[Clinical analysis of 36 cases of idiopathic intracranial hypertension complicated with iron deficiency anemia].

Objective: To investigate the clinical features, imaging findings and prognosis of idiopathic intracranial hypertension (IIH) patients complicated with iron deficiency anemia (IDA). Methods: A total of 307 cases of IIH patients hospitalized in Beijing Tongren Hospital were retrospectively screened between January 1, 2011 and February 28, 2018. There were 49 anemia cases (15.96%) and 45 IDA cases (14.66%), respectively. Finally, 36 IDA patients were enrolled. The clinical characteristics, imaging findings, treatment and prognosis of these patients were analyzed. Results: IIH combined with IDA was more common in women of childbearing age (34/36). There were 30 obese and overweight cases (83.33%), with multiple subacute or chronic course of disease. The visual symptoms in the early IIH patients were first diagnosed in the Department of Ophthalmology. The first symptom was headache with/without visual symptoms (27 cases (75%)). Head MRI detected empty sella or partial empty sella, and 2 cases of venous sinus thrombosis were found in DSA examination. Of the 34 female patients, 24 had simple menometrorrhagia or menstrual disorder. All patients were given methyl acetate to reduce the intracranial pressure and iron therapy. Five patients received low molecular weight heparin-warfarin sequential treatment, 5 cases underwent gynecologic surgery and 2 male cases received hemorrhoid operation. There were 7 cases underwent lumbar cisterna-peritoneal shunt for visual impairment. During the follow-up, intracranial pressure decreased and visual function of patients improved significantly. Conclusions: IIH is frequently found in obese or overweight women at childbearing age and IDA may be an important cause of IIH. IIH can cause serious irreversible visual impairment. Therefore, early identification and active treatment should be performed. Correction of anemia can significantly improve the clinical symptoms of IIH. Operation should be employed for IIH patients with poor visual function or rapid progress, in order to reduce intracranial pressure and improve prognosis as soon as possible.

How can the R.E.N.A.L. nephrometry scoring system aid management of a solid renal mass?

OBJECTIVES. To investigate use of the R.E.N.A.L. nephrometry score in relation to the choice of treatment and postoperative complications for renal masses. DESIGN. Case series. SETTING. A tertiary referral hospital in Hong Kong. PATIENTS. Data of patients undergoing nephrectomy were collected retrospectively from a clinical database and analysed. A R.E.N.A.L. nephrometry score was allocated to each renal tumour by a blinded qualified radiologist, utilising computerised imaging systems. Patient demographics, choice of surgery (radical vs partial), and approaches (open vs minimally invasive) were analysed with respect to their R.E.N.A.L. score. RESULTS. In all, 74 patients were included during the study period, of which 38 underwent partial nephrectomy and 36 underwent radical nephrectomy. No differences between the groups were found with respect to patient demographics. There were significant differences between the partial and radical nephrectomy groups in terms of their mean nephrometry score (6.9 vs 9.3, P<0.001). The mean nephrometry sum was also significantly different in the open approach versus the minimally invasive approach in patients having partial nephrectomy (7.8 vs 6.0, P=0.001). There was no difference in the postoperative 90-day morbidity and mortality in the partial nephrectomy and radical nephrectomy groups. CONCLUSIONS. The R.E.N.A.L. nephrometry score of a renal mass correlated significantly with our choice of surgery (partial vs radical) and our approach to surgery (open vs minimally invasive surgery), particularly in the partial nephrectomy group. It does not, however, correlate with postoperative complications. The nephrometry score provides a useful tool for objectively describing renal mass characteristics and enhancing better communication for the operative planning directed at renal masses.

Cardiac neural regulation oscillates with the estrous cycle in freely moving female rats: the role of endogenous estrogens.

Both estrogens levels and sleep/wakefulness states have been separately reported to affect cardiac autonomic regulation. In this study, we examined the integrated effects of the estrous and sleep cycles on cardiac autonomic activity in freely moving adult female rats. Cardiac autonomic activities were measured by analyzing the power spectrum of heart rate variability. High-frequency power (HF) and low-frequency power to HF ratio are closely correlated with cardiac parasympathetic and sympathetic activity, respectively. Ten days after electrodes were implanted, electroencephalogram, electromyogram, and electrocardiogram were recorded 6 h daily for 12 consecutive days to cover at least two estrous cycles. Estrous-cycle stages were determined using vaginal smears. Sleep cycle-related heart rate variability parameter oscillations were seen in all rats. However, the estrous cyclicity and estrous-cycle-related changes were only observed in the control rats and not in ovariectomized or the estrogen receptor antagonist, tamoxifen, treatment rats. A significantly higher HF was observed in estrous rats compared with diestrous rats or ovariectomized rats no matter whether the rats were asleep or awake. However, a significantly low-frequency power to HF ratio was only observed in quiet sleep (QS) during estrus. All these differences disappeared after treatment with tamoxifen. Our results suggest that estrous-cycle-related changes in cardiac neural regulations can be mainly attributed to endogenous estrogens, and these effects are most obviously manifest during QS. Estrous rats during QS would be equivalent to the late follicular phase of the women menstrual cycle and involve strong vagal tone but weak sympathetic activity.

Determination of paroxetine levels in human plasma using gas chromatography with electron-capture detection.

A simple, rapid and sensitive procedure using gas chromatography with electron-capture detection to measure paroxetine levels in human plasma has been developed. The analyte was extracted from plasma with ethyl acetate after basification of the plasma and then derivatized with heptafluorobutyric anhydride before gas chromatographic separation. The calibration curves were linear, with typical r2 values >0.99. The assay was highly reproducible and gave peaks with excellent chromatographic properties.

Effects of phenelzine and imipramine on the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD67 and GAD65), the GABA transporter GAT-1 and GABA transaminase in rat cortex.

There is an increasing body of evidence suggesting that GABA plays an important role in the therapeutic effects of antidepressant/antipanic drugs. Phenelzine and imipramine are efficacious in the treatment of depression and panic disorder and phenelzine has been reported to elevate GABA levels while imipramine enhances GABA release in rat brains. In the present study, using a multiprobe quantitative solution hybridization assay, we measured the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD67 and GAD65), the GABA transporter GAT-1 and GABA transaminase (GABA-T) in rat cortex after treatment with constant infusion (via osmotic minipumps) of phenelzine or imipramine for a short-term (3 days) or long-term (21 days) period. We found that none of the treatments gave rise to significant changes in the steady-state levels of mRNAs encoding GAD67, GAD65 or GABA-T at any time point. The steady-state levels of GAT-1 mRNA were increased significantly (23%) after long-term, but not by short-term, treatment with phenelzine. Imipramine treatment, short- or long-term, did not alter the steady-state levels of GAT-1 mRNA. These results suggest that the GABA enhancing effects of phenelzine or imipramine in rat cortex do not affect the steady-state levels of mRNAs that encode GAD67, GAD65 and GABA-T. Further, the previously observed increases in GABA levels or GABA release induced by these drugs are probably not a consequence of changes in the expression of these genes.

Formation of formaldehyde from adrenaline in vivo; a potential risk factor for stress-related angiopathy.

Cardiovascular and cerebrovascular disorders are well known to be associated with stress related behaviors. Stress enhances excretion of adrenaline, which is deaminated by monoamine oxidase and methylamine is formed. This product can be further deaminated by semicarbazide-sensitive amine oxidase (SSAO) and converted to toxic formaldehyde, hydrogen peroxide and ammonia. SSAO is located in the cardiovascular smooth muscles and circulated in the blood. We investigated whether formaldehyde can be derived from adrenaline in vivo. Methylamine was confirmed to be a product of adrenaline catalyzed by type A monoamine oxidase (MAO-A). Irreversible and long-lasting radioactive residual activity was detected in different tissues following administration of 1-[N-methyl-3H]-adrenaline. Such irreversible linkage could be blocked by selective MAO-A or SSAO inhibitors. Endothelial cells are quite sensitive to formaldehyde and relatively resistant to hydrogen peroxide. It is possible that stimulation of adrenaline excretion by chronic stress could increase the levels of circulatory formaldehyde. Such chronic "formaldehyde" stress may be involved in the initiation of endothelial injury and subsequently angiopathy.

Dopamine- and L-beta-3,4-dihydroxyphenylalanine hydrochloride (L-Dopa)-induced cytotoxicity towards catecholaminergic neuroblastoma SH-SY5Y cells. Effects of oxidative stress and antioxidative factors.

Enhanced oxidative stress has been suggested to be involved in the degeneration of nigrostriatal dopaminergic neurons in Parkinson's disease. The high turnover rate of dopamine and/or unsequestered dopamine may cause an increase of formation of hydrogen peroxide via either oxidative deamination of dopamine by monoamine oxidase or autoxidation. Hydrogen peroxide would be converted to more toxic hydroxyl free radicals. L-beta-3,4-Dihydroxyphenylalanine hydrochloride (L-DOPA), the most useful drug in the symptomatic treatment of Parkinson's disease, has been considered to possess deteriorating degenerative side-effects. The catecholaminergic neuroblastoma SH-SY5Y cells were chosen to investigate the cytotoxic effect of dopamine and L-DOPA. Both dopamine and L-DOPA were found to be cytotoxic towards SH-SY5Y cells. Such toxic effects were accompanied by an increase of oxidative stress in the cell cultures and could be reversed effectively by catalase and to a lesser extent by superoxide dismutase. The non-enzymatic antioxidants L-ascorbic acid, glutathione, N-acetyl-L-cysteine, but not (+)-alpha-tocopherol, also completely protected SH-SY5Y cells against the cytotoxic effects induced by dopamine and L-DOPA. Antioxidative factors, namely free radical scavengers (including N-tert-butyl-alpha-phenylnitrone, salicylic acid, and D-mannitol) and a strong iron chelator, deferoxamine, however, did not protect the SH-SY5Y cells against dopamine and L-DOPA. The generation of reactive oxygen species and the resulting enhanced oxidative stress was clearly involved in the dopamine- and L-DOPA-induced cytotoxic effects. Hydrogen peroxide played the most important role related to cytotoxicity of dopamine and L-DOPA.

R(-)-deprenyl potentiates dopamine-induced cytotoxicity toward catecholaminergic neuroblastoma SH-SY5Y cells.

Autoxidation of dopamine or L-DOPA (3,4-dihydroxyphenylalanine) generates reactive oxygen species (ROS), i.e., hydrogen peroxide, superoxide, and hydroxyl radical, which are potentially cytotoxic. Increased formation of ROS has been proposed to be involved in the pathogenesis of many human diseases, including Parkinson's disease. Several reports suggest that R(-)-deprenyl (an MAO-B inhibitor and anti-Parkinsonian drug) may directly or indirectly exert antioxidant effects and thus protect neurons. We have assessed the toxic effects of dopamine and L-DOPA toward catecholaminergic neuroblastoma SH-SY5Y cells and whether R(-)-deprenyl and several structurally related compounds possess antioxidant effects in this system. The results show that both dopamine and L-DOPA are quite cytotoxic toward SH-SY5Y cells. R(-)-deprenyl rather than reducing this dopamine-induced toxicity actually enhances it. Structural analogues of R(-)-deprenyl, such as 4-methyldeprenyl, (-)-methylamphetamine, and clorgyline, exhibited similar effects. Some different MAO-B inhibitors, namely, the aliphatic N-methylpropargylamines, e.g., (+/-)-M-2-PP [N-(2-pentyl)-N-methylpropargylamine] and N-[2-hexyl]-N-methylpropargylamine, which can also protect and rescue neurons in several in vivo and in vitro models, did not exacerbate the cytotoxicity of dopamine. Neither R(-)-deprenyl nor (+/-)-M-2-PP affected the L-DOPA-induced cytotoxicity toward SH-SY5Y cells.

Rapid, sensitive procedure to determine buspirone levels in rat brains using gas chromatography with nitrogen-phosphorus detection.

Reported here is a rapid, sensitive and relatively inexpensive procedure using gas chromatography with nitrogen-phosphorus detection (GC-NPD) to quantify buspirone levels in brains of rats. The analyte was directly extracted from brain homogenate with toluene after basification and then subjected to GC-NPD analysis using a capillary column. The calibration curves were linear over the range of 10 to 320 ng per 2 ml of brain homogenate, with typical r2 values >0.99. The assay was highly reproducible and gave peaks with excellent chromatographic properties.

Neurochemical, neuroprotective and neurorescue effects of aliphatic N-methylpropargylamines; new MAO-B inhibitors without amphetamine-like properties.

A series of aliphatic N-methylpropargylamine MAO-B inhibitors have been synthesized and their structural and functional relationships have been investigated. 2-Hexyl-N-methylpropargylamine (2-HxMP), for example, has been found to be a highly potent, irreversible, selective, MAO-B inhibitor both in vitro and in vivo. The R-(-)-enantiomers are much more active than the S-(+)-enantiomers at inhibiting MAO-B activity. Some of these compounds protect mouse nigrostriatal dopamine neurons against the neurotoxin MPTP and the mouse hippocampal noradrenergic system against the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). They rescue hippocampal neurons after damage induced by ischemia and kainic acid treatment, as well as motoneurons in young mice following facial nerve axotomy. Such rescue effects are, interestingly, unrelated to inhibition of MAO-B activity. Some of the aliphatic propargylamines enhance the survival of neuroblastoma cells co-cultured with astrocytes following serum depletion. They stimulate the expression of AADC mRNA and inhibit GFAP mRNA expression. They do not possess amphetamine-like properties and exhibit no effect on noradrenaline or dopamine uptake nor do they increase hypertensive effects in the tyramine pressor test. Unlike R(-)-deprenyl, 2-HxMP does not potentiate dopamine toxicity in vitro. These new MAO-B inhibitors may possess significant chemotherapeutic implications for certain psychiatric and neurodegenerative disorders.