Lessons Learned from Glycemia Control Studies

Hyperglycemia occurs in patients with diabetes and in nondiabetic patients during acute illness. Epidemiologic and observational studies have demonstrated that hyperglycemia is associated with significant adverse outcomes. Nevertheless, studies evaluating the benefits of normalizing glycemia have produced inconsistent results. For instance, intensive control of hyperglycemia had been shown to provide microvascular benefit in type 1 and type 2 diabetic patients, but its macrovascular benefits had only been clearly demonstrated in type 1 diabetic patients. Moreover, although initial studies in critically ill patients showed decreased morbidity and mortality with tight glycemic control, subsequent studies yielded conflicting results. A series of recent studies provide further insight and show that intensive glycemic control in type 2 diabetic patients does provide macrovascular benefit but is associated with increased risk of hypoglycemia. In the critically ill patient, tight glycemic control could be detrimental; thus, a less aggressive glycemic target of 140 to 180 mg/dL is preferred.     

Studies on the Anti-Inflammatory,Analgesic and Antipyrexic Activities of Betulinic Acid Derived from Tetracera Potatoria

Background

The anti-inflammatory and anti-nociceptive activity of betulinic acid (BA) was investigated in this study. The triterpene was isolated from the ethyl acetate extract of Tetracera potatoria and its structure was verified by IR and NMR spectroscopy. The bioactivity of this compound was assessed using carrageenan-induced paw oedema in rats and carrageenan-induced pulmonary oedema in mice for the anti-inflammatory activity, while acetic acid-induced writhing test in mice and zymosan-induced fever in rats were used for analgesic test.

Materials and Methods

Rats and mice were randomly divided into groups of five animals. For each experiment, betulinic acid at 10, 20 or 40mg/kg b.w was administered intraperitoneally to the first three groups respectively. The fourth group was administered with indomethacin (10mg/kg) or acetylsalicylic acid (150mg/kg), while the fifth group was administered with distilled water (10ml/kg). Data obtained were expressed as mean±S.E.M and significant differences were determined at p<0.05.

Results

BA significantly reduced carrageenan-induced paw oedema by 11.0%, 45.7%, 68.6% or pulmonary oedema by 25.6, 29.2 and 45.13% dose dependently. 40 mg/kg of BA inhibited paw oedema by 68.6% comparably to acetylsalicylic acid (71.4%) or indomethacin (51.33%) respectively. Abdominal writhing was also significantly (p<0.05) reduced to 17.20 writhes by BA (40mg/kg) comparable to Indomethacin (16.3writhes). Fever was inhibited by BA most significantly by 3hours post-injection of zymosan (1.00, 1.45, 0.00°C) and this inhibitory effect was higher than that observed for acetylsalicylic acid (0.30°C).

Conclusion

Betulinic acid derived from Tetracera potatoria exhibited potent anti-inflammatory, analgesic or antipyrexic activity which is comparable to indomethacin or acetylsalicyclic acid.     

Tempol, an antioxidant, restores endothelium-derived hyperpolarizing factor-mediated vasodilation during hypertension

Acetylcholine releases a non-prostanoid endothelium-derived hyperpolarizing factor (EDHF) and nitric oxide from physiological salt solution perfused rat mesenteric arteries. This study reports an impairment in EDHF-mediated vasodilation in deoxycorticosterone acetate (DOCA)-salt hypertensive versus control normotensive rats. Nitric oxide-mediated vasodilation to acetylcholine was not altered in the animals. We hypothesize that free radical species generated as by-products of arachidonic acid metabolism contribute to impaired EDHF-mediated dilation in DOCA-salt hypertension. With or without reduced nicotinamide adenine dinucleotide phosphate (NADPH) as co-factor, arterial microsomes generate free radical species upon incubation with arachidonic acid. The production of free radicals was significantly higher in DOCA-salt versus control rat microsomes, and was totally eliminated by addition of cyclooxygenase-2 inhibitors NS-398 or celecoxib at 30 microM. Treatment of DOCA-salt rats with tempol (an antioxidant; 15 mg/kg, i.p., 21 days) alleviates hypertension; improves acetylcholine-induced EDHF-mediated vasodilation in DOCA-salt rats, and decreases arachidonic acid-driven microsomal free radical production. Serum level of 8-isoprostanes is elevated in DOCA-salt hypertension versus control or sham-salt rats, and the increase was reversed by tempol treatment. These results show that EDHF-mediated dilation of rat mesenteric arteries is impaired in DOCA-salt induced hypertension. Our data also suggest that cyclooxygenase-2 mediates free radical production, and that free radicals modulate the EDHF-mediated vascular response in DOCA-salt induced hypertension.     

Healthcare givers' skill and foreign bodies in the ears of children in the tropics

OBJECTIVE: The aim is to find out the place of clinical skill in the management of foreign bodies in the ear of children by various healthcare givers. METHOD: Case files of children with foreign bodies in the ears seen in the Otorhinolaryngology Department of University College Hospital, Ibadan, Nigeria from 1996 to 2005 were reviewed for all essential clinical data. RESULT: Of 323 patients studied, 171 (53.00%) males and 152 (47.00%) females, 168 (52.01%) had prior removal attempts done by anxious caregivers or general practitioners before referral; 154 (91.67%) of these had complications. Only 10 (6.45%) of the 155 (47.99%) with removal by ENT registrars had complications. CONCLUSION: Complications found appear to be related to level of clinical skill of individual health caregiver. Wherever possible, first attempt at removing aural foreign bodies should be done by an otorhinolaryngologist. Anxious parents must be discouraged from attempts but if they must attempt to remove ear foreign body, it must be by a safe ear syringing. General practitioners must be aware of their limitations and ENT registrars must be supervised by senior registrars with help of operating microscope to remove foreign bodies from the ears.     

Randomized trial of effect of transdermal continuous combined hormone replacement therapy on cardiovascular risk markers

Whether hormone replacement therapy (HRT) is beneficial for coronary heart disease (CHD) is controversial. We hypothesized that continuous combined transdermal HRT may have benefits on CHD risk markers without the potential adverse effects seen with certain other HRT regimens. Sixty apparently healthy postmenopausal women, aged 40-65 years, entered a prospective, double-blind, randomized, placebo-controlled clinical trial; 55 women completed the 6-month study. Women received either transdermal oestradiol 17beta 0.05 mg and norethisterone acetate 0.125 mg daily, or identical placebo. Circulating markers of vascular function and remodelling, forearm blood flow, lipids and lipoproteins, glucose and insulin, and haemostatic safety parameters were measured at baseline and after treatment. Compared with placebo after 6 months, HRT administration resulted in decreased E-selectin (P < 0.01), and angiotensin-converting-enzyme (ACE; P = 0.05). Cholesterol (P < 0.05), low-density lipoproteins (LDL; P < 0.05), high-density lipoprotein3 (HDL3; P < 0.05) and apolipoproteins AII (P < 0.05) and B (P < 0.05), and fasting insulin (P < 0.05) also decreased in the HRT group. Factor VII coagulation activity decreased (P < 0.01) and plasminogen activator inhibitor-1 and fibrin D-dimer increased (P < 0.05) in the HRT group, whilst prothrombin fragment 1 + 2 (P < 0.05) decreased, more so in the placebo group. There were no changes in matrix metalloproteinase (MMP)-2, or in LDL particle size. This transdermal HRT had beneficial effects on vascular function and CHD risk markers.     

Alteration in angiogenic and anti-angiogenic forms of vascular endothelial growth factor-A in skeletal muscle of patients with intermittent claudication following exercise training

The aims of this study were twofold: (1) to identify whether peripheral artery disease (PAD) patients had increased muscle concentration of angiogenic VEGF-A, anti-angiogenic VEGF???b or VEGF receptor 1 (VEGF-R1) when compared with control subjects, and (2) to evaluate whether exercise training in PAD patients was associated with changes in muscle concentration of VEGF-A, VEGF???b or VEGF-R1. At baseline, 22 PAD and 30 control subjects underwent gastrocnemius muscle biopsy. Twelve PAD patients were treated with supervised exercise training (SET) and underwent muscle biopsy after 3 weeks and 12 weeks of training and had sufficient tissue to measure VEGF-A, VEGF???b and VEGF-R1 concentrations in skeletal muscle lysates by ELISA. Muscle concentrations of VEGF-A and VEGF???b were similar in PAD patients versus controls at baseline. At both time points after the start of SET, VEGF-A levels decreased and there was a trend towards increased VEGF???b concentrations. At baseline, VEGF-R1 concentrations were lower in PAD patients when compared with controls but did not change after SET. Skeletal muscle concentrations of VEGF-A are not different in PAD patients when compared with controls at baseline. SET is associated with a significant reduction in VEGF-A levels and a trend towards increased VEGF???b levels. These somewhat unexpected findings suggest that further investigation into the mechanism of vascular responses to exercise training in PAD patients is warranted.     

Correlation of perinatal outcomes with amniotic fluid assessment techniques in high-risk pregnancies in a Tertiary Hospital in Southern Nigeria

BackgroundOligohydramnios is a predictor of fetal compromise and a useful tool in pregnancy management. It has been assessed using various techniques, including two-diameter pocket (2-DP) and amniotic fluid index (AFI).ObjectivesTo determine which of these two techniques best diagnose oligohydramnios and predicts adverse perinatal outcomes.MethodsThis was a comparative cross-sectional study conducted at Delta State University Teaching Hospital, Oghara in southern region of Nigeria over eight months period. One hundred high-risk pregnant women were recruited and ultrasound determination of amniotic fluid was performed using AFI and 2-DP. The women were followed up till delivery to determine adverse perinatal outcomes.ResultsThe indices of validity of AFI and the 2-DP were calculated and compared. The 2-DP had a higher sensitivity than AFI for adverse outcomes in high-risk pregnancies complicated by oligohydramnios.ConclusionThe 2-DP technique should preferably be used for the assessment of oligohydramnios in high-risk pregnancies.     

In vivo developmental stages in murine natural killer cell maturation

Natural killer (NK) cells develop in the bone marrow, but their in vivo stages of maturation, expansion and acquisition of receptors that guide target cell specificity are not well defined. We describe here such stages of development. We also show that developing NK cells actively proliferate at a phenotypically distinguishable immature stage after they have acquired expression of Ly49 and CD94-NKG2 receptors. These studies provide a developmental framework for NK cell maturation in vivo and suggest the possible involvement of the Ly49 and CD94-NKG2 receptors themselves in modulating expansion of NK cell populations with a given NK cell receptor repertoire.     

Abdominal ultrasonography in HIV/AIDS patients in southwestern Nigeria

Background

Though the major target of the HIV-virus is the immune system, the frequency of abdominal disorders in HIV/AIDS patients has been reported to be second only to pulmonary disease. These abdominal manifestations may be on the increase as the use of antiretroviral therapy has increased life expectancy and improved quality of life. Ultrasonography is an easy to perform, non invasive, inexpensive and safe imaging technique that is invaluable in Africa where AIDS is most prevalent and where sophisticated diagnostic tools are not readily available. Purpose: To describe the findings and evaluate the clinical utility of abdominal ultrasonography in HIV/AIDS patients in Ibadan, Nigeria

Methods

A Prospective evaluation of the abdominal ultrasonography of 391 HIV-positive patients as well as 391 age and sex-matched HIV-negative patients were carried out at the University College Hospital, Ibadan.

Results

Of the 391 cases studied, 260 (66.5%) were females; the mean age was 38.02 years, (range 15–66 years). The disease was most prevalent in the 4th decade with an incidence of 40.4%. Compared with the HIV-negative individuals, the HIV+ group of patients had a significantly higher proportion of splenomegaly (13.5% vs. 7.7%; p < 0.01), lymphadenopathy (2.0% vs. 1.3%; p < 0.70), and renal abnormalities (8.4% vs. 3.8%; p < 0.02). There were no differences in hepatic and pancreatic abnormalities between the HIV+ and HIV- groups. There were significantly fewer gallstones in the HIV+ group (1.4% vs. 5.1%; p < 0.01).

Conclusion

AIDS is a multi-systemic disease and its demographic and clinical pattern remains the same globally. Ultrasonography is optimally suited for its clinical management especially in Africa. Its accuracy and sensitivity may be much improved with clinico-pathologic correlation which may not be readily available in developing countries; further studies may provide this much needed diagnostic algorithms.