Biomedical subjects

S Rajguru

Publications and source records attributed to S Rajguru.

13 recordsLinked to original sources

PubMed2000

Alcohol modulates cytokine secretion and synthesis in human fetus: an in vivo and in vitro study.

It is well recognized that alcohol passes through the placenta and affects the fetal immune system. The underlying mechanism accounting for immune suppression is not clear. Cytokines are recognized as the principal mediators of a variety of immunologic and pathophysiologic events. The study was designed to examine whether alcohol use during pregnancy affects cytokine synthesis and secretion in the human fetus. Fetal (cord blood) and mother's blood were used for the study. Studies were conducted in vivo and in vitro. For the in vivo study, cytokine levels were measured in cord blood in mothers who drank moderate to heavy (chronic) amounts of alcohol during pregnancy. For the in vitro study, cord blood was obtained from mothers who were drug-free throughout pregnancy. Lymphocytes were isolated and stimulated with lipopolysaccharide (LPS; Escherichia coli, 26:B6). The capacity of lymphocytes to synthesize cytokines was examined in the presence of 20, 50, and 100 mM alcohol. Among the cytokines examined were the tumor necrosis factor (TNF alpha) and interleukins (IL-1 alpha and beta and IL-6). The selection of cytokines was based on their presumptive role in the pathophysiology of alcoholism. Cytokines were measured by using a specific immunoassay. When data obtained from moderate alcohol users were compared with those obtained from nonusers, no significant differences were observed in any of the cytokines examined (p>0.05). In chronic alcohol users, levels for all cytokines increased significantly (p<0.001) in both the fetus and the mother. Among the cytokines, IL-1beta, IL-6, and TNFalpha were the predominant cytokines affected by chronic use of alcohol during pregnancy. The order of stimulation was IL-6, IL-1 beta, TNFalpha, and IL-1 alpha in descending order. In the in vitro study, alcohol blunted LPS stimulation of cytokines, and the alcohol-induced decrease in cytokine synthesis was proportional to the level of alcohol in the media, suggesting a direct effect of alcohol on cytokine synthesis. In general, the blunting effect of alcohol on LPS stimulation was more prominent in the fetus compared with that in mother. We conclude that chronic alcohol use during pregnancy stimulated the fetal cytokine synthesis and secretion, and IL-1beta, IL-6, and TNF alpha were the predominant cytokines affected by alcohol. The in vitro data suggest a direct effect of alcohol on cytokine synthesis.

Adult↗

PubMed1995

Self-reported signs and symptoms in breast implant patients with novel antibodies to silicone surface associated antigens [anti-SSAA(x)].

In research animals, the immune adjuvant activity of silicone in eliciting antibodies to associated protein antigens is now well established. In humans, the immune adjuvant activity of silicone remains controversial. Clusters of data from various research groups are beginning to define the boundary conditions for future large epidemiological studies. In that spirit, this manuscript reports pilot clinical data from a serological study conducted 3 years ago and reported previously in this journal. Sera from a self-selected symptomatic population of patients with breast implants were assayed for elevated concentrations of antibodies showing binding avidity to silicone surface associated antigens [anti-SSAA(x)]. In that study of 249 patients, two distinct statistically significant subgroups were identified on the basis of the serological assay alone: patients without any elevated anti-SSAA(x) (negative) and patients with elevated anti-SSAA(x) (positive) (p < 0.001). In this study, a clinical survey returned by 226 of those patients was correlated with the previously acquired serological findings. The 11 most common clinical complaints reported by the 199 anti-SSAA(x) negative patients and by the 27 anti-SSAA(x) positive were compared and their frequencies analyzed. The 199 anti-SSAA(x) negative patients, as a group, showed a lower frequency of a variety of signs and symptoms compared to the 27 anti-SSAA(x) positive patients. Statistically significant differences were seen in three of the symptoms: fever, foot pain, and sleep disturbance (p < 0.05). In addition, the syndrome of fever in the absence of local chest pain was a significantly associated with anti-SSAA(x) positivity (p < 0.001).

Antibodies↗

PubMed1995

Preservation of surface-dependent properties of viral antigens following immobilization on particulate ceramic delivery vehicles.

B-cell stimulation for the purpose of evoking an effective neutralizing humoral immune response is a surface phenomenon that is exquisitely specific to antigen conformation. Consequently, successful delivery of antigen, such as would be desired in a vaccine, entails preservation of an antigen's apparent native surface (conformational) properties. Prior to testing the actual vaccinating efficacy of delivered antigens, the surface properties could be assessed through a variety of in vitro and in vivo assays in which the measurement standard would be the properties of the antigens in their native state (whole virus). Using surface modified nanocrystalline carbon and calcium-phosphate ceramic particulates (carbon ceramics and brushite), we evaluated the surface activity of immobilized non-nuclear material extracted from HIV-1. Physical characterization showed that the particles with immobilized antigen ("HIV decoys") measured 50 nm in diameter (HIV = 50-100 nm) and exhibited the same zeta potentials as whole (live) HIV. In vitro testing showed that the HIV decoys were recognized by both conformationally nonspecific and specific monoclonal antibodies, were recognized by human IgG from HIV antibody-positive patients, and could promote surface agglomeration among malignant T-cells similar to live HIV. Last, in vivo testing in three vaccinated animal species showed that the HIV decoys elicited humoral and cellular immune responses similar to that evoked by whole (live) HIV.

Animals↗

PubMed1994

Surface-modified nanocrystalline ceramics for drug delivery applications.

Drug delivery systems comprised of various types of carriers have long been the object of pharmacological investigation. The search has been stimulated by the belief that carriers will lead to reduced drug toxicity, dosage requirements, enhanced cellular targeting and improved shelf-life. Among the carriers investigated are complex polymeric carbohydrates, synthetic proteins and liposomal structures. For the past four years, we have been experimenting with a radically new class of carriers comprised of surface-modified nanocrystalline ceramics. While the ceramics provide the structural stability of a largely immutable solid, the surface modification creates a glassy molecular stabilization film to which pharmacological agents may be bound non-covalently from an aqueous phase with minimal structural denaturation. As a consequence of maintained structural integrity and owing to concentration effects afforded by the surfaces of the nanocrystalline materials, drug activity following surface immobilization is preserved. We have used successfully surface-modified nanocrystalline ceramics to deliver viral antigens for the purpose of evoking an immune response, oxygenated haemoglobin for cell respiration and insulin for carbohydrate metabolism. The theoretical principles, technical details and experimental results are reviewed. Surface-modified nanocrystalline materials offer an exciting new approach to the well-recognized challenges of drug delivery.

Animals↗

PubMed1992

Amniotic fluid and umbilical artery levels of sex hormones and prostaglandins in human cocaine users.

Biochemical evaluation of amniotic fluid contents is often used to monitor fetal secretory and excretory functions. To determine whether cocaine use during pregnancy affects fetal endocrine secretions, amniotic fluid and umbilical artery samples were collected at term, and selected gonadal hormones and prostaglandins were assayed. Gestational age, birth weights, and placental weights were recorded. The data showed that birth weights were significantly decreased (P less than 0.001) in cocaine users, but gestational age and placental weights were unaffected. Amniotic fluid levels of androstenedione and testosterone were decreased (P less than 0.05) in males born to cocaine users; females were not affected. Prostaglandins (PGF2 alpha and PGE2) were significantly increased (P less than 0.01) in cocaine users. In the umbilical artery, follicle-stimulating hormone was increased (P less than 0.01) in males and females, while luteinizing hormone was increased (P less than 0.01) only in males. We conclude that cocaine passes through the placenta and affects the fetal testes-hypophyseal endocrine system.

Adult↗

PubMed1991

Evidence that gonadal hormone levels in amniotic fluid are decreased in males born to alcohol users in humans.

Biochemical evaluation of amniotic fluid content is often used to monitor fetal secretory and excretory functions. It is known that alcohol freely passes through the placenta and enters the fetal tissues. The study was designed to investigate whether alcohol use during pregnancy affects amniotic fluid steroid and peptide hormone levels. Five alcohol users who drank between 40 and 45 drinks per month and consumed approximately 1 oz. of alcohol per day from beer drinking participated in the study. Thirteen controls with no history of alcohol use including essential and non-essential drugs were selected for the study. The final selection of participants was made among those who delivered male offsprings. Amniotic fluid was aspirated between 16 and 20 weeks of gestation by amniocentesis and an aliquot was used to assay steroid hormones (4-androstenedione [-4-AD], testosterone [T], estradiol [E2], dehydroepiandrosterone sulfate [DHEA-S]), and peptide hormones (FSH and LH). Birth weights, placental weights and gestation age were recorded at birth. The results showed that -4-AD, T and E2 levels were significantly decreased (P less than 0.01) in alcohol users; DHEA-S, FSH and LH levels were unaffected. Birth weights were significantly decreased (P less than 0.05) in alcohol users, the placental weights and gestation age were not affected. We conclude that alcohol passes through the placenta and affects fetal testes, capacity to synthesize steroids and the effect appears to be direct and not via the hypothalamic-hypophyseal axis.

Adult↗

PubMed1989

Facilitory role of thyroid hormone in vitamin A uptake in the rat testes.

The inter-relationship of hormones and retinol (vit. A) metabolism is under investigation in our laboratory. The investigation is designed to study the role of thyroid hormone (tetraiodothyronine, T4) in the uptake of vit. A in various rat tissues. Adult male thyroidectomized (Tx) rats, partially vit. A deficient, were administered intragastrically tritium-labeled vit. A. Twenty-four hours later, the level of radioactivity was measured in the blood plasma, liver, kidneys, testes and urine collected for 24 hrs. The data showed that in Tx rats, there was a significant decrease (P less than .01) in the level of radioactivity in the kidneys, testes and urine; in blood plasma and the liver, there was a significant increase (P less than .01). In Tx rats, treatment with T4 restored 50-70% of the radioactivity lost in the kidneys, testes and urine. The endogenous vit. A level in Tx rats treated without and with T4 followed essentially the same pattern. The capacity of cellular retinol binding protein (CRBP) to bind exogenously added vit. A was examined. The data showed a decrease in the binding capacity of CRBP in Tx rats. We conclude that T4 facilitates the uptake of vit. A in the target tissues by regulating CRBP synthesis or degradation.

Animals↗

PubMed1988

Dexamethasone suppresses sex-hormone binding globulin.

Dexamethasone suppression (DEX-S) for 14 days has been used to determine the probable source of androgen excess. The exact mechanism(s) of DEX-S is still unclear. The authors postulated that dexamethasone (DEX) inhibits either the synthesis or secretion of sex-hormone binding globulin (SHBG). To examine this hypothesis, 14 women with polycystic ovarian disease (PCOD) and 3 volunteers were given DEX for 14 days. The PCOD group included obese and nonobese women (+/- 15% ideal body weight). Plasma determinations by radioimmunoassay of total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate, luteinizing hormone; follicle-stimulating hormone; cortisol, and SHBG were made. DEX suppressed SHBG levels (P less than 0.01). SHBG levels were significantly lower in the obese than in the nonobese (P less than 0.01). All androgens were suppressed by DEX, with the exception of androstenedione post-DEX levels, which were significantly greater than pre-DEX levels in 6 of 14 subjects (P greater than 0.05). This observation is consistent with DEX suppression of SHBG.

Adult↗

PubMed1981

Blood hormone profiles in prostate cancer patients in high-risk and low-risk populations.

Epidemiologic data reveal that the incidence rate of prostate gland carcinoma among the black population in the United States (US) is several times higher than among Nigerians. A collaborative study between the two countries was undertaken, and blood hormone (testosterone [T], dihydrotestosterone [DHT], estrone [E1], estradiol [E2], and prolactin [P1]), total acid phosphatase (TP), and prostatic acid phosphatase (PAP) profiles in the two population groups were compared. In the US groups (patients and controls) there were significantly higher levels of T (P less than 0.01) and E1 (P less than 0.05) compared with the Nigerians. Also, the US patients had significantly higher levels of T (P less than 0.05) and E1 (P less than 0.01) compared with their matched controls. In the Nigerians T but not E1 levels were significantly lower (P less than 0.05) in patients compared with controls. DHT, E2, and P1 were not significantly different in patients and controls between and within the populations. Nigerian patients had higher levels (P less than 0.001) of TP and PAP compared with US patients. It is concluded that differences in blood hormone profiles in the two population groups are based on factors other than the genetic makeup of the populations.

Acid Phosphatase↗

PubMedDate not supplied

Ethanol decreases progesterone synthesis in human placental cells: mechanism of ethanol effect.

Fetal alcohol syndrome (FAS) is a set of signs and symptoms in offsprings born to mothers who abuse alcohol during pregnancy. We postulated that impairment in the placental endocrine function contribute to FAS. In this study, we examined in vitro effects of ethanol on the placental cells' (cytotrophoblast cells) capacity to synthesize progesterone. Cytotrophoblast cells were isolated from normal term placenta and were incubated (2 x 10(6)) with 20-, 30-, and 40-mM doses of ethanol for 6 h. Progesterone was measured in the incubate by RIA. The results showed that, at the 20-mM dose of ethanol, progesterone synthesis was significantly decreased (p less than 0.01), at the 30-mM dose level there was a further decrease of 20%. The differences between 30- and 40-mM ethanol dose levels were not significant. To determine the mechanism of ethanol effects on progesterone synthesis, cytotrophoblast cells were preincubated with 30 mM ethanol followed by 10 microliters of LDL (10 microliters LDL = 80 micrograms cholesterol) and vice versa. The results showed that ethanol effects on progesterone synthesis was dependent on whether ethanol was added prior to or following the addition of LDL in the medium. If ethanol was added in the medium prior to LDL, progesterone synthesis was decreased significantly (p greater than 0.01); however, when ethanol was added after the LDL, ethanol had no effect on progesterone synthesis. In the experiment where ethanol and LDL were added simultaneously in the medium, ethanol blunted the stimulatory effect of LDL on progesterone synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug↗

PubMedDate not supplied

Surface-modified diamond nanoparticles as antigen delivery vehicles.

Recognition of antigens by immunocompetent cells involves interactions that are specific to the chemical sequence and conformation of the epitope (antigenic determinant). Adjuvants that are currently used to enhance immunity to antigens tend to either alter the antigen conformation through surface adsorption or shield potentially critical determinants, e.g., functional groups. It is demonstrated here that surface-modified diamond nanoparticles (5-300 nm) provide conformational stabilization, as well as a high degree of surface exposure to protein antigens. By enhancing the availability and activity of the antigen in vivo, a strong, specific immune response can be elicited. Results are demonstrated for mussel adhesive protein (MAP), a substance for which conventional adjuvants have proven only marginally successful in evoking an immune response. Surface-modified diamond nanoparticles as antigen delivery vehicles are a novel example of the exciting marriage of materials science, chemistry, and biology.

Animals↗

PubMedDate not supplied

Low levels of ethanol stimulate and high levels decrease phosphorylation in microtubule-associated proteins in rat brain: an in vitro study.

Phosphorylation and dephosphorylation of proteins associated with microtubules (MAPs) modulate the functional properties of microtubules (MT). A study was designed to test the hypothesis that ethanol at pharmacologically relevant levels affects phosphorylation of MAPs. Low (6, 12, 24, and 48 mM) and high (96, 384, and 768 mM) levels of ethanol were used in the study. MT prepared from rat brain by successive cycles of assembly-disassembly were found to contain two high molecular weight proteins (MAP2 and MAP1), tubulin, and 70-kDa neurofilament. The kinase activity was determined using [gamma(32)P]ATP as a phosphate donor. The results showed that ethanol primarily stimulated MAP2 phosphorylation. Low levels of ethanol stimulated, whereas high levels decreased, the kinase activity. MAP1 was phosphorylated to a lesser extent. 70-kDa neurofilament and tubulin were phosphorylated, however, the dose-dependent biphasic effect of ethanol on phosphorylation was not found in these cytoskeleton proteins. To determine whether the ethanol-induced kinase activity was cAMP-dependent, the catalytic subunit of cAMP-dependent protein kinase was isolated, purified, and kinase activity was determined with and without ethanol. The results showed that cAMP was not involved in ethanol-induced kinase activity. We conclude that ethanol predominantly stimulates phosphorylation of MAP2 in a dose-dependent manner.

Animals↗

PubMedDate not supplied

Zinc inhibits protein phosphorylation in isolated sperm head membranes in Spisula solidissima.

Zinc, when added to the media in concentrations as low as one micromolar, decreased protein phosphorylation in the isolated sperm head membranes in Spisula solidissima, 70-75%. Other divalent cations barium, strontium, cobalt, and copper, in similar concentrations exerted no effect. Sodium fluoride, a phosphatase inhibitor, had no effect on the zinc induced inhibition on protein phosphorylation and, when zinc was added to the media after the phosphorylation reaction of proteins, the inhibitory effect of zinc was lost. The autoradiography of -32P labeled proteins on SDS gel confirmed the inhibitory effect of zinc on protein phosphorylation. The inhibitory role of zinc on protein phosphorylation in the sperm membranes suggests a physiological role of this cation on membrane activity in the process of fertilization.

Animals↗