Association between C-Reactive Protein and low-grade Inflammation among Nigerian women with Polycystic Ovarian Syndrome.

BACKGROUND: There is evidence of a low-grade chronic inflammation reflected by minor but significant increases in circulating levels of inflammatory mediators in polycystic ovary syndrome (PCOS). There is uncertainty about the causal relationship whether it is obesity, insulin resistance, or PCOS. There is a paucity of studies from the West African subregion. OBJECTIVES: The study investigated C-reactive protein (CRP) concentration in Nigerian women with PCOS, and determined the factors that affect their concentration. METHODS: The study was conducted on 71 Nigerian women with PCOS and 76 normal ovulating women, recruited from the University of Benin Teaching Hospital and the Women's Health and Action Research Centre, in Nigeria. CRP levels were measured by the enzyme-linked immunosorbent assay (ELISA) method. Insulin resistance and insulin sensitivity were estimated using the Homeostatic Model Assessment Index and Quantitative Insulin-sensitivity Check Index respectively. RESULTS: The CRP levels were significantly elevated in Nigerian women with PCOS compared to controls (9.93 ± 8.38 vs 5.54 ± 5.93 mg/L; p=0.000). It positively correlated with age (r = 0.297, p = 0.012), Weight (r =0.313, p = 0.008) and BMI (r = 0.339, p = 0.004). Multiple linear regression analysis revealed that CRP values are positively associated with BMI (ß = 0.274, p = 0.001) and PCOS (ß = 0.382, p = 0.001). The CRP values were positively associated with BMI (ß = 0.372, p = 0.012) and negatively associated with QUICKI (ß = -0.644, p = 0.073). CONCLUSIONS: Among Nigerian women with PCOS, inflammation may be mediated through adiposity since the main predicting factor for increased CRP is BMI.

CONTEXTE: Il existe des preuves d'une inflammation chronique de faible intensité, se manifestant par des augmentations mineures mais significatives des taux circulants de médiateurs inflammatoires, dans le syndrome des ovaires polykystiques (SOPK). Il existe une incertitude quant à la relation causale, qu'il s'agisse de l'obésité, de la résistance à l'insuline ou du SOPK. Les études de cette région d'Afrique de l'Ouest sont rares. OBJECTIFS: L'étude a examiné la concentration de la protéine C-réactive (CRP) chez les femmes nigérianes atteintes du SOPK et a déterminé les facteurs qui influent sur leur concentration. MÉTHODES: L'étude a été menée auprès de 71 femmes nigérianes atteintes du SOPK et de 76 femmes à ovulation normale, recrutées à l'hôpital universitaire de Benin et au Centre de recherche sur la santé des femmes et l'action (Women's Health and Action Research Centre) au Nigéria. Les niveaux de CRP ont été mesurés à l'aide de laméthode ELISA (dosage immuno-enzymatique). La résistance à l'insuline et la sensibilité à l'insuline ont été estimées à l'aide de l'indice du modèle homéostatique d'évaluation et de l'indice de vérification quantitative de la sensibilité à l'insuline. RÉSULTATS: Les taux de CRP étaient significativement élevés chez les femmes nigérianes atteintes du SOPK par rapport aux témoins (9,93 ± 8,38 contre 5,54 ± 5,93 mg/L ; p = 0,000). Ils étaient positivement corrélés à l'âge (r = 0,297, p = 0,012), au poids (r = 0,313, p = 0,008) et à l'IMC (r = 0,339, p = 0,004). L'analyse de régression linéaire multiple a révélé que les valeurs de la CRP sont positivement associées à l'IMC (ß = 0,274, p = 0,001) et au SOPK (ß = 0,382, p = 0,001). Les valeurs de la CRP étaient positivement associées à l'IMC (ß = 0,372, p = 0,012) et négativement associées au QUICKI (ß = -0,644, p = 0,073). CONCLUSIONS: Chez les femmes nigérianes atteintes du SOPK, l'inflammation pourrait être médiée par l'adiposité, car le principal facteur prédictif d'une augmentation de la CRPest l'IMC. Mots-clés: Protéine C-réactive, inflammation chronique, syndrome des ovaires polykystiques, indice de vérification quantitative de la sensibilité à l'insuline, indice du modèle homéostatique d'évaluation.

Association of oxidative stress markers with atherogenic index of plasma in adult sickle cell nephropathy.

This paper evaluates the association of oxidative stress and atherogenic index of plasma in order to assess the cardiovascular risk in Sickle cell nephropathy especially as lipoprotein levels are lower in SCD than non-SCD patients. Antioxidant enzymes, malondialdehyde(MDA), urea, creatinine, and glomerular filtration rate were evaluated in 110 confirmed sickle cell disease patients: 65 males in steady state, aged 21.1 ± 6.0 years, 30 males with macroalbuminuria, aged 24.5 ± 7.0, years and 15 with chronic kidney disease (CKD), aged 31.8 ± 2.0 years. The mean activity levels of glutathione peroxidase (GPx), superoxide dismutase (Cu/ZnSOD), and catalase (CAT) were significantly lower (P < 0.001) in SCD with macroalbuminuria and CKD while MDA was higher (P < 0.001) in SCD with macroalbuminuria and CKD compared with controls. There was negative correlation between GPx (P < 0.001), Cu/ZnSOD (P < 0.02), and Atherogenic index of plasma in SCD with CKD, while MDA shows a positive correlation (P < 0.001) with AIP in SCD with CKD. There was however no correlation between CAT and AIP. Decreased activity levels of antioxidant enzymes and low HDL-cholesterol concentration were confirmed in adult SCD with CKD in Nigerians. The increase oxidative stress and high atherogenic index in CKD may accelerate the process of cardiovascular complications in adult SCD patients. Atherogenic index of plasma was negatively correlated with antioxidant enzymes and positively with MDA.

Proteinuria among adult sickle cell anemia patients in Nigeria.

BACKGROUND/OBJECTIVE: The life expectancy of patients with sickle cell anemia (SCA) has improved with modern medical care, and this has led to frequent observation of various chronic complications of the disease including abnormalities in renal function. Proteinuria is not only a marker of renal disease but is also a predictor of disease progression. This screening study was aimed at evaluating the prevalence of proteinuria among adult SCA patients in Kano, Nigeria, which has not been reported previously. MATERIAL AND METHODS: A total of 200 adult SCA patients were studied. They consisted of 100 men and 100 women. Blood was collected for the assay of serum urea, sodium, potassium, chloride, bicarbonate, and creatinine and estimated glomerular filtration rate (eGFR) was determined using the Cockcroft-Gault formula. Urine dipstick test for the presence of proteinuria and other abnormalities was done, and 24-hour urine protein was measured in those with significant proteinuria. RESULTS: Mean age of the male patients was 25.1 ± 1.0 years, whereas the mean age of the female patients was 22.8 ± 4.2 years. Twenty eight percent (32 males, 24 females) of the subjects were observed to have significant proteinuria. The mean estimated eGFR of the males was 88 ± 19.6 ml/min while that of the females was 92 ± 10.2 ml/min. The male SCA patients with proteinuria had a mean eGFR of 70 ± 6.9 ml/min, whereas the female SCA patients with proteinuria had mean eGFR of 101 ± 2.5 ml/min. Among the male patients with proteinuria, 50% had chronic kidney disease (CKD). CONCLUSION: Proteinuria which is a marker of renal insufficiency is common among adult SCA patients, and routine screening for proteinuria may help detect those at increased risk of renal disease. CKD prevalence is high among SCA patients with significant proteinuria.

Correlation of oxidative stress and inflammatory markers with the severity of sickle cell nephropathy.

BACKGROUND: Reactive oxygen species have been shown to mediate inflammatory process and may be involved in lipid peroxidation. METHODS: This study evaluates superoxide dismutase, glutathione peroxidase, catalase, malondialdehyde, C- reactive protein and fibrinogen in the serum of patients with sickle cell disease and their correlation with renal insufficiency. Superoxide dismutase, glutathione peroxides and C - reactive protein were assayed using sandwich ELISA technique while malondialdehyde and fibrinogen were determined using thiobarbituric reactive substance and turbidometric technique, respectively. RESULTS: The study group consisted of 40 patients with sickle cell disease along with macroalbuminuria, 16 with chronic kidney disease and 144 sickle cell disease controls. Superoxide dismutase, glutathione peroxidase and catalase were decreased while malondialdehyde, C-reactive protein and fibrinogen were increased in patients with sickle cell disease along with renal insufficiency. These parameters correlated with the severity of renal disease. CONCLUSION: Oxidative stress and inflammatory parameters correlate with sickle cell disease nephropathy.

Lipid Profile in Sickle Cell Disease Patients with Chronic Kidney Disease

Background: Dyslipidaemia is reported to occur in patients with sickle cell disease as well as patients with chronic kidney disease irrespective of the haemoglobin genotype. This study aimed at evaluating lipid profile in subjects with sickle cell anaemia (HbSS); sickle cell trait (HbAS) and normal haemoglobin genotype (HbAA); and comparing the lipid parameters between sickle cell disease patients with and those without chronic kidney disease. Methods: A total of 66 patients with chronic kidney disease: 26 HbAA; 24 HbAS and 16 HbSS and 60 apparently healthy controls were recruited for the study. Lipoproteins; urea; creatinine; estimated glomerular filtration rate and electrolytes were determined using standard procedures in both patients and controls. Results: The mean total cholesterol; low density lipoproten cholesterol and high density lipoproten cholesterol in stable HbSS subjects were significantly lower (p

Male infertility and endocrinopathies in Kano, Northwestern Nigeria.

BACKGROUND/OBJECTIVE: Endocrinologic disorders and infertility are common all over the world; the prevalence of infertility is high in sub-Saharan Africa. Several authors have suggested that the increased incidence of infertility in Africa is due to high prevalence of sexually transmitted diseases. To evaluate the contributions of endocrine abnormalities to infertility in the male in Kano, Northern Nigeria. METHODS: A total of five hundred males, aged between 28 and 56 years were evaluated over a period of 4 years (2001-2004). The hormones were analyzed using electrochemiluminescene immunoassay technique. RESULTS: Hormonal abnormalities were detected in 22% oligospermic, 40.7% severe oligospermic, and 42.7% azoospermic subjects. CONCLUSION: Endocrine abnormalities are common in the infertile males. The reason for the observed endocrinopathies is not known, appropriate laboratory investigations are essential for effective patients management. Further study to ascertain the cause(s) of hormonal derangements is suggested.

Hormonal abnormalities in azoospermic men in Kano, Northern Nigeria.

BACKGROUND & OBJECTIVES: We undertook this study to observe the pattern of hormonal abnormalities and testicular pathology in azoospermic male Africans in Kano, Northern Nigeria. METHODS: Eighty consecutive azoospermic infertile males attending fertility clinic in Aminu Kano Teaching Hospital, Kano, were selected for the study. Their semen were analyzed three times at eight weeks interval, after which serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone and prolactin were assayed in serum samples, and histological examination of testicular biopsies done. RESULTS: Of the 80 subjects studied, 32 (40%) had abnormal hormonal levels, 48 (60%) had normal hormonal values and 36 (45%) had testicular pathology. INTERPRETATION & CONCLUSION: Endocrinopathies are common in azoospermia. Their contribution to male factor infertility cannot be overemphasized. The main reason for the endocrinopathies is not known but environmental factors, endocrine disruptors and genetic polymorphism have been suggested to be contributory.

Acrosin activity in spermatozoa of infertile Nigerian males.

The objective of this study was to evaluate acrosin activity in spermatozoa of infertile Nigerian men and to compare with those of the fertile men. The acrosin activity was evaluated using the Acroscreen reagent kit. The acrosin activity of the fertile men was 40.7±5.2 mIU/10(6) sperm (range 30.1-51.3) and those of the infertile men was 22.4±8.33 mIU/10(6) sperm (range 5.7-39.1). The difference in the mean was statistically significant (P<0.001). There was a subpopulation of the infertile men who had their acrosin activity within normal range of the fertile men, 32.9±1.57 mIU/10(6) sperm. But the difference in the mean was statistically significant (P<0.001). Acrosin activity decreased with increased morphological changes in the spermatozoa. It is concluded that acrosin activity in the infertile Nigerian men is significantly lower than that in the fertile men. Acrosin activity may also be affected by morphological changes in the spermatozoa.

Lipase-catalysed production of biodiesel fuel from some Nigerian lauric oils.

Fatty acids esters were produced from two Nigerian lauric oils, palm kernel oil and coconut oil, by transesterification of the oils with different alcohols using PS30 lipase as a catalyst. In the conversion of palm kernel oil to alkyl esters (biodiesel), ethanol gave the highest conversion of 72%, t-butanol 62%, 1-butanol 42%, n-propanol 42% and iso-propanol 24%, while only 15% methyl ester was observed with methanol. With coconut oil, 1-butanol and iso-butanol achieved 40% conversion, 1-propanol 16% and ethanol 35%, while only traces of methyl esters were observed using methanol. Studies on some fuel properties of palm kernel oil and its biodiesel showed that palm kernel oil had a viscosity of 32.40 mm2/s, a cloud point of 28 degrees C and a pour point of 22 degrees C, while its biodiesel fuel had a viscosity of 9.33 mm2/s, a cloud point of 12 degrees C and a pour point of 8 degrees C. Coconut oil had a viscosity of 28.58 mm(2)/s, a cloud point of 27 degrees C and a pour point of 20 degrees C, while its biodiesel fuel had a viscosity of 7.34 mm2/s, a cloud point of 5 degrees C and a pour point of -8 degrees C. Some of the fuel properties compared favourably with international biodiesel specifications.

Antimalarial activity of cyclosporins A, C and D.

Cyclosporin A (CsA) is an immunosuppressive drug widely used in organ transplants. It is also accumulated by the erythrocyte, a site that accommodates one of the stages of malaria parasite. We observe that CsA and its less potent immunosuppressive analogues CsC and CsD were as effective as chloroquine in inhibiting P. berghei malaria parasite development in vivo (when administered orally) and P. falciparum parasite in vitro. They were, however, not inhibitory to the liver stages and the gametocytes. In vivo the minimum effective dose was 10 mg/Kg administered on two consecutive days whereas, in vitro CsA and its analogues inhibited parasite development at concentrations of 10 micrograms/ml and above.

Lack of Ir gene control in the immune response to malaria. I. A thymus-independent antibody response to the repetitive surface protein of sporozoites.

The anamnestic antibody response to synthetic peptide antimalarial vaccines is under Ir gene control. It has therefore been inferred that the development of antibody responses to the native repetitive Ag of malaria parasites also requires linkage of T and B cell epitopes, presentation of Ag in the context of MHC class II components, and cognate T cell help for antibody production. In this study, we sought to test this assumption, by utilizing classical protocols to determine whether the antibody response to the repetitive surface Ag of malaria sporozoites, the circumsporozoite (CS) protein, is under Ir gene control. In contrast to vaccine constructs, such as recombinant proteins or synthetic peptides, secondary responses to the repetitive oligomeric domains of the native CS protein of intact malaria sporozoites do not require the presence of Ag-specific Th cells. Conferral of CS-specific Th cells does not appear to influence the magnitude of this thymus-independent response to sporozoites. In further contrast to synthetic CS analogs, exposure to the parasite appears to be associated with low levels of Ag-specific Th cell sensitization. These observations suggest a functional role in immune evasion for the immunodominant repetitive domains found within protein Ag of malaria and other parasites.

Hydrolysis of methotrexate-immunoglobulin conjugates by liver homogenates and characterization of catabolites.

Methotrexate (MTX) linked to antitumor antibodies inhibits tumor growth better than free MTX, free antibody, or MTX linked to normal rabbit IgG (NRG), in spite of the less effective inhibition of the target enzyme dihydrofolate reductase (DHFR) by conjugated MTX. In addition to the demonstrated higher uptake of MTX linked to antitumor antibodies (compared with the uptake of free MTX or nonspecific IgG conjugates), a contributory factor to the superior tumor inhibitory action of MTX-IgG conjugates may be the prolonged release of active drug from the internalized conjugate. Therefore, we have investigated whether an MTX-IgG conjugate could be hydrolyzed to release free MTX or fully active MTX-containing fragments after incubation with liver homogenates and have characterized the catabolites according to the presence of free MTX and their capacity to inhibit DHFR. Catabolism was optimal at pH 4.6, activated by dithiothreitol, and inhibited by antipain and N-alpha-p-tosyl-L-lysine chloromethyl ketone, thus implicating lysosomal enzymes. Liver homogenates produced an MTX-containing, low-molecular-weight fraction that was isolated by gel filtration. Further purification of this fraction by DEAE-cellulose chromatography gave two MTX-containing peaks, neither of which migrated as free MTX on thin-layer chromatography or inhibited DHFR more effectively than the parent conjugate. However, the presence of amino acid residues in these catabolites could contribute to their observed prolonged intracellular retention and superior antitumor action.

Uptake of methotrexate linked to polyclonal and monoclonal antimelanoma antibodies by a human melanoma cell line.

[3H] Methotrexate [( 3H]MTX) was covalently linked to monoclonal antibody (MoAb) 225.28S against human melanoma, to a rabbit anti-human melanoma IgG absorbed either with human red blood cells (AHMGR) or with red blood cells and a variety of normal human tissues (AHMGR + T), or to normal rabbit IgG (NRG). Human melanoma M21 cells were incubated at 0 degrees C or 37 degrees C with 10 microM free MTX or 10 microM MTX linked to one of the above carriers. The order of net uptake of MTX during 6 hours was MTX-MoAb 225.28S greater than MTX-AHMGR greater than MTX-AHMGR + T greater than MTX-NRG greater than or equal to MTX. This order of uptake by the three antibody conjugates corresponded to the amount of conjugate bound at equilibrium at 0 degrees C and to the immunofluorescence titers. Binding sites for MoAb 225.28S were more efficient for internalization of MTX than were those for the two polyclonal antibody preparations. When M21 cells preloaded with MTX by incubation at a drug concentration of 1.0 or 10 microM were incubated in drug-free medium, the amount of cell-associated MTX rapidly declined to 1.8 pmol/mg protein, i.e., the level of intracellular dihydrofolate reductase (DHFR). However, when cells preloaded to a drug content of 112 pmol/mg protein by incubation with 10 microM MTX linked to AHMGR were transferred to conjugate-free medium, 65 pmol MTX/mg remained cell associated after 12 hours. The efflux was inhibited by chloroquine. Both the efflux medium and M21 cells after a 9.5-hour incubation period had MTX-containing catabolic fragments that inhibited DHFR.

Tumor and tissue distribution of a methotrexate-anti-EL4 immunoglobulin conjugate in EL4 lymphoma-bearing mice.

The uptake and tissue distribution of [3H]methotrexate [( 3H]MTX) at doses of 5 mg/kg i.p. either free or linked to anti-EL4 immunoglobulin G (AELG) or normal rabbit globulin (NRG) was studied in EL4 lymphoma-bearing C57BL/6J mice. When the uptakes of MTX-AELG, MTX-NRG, and free MTX were assayed as cell-associated 3H activity, comparison 3 hr after administration showed that uptake of MTX administered as the AELG conjugate was 2.5 times the uptake of MTX administered as the NRG conjugate and 6 times the uptake of MTX administered free. In contrast to the difference in the uptake of MTX-AELG and MTX-NRG by tumor cells, the pattern of uptake in all the other tissues studied was generally similar for the two conjugates. Conjugated MTX persisted in all tissues and serum and ascites fluid, whereas free MTX declined rapidly after reaching peak levels around 1 hr, except in EL4 cells where 45% was retained at 24 hr. The levels of intracellular MTX after administration of these three agents exceeded the intracellular dihydrofolate reductase level and correlated with the relative tumor-inhibitory effect in vivo of the agent (MTX-AELG greater than MTX-NRG greater than MTX).

Uptake of methotrexate linked to an anti-EL4-lymphoma antibody by EL4 cells.

To study the mechanism of tumor inhibition, the uptake of methotrexate (MTX) covalently linked to a rabbit IgG antibody against a tumor-associated antigen on the surface of mouse EL4 lymphoma cells (AELG) has been compared with the uptake of free MTX and of MTX covalently linked to normal rabbit IgG (NRG). When EL4 cells were incubated at 37 degrees C with 10 microM free MTX uptake leveled off after 30 min, at 30 pmol/mg protein. In contrast, uptake of both conjugates under these conditions continued throughout an observation period of 6 h. At 6 h the net uptake of MTX bound to AELG was 40 pmol/mg protein and that of MTX bound to NRG was 24 pmol/mg protein. These results show that both MTX-AELG and MTX-NRG conjugates are taken up by EL4 cells. The rate at which EL4 cells took up bound MTX was much slower than that of free MTX but, at 6 h, the net uptake of MTX-AELG exceeded that of the free drug.