J. De Cree

Unchanged levels of interleukins, neopterin, interferon-γ and tumor necrosis factor-α in cerebrospinal fluid of patients with dementia of the Alzheimer type

Abstract Several histopathological studies suggest that amyloidogenesis in dementia of the Alzheimer type is accompanied by activated glia and glia-derived cytokines, leading to chronic, self-propagating, cytokine-mediated molecular and cellular reactions. As studies regarding inflammatory changes in cerebrospinal fluid of patients with dementia of the Alzheimer type has been inconclusive, we set up a prospective study to assess cerebrospinal fluid levels of interleukin-1 β , interleukin-6, interleukin-10, interleukin-12, soluble interleukin-2 receptor, interferon- γ , tumor necrosis factor- α and neopterin in 20 patients with dementia of the Alzheimer type and 20 age- and sex-matched controls. Comparing both groups, no significant differences in concentrations and specific activities could be revealed. An additional 22 patients were included to enlarge the study population. No statistically significant differences were shown comparing patients ( n =42) with the control group ( n =20). We conclude that the immune-mediated inflammatory changes found in histopathological studies are not reflected in cerebrospinal fluid of patients with dementia of the Alzheimer type. Probably, cytokine production appears very localized in the central nervous system, not allowing representative detection in cerebrospinal fluid. Further studies assessing cytokine levels in various regions of central nervous system of patients with dementia of the Alzheimer type will be of interest to confirm this hypothesis.

Oxatomide, a new orally active drug which inhibits both the release and the effects of allergic mediators.

Oxatomide is a new potent inhibitor of anaphylactic and allergic reactions. After oral administration, the compound both inhibits the release of endogenous histamine and prevents the effects of exogenous histamine, at comparable doses. The combination of these effects appears to be the basis of the effectiveness of oxatomide in allergic reactions and may lead to clinical applications different from classical antihistaminics and from cromoglycate.

The Antihypertensive Effects of a Pure and Selective Serotonin-Receptor Blocking Agent (R 41 468) in Elderly Patients

In a first experiment, an acute intravenous administration of 10 mg R 41 468, a pure serotonin-receptor blocking agent with high selectivity for blood vessels and thrombocytes and devoid of central effects, dramatically reduced systolic and diastolic blood pressure in 23 elderly hypertensive patients. Heart rate and cardiac output remained virtually unchanged. In a second double-blind placebo-controlled cross-over study a highly significant decrease of systolic and diastolic blood pressure was obtained in 14 elderly hypertensive patients during an 8-day oral treatment with 40 mg t.i.d. of R 41 468. No serious side-effects were observed. An oral maintenance therapy with R 41 468 for 3 weeks showed a further reduction of blood pressure, resulting in a normalization of blood pressure, taking into account the advanced age of the patients. R 41 468 most probably acts by decreasing the venous capacitance bed constriction. Essential hypertension might be causally related to an impair ment of venous function, in which serotonin might be an important pressor factor.

The Rheological Effects of Cinnarizine and Flunarizine in Normal and Pathologic Conditions

From the Clinical Research Unit, St. Bartholomeus, Antwerp, Belgium. Cinnarizine and its difluoro derivative, flunarizine, are long-lasting polyvalent antagonists of vasoconstrictive agents.’ They selectively inhibit the calcium transfer to the depolarized vascular smooth muscle.2~3 Both drugs improve exercise tolerance in patients with peripheral obliterative disease’ and enhance blood flow of the lower limbs in both healthy subjects’ and patients with vascular disease. 6-9

Nebivolol: Comparison of the Effects of dl-Nebivolol, d-Nebivolol, l-Nebivolol, Atenolol, and Placebo on Exercise-Induced Increases in Heart Rate and Systolic Blood Pressure

The effects of racemic nebivolol, 2.5, 5.0, and 10.0 mg; d-nebivolol, 2.5 mg; l-nebivolol, 2.5 mg; atenolol, 50 mg; and placebo, each given once daily for 7 days, on exercise-induced increases in heart rate and systolic blood pressure were compared in a seven-way double-blind randomized crossover trial in 14 healthy male volunteers. Observations on these variables were made 3 and 24 hours after dosing on the first and last days of therapy. Similar effects on both exercise-induced tachycardia and increases in systolic blood pressure were seen with nebivolol 5.0 mg and with d-nebivolol 2.5 mg; l-nebivolol 2.5 mg was no different from placebo. These data show that the beta-blocking effects of nebivolol reside in the d-isomer. A dose-related response was evident with racemic nebivolol in inhibiting exercise-induced tachycardia over the range of doses studied. Whereas the effects of atenolol on both exercise-induced tachycardia and increases in systolic blood pressure were fully evident on the first day of treatment, those of nebivolol, especially with regard to heart rate, and, to a lesser degree, systolic pressure, were greater on the final than on the first day. Nebivolol had a clearly superior trough-to-peak efficacy ratio than atenolol.The effects of racemic nebivolol, 2.5, 5.0, and 10.0 mg; d-nebivolol, 2.5 mg; l-nebivolol, 2.5 mg; atenolol, 50 mg; and placebo, each given once daily for 7 days, on exercise-induced increases in heart rate and systolic blood pressure were compared in a seven-way double-blind randomized crossover trial in 14 healthy male volunteers. Observations on these variables were made 3 and 24 hours after dosing on the first and last days of therapy. Similar effects on both exercise-induced tachycardia and increases in systolic blood pressure were seen with nebivolol 5.0 mg and with d-nebivolol 2.5 mg; l-nebivolol 2.5 mg was no different from placebo. These data show that the beta-blocking effects of nebivolol reside in the d-isomer. A dose-related response was evident with racemic nebivolol in inhibiting exercise-induced tachycardia over the range of doses studied. Whereas the effects of atenolol on both exercise-induced tachycardia and increases in systolic blood pressure were fully evident on the first day of treatment, those of nebivolol, especially with regard to heart rate, and, to a lesser degree, systolic pressure, were greater on the final than on the first day. Nebivolol had a clearly superior trough-to-peak efficacy ratio than atenolol.

Histamine receptor-bearing T lymphocytes in patients with allergy, autoimmune disease, or recurrent infection.

Abstract Histamine receptor-bearing T lymphocytes were demonstrated in the peripheral blood of patients with allergic disorders, autoimmune diseases, and recurrent infections but not in that of cancer patients and of healthy subjects. The method employed was the histamine-induced inhibition of E-rosette formation. Cimetidine as well as mepyramine prevented the histamine-induced inhibition of E-rosette formation.

Measurement of mitogen stimulation of lymphocytes with a glucose consumption test.

The increase of glycolysis in mitogen-stimulated lymphocytes was used to quantify lymphoblast transformation. Results correlated well with those by common methods, i.e. morphological evaluation and [3H]thymidine incorporation. The advantage of the glucose consumption test is that it registers the entire event of lymphocyte proliferation whereas other methods evaluate only viable transformed cells at the end of culture.

The effects of R 17934 (NSC 238159), a new antimicrotubular substance, on the ultrastructure of neoplastic cells in vivo

Abstract Ultrastructural investigations on 3 experimental neoplasms and on 1 human malignancy show that the in vivo antitumoral activity of R 17934 can be explained by its antimicrotubular properties. The induced disappearance of microtubules results in the disorganization and necrosis of dividing and non-dividing cancer cells. Mitotic normal cells (e.g., in the intestinal crypts) seem to be equally sensitive to the antimicrotubular action of R 17934 , as malignant cells. Interphase normal cells however are much more resistant than their neoplastic counterparts. The lysosomotropic properties of the compound, when given as a micronized suspension, ensure a slow release effect and a local accumulation of the compound which can be favourably exploited in the treatment of malignant effusions.

Immune Responses in Elderly Cuti-Negative Subjects and the Effect of Levamisole

A progressive decline in tuberculin sensitivity with advancing age is a common finding in large-scale tuberculin surveys [1 to 8]. Likewise BCG vaccination in elderly people results in relatively few tuberculin conversions [8]. Already in 1929 Troisier described “l’anergie tuberculinique senile” [9].

An enzyme immunoassay for the enumeration of peripheral human T-lymphocytes with OKT3.PAN monoclonal antibody

Abstract An enzyme immunoassay is described for the enumeration of peripheral human T-lymphocytes with a monoclonal antibody OKT3.PAN defining an antigenic determinant present on all mature T-lymphocytes. The method is compared with the indirect immunofluorescence technique and with an E-rosette test.