Vitamin C supplementation promotes locomotor and exploratory behaviors in male Wistar rats exposed to varying stress models.

Constant exposure to environmental stress has negative behavioral outcomes. Considering the inverse relationship between stress and Vitamin C intake, this study was aimed at investigating variable stress techniques and Vitamin C supplementation on exploratory/locomotor behaviors in male Wistar rats. Twenty-eight male Sprague-Dawley rats (100g-120g) were allotted into four groups (n=7). Control received 10ml/kg distilled water, group two received 100 mg/kg vitamin C, group three was exposed to different models of stress while group four was stressed alongside 100 mg/kg vitamin C. Vitamin C treatments were given orally for 2 weeks. Animals in groups 3 and 4 were stressed every other day with models such as multiple cage changes, exposure to noise, overnight strange objects, overnight wetting of beddings, and immobility. Explorative and locomotor activities were assessed with the open field test, novel object recognition test, and Y maze test using a Logitech camera and ANY-maze software to track the movement of the rats. Cortisol was assayed in the serum using Enzyme-linked Immuno Assay (ELISA) kit. Superoxide Dismutase, catalase, and lipid peroxidase; malondialdehyde (MDA) were also assayed in the serum. The results show that locomotor activities such as distance traveled, average speed, and time spent in the center square was significantly reduced by stress. These activities were improved with the intake of vitamin C compared with stress. Explorative activities such as locomoting around the environment, orientating towards novelty, and touching or sniffing novel objects were significantly increased in the rats on Vitamin C supplements and reduced in the stressed group. In the serum, cortisol level was significantly increased in rats exposed to stress and decreased with Vitamin C intake. Stress also significantly increased MDA and decreased SOD and CAT while vitamin C supplement decreased MDA and increased SOD and CAT. In conclusion, oral intake of vitamin C enhanced explorative/locomotor behavior and increased oxidative stress in rats exposed to different models of stress.

L-arginine supplementation lowers blood pressure, protein excretion and plasma lipid profile in experimental salt-induced hypertension in pregnancy: Relevance to preeclampsia.

This study aimed to investigate the effects of L-arginine supplementation on blood pressure, protein excretion, lipid profile in salt-induced hypertensive pregnant rats. Female Sprague-Dawley rats were divided into 4 groups. Control Preg (normal rat chow). Control Preg + L-ARG (normal rat chow and daily oral L-Arginine from 16th - 20th week). Salt Preg (high salt diet, 8%). Salt Preg + L-ARG (high salt diet, 8% and daily oral L-Arginine from 16th - 20th week. Non-invasive BP was recorded using a tail-cuff machine at 1 st and 2nd trimesters. On day 19 of pregnancy, invasive BP was obtained by carotid artery cannulation connected to LabChart-7 pro software. This was followed by blood samples collection for lipid profile analysis. L-arginine significantly reduced (P < 0.05) systolic, diastolic, MAP at 1 st, 2nd trimesters, day 19 of pregnancy, LDL, plasma and urinary creatinine and protein levels in Control Preg + L-ARG and Salt Preg + L-ARG groups compared to other groups. Urinary Na + and K + were significantly higher (P < 0.05) in Salt Preg + L-ARG group compared to other groups. Total cholesterol level was significantly higher (P < 0.05) in salt groups compared to control groups. Triglyceride level and urine volume were significantly higher (P < 0.05) in Salt Preg group compared to other groups. It also significantly increased (P < 0.05) HDL in Control Preg + L-ARG and Salt Preg + L-ARG groups compared to other groups. L-arginine supplementation ameliorates some deleterious effects in salt- induced hypertensive pregnant rats possibly through its known NO vasodilatory effect and might also mediate a diuretic like action.

L-Arginine Co-Administration with Carbamazepine Improves Cognition in Male Sprague-Dawley Rats.

Cognitive impairment is a common adverse effect associated with carbamazepine use. One of the proposedmechanisms for cognitive impairment may be attributed to the pro-oxidant properties of carbamazepine. This studyinvestigated the effects of L-Arginine supplementation with carbamazepine on cognition in adult male non-epileptic rats.Adult male Sprague-Dawley rats with average weight 200g to 220g were divided into 4 groups; (1) Control group treatedwith distilled water, (2) L-Arginine group treated with L-Arginine (100mg/kg BW) in distilled water, (3) Carbamazepinegroup treated with carbamazepine (25mg/kg BW twice daily) in distilled water, and (4) Carbamazepine + L-Arginine grouptreated with Carbamazepine and L-Arginine as above for two weeks to assess the acute changes in cognition and oxidativestress markers. Following two weeks of treatment, cognition was assessed using the Y-maze, after which the rats werehumanely sacrificed with the hippocampus and frontal lobes isolated from the brain and subsequently homogenized forassessment of oxidative stress markers [(Catalase, superoxide dismutase (SOD), malondialdehyde (MDA), and reducedGlutathione (GSH)]. Arm entry and correct alternation were significantly higher (p < 0.05) in the L-Arginine and L-Arginine+ Carbamazepine groups compared to carbamazepine group. In the frontal lobe, L-Arginine significantly increased (p < 0.05)catalase and GSH levels compared to other groups while in the hippocampus, it significantly (p < 0.05) reduced MDA withno change in other parameters. Likewise, SOD and MDA levels were significantly lower (p < 0.05) in the L-Arginine +Carbamazepine group compared to other groups. Oral L-Arginine supplementation with carbamazepine improved cognitiveperformance on Y maze.

A prospective cohort study on the clinical utility of second trimester mean arterial blood pressure in the prediction of late-onset preeclampsia among Nigerian women.

BACKGROUND: Early detection of preeclampsia will help reduce the morbidities and mortalities associated with the disorder. Late-onset preeclampsia was the predominant presentation in this cohort. The search for biomarkers for predicting preeclampsia is still ongoing. Mean arterial blood pressure (MABP), which has the advantage of presenting a single cutoff value compared with the use of systolic and diastolic blood pressure measurements, merits evaluation. AIM: The study aims to evaluate the clinical utility of second trimester MABP in the prediction of preeclampsia. METHODS: This was a prospective cohort study of 155 normotensive, nonproteinuric pregnant women without prior history of gestational hypertension. The women were booked patients attending the antenatal clinic at the Lagos University Teaching Hospital and were all in their second trimesters of pregnancy. The outcome measures were systolic blood pressure, diastolic blood pressure, and MABP. The end point of the study was the development of preeclampsia. The diagnosis of preeclampsia was made by the attending obstetrician. The data were analyzed using the IBM SPSS statistical software. Statistical significance was set at P < 0.05. RESULTS: One hundred and fifty-five pregnant women participated in the study. Eleven (7.1%) of the women developed preeclampsia after 34 weeks gestation and 144 (92.9%) had normal pregnancy. The mean gestational age at the time of assessment was 18.88 ± 3.15 weeks with a range of 14 weeks to 27 completed weeks. There was a statistically significant increase in the systolic blood pressure, diastolic blood pressure, and MABP values in the group of women who later developed preeclampsia, P = 0.005, 0.001, and <0.001, respectively. At a false-positive rate of 10%, MABP value of 88.33 mmHg predicted preeclampsia with a specificity of 90% and a sensitivity of 45.5%, P <0.05. The area under the receiver-operative characteristics curve (AUC) was 0.732 (95% confidence interval, 0.544-0.919, P = 0.011). The negative predictive value (NPV) was 88.88% and the positive predictive value (PPV) was 45.45%, P < 0.05. At an MABP cutoff of 88.33 mmHg, preeclampsia was predicted with a relative risk of 4.44 and a positive likelihood ratio of 6.46, P < 0.05. CONCLUSIONS: With an AUC of 0.732, MABP performed moderately (considering that excellent performance has an AUC of 1.0) in the prediction of late-onset preeclampsia in Nigerian women. Its high NPV suggests a strong ability to rule out preeclampsia and help to appropriate management.

Early pregnancy plasminogen activator inhibitor-1 levels in Nigerian women and its relationship with preeclampsia.

AIM: This study compared early plasma levels of plasminogen activator inhibitor-1 (PAI-1) in normal pregnancy and preeclampsia and determined its relationship with disease severity. SUBJECTS AND METHODS: This was a prospective cohort study of 195 normotensive, aproteinuric pregnant women without prior history of gestational hypertension. The women were attending the Antenatal Clinic at The Lagos University Teaching Hospital and were within 24 weeks gestation at recruitment. The outcome measures were PAI-1, systolic blood pressure (SBP), diastolic blood pressure (DBP), and significant proteinuria. The endpoint of the study was the development of preeclampsia. The diagnosis of preeclampsia was made by the attending Obstetrician. The data were analyzed using the IBM SPSS statistical software. Statistical significance was set at P < 0.05. RESULTS: First trimester PAI-1 levels were significantly higher in the women who later developed preeclampsia compared to those who had a normal pregnancy (P < 0.0001). In these group of women who later developed preeclampsia, PAI-1 had an inverse relationship with gestational age (r = 0.878) whereas in normal pregnancy, PAI-1 and gestational age had a direct relationship (r = 0.017). Second trimester systolic and DBP values were also significantly higher in the women who later developed preeclampsia compared to normal pregnancy, P = 0.007 and 0.004, respectively. There was, however, no correlation between PAI-1 values and SBP, DBP and proteinuria in the women who developed preeclampsia. CONCLUSION: Plasma levels of PAI-1 are increased early in pregnancies complicated by preeclampsia, but the lack of correlation of this marker with disease severity may limit its clinical utility.

Early pregnancy plasminogen activator inhibitor-1 levels in Nigerian women and its relationship with preeclampsia

Aim: This study compared early plasma levels of plasminogen activator inhibitor-1 (PAI-1) in normal pregnancy and preeclampsia and determined its relationship with disease severity. Subjects and Methods: This was a prospective cohort study of 195 normotensive, aproteinuric pregnant women without prior history of gestational hypertension. The women were attending the Antenatal Clinic at The Lagos University Teaching Hospital and were within 24 weeks gestation at recruitment. The outcome measures were PAI-1, systolic blood pressure (SBP), diastolic blood pressure (DBP), and significant proteinuria. The endpoint of the study was the development of preeclampsia. The diagnosis of preeclampsia was made by the attending Obstetrician. The data were analyzed using the IBM SPSS statistical software. Statistical significance was set at P < 0.05. Results: First trimester PAI-1 levels were significantly higher in the women who later developed preeclampsia compared to those who had a normal pregnancy (P < 0.0001). In these group of women who later developed preeclampsia, PAI-1 had an inverse relationship with gestational age (r = 0.878) whereas in normal pregnancy, PAI-1 and gestational age had a direct relationship (r = 0.017). Second trimester systolic and DBP values were also significantly higher in the women who later developed preeclampsia compared to normal pregnancy, P = 0.007 and 0.004, respectively. There was, however, no correlation between PAI-1 values and SBP, DBP and proteinuria in the women who developed preeclampsia. Conclusion: Plasma levels of PAI-1 are increased early in pregnancies complicated by preeclampsia, but the lack of correlation of this marker with disease severity may limit its clinical utility

Calcium and Magnesium Metabolism in Pre-Eclampsia.

BACKGROUND: Preeclampsia is a multisystem disorder associated with high maternal and perinatal mortality and morbidity. The cause of the disorder is largely unknown and its pathogenesis is complex and poorly understood. Calcium and magnesium are divalent ions which may have roles to play in the manifestations of the disease. An understanding of their metabolism in preeclampsia may aid our management of pregnant women who develop the disease. OBJECTIVE: To determine the plasma and urinary concentrations of calcium, magnesium and parathyroid hormone in women with mild, severe preeclampsia and in normal pregnancy. METHODS: This is was a case control study of fifty women with mild preeclampsia, fifty women with severe preeclampsia and fifty women with normal pregnancy as controls, drawn from The Antenatal Clinic at the Lagos University Teaching Hospital, Lagos, Nigeria. The women were consecutively recruited after signing an informed consent form. Ethical approval was obtained from the medical ethics committee of the hospital. RESULTS: The three groups of women were similar in their socio demographic characteristics. Plasma calcium was low in mild and severe preeclampsia compared to normal pregnancy controls (p=0.021). Urine calcium/creatinine ratio was lower in mild and severe preeclampsia compared to normal pregnancy controls (p= 0.030). Fractional excretion of calcium and levels of parathyroid hormone were similar across all three subgroups of women. Plasma magnesium was higher in mild and severe preeclampsia compared to normal pregnancy controls (p=0.011) and showed a positive correlation with plasma creatinine (r=0.48, p=0.045). Parathyroid hormone levels were similar across the study groups. CONCLUSION: Preeclampsia is associated with significant changes in calcium and magnesium metabolism. This study noted significant hypocalcaemia in mild and severe preeclampsia with significantly low urine calcium/creatinine levels. Calcium supplementation may have a place in patient's management. Hypermagnesemia was observed in mild and severe preeclampsia and appeared related to renal function.

The prevalence of metabolic syndrome in persons with type 2 diabetes at the Lagos University Tteaching Hospital, Lagos, Nigeria.

BACKGROUND: Over the past decade, Lagos state has witnessed greater industrialization and increased economic prosperity. Lifestyle has become increasingly westernized, characterised by intake of excesscalories and physical inactivity. It is possible that these changes would lead to increases in the prevalence of metabolic syndrome and type 2 diabetes which are known cardiovascular risk factors. It became important therefore to study the prevalence of metabolic syndrome in type 2 diabetes in Lagos, Nigeria as at the present time and compare it with previous prevalence rates as well as rates from other centres as a way of assessing current cardiovascular risk burden in this population. OBJECTIVES: This study is to determine the prevalence of metabolic syndrome in type 2 diabetes and to correlate the presence of microalbuminuria with glycaemic control. METHODS: One hundred subjects with type 2 diabetes were selected by simple random sampling from patients attending The Diabetic Clinic at the Lagos University Teaching Hospital, Lagos, Nigeria.Age and sex matched controls were recruited from members of staff of the hospital.Clinical data was obtained by interviewing the participants. Anthropometric measurements were made and blood and urine specimens were collected for analysis. The World Health Organisation (WHO) criteria which is specified for the diagnosis of metabolic syndrome in the setting of type 2 diabetes was used to determine the prevalence of metabolic syndrome in this population. RESULTS: Central obesity had the highest prevalence (79%) among persons with diabetes,followed by hypertension (69%), low HDL (50%), general obesity (40%), microalbuminuria (24%) and hypertriglyceridemia (10%). The prevalence of metabolic syndrome was 86%in this group. The commonest occurring metabolic syndrome component among patients with type 2 diabetes and metabolic syndrome was obesity (91.9%). There was a moderate positive correlation(r=0.52; p=0.01) between HbA1c values and microalbuminuria in persons with diabetes and the metabolic syndrome. CONCLUSION: The prevalence of metabolic syndrome is very high among patients with type 2 diabetes in The Lagos University Teaching Hospital, Lagos, Nigeria.

Effects of streptozotocin, fructose and sucrose-induced insulin resistance on plasma and urinary electrolytes in male Sprague-Dawley rats.

BACKGROUND: Several groups in recent times have related the pathogenesis of renal haemodynamic changes in diabetes and most of the experimental diabetic conditions studied so far were carried out using streptozotocin injection only. OBJECTIVE: The aim of the present study was to examine the effects of streptozotocin, fructose and sucrose induced insulin resistance on plasma and urinary electrolytes. Closely related to this aim, was the view to suggest which profoundly potentiate insulin resistance more between fructose and sucrose. METHODS: Thirty-six male Sprague-Dawley rats were randomly divided into 6 groups Group 1 > control group. Group 2 > served as streptozotocin group, rendered diabetic by a single dose IP injection of Streptozotocin 45 mg/kg in 0.1 M freshly dissolved in Na+ citrate buffer pH 4.5. Hyperglycaemia confirmed after 48 hours. Groups 3 and 4 > served as 25% fructose and 50% fructose groups respectively; fed on a diet containing 25% and 50% fructose (W/W) for 12 weeks. Groups 5 and 6 > served as 25% sucrose and 50% sucrose groups respectively; fed on a diet containing 25% and 50% sucrose (W/W) for 12 weeks. Hyperglycaemia confirmed at the 12th week. RESULTS: Plasma and urinary sodium and potassium were significantly higher (P < 0.05) in the 25% and 50% sucrose groups compared to the other groups. Plasma and urinary chloride was significantly higher (P < 0.05) in the 25% and 50% fructose groups compared to the other groups. Plasma creatinine and urea was significantly higher (P < 0.05) in the streptozotocin, 25% and 50% Sucrose groups compared to all the other groups. Urinary creatinine and urea was significantly higher (P < 0.05) in the streptozotocin, and 25% Fructose groups compared to all the other groups. CONCLUSION: The elevated levels of plasma and urinary electrolytes are presumptive markers of diabetes associated lesions in the kidneys of rats. Fructose potentiated insulin resistance effect more than sucrose though sucrose might have more effect on renal sodium handling.

Streptozotocin diabetes and insulin resistance impairment of spermatogenesis in adult rat testis: central vs. local mechanism.

Mammalian reproduction is dynamically regulated by the pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones are synthesized in the pituitary gland following stimulation by the gonadotropin-releasing hormone (GnRH) and act by stimulating steroid production and gametogenesis in both males and females. Male adult Sprague-Dawley rats (120 - 140 g) were randomly divided into 7 groups. Group 1 > Control group; fed on normal rat pellets. Group 2 > Streptozotocin group; received a single dose IP injection of streptozotocin 45 mg/kg BW in Na+ citrate buffer pH 4.5. Group 3 > Streptozotocin-insulin treated group; received a single dose IP injection of streptozotocin as in group 2 above and treated with insulin sub-cutaneously. Group 4 > Streptozotocin-ginger treated group; received a single dose IP injection of streptozotocin as in group 2 above and treated with 500 mg/Kg Ginger extract orally. Group 5 > Insulin resistant group; fed ad libitum on a special diet containing 25% fructose mixed with 75% normal rat chow (w/w). Group 6 > Insulin resistant-pioglitazone treated group; fed ad libitum on a special diet as in group 5 above and treated with Pioglitazone 15 mg/kg orally. Group 7 > Insulin resistant-ginger treated group; fed ad libitum on a special diet as in group 4 above, and also treated with 500 mg/Kg Ginger extract orally. Hormonal and tissue biochemistry analyses revealed that both central and local mechanisms are implicated in the impairment of spermatogenesis by diabetes but the hypothalamo-pituitary testicular axis alteration might not likely have a major impact as the local defect on steroidogenesis in the testis. This local defect could also predispose to male hypogonadism, i.e. failure of gonadal function.

Anti-diabetic and anti-oxidant effects of Zingiber officinale on alloxan-induced and insulin-resistant diabetic male rats.

This study was designed to investigate the hypoglycaemic and anti-oxidant effects of Zingiber officinale on experimentally induced diabetes mellitus using alloxan and insulin resistance. Aqueous extracts of raw ginger was administered orally at a chosen dose of 500mg/ml for a period of 4 weeks to alloxan-induced diabetic and insulin resistant diabetic rats. The experimental rats exhibited hyperglycaemia accompanied with weight loss to confirm their diabetic state. Ginger effectively reduced fasting blood glucose and malonydealdehyde levels in alloxan-induced diabetic and insulin resistant diabetic rats compared to control and ginger only treated rats. Furthermore, ginger increased serum insulin level and also enhanced insulin sensitivity in alloxan-induced diabetic and insulin resistant diabetic rats compared to control and ginger only treated rats. The results of the study clearly show that dietary ginger has hypoglycaemic effect, enhances insulin synthesis in male rats and has high antioxidant activity. One of the likely mechanisms is the action of malonydealdehyde, which acts as a scavenger of oxygen radicals.

Alloxan-induced and insulin-resistant diabetes mellitus affect semen parameters and impair spermatogenesis in male rats.

The purpose of this study was to determine the effects of diabetes mellitus and insulin resistance on semen parameters, histology of reproductive organs and serum concentrations of testosterone and luteinizing hormone (LH). Male Sprague-Dawley rats weighing 180 - 200g were made diabetic by intravenous injection of alloxan (40 mg/kg): and insulin resistant by chronic fructose feeding (25% fructose) for 12 weeks. Rats were anaesthetized, followed by laparatomy. Blood was obtained by cardiac puncture for measurement of testosterone and LH concentrations by radioimmunoassay. Semen analysis was carried out; reproductive organs were isolated, fixed in Bouin's fluid and processed for histological studies. All semen parameters analyzed were significantly reduced (P < 0.05) in the diabetic and insulin resistant rats compared to control rats. Body weight and weight of reproductive organs were also significantly reduced (P < 0.05). Furthermore, tissue fixation studies revealed changes in the cytoarchitecture of reproductive organs in the diabetic and insulin resistant rats compared to control rats. However, serum concentrations of testosterone and LH were not significantly different in all the groups. We conclude that diabetes mellitus and insulin resistance affect semen parameters and impair distinct phases of spermatogenesis in male rats. Some mechanisms responsible for this impairment are suggested.

Effects of diabetes and insulin resistance in pregnant rats on ex vivo vascular reaction to magnesium.

The purpose of this study was to investigate the effects of diabetes and insulin resistance during pregnancy on the ex vivo vascular reaction to magnesium. Female Sprague-Dawley rats were made diabetic by intravenous injection of alloxan, or insulin resistant by fructose feeding. The rats were allowed to mate and sacrificed on Day 19 of pregnancy. Aortic rings were isolated and mounted in organ baths for measurement of isometric tension. The rings were contracted with 10(-7) M phenylephrine and cumulative concentration-response curves for magnesium (1-12 mM) were determined in the presence and absence of 10(-4) M Nomega-nitro-L-arginine methyl ester (L-NAME) or 10(-5) M indomethacin. The relaxation response to magnesium was significantly decreased in pregnant rats compared with non-pregnant rats. Pregnant rats with diabetes or insulin resistance had greater impairment in the relaxation responses to magnesium compared with normal pregnant rats. The effects of diabetes and insulin resistance on magnesium-induced relaxation in pregnant rats were not altered in the presence of L-NAME and indomethacin. The results suggest that diabetes and insulin resistance aggravate the alteration in magnesium-induced vascular relaxation observed in pregnancy, and this may be due in part to impairment to mechanisms other than the nitric oxide-cyclic guanosine monophosphate and cyclooxygenase pathways.