Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner preference and anxiety in male mice.

The posterodorsal medial amygdala (MePD) is a neural site in the limbic brain involved in regulating emotional and sexual behaviours. There is, however, limited information available on the specific neuronal cell type in the MePD functionally mediating these behaviours in rodents. The recent discovery of a significant kisspeptin neurone population in the MePD has raised interest in the possible role of kisspeptin and its cognate receptor in sexual behaviour. The present study therefore tested the hypothesis that the MePD kisspeptin neurone population is involved in regulating attraction towards opposite sex conspecifics, sexual behaviour, social interaction and the anxiety response by selectively stimulating these neurones using the novel pharmacosynthetic DREADDs (designer receptors exclusively activated by designer drugs) technique. Adult male Kiss-Cre mice received bilateral stereotaxic injections of a stimulatory DREADD viral construct (AAV-hSyn-DIO-hM3 D(Gq)-mCherry) targeted to the MePD, with subsequent activation by i.p. injection of clozapine-N-oxide (CNO). Socio-sexual behaviours were assessed in a counter-balanced fashion after i.p. injection of either saline or CNO (5 mg kg-1 ). Selective activation of MePD kisspeptin neurones by CNO significantly increased the time spent by male mice in investigating an oestrous female, as well as the duration of social interaction. Additionally, after CNO injection, the mice appeared less anxious, as indicated by a longer exploratory time in the open arms of the elevated plus maze. However, levels of copulatory behaviour were comparable between CNO and saline-treated controls. These data indicate that DREADD-induced activation of MePD kisspeptin neurones enhances both sexual partner preference in males and social interaction and also decreases anxiety, suggesting a key role played by MePD kisspeptin in sexual motivation and social behaviour.

Behavioural and anthropometric risk factors for diabetes mellitus among newly admitted undergraduates in a Nigerian University.

BACKGROUND: Type 2 diabetes mellitus (DM) is fast becoming a global epidemic, and its prevalence is increasing in children and young adults. The aim of the study was to identify young adults who had type 2 DM or impaired fasting glucose as well as those at risk of these conditions using anthropometric data and behavioral pattern. METHODOLOGY: Two hundred and twenty newly admitted undergraduates who were randomly selected during the registration process were involved in the study. Anthropometric parameters were measured while information on demographic details, medical history, and family history were obtained using a standard questionnaire. Fasting blood glucose was measured using the glucose oxidase method. RESULTS: Two hundred and seven (94%) participants had serum glucose within reference range, 10 (4.6%) had impaired fasting glucose, and 3 (1.4%) had serum glucose> 7.1 mmol/L, which is indicative of DM. A large number (91.4%) of individuals engaged in physical activity equivalent to a walk of at least 30 min/day. Most of them (93.2%) had body mass index <25.0 while 6.8% were overweight. One hundred and three participants (46.8%) indicated that they eat 3 or more servings of whole grain per day. CONCLUSION: Most of the participants are involved in healthy lifestyle. This has resulted in very low prevalence of impaired fasting glucose and type 2 DM among the group. It will be useful to follow up the group and note if they are able to maintain this trend since the risk of developing DM is known to increase with age.

Oestrual Phase at first exposure to Predator-induced Stress Determines Pattern of Alterations in Oestrous Cycle and Endocrine Response in the Rat.

Stress has been acknowledged as one of the aetiologies of female reproductive dysfunction, yet the mechanismsinvolved are not totally elucidated. Based on the paucity of information on how predator-induced stress (PS) affects oestrouscycle in rats, this study was designed to investigate the effect of PS on the oestrous cycle in rats. Forty-eight (48) SpragueDawley rats were used for this study. They were randomly divided into Control and PS group. Each group was divided intofour subgroups (n=6/group) according to the phases of oestrous cycle. Stress was induced by exposing rats to cat (predator)for 60 minutes/day for 14 consecutive days. PS caused significant disruption of the oestrous cycle. In animals subjected toPS at proestrus (PS-proestrus) and oestrus (PS-oestrus), percentage occurrence of proestrus, oestrus and metestrus phaseswere significantly reduced compared with control. In animals subjected to PS at metestrus (PS-metestrus) and diestrus (PSdiestrus), percentage occurrence of oestrus phase was not significantly affected. In all animals exposed to PS, percentageoccurrence of diestrus was significantly increased regardless of the phase of first exposure compared with control.Corticosterone and prolactin levels were significantly elevated in PS groups compared with control. Progesterone wassignificantly increased in animals at diestrus phase compared with oestrus phase and respective phases in control. Oestradiolwas significantly reduced in PS group compared with control at oestrus phase but not significantly different at diestrus phase.Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were significantly lower in PS groups at oestrusphase compared with diestrus phase. This study shows that PS disrupts the oestrous cycle secondary to perturbation ofhormonal control of female reproduction and is influenced by the phase at first exposure to stress.

Coffee consumption attenuates insulin resistance and glucose intolerance in rats fed on high-sucrose diet.

Several epidemiological evidences indicate that consumption of coffee is associated with a lower risk of type 2 diabetes mellitus (T2DM) however; there is dearth of experimental data to support these observations. Given that associations do not necessarily infer causality, the present study was designed to investigate the effect of coffee consumption on glucose regulation, T2DM and the probable mechanisms of action, using an animal model. The effect of coffee (2-fold dilution) by oral gavage on normal and high sucrose-solution (HSS) fed (30 % w/v) rats was evaluated. The results showed that consumption of coffee significantly increase glucose tolerance and insulin sensitivity (p<0.05) along with significant improvement in SOD and GSH activities. In addition, lipid indices such as TG and LDL as well as the lipid peroxidation marker (MDA) were markedly reduced (p<0.05) in rats fed with coffee compared with that of the HSS fed rats. These findings suggest that coffee consumption improves insulin sensitivity, glucose tolerance in HSS-fed rat possibly via inhibition of oxidative stress.

Voluntary physical activity and leucine correct impairments in muscle protein synthesis in partially pancreatectomised rats.

AIMS/HYPOTHESIS: Poorly controlled type 1 diabetes mellitus can cause reduced skeletal muscle mass and weakness during adolescence, which may affect long-term management of the disease. The aim of this study was to determine whether regular voluntary physical activity and leucine feeding restore rates of protein synthesis and deficits in skeletal muscle mass in a young, hypoinsulinaemic/hyperglycaemic rat model of diabetes. METHODS: Four-week-old male Sprague-Dawley rats were partially pancreatectomised (Px) to induce hypoinsulinaemia/hyperglycaemia and housed with/without access to running wheels for 3 weeks (n = 12-14/group). Sham surgery rats (shams) served as sedentary controls (n = 18). Protein synthesis and markers of protein anabolism were assessed in the fasted state and following leucine gavage. Fibre type and cross-sectional areas of the gastrocnemius muscle were measured using a metachromatic ATPase stain. RESULTS: Compared with sedentary behaviour, regular activity lowered fasting glycaemia and reduced fed hyperglycaemia in Px rats. Active-Px rats, which ran 2.2 ± 0.71 km/night, displayed greater muscle mass and fibre areas similar to shams, while sedentary-Px rats displayed a 20-30% loss in muscle fibre areas. Muscle protein synthesis (basal and in response to leucine gavage) was impaired in sedentary-Px (by ~65%), but not in active-Px rats, when compared with shams. Following leucine gavage, the phosphorylation status of eIF4E binding protein 1 (4E-BP1) and ribosomal S6 kinase 1 (S6K1), markers of mammalian target of rapamycin complex 1 (mTORC1) signalling, increased in shams (by two- and ninefold, respectively) and in active-Px (1.5- and fourfold, respectively) rats, but not in sedentary-Px rats. CONCLUSION/INTERPRETATION: Moderate physical activity in young Px rats normalises impairments in skeletal muscle growth and protein synthesis. These findings illustrate the critical compensatory role that modest physical activity and targeted nutrition can have on skeletal muscle growth during periods of hypoinsulinaemia in adolescent diabetes.

Antifertility effect of calcium channel blockers on male rats: association with oxidative stress.

PURPOSE: Calcium ions are vital in many biologic processes including a variety of enzymatic reactions, activation of excitable cells, coupling of electrical activation to cellular secretion, haemostasis, bone metabolism and sperm functions. Calcium channel blockers (CCB) appear to have a reversible anti-fertility effect on male rats which does not occur through inhibition of the pituitary-gonadal axis. While the effects of CCB on male reproductive function have been investigated, less information is available regarding other reproductive indices and the underlying mechanism in the pathogenesis of male reproductive dysfunction. Therefore, the involvement of oxidative mechanisms in the adverse manifestation induced by CCB on male reproductive functions is investigated in this study. METHODS: For this purpose, lipid peroxidation; enzymatic antioxidants such as superoxide dismutase, catalase and glutathione reduced; epididymal sperm count, motility; histopathology of the testes, epididymis, seminal vesicle, prostate glands; and reproductive performance were determined. RESULTS: CCB administration in rats causes significant oxidative stress in the male reproductive milieu in term of increase in malondialdehyde (MDA) level and a concomitant decrease in catalase, superoxide dismutase and reduced glutathione enzyme activities in the testes. In addition, CCB treatment significantly decreased the sperm count, sperm motility, fertility index, implantation count, and litter size in this study. CONCLUSION: There is substantial evidence that CCB induces significant oxidative stress in the testes, which appears to be responsible for the adverse effects of decreased sperm count and motility ultimately leading to reduced fertility in rats.

Antibiotic Susceptibility Pattern and Beta-lactamase Production in Isolates of Staphylococcus aureus from Recurrent Furunculosis in Southwestern; Nigeria

Furuculosis is a skin infection caused by Staphylococcus aureus. It is characterised by honey crusted 'cropped' latent boil with potential to recur in a susceptible host. Isolates of S.aureus obtained from both hospitalised and non-hospitalised patients with furuncles in Southwest; Nigeria were characterised in relation to their resistance to commonly used antimicrobial agents. Exudates of 'cropped-boils' from one hundred and forty (140) individuals consisting of forty (40) hospitalised and one hundred (100) non-hospitalised cases of recurrent furunculosis were screened for S. aureus. One hundred and two (102) were positive for the organism by conventional biochemical tests. Detection of ?-Iactamase was determined by cell-suspension iodometric method. Of the 102 isolates; 30(29.4) strains possessed ?-lactamase and the minimum inhibitory concentration (MIC) of selected antibiotics was in the range of 3.95- 250?g/ml. The multiple drug resistance as evident in high MICs of the antibiotics tested could probably be due to abuse/misuse of antibiotics resulting in recurrence of furuncles in the patients

Plasma glucose level in Nigerian Africans with head injury.

Trauma is often associated with increased plasma glucose concentrations. This prospective study was designed to determine random plasma glucose concentrations in patients with head injury in our center and to determine if this is related to injury severity and outcome. Patients with head injury in whom the plasma glucose concentration could be determined at our accident and emergency unit during the study period were included. We obtained information on demographic data, diagnosis, injury severity using Glasgow Coma Scale scores, treatment with glucose-containing fluid prior to presentation in our center, plasma glucose on admission, 24 hours later and 72 hours later and outcome at discharge using the Glasgow Outcome Scale score. Hyperglycemia was defined as glucose concentrations above 11.1 mmol/L. Fifty eight patients were included in the study from October 2004 to December 2005. There were 46 males and 12 females (4:1). The mean age (+/- standard deviation [SD]) was 31.3 (16.4) years. Fourteen patients (24.1%) had mild head injury, 21 patients (36.2%) had moderate head injury and 23 patients (39.7%) had severe head injury. The outcome was good in 29 patients (50%), moderate disability in five patients (8.6%), severe disability in one (1.7%) and death in 10 (17.2%). Eighty percent of the patients who died had severe head injury. Most of the patients had a plasma glucose in the normal range irrespective of the severity of the head injury. Only one patient had a plasma glucose in the hyperglycemic range and that patient had a severe head injury. Fifty percent of the patients who died had a plasma glucose concentration in the normal range; none in the hyperglycemic range. This study shows that the plasma glucose is generally below hyperglycemic concentration in our patients irrespective of the severity of head injury.

Hibiscus sabdariffa ethanolic extract protects against dyslipidemia and oxidative stress induced by chronic cholesterol administration in rabbits.

Excessive intake of cholesterol (CHOL) and induction of free radical production play a critical role in the pathophysiology of several human diseases. Dietary therapy with plant products rich in flavonoids has been shown to provide benefits without the adverse effects of agents used in clinical practice. Hibiscus sabdariffa (HS) has been used for various purposes due to myriads of flavonoids present in it. In this study, the chemopreventive property of HS ethanolic extract (HSE) was investigated in dyslipidemia and oxidant stress associated with prolonged CHOL administration in rabbits. Twenty-five (25) adult male rabbits weighing between 1.5 and 1.7 kg were used and randomly divided into five groups of five rabbits per group. The CHOL-fed rabbits received 1 g/kg/day of CHOL suspended in 1 ml of corn oil for 8 weeks. Group 1 received 1 ml of corn oil and served as control. Group 2 was fed with CHOL only while groups 3, 4 and 5 received daily doses ofcholestyramine (questran, 260 mg/kg), HSE 200 mg/kg and HSE 300 mg/kg respectively along with CHOL. Animals were sacrificed by cervical dislocation 24-hours after last dose. Enzymic and non-enzymic markers of oxidative stress and lipid profile were analysed in serum, liver, kidney and heart of rabbits. HSE significantly attenuated the alteration in lipid levels and antioxidant status induced by high CHOL intake in rabbits in this study. Both serum and tissue levels of low density lipoprotein-CHOL, triglycerides, phospholipids, and total CHOL decreased with increase in high density lipoprotein-CHOL except in the heart, following treatment with HSE in CHOL-fed rabbits when compared with the untreated group (p<0.05). Similarly, HSE prevented CHOL-induced depletion of enzymic (superoxide dismutase, catalase) and non-enzymic (reduced glutathione, vitamin C) antioxidants with the attendant increases in lipid peroxidation and xanthine oxidase activity in these animals. The effectiveness of HSE in this condition was comparable with that of cholestyramine but with greater in potency. Data from this study demonstrate the hypolipidaemic and antioxidant activities of HSE and suggest its therapeutic potential in disorders of lipid metabolism and cardiovascular events associated with hypercholesterolemia.

Pharmaceutical Equivalence of Some Commercial Samples of Artesunate and Amodiaquine Tablets Sold in Southwestern Nigeria

Purpose: To study the physical properties and dissolution profiles of commercial samples of artesunate and amodiaquine tablets. Methods: Fifteen generic brands of artesunate and five generic brands of amodiaquine tablets were obtained from drug retail outlets in Oyo and Ogun States in southwestern Nigeria. The tablets were subjected to various compendial tests including identification; weight uniformity; uniformity of content; content of active ingredient and uniformity of diameter. Additional tests used as a basis for the assessment of the pharmaceutical equivalence of the products include hardness; disintegration time and dissolution rate. Data obtained were analysed by correlation analysis; Chi-square and ANOVA. Results: Thirteen generic brands of artesunate (87) and four amodiaquine brands (80) investigated were imported. Two brands of the imported artesunate brands were found to contain undetectable amount of artesunate while another 8 samples contained overages. All the amodiaquine brands passed the assay test as stipulated by United States Pharmacopoeia (USP) for amodiaquine tablets while tablet disintegration time of amodiaquine products ranged from 5.8 - 20.7 min. All but one artesunate sample passed the disintegration test too. A majority of the artesunate brands tested had significantly different dissolution profiles (p 0.05). Four (80) of the amodiaquine tablet brands tested had similar dissolution profiles and percent drug released within 30 min (p 0.05). One amodiaquine brand demonstrated poor dissolution profile as it did not meet minimum dissolution requirements within 30 min. Conclusion: The detection of substandard artesunate tablets and a poorly formulated amodiaquine tablet amongst the few sample brands studied highlights the need for increased drug surveillance and monitoring of the qualities of antimalarial medicines currently in use in order to prevent widespread treatment failure

HELLP syndrome: the experience at Ile-Ife, Nigeria.

Between 1 January and 31 December, 2006, 34 consecutive cases of severe pre-eclampsia (12), imminent eclampsia (10) and eclampsia (12) who were admitted at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife in the south-western part of Nigeria, were investigated for the development of HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome in a prospective study. The ages of the women ranged from 18 to 38 years, parity 0-5 and the estimated gestational age from 18-41 weeks at presentation. A total of 26 (76.5%) of the patients were unbooked, six (17.6%) of the 34 cases developed HELLP syndrome. Four (33%) of the 12 eclamptics developed HELLP syndrome, while only one (10%) of the cases of imminent eclampsia and 1 (8.3%) of severe pre-eclamptic cases developed the syndrome. Using the Mississippi Triple class system, none of the HELLP syndrome cases belonged to Class I; 4 were categorised in Class II while 2 were in Class III. All of the four eclamptic cases with HELLP syndrome died giving a 100% fatality rate while none of the imminent eclamptic and severe pre-eclamptic patients with the syndrome died. Furthermore, there were six (15.8%) perinatal deaths among the 38 infants delivered by the 34 mothers with severe pre-eclampsia/eclampsia. Our data suggest that the development of HELLP syndrome is more likely in eclamptic patients and when it occurs in them, it is highly fatal. Most of the cases in this study were unbooked. Substandard care may have contributed to the progression of the disease state and consequently, to maternal mortality. It is imperative to draw up an action plan for the identification of the risk factors for the development of pre-eclampsia/eclampsia at peripheral hospitals and maternity centres and for prompt referral of such cases afterwards. Efforts should also be geared towards the minimising of treatment delay in all phases, so as to minimise both perinatal and maternal morbidity and mortality.

Acute oral toxicity test and phytochemistry of some West African medicinal plants.

BACKGROUND: Although there is increased acceptance and utilization of medicinal plants worldwide, many are used indiscriminately without recourse to any safety test. Thus, the need for toxicity tests to determine the safe dose for oral consumption. OBJECTIVE: LD50 and phytochemistry of four medicinal plants of West Africa were investigated. METHODS: Thirty male and non pregnant female Swiss albino mice weighing 20grams each were used for this study. They were divided into the Control (C), Oldenlandia corymbosa L. aqueous leaf-extract treated (OCG), Parquetina nigrescens aqueous leaf extract treated (PNG), Hybanthus enneaspermus aqueous leaf extract treated (HEG), Ficus carica leaf extract treated (FCG) and Sesamum indicum aqueous seeds extract treated group (SIG). Each group except the control was further divided into four sub-groups of six mice each, and were administered orally, graded doses (SI; 1, 2, 4 and 8, PN; 2.5, 5, 10 and 20, OC; 5, 10, 20 and 40, FC; 1, 2, 4 and 8, HE; 4, 8, 16, 32) of the aqueous extract of each plant (g/kg body weight) after 12 hours fasting. RESULTS: The dry aqueous leaf extracts of HE, OC, PN, FC all have dark brown colour and pH ranging from 6.1 to 7.2 while the seed extract of SI has a light brown color with pH of 7.0. Flavonoids, cardiac glycosides, anthocyanosides, saponin, and reducing sugar were present in all extracts, while cyanogenic glycoside was present only in HE. LD50 determination results obtained using Thompson and Finney methods were as follows; OC; 14.14 +/- 0.27 and 10.56 +/- 0.20, PN; 12.60 +/- 0.10 and 13.10 +/- 0.10, HE; 8.14 +/- 0.30 and 8.24 +/- 0.35, FC; 3.36 +/- 0.26 and 4.00 +/- 0.04, SI; 4.00 +/- 0.10 and 3.10 +/- 0.22 respectively (LD50 values are in g/kg body weight. CONCLUSION: The results of this study have provided an oral LD50 from where a safe dose can be chosen for further research into the merits of the consumption of these medicinal plants.

Mechanism of the delayed puberty onset in offspring of rats that consumed aqueous extract of Hibiscus sabdariffa during pregnancy.

Consumption of extracts of Hibiscus sabdariffa (family: malvaceae) during pregnancy has been shown to cause maternal malnutrition which has been linked to various adverse conditions like increased postnatal weight gain, delayed puberty onset and elevated body weight and body mass index at onset of puberty in the female offspring. The present study was designed to investigate the possible mechanism underlying this. Eighteen in-bred pregnant Sprague-Dawley rats were on day 1 of pregnancy, randomly divided into three groups of six animals each. Group A (control) was given tap water to drink. Group B was given 0.6g extract/100ml while Group C was given 1.8g extract/100ml as their drinking solution. All groups received normal rat chow and their drinking solution ad libitum. Fluid and food intake and dam weights were measured daily throughout pregnancy. On gestational day 18, blood sample was withdrawn from each rat for estimation of plasma Na ion and corticosterone levels. On the day of delivery, the solutions of the extracts of Hibiscus sabdariffa were withdrawn and replaced with tap water. After 21 days, the pups were weaned to tap water and food ad libitum. Pups weight and age and body mass index at onset of puberty were measured. The results of the present study showed that the increased postnatal weight gain, delayed puberty onset and elevated body mass index at onset of puberty in the offspring of rats that consumed HS during pregnancy was associated with elevated maternal plasma Na ion and corticosterone levels during pregnancy.

Maternal consumption of an aqueous extract of Hibiscus sabdariffa during lactation accelerates postnatal weight and delays onset of puberty in female offspring.

The present study was designed to investigate whether maternal consumption of aqueous extract of Hibiscus sabdariffa (HS) during lactation will affect the postnatal growth and onset of puberty in the female offspring. Eighteen in-bred virgin female Sprague-Dawley rats aged between 10-12 weeks and weighing 125 +/- 5.5g (mean +/- SEM) with two consecutive regular 4-day estrus cycles were randomly assigned to one of three groups of 6 rats per group. One group had tap water (Control); another had 0.6g/100ml while the third group had 1.8g/100ml in their drinking water throughout lactation (21 days). Results showed that HS consumption during lactation significantly (P < 0.05) decreased maternal fluid and food intake, increased postnatal weight gain and delays the onset of puberty in the female offspring.

Seroprevalence of hepatitis C virus infection in Nigerians with type 2 diabetes mellitus.

BACKGROUND: Several studies have suggested a strong epidemiologic association between Diabetes Mellitus (DM) and Hepatitis C Virus (HCV) infection in some populations. However, the reasons why chronic HCV infection is prevalent in DM remain unknown. Our aims were to determine the prevalence of HCV infection in a population of Nigerian diabetics compared with the general population as well as assess the influence of sex and age on HCV infection in the same diabetic population. DESIGN AND METHODS: A total of 115 diabetic patients were compared with 2,301 blood donors matched by recognized risk factors to acquire HCV infection. Serologic testing for anti HCV was done using a commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Sixty (60) type 2 diabetic patients were males while fifty-five (55) were females. Their mean age was 55.4 +/- 9 years and mean blood glucose level was 8.5mmol/l. One subject tested positive for HCV infection. The control group consisted of 2,031 adults recruited from the blood donor's clinic. Forty five of them (2.2%) tested positive for HCV. CONCLUSION: Our preliminary results suggest a low sero-prevalence of HCV infection among our patients with type 2 diabetes. Presently, routine screening for HCV infection in persons with diabetes may not be necessary.

Formulation of the Extract of the Stem Bark of Alstonia Boonei as Tablet Dosage Form

Purpose: To formulate the extracts of the stem bark of Alstonia boonei; an important antimalarial herb; into tablet dosage form. Methods: Tablets were formulated using direct compression and wet granulation methods. The mechanical properties of the tablets were assessed using crushing strength and friability and the crushing strength:friability ratio (CSFR) while drug release properties were evaluated using disintegration and dissolution times. Results: There were statistically significant (p0.01) differences in the CSFR values and drug release properties of A. boonei tablets prepared by both methods. The differences depended on the type and concentration of excipient and binder employed in the formulation. Conclusions: The method of preparation of the A. boonei tablets needs to be carefully selected to ensure the production of tablets with adequate bond strength to withstand the rigours of handling and at the same time release the active compound (s) for biological action

Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover.

AIMS/HYPOTHESIS: Increased circulating methylarginines (MA) have been linked to the metabolic syndrome to explain endothelial dysfunction and cardiovascular disease risk. Proteins that contain MA are regulatory and release them during catabolism. We hypothesised that increased protein turnover in insulin-resistant states contributes to an increase in circulating MA. MATWERIALS AND METHODS: We performed hyperinsulinaemic, euglycaemic, and isoaminoacidaemic experiments on 49 lean, obese and elderly subjects, with measurements of the kinetics of glucose and protein metabolism. Plasma MA, i.e. asymmetrical dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), and N -monomethyl-L-arginine (NMMA), lipids and body composition were measured. RESULTS: Insulin resistance of glucose and protein metabolism occurred in obese and elderly subjects. ADMA concentrations were 29 to 120% higher in obese and 34% higher in elderly than in lean subjects. SDMA were 34 and 20% higher in obese than in lean and than in elderly subjects, respectively. NMMA were 32% higher in obese than in lean subjects. ADMA differed by sex, being higher in men, namely by 1.75x in obese men and by 1.27x in elderly men. Postabsorptive ADMA (r=0.71), SDMA (r=0.46), and NMMA (r=0.31) correlated (all p<0.05) with rates of protein flux. All three MA correlated negatively with clamp glucose infusion rates and uptake (p<0.001). ADMA and SDMA correlated negatively with net protein synthesis and clamp amino acid infusion rates (p<0.05). All MA also correlated with adiposity indices and fasting insulin and triglycerides (p<0.05). CONCLUSIONS/INTERPRETATION: Obesity, sex and ageing affect MA. Elevations of the three MA in obese, and of ADMA in elderly men, are related to increased protein turnover and to lesser insulin sensitivity of protein metabolism. These interrelationships might amplify insulin resistance and endothelial dysfunction.

Comparative Analysis of Eight Brands of Sulfadoxine-Pyrimethamine Tablets

PURPOSE : The aim of the present study is to investigate the physicochemical equivalence of eight brands of tablets containing sulfadoxine-pyrimethamine (antimalarial drug combination) sourced from different retail Pharmacy outlets in the Nigerian market. METHOD : The quality and physicochemical equivalence of eight different brands of sulfadoxine-pyrimethamine combination tablets were assessed. The assessment included the evaluation of uniformity of weight; friability; crushing strength; disintegration and dissolution tests as well as chemical assay of the tablets. RESULTS : All the eight brands of the tablets passed the British Pharmacopoeia (BP) standards for uniformity of weight; disintegration and crushing strength. Three of the eight brands failed the friability test. One of the brands did not comply with the standard assay of content of active ingredients while another brand did not comply with the USP specifications for dissolution test for sulfadoxine-pyrimethamine tablets. There were no significant differences in the amounts of pyrimethamine and sulfadoxine released from the different brands (P greater than 0.05). CONCLUSION: Only three brands (registered by NAFDAC) out of the eight brands of sulfadoxine-pyrimethamine tablets that were analysed passed all the BP quality specifications and were physically and chemically equivalent. This study highlights the need for constant market monitoring of new products to ascertain their equivalency to the innovator product

Anabolic and catabolic mediators of intestinal protein turnover: a new experimental approach.

Studies on regulation of protein turnover in skeletal muscle have revealed the important contributions of protein synthesis and catabolism to tissue protein balance, and have identified a host of specific anabolic and catabolic stimuli and biochemical mechanisms that regulate these processes. This knowledge is critical to current efforts designed to promote anabolism and limit atrophy. Of the tissues with a potentially large contribution to whole-body amino acid metabolism, protein turnover of the intestine stands out as being poorly understood. The intestine is subject to complexities in regulation of its metabolism that are not apparent for other tissues. The study of intestinal protein turnover also entails some important technical challenges. We recently developed an in-situ experimental system for study of intestinal mucosal protein synthesis with the following unique features: multiple observations within an animal; controlled delivery of nutritional stimuli to the apical side, basolateral side, or both; and luminal delivery of tracer in a flooding dose for determination of protein synthesis. We have begun to use the system to test the specific roles of individual luminal nutrients in regulation of mucosal protein synthesis. We have also used protease gene expression as an index of potential regulation of catabolic pathways.