Activation of the inflammatory reaction within minutes after birth in ventilated preterm lambs with neonatal respiratory distress syndrome

To study the activation of the inflammatory reaction within minutes after birth, we measured parameters of inflammation before and immediately after birth. To assess whether respiratory distress syndrome (RDS) or birth itself initiates activation, we compared preterm ventilated lambs with term nonventilated lambs. Preterm lambs were delivered by cesarean section at 132 days gestational age (term 145 days) and were ventilated by conventional ventilation (n = 9). Before clamping the cord, 5, 10 and 15 min after birth, blood was sampled from umbilical catheters. Term lambs (n = 9) were born spontaneously after 140-145 days gestational age. Immediately after birth, a venous umbilical catheter was inserted. Blood was sampled before the first breath and 5, 10, 15 and 20 min after birth while the lamb was breathing spontaneously. Blood was analyzed for AP50 (complement activation), number of polymorphonuclear leukocytes (PMNs) and beta-glucuronidase (released from activated PMNs). In preterm lambs, we found a decreased number of PMNs and increased levels of beta-glucuronidase already at 5 min after birth. In the term lambs, we found only a short-term mild decrease in PMNs and short-term increase in beta-glucuronidase. We conclude that systemic activation of the inflammatory reaction can be found in ventilated preterm lambs with RDS within 5 min after birth. This very early activation is mild, transient and less pronounced in term-born spontaneously breathing lambs compared with preterm, ventilated lambs with RDS.     

Cyclorocaglamide,the first bridged cyclopentatetrahydrobenzofuran,and a related "open chain" rocaglamide derivative from Aglaia oligophylla

Two rocaglamide-related natural products, the previously known compound 6-demethoxy-10-hydroxy-11-methoxy-6,7-methylendioxyrocaglamide (3), and cyclorocaglamide (4), its 8b,10-anhydro analogue, have been isolated from the tropical plant Aglaia oligophylla. Compound 4 is the first bridged cyclopentatetrahydrobenzofuran natural product, and it exhibited a CD spectrum virtually opposite that of all the other rocaglamide natural products known so far, but it still has the same absolute configuration at all stereogenic centers of the basic molecular framework. This was shown unequivocally by quantum chemical CD calculations (here based on molecular dynamics-weighted force field structures) and was finally confirmed experimentally, by a "biomimetic-type" cyclization of 3 to give 4, with the expected "inversion" of the CD spectrum. The opposite chiroptical properties of 3 and 4, despite their homochiral character, underline the necessity of handling chiroptical data with the greatest care, e.g., by simulating them by quantum chemical CD calculations. Compound 3 exhibited an LC(50) of 2.5 ppm when evaluated against neonate larvae of Spodoptera littoralis, while 4 was inactive in this assay up to 100 ppm.     

Cause-specific perinatal death rates, birth weight and deprivation in the West Midlands, 1991-93

OBJECTIVES: To study the relationship between cause-specific perinatal death rates, material deprivation and birthweight among births in 3 consecutive years in the West Midlands Health Region. STUDY DESIGN: Retrospective cohort study. SETTING: West Midlands Health Region (WMHR). STUDY POPULATION: All births (live and stillbirths) to mothers with addresses in the WMHR in 1991, 1992 and 1993. MAIN OUTCOME MEASURES: Cause-specific perinatal death rates--crude and stratified by birthweight. METHODS: Perinatal deaths in the WMHR in 1991-93, collected as part of the national Confidential Enquiry into Stillbirths and Deaths in Infancy, were classified into causes of death by the extended Wigglesworth classification. Crude rates for cause-specific perinatal deaths and rates stratified by birthweight < 2500 g and > or = 2500 g were calculated for each enumeration district (ED) quintile derived by ranking enumeration districts for the whole of the region by Townsend Deprivation Index. Cause-specific rates of death were investigated for a linear trend across ED quintiles. The relative risk of death (most vs least deprived) from specific causes was calculated. Using rates for the least deprived quintile as the reference, deaths from each cause 'attributable' to social inequality were calculated. RESULTS: Positive linear trends in perinatal deaths were noted with increasing deprivation for each specific cause of death except those classified as 'other causes' (Wigglesworth Class E). Relative risk (most vs least deprived) of perinatal death with a congenital anomaly was 1.98 (confidence interval, CI: 1.36,2.89). For deaths related to antepartum events, intrapartum events and immaturity the risks were 1.81 (CI: 1.39,2.38), 1.48 (CI: 1.10,1.98) and 1.92 (CI 1.45,2.56), respectively. Forty-three (35.7%) perinatal deaths per year were due to congenital anomalies, 63 (29.7%) antepartum events, 36 (21.9%) intrapartum events and 61 (32.7%) immaturity and these were statistically 'attributable' to social inequality. Cause-specific perinatal death rates for babies < 2500 g showed no correlation with deprivation; however, for babies > or = 2500 g the association with deprivation persisted. CONCLUSIONS: All cause-specific rates except those due to 'other causes' showed a positive linear trend with increasing deprivation. These trends were found for infants born > or = 2500 g but were not seen for low birthweight infants (< 2500 g). Almost 30% of deaths were statistically 'attributable' to social inequality. The results of this study suggest that material deprivation plays an important role in the causal pathway leading to perinatal death and needs to be addressed in preventive programmes aimed at the reduction of perinatal deaths.     

Acrylamide does not cause apparent changes in genetic expression of creatine kinase in rat cerebellum

Acrylamide inhibits creatine kinase (CK) activities in the brain of rats or mice. However, its effects on genetic expression of CK have not yet been studied. CK mRNA and protein level were examined by RT-PCR and Western blotting, respectively. Neither cytosolic CK (B subunit) and mitochondrial CK (ubiquitous form) mRNA nor B subunit protein was clearly changed in the cerebellum from rats intoxicated with acrylamide (50 mg/kg/day i.p. for 8 days) and showing clinical neurotoxic signs.     

Lidocaine suppressed hyperinflammation in BALB/c mice model sterile injury via downregulation of toll-like receptor 4

Background

To study the efficacy of systemic lidocaine in suppressing toll-like receptor 4 (TLR4) protein level in BALB/c mouse with sterile injury.

DR negativity is a distinctive feature of M1/M2 AML cases with NPM1 mutation

Our previous observation of a higher incidence of FLT3-ITD in DR(-) M1/M2 AML than in DR(+) M1/M2 led to an investigation of NPM1 mutation in the same samples, since DR(-) AML and AML with NPM1 mutation share such characteristics as normal karyotype, the absence of CD34, and FLT3-ITD. NPM1 mutation was found in 18 of 26 (69.2%) of DR(-) cases, but not in any of 28 DR(+) cases. FLT3-ITD was noted in 66.7% of the cases with NPM1 mutation. These findings point to DR negativity as another phenotypic feature of AML with NPM1 mutation.     

The HPB-AML-I cell line possesses the properties of mesenchymal stem cells

Background

In spite of its establishment from the peripheral blood of a case with acute myeloid leukemia (AML)-M1, HPB-AML-I shows plastic adherence with spindle-like morphology. In addition, lipid droplets can be induced in HPB-AML-I cells by methylisobutylxanthine, hydrocortisone, and indomethacin. These findings suggest that HPB-AML-I is similar to mesenchymal stem cells (MSCs) or mesenchymal stromal cells rather than to hematopoietic cells.

Methods

To examine this possibility, we characterized HPB-AML-I by performing cytochemical, cytogenetic, and phenotypic analyses, induction of differentiation toward mesenchymal lineage cells, and mixed lymphocyte culture analysis.

Results

HPB-AML-I proved to be negative for myeloperoxidase, while surface antigen analysis disclosed that it was positive for MSC-related antigens, such as CD29, CD44, CD55, CD59, and CD73, but not for CD14, CD19, CD34, CD45, CD90, CD105, CD117, and HLA-DR. Karyotypic analysis showed the presence of complicated abnormalities, but no reciprocal translocations typically detected in AML cases. Following the induction of differentiation toward adipocytes, chondrocytes, and osteocytes, HPB-AML-I cells showed, in conjunction with extracellular matrix formation, lipid accumulation, proteoglycan synthesis, and alkaline phosphatase expression. Mixed lymphocyte culture demonstrated that CD3⁺ T-cell proliferation was suppressed in the presence of HPB-AML-I cells.

Conclusions

We conclude that HPB-AML-I cells appear to be unique neoplastic cells, which may be derived from MSCs, but are not hematopoietic progenitor cells.     

Lag time, high-risk histopathological features, metastasis, and survival interrelation in retinoblastoma: a perspective from lower-middle income country

AIM: To investigate the impact of lag time to metastasis and survival rates among patients with retinoblastoma.METHODS: This retrospective study was conducted with 52 patients from the Department of Ophthalmology and the Department of Pediatrics of Dr. Sardjito General Hospital, between 1st January 2014 and 31st December 2020. Lag time was defined as the time delay between the first sign of retinoblastoma to the diagnosis of retinoblastoma. The subjects with lag time > one year were included in the case group, while the subjects with lag time < one year were included in the control group.RESULTS: The lag time was significantly correlated with American Joint Committee on Cancer and Intraocular Classification of Retinoblastoma staging of retinoblastoma (P=0.005 and P=0.006, respectively). The lag time was also significantly correlated with both metastasis event [odds ratio (OR): 5.06, 95%Cl: 1.56-16.44, P=0.006] and mortality (OR: 4.54, 95%Cl: 1.37-15.07, P=0.011). The follow-up was continued for 32 subjects for 3y after initial diagnoses. Survival analysis revealed a significant difference among these two groups (P=0.021). Furthermore, lag time was significantly correlated with survival of retinoblastoma (r=-0.53, P=0.046).CONCLUSION: The study highlights the importance of lag time between the onset of first symptoms and the time of retinoblastoma diagnosis which significantly contribute to metastasis and mortality of patients with retinoblastoma. Examinations for the early detection of retinoblastoma should be performed for individuals at-risk to minimize lag time and improve the outcomes.     

Metabolite Profiling of Justicia gendarussa Burm. f. Leaves Using UPLC-UHR-QTOF-MS

An ultra-performance liquid chromatography ultra-high-resolution quadrupole-time-of-flight-mass spectrometry (UPLC-UHR-QTOF-MS) metabolite profiling ofxs Justicia gendarussa Burm. f. leaves was performed. PCA and HCA analyses were applied to observe the clustering patterns and inter-sample relationships. It seemed that the concentrations of Ca, P, and Cu in the soil could affect the metabolite profiles of Justicia gendarussa. Six significant metabolites were proposed.