Glucose and insulin concentration in amniotic fluid and in maternal blood in early and in late pregnancy

Glucose concentration in the amniotic fluid decreases towards the end of gestation, whereas the insulin concentration increases. The ratio between fetal (amniotic fluid) glucose to maternal glucose is reduced by about 50% at the end of pregnancy, whereas the ratio of C peptide is increased four times. The higher glucose concentration in amniotic fluid in early pregnancy could be explained by a lower fetal metabolic rate in the early stage of development and a low insulin activity of the fetus.     

Anti-malarial efficacy of pyronaridine and artesunate in combination in vitro and in vivo

Pyronaridine is a Mannich base anti-malarial with demonstrated efficacy against drug resistant Plasmodium falciparum, P. vivax, P. ovale and P. malariae. However, resistance to pyronaridine can develop quickly when it is used alone but can be considerably delayed when it is administered with artesunate in rodent malaria models. The aim of this study was to evaluate the efficacy of pyronaridine in combination with artesunate against P. falciparum in vitro and in rodent malaria models in vivo to support its clinical application. Pyronaridine showed consistently high levels of in vitro activity against a panel of six P. falciparum drug-sensitive and resistant strains (Geometric Mean IC50=2.24 nM, 95% CI=1.20-3.27). In vitro interactions between pyronaridine and artesunate showed a slight antagonistic trend, but in vivo compared to pyronaridine and artesunate administered alone, the 3:1 ratio of the combination, reduced the ED90 of artesunate by approximately 15.6-fold in a pyronaridine-resistant P. berghei line and by approximately 200-fold in an artesunate-resistant line of P. berghei. Complete cure rates were achieved with doses of the combination above or equal to 8 mg/kg per day against P. chabaudi AS. These results indicate that the combination had an enhanced effect over monotherapy and lower daily doses of artesunate could be used to obtain a curative effect. The data suggest that the combination of pyronaridine and artesunate should have potential in areas of multi-drug resistant malaria.     

Osteoporosis in celiac disease and in endocrine and reproductive disorders

As the increase in lifespan brings to light diseases that were previously not clinically detectable, osteoporosis has become an issue of worldwide significance. The disease is marked by a loss of bone mass; the bones become less dense, fragile and more prone to fracturing. Because it is regulated by endocrine and environmental factors, osteoporosis presents a multifactorial etiopathogenesis, with the genetic component accounting for 70% of an individual variation in bone mass density （BMD）, the principal determinant, with age, of fracture risk. Pathological conditions such as celiac disease （CD） exacerbate the process of bone loss, so that the occurrence of osteoporosis in celiac subjects is of particular note： indeed, the screening of osteoporosis patients for this disease is advisable, since it may be the only sign of undiagnosed CD. An increase in interleukin IL-1β, of the IL-1 system, in the relatives of celiac patients confirms the genetic predisposition to osteoporosis and its presence is evidence of an association between the two conditions. The direct effect on the bones of CD is secondary to poor absorption of calcium and vitamin D. In women osteoporosis is indirectly associated with early menopause and amenorrhea, and it may follow prolonged breast-feeding and frequent pregnancies, while in men it is associated with hypogonadism and GH deficit. These endocrine and non-endocrine factors exert their effects on bones by modulating the RANK/RANK-L/OPG system. An appropriate lifestyle from adolescence onwards, together with early diagnosis of and treatment for CD and primaryand secondary endocrine pathologies are important for the prevention of damage to the bones.     

Differentiation pathways in carcinogenesis and in chemo- and radioresistance

Cancer stem cells (CSCs) share many features with embryonic stem cells (ESCs) such as the ability for self-renewal and differentiation. Signaling pathways that are involved in these processes are also involved in chemo- and radioresistance (e.g. Wnt, Notch and Hedgehog pathways). This review is focused on the influence of three important differentiation pathways on carcinogenesis and on chemo- and radioresistance in ESCs and CSCs.     

Trends and Ethnic Differences in COPD Hospitalization and Mortality in Singapore

Study Objective. COPD mortality alone among major causes of diseases continues to rise in most countries worldwide. We examine trends, and gender and ethnic differences in COPD hospitalization and mortality in Singapore from 1991 to 1998, and examine possible explanations. Design. Analysis of population‐based health administrative data. Setting. Multi‐ethnic (Chinese, Malay and Indian) population of Singapore (3 million population). Method. Data on hospitalizations and deaths due to COPD as the underlying cause (ICD codes 491, 492, 496), extracted from national databases, were used to calculate age‐specific and standardized rates for the population aged 55 + years. COPD accounted for 4.6% of total deaths (5.8% in those aged 55 +), and 1.02% of all hospitalizations (3.1% in those aged 55 +). Results. COPD mortality in 1998 decreased steeply by ? 43.7% from 1991 (a decline that continued a steady trend since 1970), while hospitalization showed little significant change (? 3.3%). Men had 4 and 5 times higher mortality and hospitalization, and also showed less favorable trends than women. Malays, especially males, showed the highest level and least favorable decline of mortality. Conclusion. Exceptionally steady declines in COPD mortality rates, and stable rates of hospitalization are observed in Singapore in the 1990s. Differing levels and trends of hospitalization and mortality by gender and ethnicity are related to known demographic variations and trends of smoking prevalence in the country.     

Telemedicine and Advances in Urban and Rural Healthcare Delivery in Africa

Telecardiology holds great promise for Africa, from tele-echocardiography and tele-ECG s, to home monitoring and text messaging for medication adherence monitoring. The burden of disease is great and there is an extreme shortage of health professionals. Telemedicine can provide access to scarce specialist care, improve the quality of care in rural areas and reduce the need for rural patients to travel to seek medical attention. International cross border service can alleviate the shortage of doctors. But telecardiology, and telemedicine uptake in general, has been poor in Africa. Legal and ethical issues around local and cross border telemedicine have not been resolved. The literature was reviewed and obstacles to telemedicine in Africa and current telemedicine activities in Africa, are described. There are few sustained telemedicine services in Africa with the exception of tele-education. There is an expectation that mobile phones will facilitate a range of telemedicine activities in Africa. Africa needs telemedicine.     

Serotonin and Its Role in Colonic Function and in Gastrointestinal Disorders

Serotonin (5-HT) is most commonly thought of as a neurotransmitter in the central nervous system. However, the predominant site of serotonin synthesis, storage, and release is the enterochromaffin cells of the intestinal mucosa. Within the intestinal mucosa, serotonin released from EC cells activates neural reflexes associated with intestinal secretion, motility, and sensation. Two important receptors for serotonin that are located in the neural circuitry of the intestines are the 5-HT₃ and 5-HT₄ receptors; these are the targets of drugs designed to treat gastrointestinal disorders. 5-HT₃ receptor antagonists are used to treat nausea and emesis associated with chemotherapy and for functional disorders associated with diarrhea. 5-HT₄ receptor agonists are used as promotility agents to promote gastric emptying and to alleviate constipation. Because of the importance of serotonin in normal gut function and sensation, a number of studies have investigated potential changes in mucosal serotonin signaling in pathologic conditions. Despite the inconsistencies in the current literature, changes in serotonin signaling have now been demonstrated in inflammatory bowel disease, irritable bowel syndrome, postinfectious irritable bowel syndrome, and idiopathic constipation. Emerging evidence has led to many contradictory theories regarding serotonin signaling and its roles in the pathology of gut disorders. This review summarizes the current medications affecting serotonin signaling and provides an overview of our current knowledge of the changes in serotonin that occur in pathologic conditions. Supported by NIH grant DK62267, Novartis Pharmaceuticals, and NIH P20 COBRE grant RR16435. Reprints are not available.     

Progress and Challenges in Ending HIV and AIDS in Australia

This review considers Australia’s progress towards the elimination of HIV and AIDS, as specified in international targets. In particular, it considers the reaction to recent media reports that Australia has ‘ended AIDS’ and evaluates progress towards reducing HIV transmission. Recent surveillance data and research show significant improvements in HIV testing and treatment, but countervailing trends such as increased condomless sex between gay and other men who have sex with men. Pre-exposure prophylaxis (PrEP) is being implemented at scale in some jurisdictions, with the hope that this will significantly alter the trajectory of Australia’s HIV epidemic, which has been stable for the last five years (at around 1000–1100 infections per year). The ongoing challenge in maintaining investment, while also considering how to respond to the diversification of the local epidemic, means that Australia has entered a critical period in which evidence of PrEP’s impact is eagerly awaited.     

Fibrin Monomer and Platelet Aggregation in Vitro and in Vivo

S ummary . The effect of fibrin monomer or fibrinogen-fibrin monomer complexes (FFMC) on platelet aggregation was studied in vitro and in vivo . FFMC produced by limited action of thrombin in vitro did not cause spontaneous platelet aggregation and neither accelerated nor inhibited platelet aggregation induced by ADP or collagen. If FFMC were converted to gels by treatment with ethanol, platelets aggregated spontaneously. When purified rabbit fibrin monomer was infused into rabbits pretreated with heparin to block the intravascular generation of thrombin, platelet counts did not decrease significantly, indicating the lack of a plateletaggregating effect of FFMC. It is concluded that FFMC, derived from thrombin action on fibrinogen, do not initiate or accelerate platelet aggregation.     

Patterns of compartment involvement in tibiofemoral osteoarthritis in men and women and in whites and African Americans

Objective

We conducted a cross‐sectional study to describe the prevalence of tibiofemoral joint space narrowing (JSN) in medial and lateral compartments and assess whether it differs by sex and ethnic groups, and, if it does, to what extent such a difference is accounted for by knee malalignment.

Methods

The Multicenter Osteoarthritis Study is an observational study of persons ages 50–79 years with either symptomatic knee osteoarthritis or high risk of disease. Knee radiographs were assessed for JSN in each tibiofemoral compartment. Mechanical axis angle was measured using full‐extremity films. We compared the proportion of knees with medial compartment JSN and with lateral JSN between men and women, as well as between whites and African Americans, using a logistic regression model adjusting for covariates (race or sex and body mass index, age, education, and clinic site). We used generalized estimating equations to account for correlation between 2 knees within a person.

Results

Of 5,202 knees (2,652 subjects), 1,532 (29.5%) had medial JSN and 427 (8.2%) had lateral JSN. Lateral JSN was more prevalent in the knees of women than in men (odds ratio [OR] 1.9, 95% confidence interval [95% CI] 1.5–2.4) and was also higher in the knees of African Americans than in whites (OR 2.4, 95% CI 1.7–3.3). Further adjustment for malalignment attenuated the OR for sex but not the OR for race.

Conclusion

Women and African Americans are more likely to have lateral JSN than men and whites, respectively. Valgus malalignment may contribute to the higher prevalence in women.     

Tissue kallikrein and bradykinin B2 receptor in human uterus in luteal phase and in early and late gestation

This study was addressed to evaluate the temporospatial pattern of key components of the kallikreinkinin system in human uterus in luteal phase (n=7), early pregnancy (isolated spontaneous abortions, n = 11; ectopic pregnancies, n=9), idiopathic preterm deliveries (n=5), and term gestations (n=12). Tissue kallikrein mRNA and protein and the type 2 bradykinin receptor (B2R) protein were expressed in luminal and glandular epithelium and in endothelial cells of stromal and myometrial blood vessels, while tissue kallikrein mRNA and B2R, but not tissue kallikrein protein, were observed in decidual cells and in arteriolar and myometrial muscle. A greater signal intensity for tissue kallikrein mRNA and protein and of B2R protein was observed in the early pregnancy samples. The sites and variations of the tissue kallikrein mRNA and protein and of the B2R protein in the human uterus and in fallopian tubes during the luteal phase and in pregnancy coincide with those described for other vasoactive effectors such as nitric oxide, prostacyclins, growth factors, and renin. The uterine localization of the main enzyme and receptor of the tissue kallikrein-kinin system in key sites for embryo attachment, implantation, placentation, maintenance of placental blood flow, and parturition supports the notion that the kallikrein-kinin system participates in these processes, probably through vasodilation, increased vasopermeability, enhanced matrix degradation, stimulation of cell proliferation, and myometrial contractility.     

Pineal and pituitary-adrenocortical function in physiological aging and in senile dementia

The simultaneous evaluation of the circadian rhythm of plasma melatonin and ACTH and of serum cortisol and DHEAS represents a clinically reliable tool to appreciate the neuroendocrine changes occurring in physiological and pathological brain aging.

A selective impairment of the nocturnal melatonin secretion has been observed in elderly subjects, being significantly related either to the age or to the severity of dementia. A significant increase of serum cortisol levels during evening- and night-times was found in elderly subjects, particularly if demented, when compared to young controls. Besides, both the circadian amplitude of cortisol rhythm and the nocturnal cortisol increase were significantly reduced in relation either to age or to cognitive impairment. By comparison to vascular dementia, patients with Alzheimer's disease exhibited the highest cortisol concentrations throughout the 24 h. The sensitivity of the hypothalamic-pituitary-adrenal axis to the steroid feedback was significantly impaired in old subjects and particularly in the demented ones. The serum DHEAS levels were significantly lower in elderly subjects and even more in demented patients than in young controls. Consequently, a significant increase of the cortisol/DHEAS molar ratio was evident when going from young controls to healthy elderly subjects and to demented patients.

In conclusion, the aging process affects many neuroendocrine functions resulting in subtle but clinically relevant consequences; the occurrence of senile dementia seems to play an additive role.     

Subjective and objective learning effects dissociate in space and in time

Perceptual learning not only improves sensitivity, but it also changes our subjective experience. However, the question of how these two learning effects relate is largely unexplored. Here we investigate how subjects learn to see initially indiscriminable metacontrast-masked shapes. We find that sensitivity and subjective awareness increase with training. However, sensitivity and subjective awareness dissociate in space: Learning effects on performance are lost when the task is performed at an untrained location in another quadrant, whereas learning effects on subjective awareness are maintained. This finding indicates that improvements in shape sensitivity involve visual areas up to V4, whereas changes in subjective awareness involve other brain regions. Furthermore, subjective awareness dissociates from sensitivity in time: In an early phase of perceptual learning, subjects perform above chance on trials that they rate as subjectively invisible. Later, this phenomenon disappears. Subjective awareness is thus neither necessary nor sufficient for achieving above-chance objective performance.