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Biomedical subjects

C O Enwonwu

Publications and source records attributed to C O Enwonwu.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pathogenesis of oral Kaposi's Sarcoma in HIV-infection: relevance of endogenous glucocorticoid excess in blood and saliva.

Endogenous glucocorticoid excess with concomitant hypercortisolaemia and increased saliva levels of the free active hormone, is a common feature of HIV-infected/AIDS patients. Exposure of the oral tissues to virtually uninterrupted high burden of glucocorticoids through saliva may contribute to the high frequency of oral Kaposi's sarcoma (KS) in these patients. AIDS-KS cells contain unusually high levels of glucocorticoid receptor protein and recent studies indicate that growth of these cells in culture is significantly stimulated by glucocorticoids, particularly in the presence of growth factors, such as oncostatin-M. The suggestion that glucocorticoid excess may be important in the pathogenesis of KS in AIDS is not in conflict with the suspected aetiological role of newly reported KS-associated herpesviruses (KSHV), since steroid hormones may upregulate the expression of the viral gene. The latter is consistent with the observation that infection by specific oncogenic viruses does not necessarily result in cancers in the human, and does require the presence of other cellular factors or events.

Glucocorticoids↗
PubMed1996

Elevated cortisol levels in whole saliva in HIV infected individuals.

Free cortisol concentrations in unstimulated whole saliva samples, collected at 10.00 to 11.00 h, from 23 unmedicated HIV-positive patients and 14 control subjects were measured by radioimmunoassay. Mean cortisol level (nmol/l +/- SD) was significantly higher in the HIV patients than in control subjects (27.4 +/0 9.3 vs. 10.1 +/- 3.5). Two HIV patients with pseudomembranous candidiasis had the highest saliva cortisol concentrations (mean of 48.5 nmol/l). Two other HIV patients (one with Kaposi's sarcoma and the other with periodontitis) had a mean cortisol value of 29.9 nmol/l. The possibility of plasma contamination of whole saliva in the HIV patients with inflammatory oral mucosal lesions notwithstanding, our findings suggest an increased oral burden of cortisol in both the asymptomatic and symptomatic HIV-infected individuals. Glucocorticoids caused immunosuppression, provide selective growth advantage to various microorganisms including the fungi, and enhance replication or reactivation of latent viruses (e.g. EBV, CMV, Kaposi's sarcoma-associated herpes viruses). Our findings suggest a need to evaluate the relevance of endogenous glucocorticoid excess in blood and saliva to the causation of some major AIDS-associated oral lesions such as candidiasis, Kaposi's sarcoma, oral hairy leukoplakia and necrotizing gingivitis.

AIDS-Related Opportunistic Infections↗
PubMed1995

Effect of marginal ascorbic acid deficiency on saliva level of cortisol in the guinea pig.

Male guinea pigs subjected to prolonged marginal ascorbic acid deficiency developed moon facies and oedema, features of functional adrenal hypercorticism. Compared with age- and sex-matched controls fed an adequate diet for a similar period, ascorbate deficiency had no effect on submandibular gland weight but elicited a significant (p < 0.005) reduction in stimulated whole-saliva flow rate. Plasma cortisol concentration (nmol/L) was significantly increased (p < 0.005) in the deficient animals (998.21 +/- 57.19 compared to 254.66 +/- 15.62 for the controls). Associated with marked hypercortisolaemia in the deficient animals was a significant (p < 0.01) but less prominent increase in the whole-saliva cortisol level, resulting in a mean saliva/plasma cortisol ratio of 46% for this group compared to 72% for the controls. Increased corticosteroid levels suppress immunological and inflammatory responses, particularly neutrophil function, impair production of some cytokines, inhibit collagen synthesis, and impair wound healing and bone matrix formation. Numerous conditions such as ageing, stress, smoking, ionizing radiation, ingestion of drugs, protein malnutrition, diabetes, and several other pathological states, which are among the risk factors for xerostomia and periodontal/oral mucosal lesions, promote tissue depletion of ascorbate. This study suggests that increased salivary and blood levels of glucocorticoids in these conditions may be important in reducing the ability of the host to mount an effective immune response to oral pathogens.

Adrenocortical Hyperfunction↗
PubMed1995

Interface of malnutrition and periodontal diseases.

In response to periodontal pathogens neutrophils release oxidants, proteinases, and other destructive factors. The balance between these factors, the antioxidants, and endogenously synthesized antiproteinases determine the extent of periodontal damage. Malnutrition, particularly protein-energy malnutrition involving concomitant deficiencies of antioxidant nutrients, is characterized by impairment in production and cellular actions of the cytokines, diminished acute-phase protein response (APR) to infections, endocrinopathies, defective metabolism of drugs, and impaired response to stress. The APR plays a central role in promoting healing. Additionally, malnutrition elicits adverse alterations in the oral microbial ecology as well as in the volume and the antibacterial and physicochemical properties of saliva. Good dietary practices and optimal nutritional status are therefore important in mitigating the severity of inflammatory periodontal lesions but are likely of limited value if the stimuli from dental plaque are not removed.

Acute-Phase Proteins↗
PubMed1995

Bionutrition and oral cancer in humans.

Tobacco (smoking and smokeless) use and excessive consumption of alcohol are considered the main risk factors for oral cancer (ICD9 140-149). Conspicuous national and international variations in oral cancer incidence and mortality rates, as well as observations in migrant populations, raise the possibility that diet and nutritional status could be an important etiologic factor in oral carcinogenesis. As shown in this report, abuse of alcohol and tobacco has serious nutritional implications for the host, and generates increased production of reactive free radicals as well as eliciting immunosuppression. Maintenance of optimal competence of the immune system is critical for cancer surveillance. Active oxygen species and other reactive free radicals mediate phenotypic and genotypic alterations that lead from mutation to neoplasia. Consequently, the most widely used chemopreventive agents against oral cancer (e.g., vitamins A, E, C, and beta-carotene) are anti-oxidants/free radical scavengers. These anti-oxidants, both natural and synthetic, neutralize metabolic products (including reactive oxygen species), interfere with activation of procarcinogens, prevent binding of carcinogens to DNA, inhibit chromosome aberrations, restrain replication of the transformed cell, suppress actions of cancer promoters, and may even induce regression of precancerous oral lesions such as leukoplakia and erythroplakia. Malnutrition is characterized by marked tissue depletion of anti-oxidant nutrients, including GSH (gamma-glutamyl-cysteinyl-glycine), a key cellular anti-oxidant as well as a modulator of T-cell activation. GSH or its precursor cysteine inhibits activation of the nuclear transcription factor kB(NFkB), and has been shown to be protective against chemically induced oral cancer and leukoplakia. Alcohol-, tobacco-, and/or malnutrition-induced immunosuppression promotes impaired salivary gland function and oral mucosal immunity, a prominent reduction in the number of helper CD4 cells with less marked changes in number of suppressor T-cells, and depressed NK cell activity, among others. These suggest a breakdown in capacity or the malnourished to mount effective tumor surveillance. This review article underscores the compounding but important roles of nutritional/dietary factors in the long-established causal link between abuse of alcohol and tobacco (smoking and smokeless) and oral cancer.

Alcohol Drinking↗
PubMed1995

Noma: a neglected scourge of children in sub-Saharan Africa.

Poverty is the single most important risk indicator for noma (cancrum oris), a severe gangrene of the soft and hard tissues of the mouth, face, and neighbouring areas. The risk factors associated with an increased probability of noma developing include the following: malnutrition, poor oral hygiene, and a state of debilitation resulting from human immunodeficiency virus (HIV) infection, measles, and other childhood diseases prevalent in the tropics. There are many similarities between noma and necrobacillosis of the body surface of wallabies (Macropus reforgriseus), and it is proposed that noma results from oral contamination by a heavy load of Bacteroidaceae (particularly Fusobacterium necrophorum) and a consortium of other microorganisms. These opportunistic pathogens invade oral tissues whose defences are weakened by malnutrition, acute necrotizing gingivitis, debilitating conditions, trauma, and other oral mucosal ulcers. The current escalation in the incidence of noma in Africa can be attributed to the worsening economic crisis in the region, which has adversely affected the health and well-being of children through deteriorating sanitation, declining nutritional status and the associated immunosuppression, and increased exposure to infectious diseases. Prevention of noma in Africa will require measures that address these problems, and most importantly, eliminate faecal contamination of foods and water supplies.

Africa South of the Sahara↗
PubMed1994

Cellular and molecular effects of malnutrition and their relevance to periodontal diseases.

In response to periodontal pathogens, the leukocytes (PMN) elaborate destructive oxidants, proteinases, and other factors. The balance between these factors, the antioxidants and endogenously synthesized antiproteinases determine the extent of periodontal damage. Malnutrition (PEM) is characterized by marked tissue depletion of the key antioxidant nutrients, including GSH (gamma-glutamyl-cysteinyl-glycine), and impaired acute-phase protein response (APR) to infections. The latter results in diminished production of the acute-phase proteins (APP). The APR plays a key role in promoting healing, and its deficit in PEM is due to impairment in the production and cellular action of the cytokines. Other features of malnutrition include inverted helper-suppressor T-cell ratio, histaminemia, hormonal imbalance with increased blood and saliva levels of free cortisol, and defective mucosal integrity. Malnutrition, particularly of the PEM type which usually involves concomitant deficiencies of several essential macro- and micronutrients, therefore has the potential to adversely influence the prognosis of periodontal infections.

Acute-Phase Proteins↗
PubMed1994

Arginine metabolism in the salivary glands of protein-deficient rats and its potential association with the oral microflora.

Salivary glands and their secretions play key roles in the prevention of dental diseases. The antibacterial and physicochemical properties of saliva are compromised in chronic malnutrition. The present study has examined the possibility that some malnutrition-induced changes in salivary gland function are potentially capable of promoting growth and metabolic activities of pathogenic oral microorganisms. Compared to well-fed controls, rats fed a 3% protein diet for 18 days showed a significant reduction (p < 0.001) in the submandibular gland arginase (L-arginine amidinohydrolase, EC 3.5.3.1) activity. Associated with the latter finding was a marked increase (+85%) in the glandular level of free arginine, this basic amino acid accounting for 12.2% of the total essential amino acids as compared with a figure of only 4.6% for the controls. The total free amino acid pool in whole saliva was relatively unaffected by malnutrition, but the levels of the basic amino acids arginine and histidine were marginally increased. Many oral bacterial species, some of which are dominant plaque microorganisms, utilize the arginine deiminase (EC 3.5.3.6) pathway. Thus, increased availability of free arginine from salivary glands offers a plausible explanation for the frequently reported observation of differential overgrowth of several potentially pathogenic microorganisms including some mutants streptococci in protein-deficient laboratory animals and may well apply to similar findings in malnourished populations in Third World countries.

Amino Acids, Essential↗
PubMed1994

Umbilical vein serum amino acid levels in African Americans: relationship to birthweight and maternal variables.

Compared with other racial groups, African-American women show a disproportionately high risk of delivering low birthweight babies. In a retrospective study of African-American infants born at Meharry Hubbard Hospital, which predominantly serves the underprivileged inner-city poor, free amino acid concentrations were measured in umbilical venous serum from infants born following 34 to 42 weeks gestation. Significant reductions in levels of glycine, serine, alanine, the branched-chain amino acids, and the sum of the so-called dispensable amino acids were associated with decreased birthweight. Glycine, a quantitatively important residue in collagen and a component of reduced glutathione (gamma-glutamyl-cysteinyl-glycine), which is featured in the gamma-glutamyl amino acid transport cycle, was most consistently and severely affected. This study not only indicated that selective reduction in transplacental amino acid transport may be an important factor in intrauterine growth retardation in African Americans, but also confirmed the dietary necessity of the structurally simple amino acid glycine during pregnancy.

Adult↗
PubMed1993

Correlation of lactose maldigestion, lactose intolerance, and milk intolerance.

Lactose digestion and tolerance were evaluated in 164 African Americans ranging in age from 12 to 40 y who claimed intolerance to one cup (240 mL) or less of milk. With use of a breath-hydrogen test with 25 g lactose as test dose and the presence or absence of symptoms, 50% of the subjects were classified as lactose maldigesters and intolerant, 8% were maldigesters but tolerant, 15% were digesters but intolerant, and 27% were digesters and tolerant. Forty-five subjects from the lactose maldigesting and intolerant group were further tested for milk intolerance in a double-blind study. Sixty-seven percent of the subjects reacted appropriately to the presence or absence of lactose in ingested milk whereas 33% reported symptoms to both low-lactose milk and milk containing lactose. The results suggest that the cause of milk intolerance in as many as one-third of African Americans claiming symptoms after ingestion of a moderate amount of milk cannot be its lactose content.

Adolescent↗
PubMed1993

Adaptation of lactose maldigesters to continued milk intakes.

Twenty-five lactose-maldigesting and lactose-intolerant African Americans, ranging in age from 13 to 39 y, were given gradually increasing amounts of lactose in milk over a period of time until the maximum lactose dose tolerated was determined. Seventeen (77%) of the 22 subjects who completed the study tolerated > or = 12 g lactose and 5 (23%) tolerated < 12 g. Breath-hydrogen tests done on each subject with the maximum dose of lactose tolerated showed that only four (18%) had a breath-hydrogen concentration < 5 ppm above fasting concentration. This study suggests that the majority of African-American young adults who claim intolerance to moderate amounts of milk can ultimately adapt and tolerate > or = 12 g lactose in milk (the equivalent of 8 oz of full-lactose milk) with minimal or no discomfort if milk is ingested in gradually increasing amounts. The mechanism of adaptation is assumed to be an increased tolerance to colonic lactose-fermentation products.

Adaptation, Physiological↗
PubMed1992

Ascorbate status and xerostomia.

Xerostomia, the subjective feeling of dry mouth, affects millions of people particularly the elderly. It is invariably associated with hypofunction of the salivary glands. The amount, rate of secretion, and composition of saliva are regulated by both sympathetic and parasympathetic receptor systems whose stimulation transmits signals through intracellular messengers (cations, nucleotides, phospholipid derivatives) to structures and enzymes within the cell. Salivary glands express a variety of cell-surface receptors including adrenergic (alpha and beta), muscarinic-cholinergic, substance P, vasoactive intestinal peptide hormone, and ATP receptors. Ascorbate which is present in salivary acinar cells in relatively high concentrations, is closely involved in many cellular functions including the metabolism of pyrimidines, intracellular calcium, the catecholamines and other neurotransmitters which regulate salivary gland exocytosis. Ascorbate-dependent carboxyl-terminal peptide alpha-amidation enzyme similar to the pituitary peptidyl-glycine alpha-amidating monooxygase, is also present in salivary glands. It is therefore not fortuitous that the seemingly unrelated numerous factors like aging, drug ingestion, pregnancy, smoking, ionizing radiation, stress, and various pathological states such as cancer, autoimmune disorders, diabetes mellitus, and hypertension often implicated in the causation of xerostomia, all promote increased tissue requirement for and/or depletion of ascorbate.

Ascorbic Acid↗
PubMed1990

Manifest hostility may affect habituation of cardiovascular reactivity in blacks.

In a study of cardiovascular reactivity to dietary manipulation of sodium and calcium, we pretested 30 young black normotensive males who were equally divided by positive and negative parental histories of hypertension with a 12-item anger questionnaire we devised and the Cook-Medley Hostility, Manifest Hostility, Overcontrolled Hostility, and Inhibited Hostility scales of the Minnesota Multiphasic Personality Inventory. Contrary to expectations, we found no correlation of resting blood pressure or cardiovascular reactivity to repeated mental demands with the two measures of inhibited hostility. We did, however, find resistance to habituation of cardiovascular reactivity in subjects with high Manifest Hostility and positive family histories of essential hypertension. Our findings suggest that vulnerability to hypertension may be revealed by the perseveration of blood pressure reactivity to repeated mental challenge. We propose that the perseveration of blood pressure reactivity is a disinhibitory phenomenon caused by a difficulty in the management of multiple inhibitory demands that disrupts the natural course of habituation and could be an important etiologic factor in essential hypertension.

Adolescent↗
PubMed1990

Calcium attenuates cardiovascular reactivity to sodium and stress in blacks.

The roles of dietary and behavioral factors in the etiology of hypertension are not well understood. Vulnerability to hypertension is thought to be affected by a complex interaction of nutritional, genetic, neurophysiological, and psychosocial influences. We studied cardiovascular reactivity to sodium and stress in a group of 29 normotensive young men who were vulnerable to hypertension by virtue of familial and/or racial factors. Subjects with positive and negative parental histories of hypertension were provided all meals for five days during which blood pressure was monitored before each meal. Two groups were given 300 mEq/day dietary sodium with either 1100 mg/day or 410 mg/day dietary calcium. A third group consumed a 10mEq sodium diet with low dietary calcium. On the fifth day of the diet all subjects were tested for cardiovascular reactivity using a modified Stroop test as a mentally challenging task. Adaptation of systolic blood pressure (SBP) from the first to the fifth breakfast was most pronounced in subjects consuming high calcium with high sodium. Perseveration of SBP reactivity to repeated mental challenge was found in subjects who consumed high sodium with low calcium and in subjects with positive parental histories of hypertension. The perseverative phenomenon was particularly well-defined in subjects who had the highest urinary excretion of calcium. Our findings suggest a prophylactic influence of dietary calcium and its retention on cardiovascular reactivity to sodium and stress. We also elucidate a theoretical proposition concerning the role of neurophysiological inhibitory capacity in the transition from normotension to the chronic dysregulatory state of essential hypertension.

Adolescent↗
PubMed1990

Nitrogen metabolism in sickle cell anemia: free amino acids in plasma and urine.

Twenty-four hour urinary levels and fasting plasma concentrations of free amino acids (AA) were evaluated in adult sickle cell anemia (HbSS) and age-matched HbAA subjects with comparable daily energy (E) and protein (N) intake. HbSS elicited significant reduction in the sum of plasma indispensable (EAA) with no change in the dispensable (NAA) amino acids, resulting in a prominent (P less than 0.01) reduction in the EAA/NAA ratio from 71% to 55%. Arg (-38%), Leu (-32%), Val (-28%) and His (-32%) were among the AA most severely affected. Despite a twofold increase in 24-hour urine volume in HbSS compared with HbAA subjects, total urinary losses of EAA and NAA were markedly reduced in the former group, with Arg (-53%) and Gly (-56%) levels most prominently affected. Compared with HbAA controls, HbSS subjects showed a three-fourfold increase in 24-hour urinary orotate excretion that had no relationship to amount of N intake. The results indicated that adult subjects with HbSS, who consumed adequate N and E as per the RDA for healthy individuals, behaved like normal HbAA controls on a low protein diet. There was evidence that the HbSS subject might be in a precarious state with respect to sufficiency of several amino acids, particularly L-Arg, which is now classified as conditionally indispensable for the human.

Adult↗