Serum reference intervals of micronutrients, vitamins, and interleukins among healthy adults in South-Western Nigeria.

Objectives: Clinical decision making depends mostly on appropriate application of numerical pathology reports from laboratory results, interpreted by comparison with reference intervals. We determined serum reference intervals of micronutrients, vitamins, and detectable interleukins among healthy adults in South-Western Nigeria. Design and methods: This prospective study used a priori selection approach in blood-donors. They were screened for conditions that could elicit cytokine production.Serum micronutrients were assayed using Atomic Absorption Spectrophotometry; interleukins and vitamins by high Performance Liquid Chromatography. The reference intervals (RIs) were estimated at 2.5th percentile and 97.5th percentile. Results: One hundred and eighteen (118) apparently healthy subjects, aged 18-56 years; 113 (95.8%) being 18-44years, and 5 (4.2%): 45-56 years; mostly males, 13 (11.02%) females, all Africans of Yoruba ethnicity.Estimated reference limits were: Zinc: 9.49-20.54 µmol/L, Selenium: 0.50-1.11 µmol/L, Copper: 13.86-27.97 µmol/L, Iron: 14.19-32.07 µmol/L, Manganese: 6.24-16.37 nmol/L; Magnesium: 0.78-1.62 mmol/L.Vitamins: A-1.08-2.39 µmol/L; D: 59.89-164.42 µmol/L; E: 7.13-19.45 µmol/L; K: 0.16-0.42 nmol/L; B1: 74.09-201.56 nmol/L; B6: 0.12-0.29 nmol/L; B12: 155.55-407.96 pmol/L; C: 47.74-112.99 µmol/L.Detected interleukins (IL-1 to IL-18): IL-1: 0.58-1.24 ng/L, IL-2: 0.09-0.18 ng/L, IL-3: 0.39-0.89 ng/L, IL-4: 0.27-0.58 ng/L, ….to IL-18: 0.74-1.56 ng/L. Conclusions: The RI derived from this study for serum micronutrient, vitamin and interleukin concentrations are the first published for our population. They are in general agreement with those published from other geographical climes but there are differences at the lower and upper limits of the RI. The study reinforces the importance of deriving RI for the population that a clinical laboratory will serve.

Serving Two Masters: Effect of Escherichia coli Dual Resistance on Antibiotic Susceptibility.

The prevalence of multidrug-resistant bacteria and their increased pathogenicity has led to a growing interest in metallic antimicrobial materials and bacteriophages as potential alternatives to conventional antibiotics. This study examines how resistance to excess iron (III) influences the evolution of bacteriophage resistance in the bacterium Escherichia coli. We utilized experimental evolution in E. coli to test the effect of the evolution of phage T7 resistance on populations resistant to excess iron (III) and populations without excess iron resistance. Phage resistance evolved rapidly in both groups. Dual-resistant (iron (III)/phage) populations were compared to their controls (excess iron (III)-resistant, phage-resistant, no resistance to either) for their performance against each stressor, excess iron (III) and phage; and correlated resistances to excess iron (II), gallium (III), silver (I) and conventional antibiotics. Excess iron (III)/phage-resistant populations demonstrated superior 24 h growth compared to all other populations when exposed to increasing concentrations of iron (II, III), gallium (III), ampicillin, and tetracycline. No differences in 24 h growth were shown between excess iron (III)/phage-resistant and excess iron (III)-resistant populations in chloramphenicol, sulfonamide, and silver (I). The genomic analysis identified selective sweeps in the iron (III) resistant (rpoB, rpoC, yegB, yeaG), phage-resistant (clpX →/→ lon, uvaB, yeaG, fliR, gatT, ypjF, waaC, rpoC, pgi, and yjbH) and iron (III)/phage resistant populations (rcsA, hldE, rpoB, and waaC). E. coli selected for resistance to both excess iron (III) and T7 phage showed some evidence of a synergistic effect on various components of fitness. Dual selection resulted in correlated resistances to ionic metals {iron (II), gallium (III), and silver (I)} and several conventional antibiotics. There is a likelihood that this sort of combination antimicrobial treatment may result in bacterial variants with multiple resistances.

Serum Interleukin-6 and Weight Loss in Antiretroviral-naïve and Antiretroviral-treated Patients with HIV/AIDS: Relationships and Predictors.

BACKGROUND: Cachexia is usually associated with elevated serum interleukin-6 (IL.6) as it stimulates the breakdown of muscle proteins and promotes wasting. OBJECTIVE: A case-control study to evaluate the relationship between weight loss, facial fat loss, and IL-6 in antiretroviral-naïve and treated participants living with HIV/AIDS. METHODS: IL-6 was assayed by High performance liquid chromatography (HPLC) in 97 in consecutive newly diagnosed antiretroviral-naive (ART-naïve) people living with HIV/AIDS (age ≥18 years); and 118 consecutive, age-matched participants currently on Highly Active Antiretroviral Therapy (HAART), using age as a criterion. In the treated group, 78 (66.7%) subjects were on zidovudine, lamivudine with nevirapine (Z+L+N); 27(23.1%) on tenofovir, lamivudine with emtricitabine (T+L+E); 5(4.3%) on zidovudine, lamivudine with emtricitabine (Z+L+E); 4(3.4%) on zidovudine, lamivudine with tenofovir (Z+L+T); 2(1.7%) on lamivudine, tenofovir with nevirapine (L+T+N); 1(0.9%) on tenofovir, zidovudine, emtricitabine (Z+T+E). RESULTS: A total of 215 participants: 97 ART-naive and 118 HAART-treated, age-matched subjects (40.3±9.6 versus 42.7±10.20years, p=0.08). The mean IL-6 was significantly higher in naïve than treated (0.69±0.04 versus 0.66±0.04 pg/ml, p =0.002). In all, 73 subjects experienced weight loss, 56(76.7%) naive, 17(23.3%) treated, p <0.0001, with significantly higher IL-6 in those with weight loss (0.69±0.05 versus 0.67±0.05pg/ml, p= 0.047). Fifty-eight (27.0%) subjects experienced facial fat loss, 49 (84.5%) naïve, and 9 (15.5%) treated, p <0.0001, with significantly higher IL-6 in those with facial fat loss (0.7 ± 0.05 versus 0.67±0.05pg/ml, p= 0.0001). Negative correlation exists between IL-6 and CD4+ count (r=-0.141, p=0.041). In logistic regression, independent predictors of weight loss include: IL-6 (Adjusted Odds Ratio, aOR 1.3, 95%CI 0·1-2·6, p=0.047); HIV duration (aOR 11.6, p <0.0001); AIDS-defining illness (aOR 3.5, p <0.0001); CD4+ count (aOR 3.2, p=0.004); HAART status (aOR 2.7, p<0.0001). CONCLUSION: HIV infection is associated with elevation of serum interleukin-6, which likely contributes to weight and facial fat loss among the treatment-naïve participants; while HAART is associated with suppressed IL-6 levels, thereby ameliorating weight and facial fat loss. Inverse relationship exists between serum IL-6 and CD4+ count; serum IL-6 could differentiate between mild- to moderate and severe immunosuppressive states.

Serum Levels of Micronutrients, Magnesium, and Markers of Immunity (CD4+ ) in Antiretroviral-naïve HIV-infected Individuals: Relationships and Predictors.

BACKGROUND: HIV/AIDS may lead to micronutrient deficiencies and low CD4+ count. OBJECTIVES: We assessed the correlation of CD4+ count in antiretroviral-naïve patients with the serum levels of micronutrients as measures of the relationship between immunity and nutrition/malnutrition. METHODS: A case-control study of ninety consecutive newly diagnosed HIV/AIDS patients and ninety blood donors. Blood collected from controls and patients before HAART treatment were assayed for serum zinc, selenium, copper, manganese, and magnesium. RESULTS: The participants had non-significantly lower zinc (14.25±2.93µmol/l versus 14.58±3.69µmol/l, p=0.493), significantly lower selenium (0.38±0.08µmol/l versus 0.78±0.22µmol/l, p<0.001), manganese (7.06±0.87µmol/l versus 11.23±3.27µmol/l, p<0.001), and magnesium (1.02±0.21mmol/l versus 1.21±0.28mmol/l, p<0.001) when compared with the controls. The mean copper level was similar in both groups (18.88±3.1µmol/l and 18.82±5.12µmol/l, p=0.921). There was no correlation between the micronutrients and CD4+ count; however, there were strong positive correlations between the levels of zinc and copper, selenium, magnesium; copper and magnesium (p<0.001 respectively). Multivariate regression showed that all micronutrients were independent predictors of one another (p<0.001). CONCLUSION: HIV/AIDS results in serum micronutrient depletion with strong positive correlations between their levels; all micronutrients were independent predictors of one another. This significant positive relationships between the micronutrients, and magnesium; and all other micronutrients being independent predictors of each other signifies a synergistic or supportive relationship between micronutrient deficiencies and HIV/AIDS disease morbidity and progression. Serum micronutrients may not be qualified as direct markers or surrogates for CD4+ count in antiretroviral-naïve HIV-infected patients.

Serum cartilage oligomeric matrix protein as a biomarker for predicting development and progression of knee osteoarthritis.

PURPOSE: Current modes of diagnosing and monitoring knee osteoarthritis (OA) are based on weight bearing radiographs usually made by the time joint destruction is already established. Cartilage oligomeric matrix protein (COMP) is a breakdown product of cartilage and its serum levels may be a potential indicator of early destruction in OA. This study aimed to ascertain the usefulness of serum COMP (sCOMP) in diagnosis and monitoring of knee joint OA within the study environment. METHODS: Ninety consenting adults were recruited. In the control group, 45 subjects having a diagnosis of knee OA had clinical and radiological grading done and blood samples taken for assay of sCOMP using the sandwich ELISA method. Forty-five volunteers with no features of osteoarthritis also had serum collected for sCOMP assay. Values obtained were then cross referenced with demographic indices, clinical and radiological severity grade to assess for relationships. RESULTS: Serum COMP was found to be significantly elevated (p = 0.0001) in the study group. The mean values and standard deviation of sCOMP were 3400 ± 1042.9 ng/ml and 2222 ± 605.6 ng/ml for the study and control groups, respectively. Higher values of sCOMP were found to be associated with higher clinical and radiological grades of OA. CONCLUSION: The study demonstrates that sCOMP is significantly higher in patients with knee OA than in those without the disease. Values of sCOMP were also found to increase with severity of knee OA, indicating the possibility of its use as a marker of diagnosis and severity.

Renal Phosphate Handling in Antiretroviral-naive HIV-Infected Patients.

BACKGROUND: Human immunodeficiency virus (HIV) infection impairs renal function, thereby affecting renal phosphate metabolism. OBJECTIVES: We prospectively estimated the prevalence of phosphate abnormalities (mild, moderate to life-threatening hypophosphataemia, and hyperphosphataemia) before initiating antiretroviral therapy (ART). METHODS: A cross-sectional analysis was performed on 170 consecutive newly diagnosed ARTnaive, HIV-infected patients attending our HIV/AIDS clinics over a period of one year. Fifty (50) screened HIV-negative blood donors were used for comparison (controls). Blood and urine were collected simultaneously for phosphate and creatinine assay to estimate fractional phosphate excretion (FEPi %) and glomerular filtration rate (eGFR). RESULTS: eGFR showed significant difference between patients' and controls' medians (47.89ml/ min/1.73m2 versus 60ml/min/1.73m2, p <0.001); which denotes a moderate chronic kidney disease in the patients. Of the 170 patients, 78 (45.9%) had normal plasma phosphate (0.6-1.4 mmol/L); 85 (50%) had hyperphosphataemia. Grades 1, 2 and 3 hypophosphataemia was observed in 3 (1.8%), 3 (1.8%), and 1(0.5%) patient(s) respectively. None had grade 4 hypophosphataemia. Overall, the patients had significantly higher median of plasma phosphate than the controls, 1.4 mmol/L (IQR: 1.0 - 2.2) versus 1.1 mmol/L (IQR: 0.3 - 1.6), p <0.001, implying hyperphosphataemia in the patients; significantly lower median urine phosphate than the controls, 1.5 mmol/L (IQR: 0.7 -2.1) versus 8.4 mmol/L (IQR: 3.4 - 16), p <0.001), justifying the hyperphosphataemia is from phosphate retention; but a non-significantly lower median FEPi% than the controls, 0.96% (IQR: 0.3 -2.2) versus 1.4% (IQR: 1.2 -1.6), p > 0.05. Predictors of FEPi% were age (Odds ratio, OR 0.9, p = 0.009); weight (OR 2.0, p < 0.001); CD4+ cells count predicted urine phosphate among males (p = 0.029). CONCLUSION: HIV infection likely induces renal insufficiency with reduced renal phosphate clearance. Thus, hyperphosphataemia is highly prevalent, and there is mild to moderate hypophosphataemia but its life-threatening form (grade 4) is rare among ART-naive HIV patients.

The Inflammatory Response to Surgery in Sickle Cell Disease Patients Undergoing Cholecystectomy.

BACKGROUND AND OBJECTIVES: Patients with sickle cell anemia (SCA) may have elevated inflammatory markers in health, and this may be heightened after open operations. The inflammatory response of patients with SCA after minimally invasive surgeries has not been fully explored. PATIENTS AND METHODS: Consecutive patients with SCA and with hemoglobin AA (HbAA) undergoing laparoscopic cholecystectomy for acute cholecystitis were recruited into the study. Blood samples were taken before induction of anesthesia (0-h); at 4, 12, 24, and 48 h; and on postoperative day 7. Samples were analyzed for serum C-reactive protein and interleukin (IL)-1 through IL-18. RESULTS: Twenty-three patients, including 9 with SCA and 14 with HbAA, were recruited with 4 cases performed by open laparotomy. At 0-h, proinflammatory IL-1 levels (6.1 versus 4.8) and C-reactive protein levels (32.5 versus 26.6) were higher in patients with hemoglobin SS (HbSS) than in patients with HbAA, respectively. Over time, inflammatory markers were generally higher at each time-point for patients with HbSS compared with patients with HbAA for both proinflammatory and anti-inflammatory cytokines, rising immediately after surgery and up to 48 hours, then returning to baseline by postoperative day 7. There was a higher mean IL-1 level across all time-points in the HbSS group than in the HbAA group (P = .04). CONCLUSION: This exploratory study found an enhanced inflammatory response to cholecystectomy in patients with SCA compared with patients with HbAA. Minimally invasive surgical strategies for this patient group may help to mediate this response.