Reversible association of the cytokines MIP-1 alpha and MIP-1 beta with the endothelia of the blood-brain barrier.

Macrophage inflammatory proteins (MIP)-1 alpha and -1 beta have been postulated to exert their pyrogenic effects by acting directly at sites within the brain. Such activity would require circulating MIP-1s to cross the blood-brain barrier (BBB). We examined the ability of the monomer and polymer of MIP-1 alpha and the polymer of MIP-1 beta radioactively labeled with 125iodine (I-MIP-1) to cross the BBB.

Passage of peptides across the blood-brain barrier: pathophysiological perspectives.

Blood-borne peptides are capable of affecting the central nervous system (CNS) despite being separated from the CNS by the blood-brain barrier (BBB), a monolayer comprised of brain endothelial and ependymal cells. Blood-borne peptides can directly affect the CNS after they cross the BBB by nonsaturable and saturable transport mechanisms. The ability of peptides to cross the BBB to a meaningful degree suggests that the BBB may act as a modulatory pathway in the exchange of informational molecules between the brain and the peripheral circulation.

Leptin enters the brain by a saturable system independent of insulin.

Leptin, or OB protein, is produced by fat cells and may regulate body weight by acting on the brain. To reach the brain, circulating leptin must cross the blood-brain barrier (BBB). Intravenously injected radioiodinated leptin (125I-leptin) had an influx constant (Ki) into brain of (5.

Periventricular penetration and disappearance of ICV Tyr-MIF-1, DAMGO, tyrosine, and albumin.

The penetration of four radioiodinated materials-Tyr-MIF-1, DAMGO, tyrosine, and albumin-into the periventricular tissue after ICV injection was studied in rats by film autoradiography. Rates of disappearance from the CNS for the injected compounds were also determined by computer-assisted image analysis of the autoradiographic images. The four materials showed distinct patterns of dispersion from the ventricular system, with Tyr-MIF-1 moving farthest into the parenchyma of the brain and albumin primarily restricted to the ventricular space.

Reproducibility of a self-administered diet history questionnaire administered three times over three different seasons.

The reproducibility of the widely used Health Habits and History Questionnaire (HHHQ) for estimating "usual past-year" nutrient intake was examined. The HHHQ was self-administered on three occasions during three different seasons; 68 women (avg age 43 yrs) provided usable data for all three questionnaires in the appropriate seasons. Intraclass correlations (ICC) among the three administrations ranged from 0.

Selective transport of blood-borne interleukin-1 alpha into the posterior division of the septum of the mouse brain.

Film autoradiography was used to demonstrate the transport and sites of accumulation of blood-borne radioiodinated interleukin-1 alpha (II-1 alpha) and other cytokines into the brain after intravenous administration. [125 I]Il-1 alpha, [125I]Il-1 beta, [125I]interleukin-1 receptor antagonist (II-1ra), and [125I]tumor necrosis factor-alpha (TNF alpha) labeled the choroid plexus and the capillary network 30 min after injection into the blood, suggesting that these areas may serve as sites of blood-to-brain transport. [125I]Il-1alpha, but not [125I]Il-1beta, [125I]Il-1ra, [125I]TNF alpha, or [125I]interleukin-2 (Il-2), was also found localized to the caudal region of the septal nuclei.

Permeability of the blood-brain barrier to the neurotensin8-13 analog NT1.

Neurotensin (NT) has been suggested to be a neuropeptide with therapeutic potential. We used multiple-time regression analysis to measure the unidirectional influx constant (Ki) of a tritiated analog of NT8-13, NT1, with improved metabolic stability. The Ki of [3H]NT1 across the blood-brain barrier (BBB) was 5.

Systemic reactions to the Samsum ant: an IgE-mediated hypersensitivity.

Background: In the United Arab Emirates the sting of the Pachycondyla sennaarensis ant (PSA) causes allergic reactions in certain persons. It is a common problem and is becoming a public health hazard. Up to now the diagnosis has been based only on the history, because the mechanism of the reaction was not yet established.

Passage of cytokines across the blood-brain barrier.

One mechanism by which blood-borne cytokines might affect the function of the central nervous system (CNS) is by crossing the blood-brain barrier (BBB) for direct interaction with CNS tissue. Saturable transport systems from blood to the CNS have been described for interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1ra), IL-6, and tumor necrosis factor-alpha (TNF-alpha). Blood-borne cytokines have been shown to cross the BBB to enter cerebrospinal fluid and interstitial fluid spaces of the brain and spinal cord.

Permeability of the blood-brain barrier to soluble cytokine receptors.

Soluble receptors for cytokines can be important regulators of cytokine function. By binding to their cytokine ligands, they act as antagonists and carrier proteins. We investigated whether the blood-to-brain saturable transport of human tumor necrosis factor-alpha (TNF) and human interleukin-1 alpha (IL-1) radioactively labeled with 125I could be blocked by preincubation with their soluble receptors.

Regional variation in transport of pancreatic polypeptide across the blood-brain barrier of mice.

Blood-borne pancreatic polypeptide (PP) affects pancreatic secretion indirectly by acting through the central nervous system (CNS). PP, which is apparently not synthesized by brain, must cross the blood-brain barrier (BBB) to reach areas such as the cerebellum, an area rich in PP receptors, and to account for the PP found in cerebrospinal fluid (CSF). We used multiple-time regression analysis to measure the unidirectional influx constant (Ki) into brain of intravenously injected radioiodinated PP (I-PP).

Studies with [11C]alprazolam: an agonist for the benzodiazepine receptor.

We have built a system for the synthesis of high specific activity carbon-11 alprazolam (Xanax), a high affinity agonist for the benzodiazepine receptor. The system produces 30-40 mCi of the compound with a specific activity of > 12,000 Ci per millimole. Using this compound we have performed PET studies on 6 normal subjects and studied the cerebral influx and efflux of the compound.

Melanocyte-stimulating hormone release-inhibiting factor-1 (MIF-1) can be formed from Tyr-MIF-1 in brain mitochondria but not in brain homogenate.

Two samples of the peptide tyrosine-melanocyte-stimulating hormone release-inhibiting factor-1 (Tyr-MIF-1; Tyr-Pro-Leu-Gly-NH2) were tritiated on different amino acids (Tyr or Pro) and incubated together at 37 degrees C with fractions of rat brain. The amount of intact tetrapeptide remaining was determined by HPLC. By 3 min, most of the Tyr-MIF-1 was degraded.

Synthesis and in vivo disposition studies of 18F-labeled HFA-134a.

A rapid synthesis of the chlorofluorocarbon replacement compound 1,1,1,2-tetrafluoroethane (HFA-134a) was identified and utilized to prepare 99+% radiochemically pure [18F]HFA-134a in 20-35% radiochemical yield. Four rats were then exposed to no-carrier-added (NCA) [18F]HFA-134a, and monitored via coincidence detection. Following withdrawal of the test atmosphere of [18F]HFA-134a, the mean half-life of [18F]HFA-134a in four rats was determined to be 7.

Pain and depression in patients with newly diagnosed pancreas cancer.

Purpose: To evaluate the prevalence of pain and depression, their correlation, and their effect on quality of life in patients with recently diagnosed adenocarcinoma of the pancreas (PC).

Materials And Methods: Cross-sectional pain and psychosocial distress were assessed using validated instruments, including the Memorial Pain Assessment Card (MPAC), Beck Depression Inventory (BDI), Hopelessness Scale (BHS), and Functional Living Index-Cancer (FLIC). Patients were evaluated before their first operation for PC or first treatment with chemotherapy at a large tertiary-care cancer center.

Permeability of the blood-brain barrier to melanocortins.

Adrenocorticotropin (ACTH)-related compounds, termed melanocortins, produce a large number of effects on the central nervous system (CNS) after their peripheral administration. Some of the CNS effects of ACTH are mediated through the release of glucocorticoids from the adrenal gland, but there are fragments and analogues of ACTH that do not act on the adrenals. This raises the possibility that some blood-borne melanocortins may be acting directly on the brain, which would necessitate their crossing the blood-brain barrier (BBB).

Increase in plasma TYR-MIF-1-like immunoreactivity after hypophysectomy is robust and reversible by corticosterone.

Tyr-MIF-1-like immunoreactivity (Tyr-MIF-1-LI) was measured in the plasma of hypophysectomized rats. The concentrations were increased in every rat examined, regardless of sex or time after hypophysectomy, and ranged from 2.5 to 10 times greater than the concentrations in intact rats.

Permeability of the blood-brain barrier to amylin.

Amylin is co-secreted with insulin from the pancreas of patients with non-insulin dependent diabetes mellitus, and its deposition may contribute to the central nervous system (CNS) manifestations of this disease. Amylin, but not its mRNA, is found in brain, suggesting that CNS amylin is derived from the circulation. This would require amylin to cross the blood-brain barrier (BBB).

Blood-borne interleukin-1 receptor antagonist crosses the blood-brain barrier.

Recent work has shown that interleukin-1 alpha (IL-1 alpha) and IL-1 beta are transported from blood to brain across the blood-brain barrier by a saturable system. Here, we show that the endogenous IL-1 receptor antagonist (IL-1ra) radioactively labeled with either 125I or 35S is also transported across the blood-brain barrier by a saturable transport system. Between 0.