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Biomedical subjects

A S Prasad

Publications and source records attributed to A S Prasad.

At least 19 recordsLinked to original sources
PubMed2006

A stability-indicating HPLC assay method for docetaxel.

A novel stability-indicating high-performance liquid chromatographic assay method was developed and validated for docetaxel in the presence of degradation products generated from forced decomposition studies. A gradient HPLC method was developed to separate the drug from the degradation products, using a Hichrom RPB HPLC column. Mixture of water and acetonitrile was used as mobile phase. The flow rate was 1.0 ml/min and the detection was done at 230 nm. Using the above method one can carry out the quantitative estimation of impurity namely DCT-1 and docetaxel. The developed gradient LC method was subsequently validated.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Zinc activates NF-kappaB in HUT-78 cells.

Zinc is essential for human health, and its deficiency in human beings results in growth failure, immune disorders affecting Th1 functions, decreased interleukin-2 (IL-2) production, and cognitive impairment. Nearly 2000 transcription factors require zinc for their structural integrity; however, it is not known whether cellular zinc deficiency results in any change in activation of any of the transcription factors. Inasmuch as NF-kappaB binds to the promoter enhancer area of IL-2 and IL-2Ralpha genes, we investigated the effect of zinc deficiency on activation of NF-kappaB and its binding to DNA in HUT-78, a Th0 malignant human lymphoblastoid cell line. We show here for the first time that in zinc-deficient HUT-78 cells, phosphorylated IkappaB, and IKK, ubiquitinated IkappaB and binding of NF-kappaB to DNA were all significantly decreased. Zinc increased the translocation of NF-kappaB from cytosol to nucleus. We also demonstrate that the binding of recombinant NF-kappaB (p50)(2) to DNA in HUT-78 cells was zinc specific. We conclude that zinc plays an important role in the activation of NF-kappaB in HUT-78 cells.

Cell Line↗
PubMed2000

Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Adults and children in the United States get two to six colds per year. Evidence that zinc is effective therapy for colds is inconsistent. OBJECTIVE: To test the efficacy of zinc acetate lozenges in reducing the duration of symptoms of the common cold. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Detroit Medical Center, Detroit, Michigan. PATIENTS: 50 ambulatory volunteers recruited within 24 hours of developing symptoms of the common cold. INTERVENTION: Participants took one lozenge containing 12.8 mg of zinc acetate or placebo every 2 to 3 hours while awake as long as they had cold symptoms. MEASUREMENTS: Subjective symptom scores for sore throat, nasal discharge, nasal congestion, sneezing, cough, scratchy throat, hoarseness, muscle ache, fever, and headache were recorded daily for 12 days. Plasma zinc and proinflammatory cytokine levels were measured on day 1 and after participants were well. RESULTS: Forty-eight participants completed the study (25 in the zinc group and 23 in the placebo group). Compared with the placebo group, the zinc group had shorter mean overall duration of cold symptoms (4.5 vs. 8.1 days), cough (3.1 [95% CI, 2.1 to 4.1] vs. 6.3 [CI, 4.9 to 7.7] days), and nasal discharge (4.1 [CI, 3.3 to 4.9] vs. 5.8 [CI, 4.3 to 7.3] days) and decreased total severity scores for all symptoms (P < 0.002, test for treatment x time interaction). Mean changes in soluble interleukin-1 receptor antagonist level differed nonsignificantly between the zinc group and the placebo group (difference between changes, -89.4 pg/mL [CI, -243.6 to -64.8 pg/mL]). CONCLUSION: Administration of zinc lozenges was associated with reduced duration and severity of cold symptoms, especially cough. Improvement in clinical symptoms with zinc treatment may be related to a decrease in proinflammatory cytokine levels; however, in this study, the observed differences between changes in cytokine levels in zinc and placebo recipients were not significant.

Adult↗
PubMed2000

Effects of zinc deficiency on Th1 and Th2 cytokine shifts.

Nutritional deficiency of zinc is widespread throughout developing countries, and zinc-deficient persons have increased susceptibility to a variety of pathogens. Zinc deficiency in an experimental human model caused an imbalance between Th1 and Th2 functions. Production of interferon-gamma and interleukin (IL)-2 (products of Th1) were decreased, whereas production of IL-4, IL-6, and IL-10 (products of Th2) were not affected during zinc deficiency. Zinc deficiency decreased natural killer cell lytic activity and percentage of precursors of cytolytic T cells. In HuT-78, a Th0 cell line, zinc deficiency decreased gene expression of thymidine kinase, delayed cell cycle, and decreased cell growth. Gene expression of IL-2 and IL-2 receptors (both alpha and beta) and binding of NF-kappaB to DNA were decreased by zinc deficiency in HuT-78. Decreased production of IL-2 in zinc deficiency may be due to decreased activation of NF-kappaB and subsequent decreased gene expression of IL-2 and IL-2 receptors.

Adult↗
PubMed1999

Effect of zinc supplementation on incidence of infections and hospital admissions in sickle cell disease (SCD).

Zinc deficiency is a common nutritional problem in adult sickle-cell disease (SCD) patients. Hyperzincuria and increased requirement of zinc due to continued hemolysis in SCD are probable bases for zinc deficiency in these patients. Zinc deficiency affects adversely T-helper1 (TH1) functions and cell mediated immunity and interleukin (IL)-2 production is decreased in zinc deficient subjects. We hypothesized that zinc supplementation will improve T-helper1 function and decrease incidence of infections in patients with SCD. We tested this hypothesis in 32 SCD subjects who were divided in three groups (Grs A, B, and C). Grs A (n = 11) and B (n = 10) were zinc deficient based on cellular zinc criteria and Gr C (n = 11) were zinc sufficient. Gr A subjects were observed for 1 year (baseline), following which they received zinc acetate (50 to 75 mg of elemental zinc orally daily) for 3 years. Gr B subjects were observed for 1 year (baseline), following which they received placebo for 1 year and then switched to zinc supplementation (50 to 75 mg of elemental zinc orally daily) for 2 years. Gr C subjects did not receive any intervention inasmuch as they were zinc sufficient. Prolonged zinc supplementation resulted in an increase in lymphocyte and granulocyte zinc (P = 0.0001), and an increase in interleukin-2 production (P = 0.0001), decreased incidence of documented bacteriologically positive infections (P = 0.0026), decreased number of hospitalizations and decreased number of vaso-occlusive pain crisis (P = 0.0001). The predominant pathogens isolated were staphylococci and streptococci involving the respiratory tract and aerobic gram-negative bacteria, particularly Escherichia coli, involving the urinary tract. Further confirmation of our observations will require prospective studies of zinc supplementation in a larger number of SCD patients.

Administration, Oral↗
PubMed1998

Effects of zinc and nutritional status on clinical outcomes in head and neck cancer.

The head and neck cancer patient often presents with both protein malnutrition and trace element deficiencies. Zinc has been found to be deficient in many head and neck cancer patients. In this study, pretreatment zinc status and nutritional status (measured by the Prognostic Nutritional Index [PNI]) were correlated with clinical outcomes in 47 patients. The patients were followed-up for a median of 52 mo from the time of enrollment. Our results showed that the tumor size and overall stage correlated significantly to zinc status whereas no such correlation was seen with PNI, alcohol intake, or smoking in our subjects. The results also showed that impaired zinc status was associated with an increased number of treatment morbidities, unplanned hospitalizations, and treatment delays (P < 0.05). Nutritional status was not associated with any studied outcome variable. The disease-free interval was highest for the group which had both zinc-sufficient and nutrition-sufficient status. Although our data do not prove conclusively, they do suggest that impaired zinc status at presentation may contribute to treatment morbidity, and that for an optimal mean disease-free interval, a sufficient zinc and nutritional status is required.

Aged↗
PubMed1998

Zinc may regulate serum leptin concentrations in humans.

OBJECTIVE: Leptin, the product of the ob gene, plays a key role in a feedback loop that maintains energy balance by signaling the state of energy stores to the brain and by influencing the regulation of appetite and energy metabolism. Zinc also plays an important role in appetite regulation. Thus, we evaluated the relationship between zinc status and the leptin system in humans. METHODS: We studied nine healthy men with marginal zinc deficiency, induced by dietary means, before and after zinc supplementation. RESULTS: Zinc restriction decreased leptin levels while zinc supplementation of zinc-depleted subjects increased circulating leptin levels. In addition, zinc supplementation increased IL-2 and TNF-alpha production that could be responsible for the observed increase in leptin concentrations. CONCLUSIONS: Zinc may influence serum leptin levels, possibly by increasing the production of IL-2 and TNF-alpha.

Adult↗
PubMed1998

Nutritional and zinc status of head and neck cancer patients: an interpretive review.

In this review, we provide evidence based on our studies, for zinc deficiency and cell mediated immune disorders, and the effects of protein and zinc status on clinical morbidities in patients with head and neck cancer. We investigated subjects with newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx. Patients with metastatic disease and with severe co-morbidity were excluded. Nutritional assessment included dietary history, body composition, and prognostic nutritional index (PNI) determination. Zinc status was determined by zinc assay in plasma, lymphocytes, and granulocytes. Pretreatment zinc status and nutritional status were correlated with clinical outcomes in 47 patients. Assessment of immune functions included production of TH1 and TH2 cytokines, T cell subpopulations and cutaneous delayed hypersensitivity reaction to common antigens. At baseline approximately 50% of our subjects were zinc-deficient based on cellular zinc criteria and had decreased production of TH1 cytokines but not TH2 cytokines, decreased NK cell lytic activity and decreased proportion of CD4+ CD45RA+ cells in the peripheral blood. The tumor size and overall stage of the disease correlated with baseline zinc status but not with PNI, alcohol intake, or smoking. Zinc deficiency was associated with increased unplanned hospitalizations. The disease-free interval was highest for the group which had both zinc sufficient and nutrition sufficient status. Zinc deficiency and cell mediated immune dysfunctions were frequently present in patients with head and neck cancer when seen initially. Zinc deficiency resulted in an imbalance of TH1 and TH2 functions. Zinc deficiency was associated with increased tumor size, overall stage of the cancer and increased unplanned hospitalizations. These observations have broad implications in the management of patients with head and neck cancer.

Carcinoma, Squamous Cell↗
PubMed1998

Zinc and immune function: the biological basis of altered resistance to infection.

Zinc is known to play a central role in the immune system, and zinc-deficient persons experience increased susceptibility to a variety of pathogens. The immunologic mechanisms whereby zinc modulates increased susceptibility to infection have been studied for several decades. It is clear that zinc affects multiple aspects of the immune system, from the barrier of the skin to gene regulation within lymphocytes. Zinc is crucial for normal development and function of cells mediating nonspecific immunity such as neutrophils and natural killer cells. Zinc deficiency also affects development of acquired immunity by preventing both the outgrowth and certain functions of T lymphocytes such as activation, Th1 cytokine production, and B lymphocyte help. Likewise, B lymphocyte development and antibody production, particularly immunoglobulin G, is compromised. The macrophage, a pivotal cell in many immunologic functions, is adversely affected by zinc deficiency, which can dysregulate intracellular killing, cytokine production, and phagocytosis. The effects of zinc on these key immunologic mediators is rooted in the myriad roles for zinc in basic cellular functions such as DNA replication, RNA transcription, cell division, and cell activation. Apoptosis is potentiated by zinc deficiency. Zinc also functions as an antioxidant and can stabilize membranes. This review explores these aspects of zinc biology of the immune system and attempts to provide a biological basis for the altered host resistance to infections observed during zinc deficiency and supplementation.

Animals↗
PubMed1998

Cardiovascular responses to application of lower body negative pressure of male volunteers in seated position.

Lower body negative pressure (LBNP) has been used to evaluate orthostatic tolerance and for studying the effects of +Gz induced physiological strain and hence has great practical significance in aerospace medicine. Cardiovascular responses in man on application to LBNP (-40 mmHg) in seated (upright) position in a specially designed LBNP chamber have been studied in eight normal healthy male volunteers between the age group of 25-36 yrs. They were subjected to -40 mmHg negative pressure in steps of -10 mmHg for a duration of 5 min each. The total duration of the experiment was 20 min. Heart rate (HR), blood pressure (BP) Cardiac output (CO) were measured and mean blood pressure (MBP) and total peripheral resistance (TPR) were computed. The results indicate a significant increase in HR (P < 0.01), SV (P < 0.01). Studies on limited number of subjects on application to LBNP (40 mmHg) in supine position have also been carried out and compared with the physiological strain induced in subjects in seated position. Study of HR, SV, CO, responses of the subjects on exposure to LBNP in seated position elicit similar response in subjects exposed to +Gz stress as reported by other workers. It is concluded that LBNP technique can be used to study the effects of +Gz induced physiological strain in man.

Adult↗
PubMed1998

Zinc and immunity.

Nutritional deficiency of zinc is widespread throughout the developing countries and a conditioned deficiency of zinc is known to occur in many diseased states. Zinc is known to play an important role in the immune system and zinc deficient subjects may experience increased susceptibility to a variety of pathogens. We have studied the effects of a mild deficiency of zinc on T cells in an experimental model of human zinc deficiency. We showed that T cell functions were affected adversely even when the deficiency of zinc was mild in humans. Characteristically during zinc deficiency, the serum thymulin activity (a thymic hormone) was decreased which was restored following zinc supplementation. Our studies also showed that zinc deficiency caused an imbalance between TH1 and TH2 functions. The production of IFN-g, IL-2, TNF-a (products of TH1 cells) were decreased, whereas the production of IL-4, IL-6 and IL-10 (products of TH2) were not affected during zinc deficiency. T cell subpopulation studies revealed that the CD4+ CD45RA+ to CD4+ CD45RO+ ratio was decreased as a result of zinc deficiency, suggesting that zinc may be required for the regeneration of new CD4+ T cells. We further documented that zinc deficiency decreased NK cell lytic activity and caused a decrease in the percentage of CD8+ CD73+ T cells which are known to be predominantly precursors of cytotoxic T cells. In a suitable cell culture model our studies revealed that the gene expression of a DNA synthesizing enzyme TK was affected adversely which resulted in delayed cell cycle and decreased cell growth. The above immunological consequences of zinc deficiency may be responsible for decreased cell mediated immune functions in zinc deficient subjects.

Animals↗
PubMed1997

Decreased expression of CD73 (ecto-5'-nucleotidase) in the CD8+ subset is associated with zinc deficiency in human patients.

We used flow cytometry to observe the changes in T cell populations resulting from zinc deficiency in subjects with sickle cell anemia (SCA) and in healthy human volunteers without SCA. Zinc deficiency was associated with significant decreases in cellular zinc concentration, CD4+/CD8+ ratio, and percentage of CD73+ cells in the CD8+ population. The decrease in the percentage of CD73+ cells in the CD8+ subset was significantly correlated with lymphocyte zinc concentration and was accompanied by essentially no change in the percentage of CD11b+ cells in the CD8+ subset. Daily oral zinc supplementation in nine zinc-deficient human volunteers (25 mg elemental zinc) and in seven zinc-deficient SCA subjects (50 mg elemental zinc) resulted in increases in the absolute lymphocyte count and significant increases in the CD4+/CD8+ ratio and in the percentage of CD73+ cells in the CD8+ subset. In zinc-supplemented subjects, the increase in the percentage of CD73+ cells was accompanied by a significant decrease in the percentage of CD11b+ cells in the CD8+ subset. Changes in the CD4+/CD8+ and CD73+/CD11b- cell ratios in the CD8+ subset after treatment may provide a useful diagnostic criterion for zinc deficiency in humans.

5'-Nucleotidase↗
PubMed1997

Trace elements in head and neck cancer patients: zinc status and immunologic functions.

In this study we have assessed zinc status and zinc-dependent cell-mediated immune functions (interleukin-2 production by mononuclear cells, natural killer cell lytic activity, and interleukin-1 beta production by mononuclear cells) in adult patients with squamous cell carcinoma of the upper aerodigestive tract at diagnosis and before any therapy was instituted. Inasmuch as significant interactions between zinc, copper, and iron exist, we also assayed the plasma copper level, serum iron level, and total iron-binding capacity in our patients. We recruited 30 cancer subjects and 21 control subjects. On the basis of cellular zinc criteria, we diagnosed a mild deficiency of zinc in 53% of cancer subjects. The plasma zinc level was not decreased in our subjects. A univariate analysis was applied by use of one-way analysis of variance comparing study variables among the three study groups (controls and zinc-deficient and zinc-sufficient cancer patients) and Tukey's multiple comparison test, and we showed that interleukin-2 production and natural killer lytic activity were decreased in zinc-deficient cancer patients. Interleukin-1 beta production (ELISA assay) was increased in both zinc-deficient and zinc-sufficient groups. Plasma copper level was not different, but the iron utilization was decreased in both groups of cancer subjects. We conclude that zinc deficiency and zinc-dependent immunologic dysfunctions are present in more than half of the patients with head and neck cancer in the Detroit area.

Adult↗
PubMed1997

Zinc deficiency in head and neck cancer patients.

BACKGROUND: Although a great deal of attention has been given to protein and calorie malnutrition in patients with head and neck cancer, zinc status has not been assessed properly in such patients in the past. METHODS: In this study we characterized zinc status by cellular zinc criteria and assessed several measures of protein and calorie malnutrition in patients with head and neck cancer. We determined prognostic nutritional index (PNI) based on serum albumin, serum transferrin, triceps skin fold measures, and delayed hypersensitivity, as proposed by Buzby et al. In this study, the baseline zinc status and PNI of 60 head and neck cancer patients were correlated with the tumor size and overall stage of the disease. RESULTS: Our results showed that the tumor size and overall stage correlated significantly to zinc status whereas no correlation was seen with PNI, alcohol intake, or smoking in our study subjects. CONCLUSION: We conclude that zinc status is a better indicator of tumor burden and stage of the disease in head and neck cancer patients than the patients' overall nutritional status.

Aged↗