (76.7%) patients with seven patients having no recordable mfVEP in more than 66% of segments in at least one test. Only data from these 23 patients was analysed further.ResultsBoth latency and lesion length showed significant recovery during the follow-up period. Lesion length and mfVEP latency were highly correlated at 1 (r = 0.94, p = <0.0001) and 12 months (r = 0.75, p < 0.001). Both measures demonstrated a similar trend of recovery. Speed of latency recovery was faster in the early follow-up period while lesion length shortening remained relatively constant. At 1 month, latency delay was worse by 1.76ms for additional 1mm of lesion length while at 12 months, 1mm of lesion length accounted for 1.94ms of latency delay.ConclusionA strong association between two putative measures of demyelination in early and chronic ON was found. Parallel recovery of both measures could reflect optic nerve remyelination.     

Impaired Pten Expression in Human Malignant Peripheral Nerve Sheath Tumours

Malignant peripheral nerve sheath tumours (MPNST) are aggressive sarcomas that develop in about 10% of patients with the genetic disease neurofibromatosis type 1 (NF1). Molecular alterations contributing to MPNST formation have only partially been resolved. Here we examined the role of Pten, a key regulator of the Pi3k/Akt/mTOR pathway, in human MPNST and benign neurofibromas. Immunohistochemistry showed that Pten expression was significantly lower in MPNST (n = 16) than in neurofibromas (n = 16) and normal nervous tissue. To elucidate potential mechanisms for Pten down-regulation or Akt/mTOR activation in MPNST we performed further experiments. Mutation analysis revealed absence of somatic mutations in PTEN (n = 31) and PIK3CA (n = 38). However, we found frequent PTEN promotor methylation in primary MPNST (11/26) and MPNST cell lines (7/8) but not in benign nerve sheath tumours. PTEN methylation was significantly associated with early metastasis. Moreover, we detected an inverse correlation of Pten-regulating miR-21 and Pten protein levels in MPNST cell lines. The examination of NF1−/− and NF1+/+Schwann cells and fibroblasts showed that Pten expression is not regulated by NF1. To determine the significance of Pten status for treatment with the mTOR inhibitor rapamycin we treated 5 MPNST cell lines with rapamycin. All cell lines were sensitive to rapamycin without a significant correlation to Pten levels. When rapamycin was combined with simvastatin a synergistic anti-proliferative effect was achieved. Taken together we show frequent loss/reduction of Pten expression in MPNST and provide evidence for the involvement of multiple Pten regulating mechanisms.     

Optic Nerve Regeneration in Adult Fish and Apolipoprotein A-I

Fish optic nerves, unlike mammalian optic nerves, are endowed with a high capacity to regenerate. Injury to fish optic nerves causes pronounced changes in the composition of pulse-labeled substances derived from the surrounding non-neuronal cells. The most prominent of these injury-induced changes is in a 28-kilodalton (kDa) polypeptide whose level increases after injury, as revealed by one-dimensional gel electrophoresis and autoradiography. The present study identified as apolipoprotein A-I (apo-A-I) a polypeptide of 28 kDa in media conditioned by regenerating fish optic nerves. The level of this polypeptide increased after injury by approximately 35%. Apo-A-I was isolated by gel-permeation chromatography from delipidated high-density lipoproteins (HDL) that had been obtained from carp plasma by sequential ultracentrifugation. Further identification of the purified protein as apo-A-I was based on its molecular mass (28 kDa) as determined by gel electrophoresis, amino acid composition, and microheterogeneity studies. The isolated protein was further analyzed by immunoblots of two-dimensional gels and was found to contain six isoforms. Western blot analysis using antibodies directed against the isolated plasma protein showed that the 28-kDa polypeptide in the preparation of soluble substances derived from the fish optic nerves (conditioned media, CM) cross-reacted immunologically with the isolated fish plasma apo-A-I. Immunoblots of two-dimensional gels revealed the presence of three apo-A-I isoforms in the CM of regenerating fish optic nerves (pIs: 6.49, 6.64, and 6.73). At least some of the apo-A-I found in the CM is derived from the nerve, as was shown by pulse labeling with [35S]methionine, followed by immunoprecipitation. The apo-A-I immunoactive polypeptides in the CM of the fish optic nerve were found in high molecular-weight, putative HDL-like particles. Immunocytochemical staining revealed that apo-A-I immunoreactive sites were present in the fish optic nerves. Higher labeling was found in injured nerves (between the site of injury and the brain) than in non-injured nerves. The accumulation of apo-A-I in nerves that are capable of regenerating may be similar to that of apo-E in sciatic nerves of mammals (a regenerative system); in contrast, although its synthesis is increased, apo-A-I does not accumulate in avian optic nerves nor does apo-E in rat optic nerves (two nonregenerative systems).     

Cerebrospinal Fluid Parameters in Healthy Volunteers During Serial Lumbar Punctures

Lumbar punctures were performed on four occasions over a 5-day period (8:30 a.m. on days 1, 3, and 5; 2:30 p.m. on day 2) on 10 normal volunteers (five of each sex; mean age, 27.7 years) to assess, with repeated sampling, the day-to-day variation of selected CSF parameters. Two subjects abstained from the lumbar puncture on day 5 due to headache after the third puncture. Lumbar CSF was analyzed for concentrations of free and total gamma-aminobutyric acid (GABA), homocarnosine, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), total protein, albumin, and immunoglobulin (Ig)G. No significant concentration differences were found between the afternoon and next morning samples. No differences were found in concentrations of free GABA, total GABA, homocarnosine, 5-HIAA, or albumin across the study. In contrast, HVA concentrations significantly increased by day 5, whereas total protein and IgG decreased during the study. The most likely explanation for these changes involves the known concentration gradients in the CSF column.     

酮洛芬缓释片人体药动学和生物等效性研究

目的:评价受试酮洛芬缓释片与参比酮洛芬片的生物等效性。方法:采用反相高效液相色谱法测定24名健康男性志愿受试者交叉单剂量口服受试酮洛芬缓释片与参比酮洛芬片150mg后血浆中酮洛芬的浓度,用3p97程序进行数据处理。结果:口服受试和参比酮洛芬制荆后的AUC_(0-(?))分别是38.94±9.15μg·h·ml~(-1)、38.04±6.90μg·h·ml~(-1);AUC_(0-(?))分别是44.50±8.09μg·h·ml~(-1)、42.99±8.36μg·h·ml~(-1);T_(max)分别是3.87±0.55 h、1.96±0.60h;C_(max)分别是5.78±1.11μg·ml~(-1)、11.62±2.10μg·ml~(-1);t_(1/2)(Ke)分别是5.88±1.16h、1.70±1.40h。结论:受试酮洛芬缓释片与参比酮洛芬片具有生物等效性。     

Changes in Protein Content of Goldfish Optic Nerve During Degeneration and Regeneration Following Nerve Crush

Abstract: After the goldfish optic nerve was crushed, the total amount of protein in the nerve decreased by about 45% within 1 week as the axons degenerated, began to recover between 2 and 5 weeks as axonal regeneration occurred, and had returned to nearly normal by 12 weeks. Corresponding changes in the relative amounts of some individual proteins were investigated by separating the proteins by two-dimensional gel electrophoresis and performing a quantitative analysis of the Coomassie Brilliant Blue staining patterns of the gels. In addition, labelling patterns showing incorporation of [³H]proline into individual proteins were examined to differentiate between locally synthesized proteins (presumably produced mainly by the glial cells) and axonal proteins carried by fast or slow axonal transport. Some prominent nerve proteins, ON1 and ON2 (50–55 kD, pI ～6), decreased to almost undetectable levels and then reappeared with a time course corresponding to the changes in total protein content of the nerve. Similar changes were seen in a protein we have designated NF (～130 kD, pI ～5.2). These three proteins, which were labelled in association with slow axonal transport, may be neurofilament constituents. Large decreases following optic nerve crush were also seen in the relative amounts of α- and β-tubulin, which suggests that they are localized mainly in the optic axons rather than the glial cells. Another group of proteins, W2, W3, and W4 (35–45 kD, pI 6.5–7.0), which showed a somewhat slower time course of disappearance and were intensely labelled in the local synthesis pattern, may be associated with myelin. A small number of proteins increased in relative amount following nerve crush. These included some, P1 and P2 (35–40 kD, pIs 6.1–6.2) and NT (～50 kD, pI ～5.5), that appeared to be synthesized by the glial cells. Increases were also seen in one axonal protein, B (～45 kD, pI ～4.5), that is carried by fast axonal transport, as well as in two axonal proteins, HA1 and HA2 (～60 and 65 kD respectively, pIs 4.5–5.0), that are carried mainly by slow axonal transport. Other proteins, including actin, that showed no net changes in relative amount (but presumably changed in absolute amount in direct proportion to the changes in total protein content of the nerve), are apparently distributed in both the neuronal and nonneuronal compartments of the nerve.