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.     

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.     

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.     

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.     

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.     

Nitrite and thiocyanate in the fasting and secreting stomach and in saliva.

The concentrations of nitrite and thiocyanate in fasting and pentagastrin stimulated gastric juice and in saliva have been examined. Nitrite was found in all of 17 samples of fasting gastric juice, mean 4-9 +/- 1-1 muM. Stimulation of gastric secretion with pentagastrin caused no significant change in nitrite concentration. Thiocyanate was detected in all of 21 samples of fasting gastric juice and the difference in concentration between smokers and non-smokers probably reflects similar differences in saliva. In contrast to the nitrite data there was a significant drop in thiocyanate concentration of gastric juice after pentagastrin from 0-9 +/- 0-1 mM to 0-3 +/- 0-04 mM, suggesting a salivary origin for the thiocyanate in gastric juice. Thiocyanate is a powerful catalyst of nitrosation, which, together with small amounts of nitrite and naturally occurring amines could lead to the intragastric formation of carcinogenic nitrosamines and in certain circumstances be a factor in the aetiology of gastric cancer.     

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.     

Salmonellosis in children in developing and developed countries and populations

PURPOSE OF REVIEW: The present review addresses recent developments that relate to the clinical management and prevention of childhood salmonellosis in developed and developing countries. RECENT FINDINGS: Invasive disease due to serovar Typhi as well as nontyphoidal salmonellae (NTS) is common in children younger than 5 years old in developing countries, and multidrug resistance is an increasingly difficult problem to manage. A new conjugate vaccine was found to be very effective in preventing typhoid fever in young Vietnamese children and was well tolerated, showing great promise for the future. Antibiotic use in the food animal industry is an important source of disease with multidrug resistant NTS strains in the developed world. Efforts for prevention are aimed at immunization of animals, control of antibiotic use in the food animal industry and careful monitoring of food-borne outbreaks. On the other hand, although the burden of NTS disease in children is far greater in developing countries, especially in tropical Africa, knowledge of even basic epidemiology is lacking. Importantly, it may be that, as spp. acquire increasing resistance, they also acquire increasing virulence that will lead to even greater morbidity and mortality. SUMMARY: Recent developments include a better knowledge of clinical aspects of invasive salmonellosis, an increasing response to the problem of multiple antibiotic resistance (including quinolones), and excellent results from the use of a recently developed conjugate vaccine for typhoid fever in children as young as 2 years old.     

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.