The passage of 5α-dihydrotestosterone from serum into cerebrospinal fluid and LH negative feedback in castrated rhesus monkeys

1985 ◽  
Vol 104 (3) ◽  
pp. 325-330 ◽  
Author(s):  
D. H. Abbott ◽  
K. A. Batty ◽  
A. K. Dubey ◽  
J. Herbert ◽  
H. M. Shiers

ABSTRACT Seven castrated monkeys were given either 50 or 100 μg 5α-dihydrotestosterone (DHT) propionate/kg per day. There was no correlation between serum and cerebrospinal fluid (CSF) levels of DHT, which remained very low in the CSF (0·3–0·6% of blood levels) despite the presence of high, supraphysiological amounts in the circulation. There was also no relation between unbound DHT in the blood and the CSF, in which all DHT is unbound. These results differ from previous work on testosterone, the metabolic precursor of DHT. 5α-Dihydrotestosterone propionate at the higher dose maintained suppressed levels of serum LH; LH in two out of four monkeys treated at the lower dose increased to levels observed in castrated, untreated rhesus monkeys. There was no predictable relationship between the amount of DHT in the CSF and levels of LH in the blood: by contrast, DHT in the blood was correlated with serum levels of LH. Levels of LH rose in monkeys in which total blood DHT fell below about 68 nmol/l and, even more obviously, if unbound DHT decreased to less than about 2 nmol/l. Differences between the distribution of testosterone and DHT between blood and CSF cannot be explained by serum binding, lipid solubility or clearance from the brain, and suggest that there may be some mechanism for excluding DHT from the CSF. Though DHT reaches the CSF from the blood in small amounts, levels there do not relate predictably to those in the vascular compartment. It seems unlikely, therefore, that levels of intracerebral DHT are controlled by changes in those of the blood. J. Endocr. (1985) 104, 325–330

1985 ◽  
Vol 104 (3) ◽  
pp. 331-338 ◽  
Author(s):  
U. Beckford ◽  
J. Herbert ◽  
M. T. Jones ◽  
N. D. Martensz ◽  
S. A. Nicholson ◽  
...  

ABSTRACT Adrenocorticotrophin levels, measured by a cytochemical bioassay, were determined in the plasma and cerebrospinal fluid (CSF) of adult female rhesus monkeys which were ovariectomized and receiving oestrogen replacement therapy. In control monkeys, ACTH bioactivity was found in both CSF (10·2±1·8 ng/l) and plasma (186 ± 51 ng/l) in samples taken at 14.00 h (lights on: 07.00–19.00 h). Dexamethasone treatment (0·2 mg/kg) twice daily for 4 days suppressed plasma ACTH levels (52·8 ± 25·2 ng/l) but had no effect on CSF levels (7·6± 2·7 ng/l). Raising plasma ACTH, either by daily injections of a long-acting preparation of ACTH(1–24) for 6 days or by bilateral adrenalectomy (and subsequently withdrawing cortisol replacement therapy) also resulted in no detectable changes in ACTH levels in the CSF. A regression analysis between ACTH in the plasma and CSF from samples taken throughout the experiments showed no correlation. In contrast, measurement of ACTH by radioimmunoassay, whilst satisfactory for determination of this peptide in plasma, could not identify authentic ACTH in the CSF. It is concluded that bioactive ACTH does not enter the CSF in detectable quantities from either the peripheral vascular compartment or from the animal's own pituitary gland, and that reducing ACTH secretion from the pituitary also has no effect on levels of ACTH in the CSF. This is in marked contrast to other pituitary peptide hormones, including prolactin, which is secreted together with ACTH during 'stress' but which, unlike ACTH, enters the CSF relatively easily. J. Endocr. (1985) 104, 331–338


1986 ◽  
Vol 71 (6) ◽  
pp. 749-753 ◽  
Author(s):  
J. E. Maddison ◽  
D. Yau ◽  
P. Stewart ◽  
G. C. Farrell

1. Cerebrospinal fluid (CSF) γ-aminobutyric acid (GABA) levels were measured in a dog model of spontaneous chronic portosystemic encephalopathy. 2. Dogs with congenital portacaval shunts (intra- or extra-hepatic) develop neurological features of abnormal psychomotor behaviour and depressed consciousness that are consistent with the symptoms of chronic portosystemic encephalopathy in humans. In the five dogs studied, plasma ammonia was elevated, as was CSF tryptophan, both usual biochemical abnormalities in portosystemic encephalopathy. 3. CSF levels of GABA in five dogs with portosystemic encephalopathy (100 ± 13 pmol/ml) were not significantly different from those in five control dogs (96 ± 14 pmol/ml). CSF levels of GABA were not altered after ammonia infusion. 4. If enhanced GABA-ergic neurotransmission, due to influx of gut-derived GABA into the brain, is responsible for the pathophysiology of chronic portosystemic encephalopathy in this model, it is not reflected by increased levels of GABA in CSF.


PEDIATRICS ◽  
1981 ◽  
Vol 67 (3) ◽  
pp. 387-388
Author(s):  
Michael E. Speer ◽  
Edward O. Mason ◽  
John T. Scharnberg

Simultaneous serum and CSF samples were obtained following the intramuscular administration of 50,000 units/kg of aqueous procaine penicillin G in 25 neonates. Penicillin activity was detected in the sera and CSF of all patients. Peak serum levels were noted at four hours (mean ± SEM, 17.1 ± 6.3 µg/ml). Peak CSF levels were noted at 12 hours (0.70 ± 0.35 µg/ml). The serum level at 24 hours was 2.1 ± 0.98 µg/ml (range, 0.2 to 5.8 µg/ml); the CSF level at 24 hours was 0.12 ± 0.05 µg/ml (range, 0.03 to 0.27 µg/ml). These results demonstrate that spirocheticidal levels (≥0.03 µg/ml) are achieved for at least 24 hours in the CSF following the intramuscular administration of aqueous procaine penicillin G in neonates.


Science ◽  
2020 ◽  
Vol 367 (6483) ◽  
pp. eaax7171 ◽  
Author(s):  
Humberto Mestre ◽  
Ting Du ◽  
Amanda M. Sweeney ◽  
Guojun Liu ◽  
Andrew J. Samson ◽  
...  

Stroke affects millions each year. Poststroke brain edema predicts the severity of eventual stroke damage, yet our concept of how edema develops is incomplete and treatment options remain limited. In early stages, fluid accumulation occurs owing to a net gain of ions, widely thought to enter from the vascular compartment. Here, we used magnetic resonance imaging, radiolabeled tracers, and multiphoton imaging in rodents to show instead that cerebrospinal fluid surrounding the brain enters the tissue within minutes of an ischemic insult along perivascular flow channels. This process was initiated by ischemic spreading depolarizations along with subsequent vasoconstriction, which in turn enlarged the perivascular spaces and doubled glymphatic inflow speeds. Thus, our understanding of poststroke edema needs to be revised, and these findings could provide a conceptual basis for development of alternative treatment strategies.


2019 ◽  
Vol 317 (2) ◽  
pp. F296-F302 ◽  
Author(s):  
Robert DeWolfe Mair ◽  
Huy Nguyen ◽  
Ting-Ting Huang ◽  
Natalie S. Plummer ◽  
Tammy L. Sirich ◽  
...  

The accumulation of uremic solutes in kidney failure may impair mental function. The present study profiled the accumulation of uremic solutes in the cerebrospinal fluid (CSF) in acute renal failure. CSF and plasma ultrafiltrate were obtained from rats at 48 h after sham operation (control; n = 10) or bilateral nephrectomy ( n = 10) and analyzed using an established metabolomic platform. Two hundred forty-eight solutes were identified as uremic based on their accumulation in the plasma ultrafiltrate of nephrectomized compared with control rats. CSF levels of 124 of these solutes were sufficient to allow calculation of CSF-to-plasma ultrafiltrate concentration ratios. Levels of many of the uremic solutes were normally lower in the CSF than in the plasma ultrafiltrate, indicating exclusion of these solutes from the brain. CSF levels of the great majority of the uremic solutes increased in renal failure. The increase in the CSF was, however, relatively less than in the plasma ultrafiltrate for most solutes. In particular, for the 31 uremic solutes with CSF-to-plasma ultrafiltrate ratios of <0.25 in control rats, the average CSF-to-plasma ultrafiltrate ratio decreased from 0.13 ± 0.07 in control rats to 0.09 ± 0.06 in nephrectomized rats, revealing sustained ability to exclude these solutes from the brain. In summary, levels of many uremic solutes are normally kept lower in the CSF than in the plasma ultrafiltrate by the action of the blood-brain and blood-CSF barriers. These barriers remain functional but cannot prevent accumulation of uremic solutes in the CSF when the kidneys fail.


2015 ◽  
Vol 8 ◽  
pp. IJTR.S25915 ◽  
Author(s):  
Markus K. Larsson ◽  
Lilly Schwieler ◽  
Michel Goiny ◽  
Sophie Erhardt ◽  
Göran Engberg

Schizophrenia is associated with activation of the brain immune system as reflected by increased brain levels of kynurenic acid (KYNA) and proinflammatory cytokines. Although antipsychotic drugs have been used for decades in the treatment of the disease, potential effects of these drugs on brain immune signaling are not fully known. The aim of the present study is to investigate the effects of chronic treatment with antipsychotic drugs on brain levels of cytokines and KYNA. Rats were treated daily by intraperitoneally administered haloperidol (1.5 mg/kg, n = 6), olanzapine (2 mg/kg, n = 6), and clozapine (20 mg/kg, n = 6) or saline ( n = 6) for 30 days. Clozapine, but not haloperidol or olanzapine-treated rats displayed significantly lower cerebrospinal fluid (CSF) levels of interleukin-8 compared to controls. Whole brain levels of KYNA were not changed in any group. Our data suggest that the superior therapeutic effect of clozapine may be a result of its presently shown immunosuppressive action. Further, our data do not support the possibility that elevated brain KYNA found in patients with schizophrenia is a result of antipsychotic treatment.


1979 ◽  
Vol 83 (2) ◽  
pp. 131-139 ◽  
Author(s):  
W. BECK ◽  
W. WUTTKE

Six male rhesus monkeys were kept under rigidly controlled conditions for 1–2 years. During August of the first year a thyrotrophin releasing hormone (TRH) test was performed on each of the monkeys by giving 10 μg TRH as a bolus injection. Significantly increased serum prolactin levels occurred 15 min after the injection. After a training period of 2 months, during which blood samples were collected every other day by puncture of the saphenous vein, blood was collected three times a week for 14 months. Serum levels of prolactin, LH, FSH and testosterone were measured by radioimmunoassay. Mean serum prolactin levels increased significantly during June, July and August in all six animals. Peak levels were observed in August and September and then levels declined gradually to reach a minimum in April and May. Mean serum testosterone levels closely paralleled the annual pattern of prolactin. Mean serum LH levels significantly decreased during the time when mean serum prolactin and testosterone levels were increasing and they increased again at the time of decreasing mean prolactin levels, i.e. mean serum LH and prolactin were negatively correlated. In individual monkeys, however, a rigid negative correlation between serum prolactin and LH could not be demonstrated. Mean serum FSH levels did not change significantly.


1997 ◽  
Vol 12 (6) ◽  
pp. 294-299 ◽  
Author(s):  
N Müller ◽  
P Dobmeier ◽  
M Empl ◽  
M Riedel ◽  
M Schwarz ◽  
...  

SummarySoluble Interleukin-6 receptor (sIL-6R) levels are strongly related to the levels of Interleukin-6 (IL-6), and sIL-6Rs increase the immune activating properties of IL-6. We estimated sIL-6R serum levels in 25 schizophrenic patients and 25 healthy controls. In the patients, SIL-6R-CSF levels were also measured. The psychopathology was rated according to the AMDP system. We found a significant correlation between serum and cerebrospinal fluid (CSF) levels of sIL-6R, suggesting that serum levels may be a meaningful marker for the central action of sIL-6R. Moreover, significant correlations between the paranoid-hallucinatory syndrome and sIL-6R levels both in serum and CSF were observed. This finding suggests that IL-6 plays a role in the paranoid-hallucinatory symptomatology in schizophrenia. This can be understood regarding the influence of IL-6 to the catecholaminergic neurotransmission. The downregulating effects of neuroleptic treatment to sIL-6R demonstrate that the sIL-6R levels are decreased in the whole group of schizophrenic patients compared to controls.


Parasitology ◽  
1996 ◽  
Vol 112 (1) ◽  
pp. 67-73 ◽  
Author(s):  
V. W. Pentreath ◽  
R. A. Alafiatayo ◽  
B. Crawley ◽  
F. Doua ◽  
E. A. Oppenheim

SUMMARYEndotoxin levels were measured in the blood and cerebrospinal fluid (CSF) of control individuals and 2 groups of patients with African sleeping sickness. Endotoxin levels were markedly elevated in the blood (infected groups mean endotoxin values 40·2 pg/ml and 53·8 pg/ml, compared to control 11·6 pg/ml, P < 0·0001 for both increases) and CSF (infected groups mean endotoxin values 45·8 pg/ml and 50·1 pg/ml compared to control 6·3 pg/ml, P < 0·0001 for both increases) of the patients. The levels were reduced 6 weeks following different drug treatments in the 2 groups (blood levels to mean 33·8·pg/ml and 28·5 pg/ml; CSF levels to 37·4 pg/ml and 27·0 pg/ml). The blood endotoxin values correlated with the CSF values before treatment (r = 0·74 and 0·57 for the 2 groups; P < 0·0001 for both) and after treatment (r = 0·57 and 0·56 for the 2 groups; P < 0·0001 for both). It is concluded that raised endotoxin equilibrates in the blood and CSF compartments, and may contribute significantly to the pathology of sleeping sickness.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S422-S422
Author(s):  
Matthew R Davis ◽  
Sandy Chang ◽  
Pryce Gaynor ◽  
Erin K McCreary ◽  
Paul R Allyn

Abstract Background Coccidioidal meningitis (CM) causes life-threatening infection with limited treatment options. Small series have reported variable treatment success with isavuconazole. An absence of published data exists on cerebrospinal fluid (CSF) penetration of this agent. Methods Paired serum and CSF levels were measured on three patients with refractory CM treated on salvage isavuconazole therapy. Results 11 CSF levels were sent on 3 patients; 7 from ventricular sources (Ommaya reservoir or external ventricular drain) and 4 from lumbar punctures at 6-44 days after treatment initiation, 2-24.6 hours after oral or intravenous dose. All levels sent from ventricular sources were undetectable &lt; 25µg/mL despite adequate paired serum levels (mean 2.45 µg/mL, range 1.25-6.38 µg/mL; n = 7 levels). Mean lumbar CSF levels were 1.00 µg/mL (range 0.45-1.72 µg/mL; n = 4 levels) with adequate serum levels (mean 3.57 µg/mL, range 1.78-5.63 µg/mL; n = 4 levels). Table 1. Isavuconazole serum and cerebrospinal fluid concentration measurements Conclusion Isavuconazole was detected in lumbar, but not ventricular CSF in three patients treated for CM. Disclosures All Authors: No reported disclosures


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