Inhibitory effects of amitriptyline on the stimulation-induced Ca2+ increase in parotid acini

The present study demonstrates the effects of the antidepressant, amitriptyline, and the acetylcholine antagonist, atropine, on the stimulation-induced rise in cytosolic, free Ca2+ (Cai2+). The changes in Cai2+ of collagenase-isolated rat parotid acini were measured by means of the Ca2(+)-sensitive dye, fura-2. It was found that stimulation by carbachol resulted in a maximal increase of 582 +/- 34 nM (mean +/- S.E.) in Cai2+ with a ks of 5.8 +/- 1.3 microM. Adrenaline caused a rise of 380 +/- 22 nM in Cai2+ with a ks of 0.5 +/- 0.2 microM. Amitriptyline and atropine were found to inhibit the carbachol-induced rise in Cai2+ with dissociation constants (kI) of 105 and 1.25 nM, respectively, in the absence of agonist. The adrenergic-induced rise in Cai2+ was inhibited by amitriptyline with a kI of 45 nM. Amitriptyline was found to inhibit both receptor classes by a competitive or mixed type of inhibition. Similarly, atropine exerted the same type of inhibition on the acetylcholine receptor. Amitriptyline and atropine were found to be mutually exclusive for competing for substrate binding on the receptor. These findings are consistent with a common binding site for amitriptyline and atropine on the acetylcholine receptor, possibly in close proximity with, but different from the substrate binding site. The stimulation-induced cell shrinkage evoked by the loss of electrolytes and water from the acini was measured by a 90 degree light scattering signal. It was found that this method makes possible the detection of autonomic side-effects of antidepressants on acini suspended in protein-containing media.     

Metabolic response to beet fibre test meals

Test meals with 10.9 g dietary fibre from sugar beet and corresponding control meals were given to eight healthy subjects, aged 67 ± 9 years. The postprandial glucose, triglyceride, hormone and glycerol responses were monitored during 3 hours. After the beet fibre meal the insulin and C-peptide areas were reduced by 28 ( P < 0.01) and 22% ( P > 0.025), respectively, and the somatostatin levels increased by approximately 30% ( P > 0.05). Further, the maximum relative postprandial reduction of plasma glycerol levels was less evident after the fibre-rich meal than after the control meal (36 ± 4% v. 46 ± 4%, P < 0.05). There was no apparent difference in the overall glycaemic response between the meals. The triglyceride levels were similar after both test meals.
Suspension of beet fibre bread given to rats by oro-gastric intubation induced lower blood glucose response than a control bread at 15 and 30 min ( P < 0.001), respectively, but a similar insulin response.
The results suggest an effect of beet fibre on the rate of carbohydrate absorption, expressed as a lower insulin response in the healthy volunteers and a reduced glucose response in the rat.
The mechanism behind this effect in healthy subjects could possibly be mediated by an increased somatostatin response.     

Synthesis and Structure Elucidation of 5-Aminomethinimino-3-methyl-4-isoxazolecarboxylic Acid Phenylamides and Their Immunological Activity

A series of 5-aminomethinimino-3-methyl-4-isoxazolecarboxylic acid phenylamides 4 has been prepared by condensation of 5-amino-3-methyl-4-isoxazolecarboxylic acid phenylamides 1 with trichloroacetic aldehyde. Alcoholysis of trichloro derivatives 2 gave 5-alkoxymethine derivatives 3 which, on reaction with an appropriate amine, formed the corresponding compounds 4 . The compounds obtained were evaluated for their immunological activity. The properties of three compounds, described in this report, permitted inhibition of the immune response in all possible ways: diminishing both types of immune response ( 4d ), humoral immune response ( 4a ), or cellular immune response ( 4c ). Preparation 4d is comparable in its effectiveness to CsA, so it may be potentially used as an agent for prolongation of the function of transplanted organs. Two other compounds may potentially be used in cases where only one type the immune response is required for combating pathogen invasion.     

Danazol administration after gonadotrophin-releasing hormone analogue reduces rebound of uterine myomas [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.      

Prospective study of antigenemia,plasma viremia and lymphocytic viremia in HIV-infected hemophiliacs

A total of 186 blood samples from 24 HIV-1 seropositive hemophiliac patients, monitored every four months for 29 months, were investigated for the presence of viral antigen in plasma. In addition, peripheral blood mononuclear cells (PBMC) were cultured for HIV-1, using normal PBMC as a target for replication. Antigenemia was detected in 51 % of the patients and from PBMC in 87.5 % of the patients. The incidence of HIV isolation in asymptomatic patients (42.8 %) was similar to that found in symptomatic patients (51.4 %). Patients with opportunistic infections had a higher incidence of lymphocytic viremia (p<0.05). Plasma viremia was closely associated (p<0.05) with low CD4+ counts and infection progression. The persistence of antigenemia was also a marker of a poor clinical course. In treated patients, plasma viremia was the marker that better correlated with the clinical course, and it did not appear during the first nine months of therapy. Zidovudine doses of >500 mg/day significantly lowered the appearance of antigenemia and lymphocytic viremia (p<0.05).     

The use of laser scalpel in the surgical treatment of cholecystitis

A comparison of the results of 169 cholecystectomies with the use of a laser scalpel and 160--conventional methods was carried out. The CO2-laser was used for exposure of the gallbladder and coagulation of tissue of the liver in the region of its bed. Hemo- and cholestasis in all the cases was reliable, and due to this fact in 27% of the patients, the subhepatic recess was not drained. The incidence of complications after the elective cholecystectomy reduced by 11%, after the emergency one--by 9%, the lethality reduced considerably.