Pharmacokinetics of cefotaxime and desacetylcefotaxime in the blood serum and bronchial secretion in patients with chronic bronchitis after administration of a single 24-hour dose]

Concentrations of cefotaxime and its major active metabolite, desacetylcefotaxime, were determined in the serum and bronchial secretion of patients with chronic bronchitis aggravated after intramuscular injection of cefotaxime in a dose of 4 g once a day. Characteristic patterns of cefotaxime metabolism and high peak concentrations of desacetylcefotaxime in the serum (67.6 +/- 17.2 micrograms/ml) defined the prolonged retention of the metabolite both in the blood and bronchial secretion. The metabolite concentrations in more than half of the patients maintained within 2 micrograms/ml in the bronchial secretion by the 12th hour after the injection and in the blood serum by the 24th hour. Therefore, 4 g cefotaxime administered intramuscularly once a day provided the blood concentrations of the metabolite comparable with the MIC for the majority of the pathogens causing nosocomial infections of the respiratory tract practically within the whole period of the daily dosage. In the bronchial secretion such concentrations were attained within half of the period of the daily dosage.     

Effects of acute and chronic methylphenidate administration on beta-endorphin, growth hormone, prolactin and cortisol in children with attention deficit disorder and hyperactivity

The effect of 5 mg/p.o. methylphenidate (MPH) challenge on beta-endorphin (beta-EP), growth hormone (GH), prolactin (Prl) and cortisol was investigated in 16 children suffering from attention deficit disorder with hyperactivity (ADDH) before and after 4 weeks MPH treatment. The study population consisted of 13 males and 3 females aged 6-11 years. All patients were drug free for at least 3 months prior to investigation. The severity of ADDH symptomatology and response to MPH chronic treatment was assessed using parent/teacher abbreviated Conners rating scale. Blood samples for beta-EP, cortisol, Prl and GH were drawn before initiation of treatment (basal pre-treatment level), 2 hours after MPH challenge, 4 weeks after MPH treatment (basal post-treatment level) and 2 hours after re-challenge with MPH. Chronic MPH treatment resulted in a decrease in basal Prl levels (5.5 +/- 2.8 vs 3.7 +/- 1.9 ng/ml; p less than 0.05). Pre-treatment challenge stimulates significantly both beta-EP (15.0 +/- 7.5 vs 12.5 +/- 5.3 pmol/l; p less than 0.05) and cortisol secretion (20.6 +/- 6.6 vs 12.6 +/- 5.8 micrograms/dl; p less than 0.05), and suppressed Prl secretion (4.0 +/- 1.5 vs 5.5 +/- 2.8 ng/ml; p less than 0.05). Re-challenge with MPH enhanced beta-EP levels (14.9 +/- 8.6 vs 10.6 +/- 5.0 pmol/l; p less than 0.05) but failed to affect cortisol, Prl and GH secretion. The acute and chronic neuroendocrine effects of MPH administration might be related to its dopaminergic and adrenergic agonistic activity. It might be that the stimulatory effect of single and repeated acute MPH administration on beta-EP release contributes to the beneficial effect of MPH treatment in ADDH children.     

Ciprofloxacin in the prevention and treatment of surgical infections]

A clinico-laboratory study on ciprofloxacin made by Bayer (Germany) was applied to patients with extended posttraumatic wounds and performed with the aim of preventing postoperative purulent complications in patients operated on the organs of the gastrointestinal tract. In the both groups ciprofloxacin was administered orally in doses of 500 and 1000 mg and intravenously in a dose of 200 mg. The results of the assay on ciprofloxacin sensitivity of the isolates from the wound excretion and urine showed that they were more sensitive to ciprofloxacin than to aminoglycosides and cephalosporins. 15 minutes after the intravenous administration the serum concentration of ciprofloxacin amounted to 7.5 +/- 0.9 micrograms/ml and in 6 hours it was equal to 0.45 +/- 0.45 micrograms/ml, the mean concentrations of ciprofloxacin being attained in the bile (8.7 +/- +/- 3.9 micrograms/ml), gallbladder wall (5.5 +/- 3.8 micrograms/g), liver (0.73 micrograms/g), muscles (1.93 micrograms/g) and tendon (0.15 microgram/g). After the oral administration in a dose of 500 mg ciprofloxacin was detected in the blood serum in an amount of 2.0 +/- 0.7 micrograms/ml in 1 hour and in an amount of 0.9 +/- 0.13 micrograms/ml in 6 hours. After the drug oral administration in a dose of 1000 mg the maximum concentrations were: 6.34 +/- 4.2 micrograms/ml on the average and 2.1 +/- 0.8 micrograms/ml in 6 hours (0.4 micrograms/g in the muscles, 1.4 micrograms/g in the skin and 0.34 micrograms/g in the bones). The study showed that ciprofloxacin was a highly efficient antimicrobial agent in the treatment of the complicated wound infections and the prophylaxis of the purulent complications during the postoperative period in the patients operated on gastrointestinal organs.     

Immunohistochemical and ultrastructural characteristics of the bronchial mucosa in chronic inflammation

The local immunity was studied using 31 biopsy samples obtained during bronchoscopy from patients with various forms of chronic bronchitis. Attenuated IgA synthesis by plasmatic cells of bronchial mucosa lamina propria and increased LgG synthesis were established. Enhanced IgG production and penetration of various agents into bronchial mucosa lamina propria cause local immunocomplex reaction involving microcirculatory bed and resulting in perivascular sclerosis. Repeated damaging and sclerotic processes lead to disconnection of epithelial-stromal links and altered cover epithelium differentiation. The role of immunopathologic reactions in the formation of vicious circle underlying morphogenesis of chronic bronchitis is suggested.     

Whole blood serotonin and tryptophan levels in Tourette's disorder: effects of acute and chronic clonidine treatment

Whole blood serotonin (WB5HT) and tryptophan (WBTRP) levels were studied in 20 patients (aged 8 to 45 years) with Tourette's disorder under medication-free baseline conditions and following acute and chronic clonidine treatment. Compared to 87 normal controls, Tourette's disorder patients had lower mean baseline WBTRP levels (mean +/- SEM: Tourette's, 5993 +/- 304 ng/ml vs. 6822 +/- 169 ng/ml; p less than .03). No significant differences in mean baseline WB5HT levels were found. Three hours after an acute dose of clonidine (2.5 - 5.1 micrograms/kg, p.o. at 9:00 A.M.), no mean differences were observed (baseline vs. post 3 hours) in WB5HT or WBTRP levels. However, following chronic treatment (greater than 3 weeks) with clonidine (3-8 micrograms/kg/day, p.o.), WB5HT levels were increased in 9 of 14 Tourette's disorder patients. The mean increases in WB5HT levels following chronic clonidine treatment were significant when WB5HT levels were expressed per 10(9) platelets. (mean +/- SEM: baseline, 471 +/- 45 ng/10(9) platelets vs. chronic, 697 +/- 82 ng/10(9) platelets, p = .02). No mean differences in WBTRP levels were observed after chronic clonidine treatment. These findings are discussed in light of a proposed intermediary role of 5HT systems in the mode of action of clonidine in the treatment of Tourette's disorder.     

Erythromycin penetration into the cerebrospinal fluid of patients]

Permeability of erythromycin through the barrier of blood-cerebrospinal fluid in neurosurgical patients after its oral administration in a dose of 300-500 mg and intravenous administration in a dose of 200 mg was studied. The erythromycin was determined after the antibiotic single administration at intervals of 40 minutes to 6 hours. A total of 31 observations were performed. Low penetration of erythromycin into the cerebrospinal fluid of the patients was shown. The administration route (oral or intravenous) practically had no effect on the antibiotic penetration level into the subarachnoidal spaces. The highest liquor levels were observed within the period of 3 to 6 hours after the drug administration. The maximum index of penetration from the blood into the cerebrospinal fluid was about 10 per cent. The erythromycin penetration increased in cases with inflammatory changes in the meninges.     

Effect of a new synthetic free radical scavenger, 2-octadecyl ascorbic acid, on the mortality in mouse endotoxemia

Oxygen-derived free radicals have been implicated as mediators of cellular injury in several model systems. In order to clarify the role of oxygen radicals in endotoxemia, we measured the serial lipid peroxide changes resulting from systemic radical reactions using a newly developed colormetric method. To determine the effect of a free radical scavenger on mortality in endotoxemia, a new synthetic scavenger, 2-Octadecylascorbic acid (CV-3611), which overcome the detrimental properties (circulation half-life and cell penetration) of native SOD, was used in the model of mouse endotoxemia induced by the i.p. administration of E-coli endotoxin (10 mg/kg). Serial LPO (Lipid Peroxide) changes revealed significant elevations from the basal level of 4.52 +/- 0.79 nmol/ml to 10.5 +/- 2.04 nmol/ml at 2h (P less than 0.05), 12.0 +/- 2.44 nmol/ml at 8h (P less than 0.05), 32.8 +/- 12.5 nmol/ml at 12h (P less than 0.05) and 13.6 +/- 2.40 nmol/ml at 24h (P less than 0.05) following i.p. administration of E-coli. The circulation half life of CV-3611 was checked by a reversed-phase HPLC after 10 mg/kg s.c. administration. The level of CV-3611 reached peak levels of 0.54 +/- 0.10 micrograms/ml at 1h and 0.52 +/- 0.20 micrograms/ml at 2h then gradually decreased to the level of 0.04 +/- 0.004 micrograms/ml at 6h and to a non-detectable level at 24h after s.c. administration. Increased survival was seen at 2 days (P less than 0.001) after E-coli endotoxin administration in the CV-3611 treated group compared to the control group. These results suggest that oxygen derived free radicals contribute to mortality in mouse endotoxemia and that antioxidants such as CV-3611 may provide a new therapeutic avenue by improving survival of patients with gram-negative bacterial sepsis.     

Bronchodilator treatment in moderate asthma or chronic bronchitis: continuous or on demand? A randomised controlled study.

OBJECTIVE--To examine the effect of bronchodilator treatment given continuously versus on demand on the progression of asthma and chronic bronchitis and to compare the long term effects of a beta 2 adrenergic drug (salbutamol) and an anticholinergic drug (ipratropium bromide). DESIGN--Two year randomised controlled prospective ''crossover'' study in which patients were assigned to one of two parallel treatment groups receiving continuous treatment or treatment on demand. SETTING--29 general practices in the catchment area of the University of Nijmegen. PATIENTS--223 patients aged greater than or equal to 30 with moderate airway obstruction due to asthma or chronic bronchitis, selected by their general practitioners. INTERVENTIONS--1600 micrograms salbutamol or 160 micrograms ipratropium bromide daily (113 patients) or salbutamol or ipratropium bromide only during exacerbations or periods of dyspnoea (110). No other pulmonary treatment was permitted. MAIN OUTCOME MEASURES--Decline in ventilatory function and change in bronchial responsiveness, respiratory symptoms, number of exacerbations, and quality of life. RESULTS--Among 144 patients completing the study, after correction for possible confounding factors the decline in forced expiratory volume in one second was -0.072 l/year in continuously treated patients and -0.020 l/year in those treated on demand (p less than 0.05), irrespective of the drug. The difference in the decline in patients with asthma was comparable with that in patients with chronic bronchitis (asthma: 0.092 v -0.025 l/year; chronic bronchitis: -0.082 v -0.031 l/year). Bronchial responsiveness increased slightly (0.4 doubling dose) with continuous treatment in chronic bronchitis, but exacerbations, symptoms, and quality of life were unchanged. Salbutamol and ipratropium bromide had comparable effects on all variables investigated. CONCLUSIONS--Continuous bronchodilator treatment without anti-inflammatory treatment accelerates decline in ventilatory function. Bronchodilators should be used only on demand, with additional corticosteroid treatment, if necessary.     

Effect of arginine on the GHRH-stimulated GH secretion in patients with hyperthyroidism.

Patients with hyperthyroidism have reduced GH responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of arginine on GH secretion has been suggested to depend on a decrease in hypothalamic somatostatin tone. The aim of our study was to evaluate the effects of arginine on the GH-releasing hormone (GHRH)-stimulated GH secretion in patients with hyperthyroidism. Six hyperthyroid patients with recent diagnosis of Graves' disease [mean age +/- SEM, 39.2 +/- 1.4 years; body mass index (BMI) 22 +/- 0.4 kg/m2] and 6 healthy nonobese volunteers (4 males, 2 females; mean age +/- SEM, 35 +/- 3.5 years) underwent two experimental trials at no less than 7-day intervals: GHRH (100 micrograms, i.v.)-induced GH secretion was evaluated after 30 min i.v. infusion of saline (100 ml) or arginine (30 g) in 100 ml of saline. Hyperthyroid patients showed blunted GH peaks after GHRH (13.2 +/- 2.9 micrograms/l) as compared with normal subjects (23.8 +/- 3.9 micrograms/l, p < 0.05). GH peaks after GHRH were only slightly enhanced by arginine in hyperthyroid subjects (17.6 +/- 2.9 micrograms/l), whereas, in normal subjects, the enhancement was clear cut (36.6 +/- 4.4 micrograms/l; p < 0.05). GH values after arginine + GHRH were still lower in hyperthyroid patients with respect to normal subjects. Our data demonstrate that arginine enhances but does not normalize the GH response to GHRH in patients with hyperthyroidism when compared with normal subjects. We hypothesize that hyperthyroxinemia may decrease GH secretion, both increasing somatostatin tone and acting directly at the pituitary level.     

Effect of dihydrocytochalasin B on the induction of DNA synthesis by epidermal growth factor, insulin and serum in Swiss 3T3 cells

The addition of a microfilament-disorganizing agent--dihydrocytochalasin B B (5-10 micrograms/ml)--to to quiescent confluent or sparse (in 0.5% serum) Swiss 3T3 cells, 1-2 hours prior to stimulation, inhibited the initiation of DNA synthesis induced by an epidermal growth factor (7.5-10 ng/ml) and insulin (0.5-1.0 micrograms/ml), but exerted a low effect on serum stimulation. DNA synthesis was measured 21-23 hours after the growth factor administration by 14C-thymidine incorporation in acid-insoluble material and the ratio of this fraction to exogenous thymidine uptake. Moreover, the polar solvent dimethylsulfoxide, present in culture medium at low concentration (0.1-0.5%), also caused a decrease in the basal level of 14C-thymidine incorporation in resting cells, and a less decrease in the induced incorporation.     

Benzylpenicillin levels in the serum and bone tissue of the lower jaw in patients with chronic traumatic osteomyelitis after intraosseous and intramuscular administration

Penetration of benzylpenicillin into pathological foci was studied in 48 patients with chronic traumatic osteomyelitis of the lower jaw after intramuscular and intraosseous administration of the antibiotic. A group of 10 patients operated for congenital deformations of the lower jaw was used as the control. The results showed that after intramuscular administration benzylpenicillin penetration into the inflammation focus of the lower jaw was better than that into the intact bone only for the first 30 minutes. At later periods it was detected in both the cases as traces. After intraosseous administration of the drug in doses of 50,000 and 200,000 units its accumulation in the bone tissue of the patients with chronic traumatic osteomyelitis of the lower jaw in 30 minutes was respectively 75 and 160 times higher than that after the intramuscular injections. The period of its presence in the pathological focus as the therapeutic levels was also higher i. e. up to 2 hours. Intraosseous route of benzylpenicillin administration is likely to decrease the quantity of the drug needed for treating patients with chronic osteomyelitis of the lower jaw.     

Chronic growth hormone administration does not suppress endogenous growth hormone secretion in patients with neurosecretory growth hormone dysfunction.

Short children who respond normally to growth hormone (GH) stimulation, but have a subnormal spontaneous secretion of GH (neurosecretory GH dysfunction, NSD) are treated with exogenous GH which might suppress their endogenous GH secretion. The effect of chronic administration of GH (8-24 months) on plasma GH responses to GHRH, clonidine and spontaneous GH secretion were studied in 17 NSD patients. The diagnosis of NSD was based on a normal GH response to clonidine (greater than 10 micrograms/l) and an integrated concentration of (IC-GH) GH less than 3.2 micrograms/l. The GH dose used in this study was 0.25 IU/kg three times a week in 10 patients and 0.05 IU/kg daily in 7 patients. Insulin-like growth factor I levels (nmol) increased significantly on therapy from 9.3 +/- 3.8 to 24.4 +/- 22.4 (p less than 0.001). The GH response (microgram/l) to GHRH was 20.4 +/- 5.5 before treatment and 22.4 +/- 6.2 on GH. Peak GH after clonidine was 22.4 +/- 8.9 and 22.8 +/- 8.1, respectively. There was no significant decrease in the number of GH spontaneous peaks (1.8 +/- 0.7 vs. 2.0 +/- 0.7, respectively) or in the area under the curve. A subcutaneous GH bolus of 0.25 IU/kg in 4 patients resulted in a GH peak of 55-82 micrograms/l at 3-5 h and a gradual return to basal levels at 15-20 h after GH administration. The first spontaneous GH peak appeared 26-28 h after GH injection, peak amplitude was 10-15 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)     

Method for determining kallikrein of tissue origin in blood plasma and its clinical significance

Based on a study of the kininogenase activity of the total plasma kallikrein in the presence of 3 concentrations of the soybean inhibitor trypsin (0.5, 1.0, 10.0 micrograms/ml) one can measure at a time the activity of tissue kallikrein (without specifying the source) and the activity of 3 forms of plasma kallikrein, including its adsorption on kaolin that characterizes the conformational structure of the enzyme. Examination of 10 healthy subjects and 136 patients revealed a 10 to 20-fold increase in the content of tissue kallikrein in plasma of 70% of diabetes mellitus patients and a 2.5 to 3-fold elevation in 50% of patients with chronic occupational bronchitis, and in 30% of patients suffering from chronic hepatitis. The method suggested makes it possible to have a better insight into the physiological and pathogenetic role of the kinin system and may be used for laboratory control over the treatment efficacy.     

Acute effects of clonidine and growth-hormone-releasing hormone on growth hormone secretion in patients with hyperthyroidism

Patients with hyperthyroidism have reduced growth hormone (GH) responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of clonidine on GH secretion has been suggested to depend on an enhancement of hypothalamic GH-releasing hormone (GHRH) release. The aim of our study was to evaluate the effects of clonidine and GHRH on GH secretion in patients with hyperthyroidism. Eight hyperthyroid females with recent diagnosis of Graves' disease (age range 20-55 years, body mass index range 19.2-26.2 kg/m2) and 6 healthy female volunteers (age range 22-35 years, body mass index range 19-25 kg/m2) underwent two experimental trials at no less than 7-day intervals: (a) an intravenous infusion of clonidine 150 micrograms in 10 ml of saline, or (b) a bolus intravenous injection of human GHRH (1-29)NH2, 100 micrograms in 1 ml of saline. Hyperthyroid patients showed blunted GH peaks after clonidine (7.1 +/- 1.7 micrograms/l) as compared to normal subjects receiving clonidine (28.5 +/- 4.9 micrograms/l, p less than 0.05). GH peaks after GHRH were also significantly lower in hyperthyroid subjects (8.0 +/- 1.7 micrograms/l) as compared to normal subjects receiving GHRH (27.5 +/- 4.4 micrograms/l, p less than 0.05). No significant differences in the GH values either after clonidine or GHRH were observed in the two groups of subjects examined. Our data demonstrate that the GH responses to clonidine as well as to GHRH in patients with hyperthyroidism are inhibited in a similar fashion with respect to normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dopaminergic control of aldosterone secretion in hypertensive patients chronically treated with an angiotensin converting enzyme inhibitor

To investigate whether dopamine plays a role in the regulation of aldosterone secretion during long-term blockade of the renin-angiotensin system, we studied the effect of metoclopramide, a competitive antagonist of dopamine, in 6 patients with essential hypertension chronically treated with the angiotensin converting enzyme inhibitor enalapril. All but one of these patients received a diuretic in addition to enalapril. Six hours after the daily morning dose of enalapril (10-40 mg p.o.) a 10 mg bolus dose of metoclopramide was injected intravenously. In one patient a hypotensive episode developed following metoclopramide administration. In the 5 other patients plasma aldosterone significantly rose within 30 min after metoclopramide from 51 +/- 8.7 to 128.2 +/- 29.2 pg/ml. This metoclopramide-induced release of aldosterone occurred in the absence of concomitant changes in circulating angiotensin 11, potassium and ACTH levels. Metoclopramide given during chronic blockade of the renin-angiotensin system caused anxiety and agitation in 2 patients. The increase in plasma aldosterone following competitive dopamine blockade in the face of chronic angiotensin converting enzyme inhibition, unchanged plasma potassium and ACTH levels strongly suggests that in hypertensive patients, dopamine exerts a direct inhibitory effect on aldosterone secretion.     

A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma

Mucus hypersecretion is a crucial feature of pulmonary diseases such as asthma, chronic bronchitis and cystic fibrosis. Despite much research, there is still no effective therapy for this condition. Recently, we showed that the myristoylated, alanine-rich C-kinase substrate (MARCKS) protein is required for mucus secretion by human bronchial epithelial cells in culture. Having synthesized a peptide corresponding to the N-terminal domain of MARCKS, we now show that the intratracheal instillation of this peptide blocks mucus hypersecretion in a mouse model of asthma. A missense peptide with the same amino acid composition has no effect. Based on quantitative histochemical analysis of the mouse airways, the peptide seems to act by blocking mucus release from goblet cells, possibly by inhibiting the attachment of MARCKS to membranes of intracellular mucin granules. These results support a pivotal role for MARCKS protein, specifically its N-terminal region, in modulating this secretory process in mammalian airways. Intratracheal administration of this MARCKS-related peptide could therapeutically reduce mucus secretion in the airways of human patients with asthma, chronic bronchitis and cystic fibrosis.     

Rapid diagnosis of exacerbations of chronic bronchitis of pneumococcal etiology in children

The diagnostic possibilities of the microscopic examination of bronchial secretion smears, stained by Gram's method, from 56 children with chronic bronchitis at different stages of exacerbation have been studied. The following criteria have been proposed for confirming the etiological role of pneumococci in cases of endobronchitis in children: the number of paired diplococci in the visual field must exceed 10 with polynuclears covering the whole field. In 84% of cases the use of this method makes it possible to determine the pneumococcal etiology of the disease within two hours from the arrival of the pathological material to a bacteriological laboratory; this method can also be used for evaluating the effectiveness of antibacterial therapy at its different stages.     

III. Serum and sputum immunoglobulin E levels in respiratory diseases in adults

Using a solid-phase radioimmunoassay, serum IgE level was determined in 46 normal subjects, 53 patients with bronchial asthma, 44 patients with chronic bronchitis and / or emphysema, and 19 patients with restrictive lung disease. Sputum IgE was measured simultaneously in 51 of the subjects. The range of serum IgE concentration in the normal subjects was wide. It varied between 15 and 750 ng/ml with a mean of 135 ng. Asthmatic patients had significantly higher levels of serum IgE with a mean of 579 ng/ml, but only 30% fell outside the normal 95% confidence limits. Patients with chronic bronchitis, emphysema and restrictive lung diseases had normal IgE levels. There was a significant correlation between serum and sputum IgE levels.     

A suppression of gonadotropin secretion by cortisol in castrated male rhesus monkeys (Macaca mulatta) mediated by the interruption of hypothalamic gonadotropin-releasing hormone release

Four orchidectomized rhesus monkeys (3-3.5 yr of age) were treated for 62 days with daily i.m. injections of hydrocortisone acetate (HCA) at a dose of 10-20 mg/(kg BW X day), and blood samples were obtained daily or every other day before, during, and after treatment. Hydrocortisone acetate injections resulted in a progressive rise in mean plasma cortisol from basal concentrations of 17-35 micrograms/100 ml prior to initiation of steroid treatment to approximately 150 micrograms/100 ml 5 wk later. When serum cortisol concentrations reached 100 micrograms/100 ml, 3-4 wk after the initiation of HCA treatment, circulating luteinizing hormone (LH) and follicle-stimulating hormone (FSH) began to decline, reaching nondetectable concentrations 35 days later. Withdrawal of HCA resulted in a return in plasma cortisol concentrations to pretreatment control levels, which was associated with a complete restoration of gonadotropin secretion. In 2 animals, administration of an intermittent i.v. infusion of gonadotropin-releasing hormone (GnRH) (0.1 micrograms/min for 3 min once every hour), which appears to stimulate the gonadotropes in a physiologic manner, reversed the cortisol-induced inhibition of gonadotropin secretion, restoring circulating LH and FSH concentrations to within 80-100% of control. These results suggest that, in the rhesus monkey, the major site of the inhibitory action of cortisol on gonadotropin release resides at a suprapituitary level and is mediated by interruption of hypothalamic GnRH release.     

Cyclic nucleotide levels in activated human T lymphocytes

Phytohemagglutinin (PHA)-MR69 was used to activate human peripheral blood lymphocytes. The PHA concentration in the range of 1 to 4 micrograms/ml was optimal for lymphocyte stimulation. Cell activation occurred only in the presence of Ca ions and 5 min after it was followed by an increase in cGMP but not in cAMP. Immunomodulator, methylene bisphosphonic acid (10(-7) M and 4.10(-5) M), did not influence in culture. The cAMP and cGMP levels in PHA activated cells. Methylene bisphosphonic acid similar to 1-hydroxyenthylidene-1,1-bisphosphonic acid, aminomethylene bisphosphonic acid and phosphoneacetic acid on its addition to the culture (in the range from 10(-8) to 10(-4)M) 60 min before PHA or 24 or 48 hours after PHA administration produced no effect on the [3H]-incorporation into PHA-activated human blood lymphocytes.