Heparin octasaccharides inhibit angiogenesis in vivo.

BACKGROUND: In previous experiments, we showed that heparin oligosaccharides inhibit the angiogenic cytokine fibroblast growth factor-2. Here, we present the first in vivo study of size-fractionated heparin oligosaccharides in four models of angiogenesis that are progressively less dependent on fibroblast growth factor-2. EXPERIMENTAL DESIGN: Heparin oligosaccharides were prepared using size-exclusion gel filtration chromatography and characterized through depolymerization and strong anion exchange high-performance liquid chromatography. Size-defined oligosaccharides (20 mg/kg/d) were given to mice bearing s.c. sponges that were injected with fibroblast growth factor-2 (100 ng/d). After 14 days, octasaccharides and decasaccharides reduced the microvessel density to levels below control. In a second experiment, HEC-FGF2 human endometrial cancer cells that overexpress fibroblast growth factor-2 were implanted in a hollow fiber placed s.c. in vivo. Oligosaccharides were given at 20 mg/kg/d for 2 weeks and the data again showed that octasaccharides significantly reduced microvessel density around the fiber (P = 0.03). In a more complex model, where angiogenesis was induced by a broad spectrum of growth factors, including vascular endothelial growth factor, we implanted H460 lung carcinoma cells in hollow fibers and treated the animals with oligosaccharides at 20 mg/kg/d over 3 weeks. Octasaccharides reduced the microvessel density to that of control. Preliminary investigation of 6-O-desulfated heparins showed that these also had antiangiogenic activity. RESULTS: Finally, we examined the inhibitory potential of hexasaccharides and octasaccharides given at 20 mg/kg/d and these inhibited the growth of H460 lung carcinoma in vivo. At clinically attainable concentrations, significant anticoagulation (activated partial thromboplastin time, anti-factor Xa, and anti-factor IIa) was not observed in vitro unless species containing > or =16 saccharide residues were investigated. CONCLUSIONS: Thus, our preclinical data show that heparin octasaccharides represent novel antiangiogenic compounds that can be given without the anticoagulant effects of low molecular weight heparin.     

Determination of the pericardial to serum myoglobin ratio for the early diagnosis of perioperative myocardial infarction after coronary artery bypass grafting.

Pericardial fluid reflect the composition of cardiac interstitium in myocardial ischemia. This study investigated the value of the pericardial and serum myoglobin (MG) measurements for the diagnosis of perioperative myocardial infarction (MI) after coronary artery bypass grafting (CABG). Postoperative arterial and pericardial blood samples were taken in 64 subjects undergoing elective CABG allocated to two groups according to the 12-lead electrocardiogram (ECG) abnormalities observed during the first postoperative 24h. Group 1=normal and nonspecific ECG abnormalities, and Group 2=perioperative Q-wave MI. The occurrence of perioperative MI was associated with a dramatic increase in both serum and pericardial cardiac troponin I (CTnI) and MG concentrations. Pericardial concentrations were higher than serum concentrations during the first postoperative 24h in all subject. However, pericardial/serum CTnI ratio in subjects in Group 2 was not statistically different from Group 1 at the time of admission to the intensive care unit (ICU) and did not significantly change at time intervals. On the other hand, more than two-fold increase in the pericardial/serum MG ratio was determined for all patients who experienced perioperative Q-wave MI with the lowest value as 2.75, whereas only 1 of 59 patients in group 1 had the ratio higher than 2 with the highest value as 2.15 at the time of admission to the ICU. In conclusion, determination of pericardial/serum MG ratio may be a useful tool for the early diagnosis of the perioperative MI after CABG.     

Mother's dietary diversity and association with stunting among children <2 years old in a low socio‐economic environment: A case–control study in an urban care setting in Dhaka,Bangladesh

Mothers are often responsible for preparing nutritious foods in their households. However, the quality of mother's diets is often neglected, which may affect both mother's and child's nutrition. Because no single food contains all necessary nutrients, diversity in dietary sources is needed to ensure a quality diet. We aimed to study the association between mother's dietary diversity and stunting in children <2 years attending Dhaka Hospital of icddr,b, a diarrhoeal disease hospital in Dhaka, Bangladesh. A case–control study (n = 296) was conducted from November 2016 to February 2017. Data were collected from mothers of stunted children <2 years (length‐for‐age z score [LAZ] < ?2) as “cases” and nonstunted (LAZ ≥ ?1) children <2 years as “controls.” Mothers were asked to recall consumption of 10 defined food groups 24 hr prior to the interview as per Guidelines for Minimum Dietary Diversity for Women. Among the mothers of cases, 58% consumed <5 food groups during the last 24 hr, compared with 45% in control mothers (P = 0.03). Children whose mothers consumed <5 food groups were 1.7 times more likely to be stunted than children whose mothers consumed ≥5 food groups (P = 0.04). Intake of food groups such as pulses, dairy, eggs, and vitamin A rich fruit was higher in control mothers. Proportion of mother's illiteracy, short stature, monthly family income <BDT 11,480, absence of bank account, and poor sanitation was also found to be higher in stunted group. Further study particularly intervention or longitudinal study to see the causality of mother's dietary diversity with child stunting is recommended.     

Real-world effectiveness of BNT162b2 mRNA vaccine: a meta-analysis of large observational studies

Inflammopharmacology - This paper aims to summarize through meta-analyses the overall vaccine effectiveness of the BNT162b2 mRNA vaccine from observational studies. A systematic literature search...     

The risk of mortality in patients with COVID-19 with pre-diagnosis use of NSAIDs: a meta-analysis

Inflammopharmacology - The notion that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may lead to adverse outcomes upon acquisition of coronavirus disease 2019 (COVID-19) should be...     

Fibrodysplasia ossificans progressiva without characteristic skeletal anomalies

Fibrodysplasia ossificans progressiva (FOP) is a rare but extremely disabling genetic disease of the skeletal system. This disease is characterized by progression of heterotopic ossification within skeletal muscles, ligaments and tendons. Most patients with FOP are misdiagnosed early in life before the appearance of heterotopic ossification and undergo diagnostic procedures such as biopsy that can cause lifelong disability. Almost all of the patients have some peculiar congenital anomalies, including short great toes, hallux valgus, short thumbs and hypoplasia of digital phalanges. These congenital defects support the diagnosis of FOP, but are not constantly observed in the totality of patients. If necessary, genetic studies can be performed to confirm the diagnosis. Once diagnosed, patients should be advised in order to avoid unnecessary traumas, surgical procedures, biopsies, intramuscular injections and vaccinations. Here, we describe a patient with FOP without characteristic congenital skeletal anomalies.