Immunohistochemical study of copper-zinc and manganese superoxide dismutases in the lungs of human fetuses and newborn infants: Developmental profile and alterations in hyaline membrane disease and bronchopulmonary dysplasia

To determine the late gestational development of copper-zinc (CnZn) and manganese (Mn) superoxide dismutases (SOD) in human lung, immunohistochemical localization was performed for each SOD. The lung samples were taken from five aborted fetuses, four fetuses in which intrauterine death occurred, one full-term neonate, two premature infants with hyaline membrane disease and one premature infant with bronchopulmonary dysplasia (BPD). Morphometry was performed, and the percent area of positive staining was computed. The bronchial epithelium was intensely stained from the early stages of gestation (i.e. 17 weeks), while the staining intensity for both CuZnSOD and MnSOD in the peripheral airways increased gradually during lung development. The mean percent area of the staining for CuZnSOD and MnSOD from 16 to 38 weeks was increased 30-fold and 8-fold, respectively, and further increases were observed postnatally. CuZnSOD staining was markedly decreased in lungs with respiratory disorders. However, proliferating type II pneumocytes were intensely stained for MnSOD in the BPD lungs, making the staining area 3-fold larger than that in the control lungs. These results clearly depict age-related increases in staining for both CuZnSOD and MnSOD and an alteration in SOD distribution associated with neonatal respiratory disorders.     

Discovery of 4-(2-(dimethylamino)ethoxy)benzohydrazide derivatives as prospective microtubule affinity regulating kinase 4 inhibitors

Microtubule affinity regulating kinase 4 (MARK4) is a Ser/Thr kinase, considered as a potential drug target for cancer, diabetes and neurodegenerative diseases. Due to its significant role in the development and progression of cancer, different in-house libraries of synthesized small molecules were screened to identify potential MARK4 inhibitors. A small library of hydrazone compounds showed a considerable binding affinity to MARK4. The selected compounds were further scrutinized using an enzyme inhibition assay and finally two hydrazone derivatives (H4 and H19) were selected that show excellent inhibition (nM range). These compounds have a strong binding affinity for MARK4 and moderate binding with human serum albumin. Anticancer studies were performed on MCF-7 and A549 cells, suggesting H4 and H19 selectively inhibit the growth of cancer cells. The IC₅₀ value of compound H4 and H19 was found to be 27.39 μM and 34.37 μM for MCF-7 cells, while for A549 cells it was 45.24 μM and 61.50 μM, respectively. These compounds inhibited the colonogenic potential of cancer cells and induced apoptosis. Overall findings reflect that hydrazones/hydrazone derivatives could be exploited as potential lead molecules for developing effective anticancer therapies via targeting MARK4.

Inhibition studies of MARK4 with selected hydrazone derivatives.     

Effect of birth weight on adulthood renal function: A bias‐adjusted meta‐analytic approach

While the association between low birth weight (LBW; <2500 g) and development of adult chronic renal disease (CKD) is inconsistently reported, less information is available regarding association of high birth weight (HBW; ≥4000 g) with CKD. We undertook a systematic review and meta‐analysis on studies published before 30 September 2015 and report associations between birth weight and renal function. Blood (glomerular filtration rate (GFR)) and urine (microalbuminuria/albumin excreation rate (AER)/urinary albumin creatinine ratio (ACR)) parameters were used to define CKD. Three different effect size estimates were used (odds ratio, regression coefficient and mean difference). The odds of developing CKD in the life course among those born LBW was 1.77 (95% CI: 1.42, 2.20) times and 1.68 (1.27, 2.33) times, assessed by blood and urine parameters respectively. Higher risk was also observed among Asian and Australian populations (blood: OR 2.68; urine: OR 2.28), individuals aged ≤30 years (blood: OR 2.30; urine: OR 1.26), and ≥50 years (blood: OR 3.66; urine: OR 3.10), people with diabetes (blood: OR 2.51), and aborigines (urine: OR 2.32). There was no significant association between HBW and CKD. For every 1 kg increase in BW, the estimated GFR increased by 2.09 mL/min per 1.73 m² (1.33–2.85), and it was negatively associated with LogACR (ß ?0.07, 95% CI: ?0.14, 0.00). LBW inborn had lower mean GFR ?4.62 (?7.10, ?2.14) compared with normal BW. Findings of this study suggest that LBW increased the risk of developing CKD, and HBW did not show any significant impact.     

First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications

Objective To examine the value of first trimester maternal serum free β human chorionic gonadotrophin (β hCG) and pregnancy associated plasma protein A (PAPP-A) as predictors of pregnancy complications.
Design Screening study.
Setting Antenatal clinics.
Population Singleton pregnancies at 10–14 weeks of gestation.
Methods Maternal serum free β hCG and PAPP-A were measured at 10–14 weeks of gestation in 5584 singleton pregnancies. In the 5297 (94.9%) pregnancies with complete follow up free β hCG and PAPP-A were compared between those with normal outcome and those resulting in miscarriage, spontaneous preterm delivery, pregnancy induced hypertension or fetal growth restriction and in those with pre-existing or gestational diabetes.
Results Maternal serum PAPP-A increased and β hCG decreased with gestation. The multiple of median maternal serum PAPP-A was significantly lower in those pregnancies resulting in miscarriage, pregnancy induced hypertension, growth restriction and in those with pre-existing or gestational diabetes mellitus, but not in those complicated by spontaneous preterm delivery. The level was < 10th centile of the reference range in about 20% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 27% of those that developed gestational diabetes. Maternal serum free β hCG was < 10th centile of the reference range in about 15% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 20% of those that developed gestational diabetes.
Conclusion Low maternal serum PAPP-A or β hCG at 10–14 weeks of gestation are associated with subsequent development of pregnancy complications.     

Simultaneous bilateral percutaneous nephrolithotomy in children

In the paediatric section, two papers relating to the upper urinary tract are presented. The first, from Hungary, describes simultaneous bilateral percutaneous nephrolithotomy in 13 patients, where it was deemed feasible; this is the first such report. Authors from London report on unilateral nephrectomy in patients with nephrogenic hypertension, and found that it was successful in normalising blood pressure in patients with renal hypertension with a normal contralateral kidney. OBJECTIVE: To evaluate the efficacy of removing bilateral kidney stones simultaneously from children, in one session. PATIENTS AND METHODS: Thirteen patients (three girls and 10 boys, 26 kidneys; mean age 8 years, range 3-14) underwent simultaneous bilateral percutaneous nephrolithotomy (PCNL) in the same session, under general anaesthesia, starting with ureteric catheter insertion into both kidneys and using a 26 F adult nephroscope. The mean (range) stone diameter was 2 (1-3.5) cm. Three patients had staghorn stones in one of their kidneys. Ultrasonic disintegration was used; two patients had bilateral and two others unilateral endopylotomy, and one patient had percutaneous suprapubic cystolithotomy in the same session. The mean (range) operative duration was 65 (55-90) min. RESULTS: All patients were rendered stone-free; there was no severe bleeding or any other complication. On one side in one of the patients, a second session was needed because of residual stone. The nephrostomy tubes were removed 3 and 4 days after PCNL and the hospital stay was 6 (1-11) days. CONCLUSION: The advantages of simultaneous bilateral PCNL are reduced psychological stress, one cystoscopy and anaesthesia, less medication and a shorter hospital stay and convalescence, with considerable savings in cost. In experienced hands this method can be used not only in adults but also in children. To our knowledge this is the only report of this technique in children.     

Synthesis of some novel substituted phenylisoxazol phenoxy 2-methylpropanoic acids and there in vivo hypolipidemic activity

The novel series of phenylisoxazol phenoxy 2-methylpropanoic acid derivatives were synthesized and evaluated for their in vivo hypolipidemic activity by triton WR-1339-induced hyperlipidemia in rats. The newly synthesized compounds 5a and 5i showed significant decrease in the serum TCH, TG, LDL and VLDL along with an increase in serum HDL levels as compared to standard drug Fenofibrate. The treated groups also showed significant decrease in the atherogenic index, TC:HDL risk ratios compared to cholesterol-induced hyperlipidemic control group. These molecules indeed have the potential to be developed as antihypolipidemic molecules.     

Simultaneous bilateral compared with unilateral percutaneous nephrolithotomy

OBJECTIVE: To compare simultaneous bilateral percutaneous nephrolithotomy (SBPCNL) and unilateral PCNL in separate sessions in patients with bilateral renal stones for several variables before and after surgery. PATIENTS AND METHODS: The results from SBPCNL carried out at two centres in different countries on 198 patients (aged 1.25-70 years) were compared with those from 300 patients undergoing unilateral PCNL in separate sessions. At one centre where extracorporeal shockwave lithotripsy (ESWL) was available SBPCNL was used for stones where at least two sessions of ESWL would have been required on each side. Other associated procedures were also used wherever required. RESULTS: The stones were cleared bilaterally in one session of SBPCNL in 190 patients; in eight, fragments of < 3 mm remained but were not clinically significant. A second session was required in six patients on one side only. Variables assessed before and after treatment (e.g. hospital stay, analgesia requirements and complications) were not significantly different between SBPCNL and PCNL. The mean (range) total operative duration for SBPCNL was 46 (20-100) min and the hospital stay 4.3 (3-8) days. CONCLUSION: From this experience, SBPCNL is a cost-effective and beneficial solution for selected patients, with clear advantages over separate unilateral PCNL in patients with bilateral stones.