The microbial factor in the chemiluminescence of the peripheral blood neutrophils of patients with suppurative surgical infection

The luminol-dependent chemiluminescence of neutrophils in the peripheral blood of 30 healthy adults and 39 patients with the local and generalized forms of purulent infection was studied. Nonstimulated chemiluminescence and the index of chemiluminescence stimulation in the presence of opsonized Staphylococcus aureus added in vitro were determined. The former characteristic was found to be directly and the latter one, inversely related to the concentration of S. aureus, Escherichia coli and Candida albicans, but not E. epidermidis, Pseudomonas aeruginosa or Citrobacter, in the primary focus. At the microbial concentration exceeding 10(4) cells/g of tissue, the former characteristic was essentially higher than the level of chemiluminescence in healthy persons. With the improvement of the general state of the patients and in the absence of microorganisms in the wound as the result of complex treatment this characteristic decreased to values comparable with the reaction of neutrophils in healthy persons.     

Tn polyagglutinability occurring in a patient with B cell lymphoma

A case of polymorphic immunocytoma (B cell lymphoma) coinciding with expression of Tn antigen on a population of erythrocytes is presented. Tn activation was found incidentally by screening blood samples of patients suffering from hematologic malignancies with a Tn specific lectin from Salvia sclarea. So far, Tn activation has been reported only in apparently healthy subjects or in subjects suffering from or developing myeloid leukemia.     

Pentoxifylline Diminishes the Oxidative Damage to Renal Tissue Induced by Streptozotocin in the Rat

Oxidative damage has been suggested to be a contributing factor in the development to diabetic nephropathy (DN). Recently, there has been evidence that pentoxifylline (PTX) has free radical-scavenging properties; thus, its antiinflammatory and renoprotective effects may be related to a reduction in reactive oxygen species production. It is likely that the pharmacological effects of PTX include an antioxidant mechanism as shown in in vitro assays. The aim of this study was to evaluate whether the reported renoprotective effects of PTX could be the result of its antioxidant actions in streptozotocin (STZ)-induced DN in rats. The administration of PTX over a period of 8 weeks, in addition to displaying renoprotective effects, caused a significant reduction in lipoperoxide levels (LPOS) in the diabetic kidney (P < 0.05), compared to untreated rats. These levels were comparable to those in the healthy kidney of experimental animals (P > 0.05). All untreated STZ rats exhibited an increase in LPOS as opposed to healthy controls (H) (P < 0.001). The total antioxidant activity (TAA) in plasma was increased significantly already after 2 days of STZ (P < 0.05). When we examined the progression of TAA in STZ rats, there was a significant decrease over 8 weeks (P < 0.05). PTX treatment caused an increase in TAA when compared to untreated STZ rats (P < 0.05). Renal hypertrophy was less evident in PTX-treated STZ than in untreated STZ rats, evaluated by kidney weight/body weight ratio. These results indicate that PTX decreases the oxidative damage induced by these experimental procedures and may increase antioxidant defense mechanisms in STZ-induced diabetes in rats.     

Discovery of diphenylcarbamate derivatives as highly potent and selective IP receptor agonists: orally active prostacyclin mimetics. Part 3

The new classes of diphenylcarbamate derivatives with a tetrahydronaphthalene skeleton as highly potent and selective IP agonists have been discovered. The optimized diphenylcarbamate type compound FK-788: (R)-4 exhibited potent antiaggregative potency with an IC50 of 18 nM and high binding affinity for the human recombinant IP receptor with K(i) values of 20 nM and selectivity for human IP over all other members of the human prostanoid receptor family. Compound (R)-4 was shown to exhibit good pharmacokinetic properties in rats and dogs, and also good bioavailability in healthy volunteers.     

In-vitro induction of some features of hairy cell leukemia in chronic lymphocytic leukemia and immunocytoma cells

In an attempt to induce in vitro differentiation we exposed cells from patients with chronic lymphocytic leukemia (CLL) and with immunocytoma (IC) to 12-0-tetra-decanoylphorbol-13-acetate (TPA) at 160 nM. After 3 to 5 days of culture cells became enlarged and the CLL cells developed a basophilic cytoplasm with an excentric nucleus. In some instances cells with many fine projections were seen. We then employed the monoclonal antibody (MAB) HD 6, which was generated against hairy cell leukemia (HCL) cells and reacts most strongly with such cells but is unreactive with plasmocytoma cells and with most CLL cells. TPA treatment induced a greatly enhanced HD 6 binding in CLL and IC cells compared to controls as demonstrated by indirect immunofluorescence. Cytochemical studies revealed that at the same time an acid phosphatase was induced, which was found to be tartrate-resistant in every instance tested. Thus, several features of HCL can be induced in CLL and IC demonstrating the close relatedness of these entities.     

Effects of phentolamine on hepatic PO2 in endotoxemia

The effect of phentolamine, an alpha-adrenergic blocker, on hepatic oxygen supply, plasma glucose, and lactate, and survival in fasted male rats administered Echerichia coli endotoxin (25 mg/kg, ip) has been studied. Survival at 24 h was 8% in untreated endotoxic rats, 83% in rats receiving phentolamine (5 mg/kg, ip) and endotoxin, and 100% in phentolamine controls. Measurements during the initial 8 h postendotoxin recorded transiently lower systemic arterial pressure in the phentolamine-endotoxic rats. Arterial PO2 and increases of pH and heart rate were similar in both endotoxic groups. Lactacidemia, present by 4 h in untreated endotoxic rats, did not develop in the phentolamine group and plasma glucose was significantly higher at 8 h (98 +/- 2.5 vs. 77 +/- 5.6 mg%, mean +/- SE). Mean hepatic PO2 at 6 h in phentolamine-endotoxic rats was 9.6 mmHg with 28% of the values below 5 mmHg. By contrast, the mean in untreated endotoxic rats was 1.9 mmHg with 88% of values below 5 mmHg. Phentolamine controls were stable over 8 h; mean hepatic PO2 was 17.7 mmHg. The differences in plasma glucose and lactate suggest protection of hepatic metabolism in phentolamine-treated endotoxic rats by prevention of excessive hepatic hypoxia.     

Indices of Coherence of EEG Rhythms in the Course of Cognitive Activity as Markers of Creative Thinking: Gender Specificity

According to the results of psychological testing, persons aged 18 to 21 years were divided into four groups, women and men with low and high productivity of divergent (creative, nonroutine) thinking (n = = 18 to 23). Results of EEG recording (19 leads) were used for calculation of the coherence coefficients for oscillations of the delta, theta, alpha1, alpha2, alpha3, beta, and gamma frequencies in lead pairs and estimation of integral indices of coherence within the anterior and posterior cortical regions and between these zones (interaction coefficients, IC1-IC3, respectively). EEG was recorded in the resting state and in the course of resolving convergent- and divergent-type cognitive test tasks. It was found that, during the performance of tests of both types, men with a higher productivity of divergent thinking demonstrated significantly higher values of IC1 (that characterizes the coherence in associative linkages within the anterior cortex) for oscillations of all EEG frequency ranges compared with the respective estimates for “low-creative” men. Similar increments were typical of the IC2 values for low- and midfrequency EEG rhythms (delta, theta, and alpha). At the same time, values of the “interregional” IC3 for theta, beta, and gamma activity in “high-creativity” men were significantly lower. In women of both groups (low and high creativity), such specificity of the IC1-IC3 patterns was practically not observed, i.e., the respective aspect demonstrated clear gender specificity. The sex of the subjects and type of the performed cognitive tests could not be considered factors significantly affecting the calculated absolute IC values. The observed specificities of integral coherence indices are probably associated with different strategies of the performance of cognitive tasks in men and women. Our findings allow us to believe that the above interrelations between integrated coherence indices can be used as EEG markers of high productivity of divergent thinking in men. The more flexible strategies of thinking in women are probably related to more variable neurophysiological cortical mechanisms (compared with those in men), and this type of organization is not clearly reflected in the pattern of intracortical interactions estimated by coherence indices.     

Selective Alterations of Opiate Receptor Subtypes in Mono sodium Glutamate-Treated Rats

Neonatal treatment of rats with monosodium glutamate (MSG) has been demonstrated to destroy cell bodies of neurons in the arcuate nucleus including the brain beta-endorphin (B-END) system. The effects on opiate receptors of the loss of B-END is unknown. Neonatal rats were treated with MSG as previously described. After reaching maturity (7-9 months), MSG-treated rats and litter-matched untreated control rats were decapitated and brains dissected into brain regions. Opiate receptor assays were run with [3H]morphine (mu receptor ligand) and [3H]D-alanine2-D-leucine5 (DADL) enkephalin (delta receptor ligand) for each brain region for both MSG and control rats simultaneously. Scatchard plot analyses showed a selective increase in delta receptors in the thalamus only. No corresponding change in mu receptors in the thalamus was found. The cross-competition IC50 data supported this conclusion, showing a loss in the potency of morphine in displacing [3H]DADL enkephalin in the thalamus of MSG-treated rats. This shift in delta receptors produced an IC50 displacement pattern in thalamus, ordinarily a mu-rich area, similar to that of striatum or cortex, delta-rich areas, again indicating an increase in delta receptors. Similar changes in delta receptors in other brain regions were not found. These results represent one of the few examples of a selective and localized shift in delta with no change in mu sites. Furthermore, the delta increase may reflect an up-regulation of the receptors in thalamus after chronic loss of the endogenous opioid B-END.     

Effect of telmisartan on preexistent cardiac and renal lesions in spontaneously hypertensive mature rats

Fifteen adult male spontaneously hypertensive rats (one year old) (SHR) were separated into three groups (n=5 each) during 15 weeks as follows: initial control group (IC); final control group (FC); and telmisartan group (T) (1.2 mg/kg/day of telmisartan). Serum and urinary creatinine and proteinuria were not different comparing untreated and telmisartan-treated SHRs. FC rats showed a continuous BP increase during the study while T rats reached the 15th week with a significantly low BP. The LV mass index was significantly smaller in the T group than in the FC group, as was the glomerular hypertrophy. The cardiomyocyte nuclei density per area and the cardiomyocyte mean cross-sectional area were smaller in the T group than in both the IC and FC groups. Intramyocardial artery densities (per area and per volume) were greater in the T group than in untreated SHRs, but myocardial fibrosis was reduced. In conclusion, telmisartan monotherapy effects on BP and also on the hypertension target organs, heart and kidney, are favorable. Telmisartan is able to attenuate SHR cardiomyocyte and glomerular hypertrophies, and myocardial reactive fibrosis as well. It also is favorable to the intramyocardial microcirculation.     

Individual variability of cardiovascular reactivity during protective cardiac reflex in humans

Fail of fast recovering to normal state after aversive event is the key feature of individual intolerance to emotional stress. Within the framework of this idea, dynamics of the arterial blood pressure reactivity was studied studied using defensive reaction of the cardiac defense response elicited by strong aversive acoustic stimuli. Dynamical patterns of cardiovascular responses observed in this reaction makes made it possible to perform affective chronometry of defensive arousal. Healthy male volunteers with normal arterial blood pressure and patients with firstly diagnosed and untreated essential hypertension were studied. The beat-by-beat dynamics of blood pressure values were registered by means of finger-cuff Finapres technology. It was shown that among healthy individuals with normal resting blood pressure values hyperreactive persons with delayed late systolic and diastolic blood pressure increases ocurred. It was suggested that similiarity of delayed pressor effects ofhypereactive healthy individuals and those of hypertension patients incate a high risk of essential hypertension in highly reactive individuals.     

Carriers of ataxia-telangiectasia gene display additional protein fraction and changes in the environment of SH groups in erythrocyte membrane

Additional protein fraction migrating slower than spectrin has been detected in erythrocyte membranes from an ataxia-telangiectasia (A-T) patient and from his mother (A-T heterozygote). In erythrocyte membranes labelled with maleimide spin label changes in signal of the weakly immobilized spin label as related to that of strongly immobilized one (w/s) were noted. In comparison to age-matched control groups the values of w/s were lower in A-T heterozygotes (ten persons) and higher in A-T homozygotes (four persons). In control persons the values of w/s increased with age, whereas in families with A-T no significant differences in this parameter were noted between children and parents. The presence of additional protein fraction in erythrocytes membranes of A-T patient and A-T heterozygote indicates that these phenotypes can be differentiated from the healthy control persons for the first time on the basis of changes detected in the erythrocytes. This change in erythrocyte membrane may explain the decrease in the w/s parameter of electron spin resonance in A-T heterozygotes. On the other hand increased values of w/s in A-T patients may be caused by disease process.     

In vitro sensitivity of Plasmodium falciparum to amodiaquine compared with other major antimalarials in Madagascar

Chloroquine has been used in Madagascar since 1945 and remains the first-line treatment for uncomplicated cases of malaria. Low-grades of resistance type R1 and R2 have been reported. Thus, in vitro tests were performed in order to monitor the drug sensitivity of Plasmodium falciparum from different study sites, with the aim of identifying alternatives to chloroquine. Chloroquine IC50 values ranged from 0.2 nM to 283.4 nM (n = 190, mean IC50 = 52.6 nM; 95% CI = 46.1-59.1 nM). Fifteen isolates (7.9%) were chloroquine-resistant. One mefloquine-resistant isolate was detected (1/139). The test isolates were sensitive to amodiaquine (n = 118), quinine (n = 212), pyrimethamine (n = 86) and cycloguanil (n = 79). The median IC50 for amodiaquine was 12.3 nM (mean IC50 = 15.3 nM, 95% CI = 13.3-17.3 nM). Amodiaquine was 3.4 times as active as chloroquine in vitro and 7 times as active as quinine against P. falciparum. These results indicate that amodiaquine may be a potent alternative to chloroquine in Madagascar. There was positive correlation between tested quinoline-containing drugs activities, which suggests in vitro cross-susceptibility.     

Synthesis of anticonvulsive AMPA antagonists: 4-oxo-10-substituted-imidaz

The overstimulation of excitatory amino acid receptors such as the glutamate AMPA receptor has been implicated in the physiopathogenesis of epilepsy as well as in acute and chronic neurodegenerative disorders. An original series of readily water soluble 4-oxo-10-substituted-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-carboxylic acid derivatives was synthesized. The most potent derivative 6a exhibited nanomolar binding affinity (IC50 = 35nM) and antagonist activity (IC50 = 6nM) at ionotropic AMPA receptor. This compound also demonstrated potent anticonvulsant properties in MES in mice and rats with long durations of action with ED50 values in the 1-3 mg/kg dose range following ip and iv administration.     

Features of the spectral power of the EEG rhythms in autistic children and their relation with the progress of different symptoms in schizophrenia

Right hemispheric dominance of the baseline alpha-band spectral power was revealed in 5-7 years boys with autism. This feature persisted during performance of a cognitive task (counting). Also, boys with autism showed lowered level of the alpha spectral power as compared with healthy children. In healthy children, the gamma spectral power increased during performance of the cognitive task as compared to baseline state. Autistic persons showed higher values of the gamma spectral power as compared with normal boys. Boys with autism showed less expressed changes in the gamma spectral power during the cognitive task than healthy children. The reduced spectral power of the alpha band in autistic boys may serve as a precursor of conversion from autism to schizophrenia. Higher level of the gamma spectral power in autistic boys is characteristic also of schizophrenic patients with positive symptoms. Lowered levels of fast rhythms reactivity revealed in autistic boys and the same effect earlier described in schizophrenic adults probably have the similar nature.     

Taxonomy of the microangiological changes in the ocular conjunctiva]

By means of biomicroscopical investigations of bulbar conjunctiva in healthy persons of different age certain characteristics on normal microcirculatory bed have been obtained. Morphometric analysis of the vital microscopical observations has revealed some age peculiarities in microcirculation of the conjunctiva. As a result of clinical examination of the persons, it has been stated that the phenomena noticed at biomicroscopy which characterize certain anomalies of microcirculatory parameters correlate with latent pathology, closely related diseases or developmental anomalies. Therefore, it is possible to consider the method of biomicroscopical investigation of the conjunctiva with a subsequent morphometric analysis of the data obtained as suitable for application not only for clinical but also for prophylactic examination of healthy persons.     

Calcium infusion and pentagastrin injection in diagnosis of medullary thyroid carcinoma.

Calcium infusion and pentagastrin injection were compared as tests to stimulate calcitonin secretion for the detection of medullary carcinoma of the thyroid. Plasma concentrations of immunoreactive calcitonin were measured by radioimmunoassay before and during both stimulation tests in 2 persons who had been found at operation to have medullary thyroid carcinoma, 1 relative in whom a cervical lymph node biopsy had shown medullary thyroid carcinoma and 36 asymptomatic relatives. The tests were carried out on separate days by intravenous infusion of calcium gluconate for 2 hours, to provide 3.75 mg/kg of elemental calcium per hour, and rapid intravenous injection of 0.5 microgram/kg of pentagastrin. Before stimulation immunoreactive calcitonin was undetectable in the plasma of 34 of the 36 asymptomatic persons; the 2 with elevated baseline concentrations of the hormone had a positive response to both tests. Seven others showed an increase in plasma immunoreactive calcitonin concentration only after pentagastrin injection. The two persons with initially elevated values and three of the seven with increased values after pentagastrin injection were found at subsequent operation to have focal medullary carcinoma and parafollicular cell hyperplasia; after the operation immunoreactive calcitonin was undetectable in the plasma, even after stimulation. Rapid injection of pentagastrin is more reliable than slow infusion of calcium as a stimulation test for the early detection of medullary thyroid carcinoma.     

Phenotypic modulation of chronic lymphocytic, prolymphocytic, and lymphoplasmacytic leukemia cells by TPA: induction of TRAP isoenzyme 5 and HD6 (CD22) antigen and enhancement of IgM messenger RNA

B-cell neoplasias such as CLL can be viewed as models of monoclonal populations restricted within discrete ranges of B-cell maturation. It is unknown whether other B-cell leukemias such as prolymphocytic leukemia (PLL), lymphoplasmacytoid immunocytoma (IC), and hairy cell leukemia (HCL) involve different B lineages or are malignant variants of B cells in successive stages of development along the same lineage. Therefore in vitro maturation was induced with the phorbol ester TPA in leukemic cell samples from 10 CLL, 4 PLL, and 4 IC patients. Morphologically, both plasmacytic and hairy cell-like phenomena were induced. The latter unexpected finding was confirmed by reaction with HD6 (CD22) antibody which stains HCL but is unreactive with plasma cells, multiple myeloma, and CLL cells. Tartrate-resistant acid phosphatase was demonstrated in TPA-cultured CLL, PLL, and IC cells, and the same isoenzyme band as in HCL was revealed by isoelectrofocusing. On the other hand, an increase of IgM messenger RNA was detected in up to 20% of the cells in CLL cultures by single-cell in situ hybridization with fluoro-chrome-labeled DNA probes. An abundance of IgM messenger RNA characterizes lymphoplasmacytoid cells as found in IC. Our data demonstrate that CLL, PLL, and IC can be induced to realize a common genetic program which bears characteristics of HCL indicating that these four entities are more closely related than previously thought.     

In vitro alpha-glucosidase and alpha-amylase enzyme inhibitory effects of Andrographis paniculata extract and andrographolide

There has been an enormous interest in the development of alternative medicines for type 2 diabetes, specifically screening for phytochemicals with the ability to delay or prevent glucose absorption. The goal of the present study was to provide in vitro evidence for potential inhibition of alpha-glucosidase and alpha-amylase enzymes, followed by a confirmatory in vivo study on rats to generate a stronger biochemical rationale for further studies on the ethanolic extract of Andrographis paniculata and andrographolide. The extract showed appreciable alpha-glucosidase inhibitory effect in a concentration-dependent manner (IC(50)=17.2+/-0.15 mg/ml) and a weak alpha-amylase inhibitory activity (IC(50)=50.9+/-0.17 mg/ml). Andrographolide demonstrated a similar (IC(50)=11.0+/-0.28 mg/ml) alpha-glucosidase and alpha-amylase inhibitory activity (IC(50)=11.3+/-0.29 mg/ml). The positive in vitro enzyme inhibition tests paved way for confirmatory in vivo studies. The in vivo studies demonstrated that A. paniculata extract significantly (P<0.05) reduced peak blood glucose and area under curve in diabetic rats when challenged with oral administration of starch and sucrose. Further, andrographolide also caused a significant (P<0.05) reduction in peak blood glucose and area under the curve in diabetic rats. Hence alpha-glucosidase inhibition may possibly be one of the mechanisms for the A. paniculata extract to exert antidiabetic activity and indicates that AP extract can be considered as a potential candidate for the management of type 2 diabetes mellitus.     

The effect of the alpha 2-HS-glycoprotein on the mitogen-induced lymphoblastic transformation and IL-2 production

Authors investigated the in vitro effect of alpha 2-HS-glycoprotein on the lymphoblastic transformation and interleukin-2 production. The observations were made on the peripheral blood lymphocytes of healthy persons, on those of women taking oral contraceptives and on those of patients with systemic lupus erythematosus. The alpha 2-HS-glycoprotein inhibited the mitogen responses both in physiologic and in the halved concentrations. The inhibition of the interleukin-2 production seemed less remarkable.     

Lipid droplets of interstitial medullary cells of intact rat kidney with two-kidney Goldblatt hypertension.

Electron microscopic studies have been carried out of the interstitial cells (IC) of the renal medulla in rats with Goldblatt hypertension. Analysis of variance has not revealed any differences in the number of droplets of "unclamped" kidney in the hypertensive rats as compared to the normotensive rats ("resistant" rats, rats with unilateral nephrectomy, and intact rats) at periods from 3 weeks to 1 year. The total volume of the droplets in the IC cytoplasm in hypertensive and intact animals also revealed no difference 3 weeks after the beginning of the experiment. A positive correlation has been found between the number of the droplets and their volume but the low value of the correlation coefficient (r = +0.28) suggests that the number of the droplets cannot be a reliable indicator of the variation of the amount (volume) of thelipid material contained in them. Since it is just the latter parameter that carries the most information for evaluating the content of the droplet material in the IC, preference should be given to calculating the droplet volume rather than counting the number of droplets. The IC in the animals of the experimental groups revealed hypertrophy and hyperlasia of the endoplasmic reticulum and the Golgi complex, which were especially marked at the earlier stages of the experiments.