Neurology of sex steroids and oral contraceptives

Under normal circumstances, sex steroids interact with diverse neural substrates to modulate a host of activities essential to the preservation of the individual and the species. In addition, sex hormones play an important role in various human neurologic conditions including strokes, migraine, certain movement disorders and peripheral neuropathies, and possibly even the behavior of CNS neoplasms.     

Statin expression in the untreated and SarCNU-exposed human glioma cell line,SK-MG-1

Summary Cytokinetic analyses of gliomas and other neoplasms rely exclusively on the use of proliferation-dependent markers such as [³H]-thymidine and BuDR incorporation and the detection of growth-dependent proteins such as proliferating cell nuclear antigen (PCNA) and Ki-67. In normal tissues, the monoclonal antibody S-44 recognizes statin, a nuclear protein expressed only in nonproliferating cells. In the present study, indirect immunofluorescence microscopy using S-44 identified nuclear statin in 5.9% of a population of untreated human SK-MG-1 glioma cells in vitro. Incremental doses of the alkylating agent sarcosinamide chloroethylnitrosourea (SarCNU) induced a linear increase in the fraction of statin-positive SK-MG-1 cells. Labeling of nuclear statin with the monoclonal antibody S-44 may be a potentially useful marker of the cytotoxic effects of anticancer drugs in gliomas and other neoplastic tissues.     

Glial peroxidase activity in the hypothalamic arcuate nucleus: effects of estradiol valerate-induced persistent estrus

To test the hypothesis that stimulation of glial peroxidase activity by estrogens may play a role in the pathogenesis of the previously reported degenerative changes in the hypothalamic arcuate nucleus that occur in female rats treated with a long-acting estrogen preparation, the cellular localization and number of peroxidase-positive granules in the hypothalamus were determined in adult female rats treated with a single intramuscular injection of 2 mg of estradiol valerate. The persistent estrus state, manifested as persistent vaginal cornification and polycystic ovaries, was induced in 80% of the animals. In comparison with normally cycling controls, the arcuate nuclei of persistent estrus rats exhibited a 3- and 2.8-fold increase in numbers of diaminobenzidine-positive granules and granule clusters, respectively (P less than 0.01 for both comparisons). These peroxidase-positive granules were identified in astrocytes by double-label immunohistochemistry utilizing antiserum to glial fibrillary acidic protein. Diaminobenzidine staining occurred over a pH range of 4-10.5 and was resistant to the catalase inhibitor, aminotriazole, and to tissue pre-heating, indicating that the histochemical reaction was not due to tissue enzyme activity. Rather, these findings indicate that a non-enzymatic, pseudoperoxidation reaction has been induced in these cells by estrogen administration. Possible mediators of this reaction are metallo-porphyrins known to be present in rodent hypothalamus. The mechanisms by which astrocyte peroxidase activity may play a role in estrogen-related neural damage are discussed.     

The Nasal Mucociliary Clearance: Relevance to Nasal Drug Delivery

Mucociliary clearance is an important physiological defense mechanism of the respiratory tract to protect the body against noxious inhaled materials. This process is responsible for the rapid clearance of nasally administered drugs from the nasal cavity to the nasopharynx, thereby interfering with the absorption of drugs following intranasal application. This review describes the mucociliary system and the methods used for its characterization. Examples are given of the effects of drugs and additives on its functioning. Further, possible approaches are presented for increasing the residence time of drugs in the nasal cavity, thereby improving intranasal drug delivery.     

Viscero‐somatic reflexes in referred pain areas evoked by capsaicin stimulation of the human gut

The interaction between visceral pain and the sympathetic nervous system is only sparsely investigated in quantitative human studies. Referred visceral pain can be evoked experimentally by application of substances such as capsaicin (the pungent substance of chilli pepper) to the gut. The aim of the present study was to induce referred visceral pain from the small and large intestine in 32 volunteers via the stomal opening in patients with ileo‐ or colostomy and quantify the viscero‐somatic reflex responses in these referred pain areas by thermography and laser doppler flowmetry. Capsaicin evoked pain and referred pain areas in all subjects. In the referred pain area, the temperature increased by approximately 0.6°C (P<0.001) and the blood flow by approximately 35AU (P<0.001). Saline was used in a control experiment, and no temperature and blood flow changes were found. The present quantitative human study of viscero‐somatic reflexes showed dramatic sympathetic responses in the referred pain areas after experimentally induced gut pain.     

Progressive inflammatory lesions of the brain parenchyma in localized scleroderma of the head

Summary A patient with localized scleroderma of the head, uveitis, and Raynaud's phenomenon presented with generalized seizures, spastic hemiparesis, and local IgG production in the cerebrospinal fluid. Magnetic resonance imaging revealed progressive cortical and subcortical brain parenchymal lesions mainly adjacent to the cutaneous and bony lesions and probably of inflammatory origin.     

Statin immunolocalization in human brain tumors. Detection of noncycling cells using a novel marker of cell quiescence.

Surgical specimens of 35 human brain tumors were examined with a novel monoclonal antibody, S-44, immunoreactive to statin, a nuclear protein specifically expressed in quiescent (noncycling) G0-phase cells. Benign tumors typically were statin positive with labeling indices (LI) between 22% and 96%: acoustic schwannomas (n = 3, mean = 29.9 +/- 19.4%); meningiomas (n = 4, mean = 59.0 +/- 15.1%); pituitary adenomas (n = 3, mean = 79.9 +/- 28.2%), and an epidermoid cyst (41.0%). By contrast, the statin LI of 18 of 24 (75%) malignant brain tumors was less than or equal to 2%: medulloblastomas (n = 7, mean = 0.3 +/- 0.2%); anaplastic astrocytomas (n = 3, mean = 1.6 +/- 2.7%); glioblastomas (n = 10, mean = 10.3 +/- 14.4%); metastatic carcinomas (n = 3, mean = 3.0 +/- 4.6); and a germinoma (0.2%). The vascular endothelium among diverse tumors typically was statin positive. All 21 tumors with a statin LI less than 10% were malignant, and all nine tumors with a statin LI greater than 40% were benign. The statin LI of benign tumors (n = 11, mean = 55.1 +/- 26.7%) was significantly higher than that of the malignant tumors (n = 24, mean = 5.2 +/- 10.5%, P less than 0.001). The absence of statin expression is a new way to determine the malignancy of human brain tumors. The statin LI may be useful to guide the prognosis and treatment of individual patients. The mechanisms that control statin expression are important in therapy seeking to shift the proliferating, cycling cells to the quiescent, G0 compartment.     

Treatment of the human retinoblastoma cell line Y-79 growing in the athymic mouse eye with fractionated hyperthermia and/or radiation

Concentrated cell suspensions of the human retinoblastoma cell line Y-79 were injected into the eyes of athymic nude mice. Three to four weeks after implantation the eyes were treated with fractionated hyperthermia and/or radiation according to various protocols. Radiation was applied with 250 kV X-rays in fractions of 3 Gy, three fractions a week (3 x XT). Hyperthermia was applied once a week for 30 min at 43-45 degrees C (1 x HT). A coaxial microwave applicator (2450 MHz) has been developed for hyperthermia treatment of the mouse eye. The effect of the treatment was evaluated by visual observation of the eyes during a follow-up of several months, and by histopathological examination. No tumour regression was observed after hyperthermia alone (3 x HT). Treatment with 3 x XT or 3 x XT + 1 x HT initially caused tumour regression followed by regrowth in most cases. A treatment protocol of 6 x XT resulted in regrowth in 10 out of 15 eyes. However, after 6 x XT + 2 x HT regrowth was observed in only 3 out of 13 eyes. The difference between these two groups is statistically significant (P less than 0.05). Thus it is concluded that hyperthermia enhances the effect of radiation when the Y-79 cell line is transplanted to the athymic mouse eye, using the fractionation scheme presented here.     

361. Beziehung der urin- und serumosmolalität zum Wasserhaushalt bei intensivpatienten

Zusammenfassung Bei 14 Intensivpatienten mit unterschiedlichen Diagnosen wurden jeweils 2mal im Abstand von 4 h die Urin- und Serumosmolalität, die Flüssigkeitsein- und -ausfuhr, der Hb und Hk gemessen. Untersucht wurde die Korrelation mittels einfacher Regressionsanalyse mit Vertrauensintervall von der Urinosmolalität mit der Serumosmolalität, mit der Flüssigkeitsbilanz, mit Hb und Hk im Vergleich zu 10 Kontrollpatienten. Bei den Intensivpatienten korrelierte die Urinosmolalität signifikant (P < 0,05) mit der Flüssigkeitsbilanz, mit dem Hb und Hk. Zwischen Urin- und Serumosmolalität wurde keine Korrelation gefunden.