Fetal pulse oximetry and neonatal outcome: a study in a developing country.

BACKGROUND: The aim of this cohort, prospective study was to compare the diagnostic value of intrapartum fetal pulse oximetry (FPO) with that of fetal scalp blood gas (FSBG) for an abnormal neonatal outcome in cases with abnormal fetal heart rate (FHR) tracings. METHODS: Fetal oxygen saturation was continuously monitored with Nellcor N-400 FPO during labor. Simultaneous FSBG determinations were obtained. The results were analyzed in relation to umbilical arterial cord blood pH and neonatal outcome. Studied FPO cutoff levels were 30 and 40% hemoglobin saturation and that of FSBG pH was 7.2. RESULTS: During the study, there were 9825 deliveries; 415 had abnormal FHR. Only 150 fulfilled the whole screening panel. When the outcome variable was umbilical arterial pH, the positive predictive values of the three methods (FPO30, FPO40, FSBG) were 57, 61 and 65% and the negative predictive values were 43, 39 and 35% respectively. The sensitivity of FPO30 was highest (75%). Considering abnormal neonatal outcome, again the sensitivity was also highest for FPO30 (89%). The sensitivity of FSBG was 82%. The specificity of the three methods were 53, 49 and 38% respectively. CONCLUSION: The diagnostic value of intrapartum FPO compares favorably with FSBG. FPO seems to be a reliable and less invasive tool and may decrease unnecessary interventions and unnecessary fetal scalp blood sampling in cases of suspected fetal distress. The FPO cutoff of 30% saturation defined by previous studies appears to be appropriate.     

Intestinal parasitic infection: prevalence,knowledge, attitude,and practices among schoolchildren in an urban area of Taiz city,Yemen

BackgroundIntestinal parasitic infections (IPIs) are regarded as one of the main public health problems and socio-economic issues adversely affecting the health of millions of people worldwide. Our study aimed to describe the knowledge, attitude, and practices of local urban schoolchildren in Taiz City towards intestinal parasitic infections.Methods and materialThis is a cross-sectional study conducted in Taiz, Yemen from March to May 2019. A total of 385 schoolchildren were selected using a random sampling technique from 7 primary schools. Wet-mount microscopic examination, formol-ether concentration techniques, and Lugols'' iodine were employed in parasite detection and cyst identification.ResultsOf the 385 schoolchildren examined for IPIs, 107 (27.8%) were positive for the presence of enteric parasites, some having multiple infections. The prevalence was slightly higher in males 46 (28.6%) than in females 61 (27.2%) but have no statistical difference (P = 0.77). Entamoeba histolytica/dispar was the most common infection with 16.4% of cases. A substantial percentage (40.5%) of the respondents displayed poor knowledge. The respondents also revealed inappropriate attitudes and practices that contribute to the prevalence of IPIs in the study.ConclusionsThe study revealed the prevalence of intestinal parasites among the schoolchildren in Taiz, Yemen, suggesting that IPIs remain a major public health problem. Entamoeba histolytica/dispar was the most prevalent intestinal parasites identified among the schoolchildren. Age, poor knowledge of the mode of transmission, prevention, and acquisition of IPIs, and poor habitual hygiene practices increase the risk of acquiring intestinal infections.     

Catechol estrogens induce proliferation and malignant transformation in prostate epithelial cells

In the current study, the non-transformed prostatic epithelial cells (BPH-1) were exposed to the catechol estrogens (CE) 2-hydroxyestradiol (2-OHE₂) or 4-hydroxyestradiol (4-OHE₂), or the parent hormone 17-β-estradiol (E₂) at an equimolar concentration (1 μM) for a period of 6 weeks. It was found that both 2-OHE₂ and 4-OHE₂ have more potent proliferation-enhancing effect than E₂. Exposure to 2-OHE₂, 4-OHE₂ or E₂ resulted in a significant increase in the protein abundance of cyclin D₁ and c-myc. The treated cells exhibited a shift toward the proliferative phase as indicated by FACScan. BPH-1 cells treated with 4-OHE₂ showed increased abundance of estrogen receptor-α (ERα) and its downstream IGF-1R. Reduced abundance of estrogen receptor-β (ERβ) and its downstream tumor suppressor FOXO-1 were observed in cells exposed to E₂, 2-OHE₂ and, to a greater extent, 4-OHE₂. Comet assay revealed that CE, especially 4-OHE₂, elicited significant genotoxic effects as compared to E₂. 4-OHE₂ showed greater ability to neoplastically transform BPH-1 cells as indicated by increased colony forming capacity in soft agar and matrix invasion. In conclusion, in vitro exposure to CE could neoplastically transform human prostatic epithelial cells. Further, 4-OHE₂ is more carcinogenic to prostate epithelial cells than the parent hormone E₂.     

Design and synthesis of novel phenylaminopyrimidines with antiproliferative activity against colorectal cancer

New phenylaminopyrimidine (PAP) derivatives have been designed and synthesised as potential tyrosine kinase inhibitors for the treatment of cancer. The synthesized compounds share a general structure and vary in the substitution pattern at position-2 of the pyridine ring. Several derivatives have demonstrated potent anticancer activities against HCT-116, HT-29 and LS-174T colorectal cancer cells. Furthermore, a number of hits showed good selectivity to Src-kinase. The cytotoxic mechanisms of these compounds were also investigated by studying their effects on cell-cycle distribution. Among all the compounds examined, compound 8b (with a terminal pyridin-3-yl moiety at the pyridine ring) showed the highest inhibitory selectivity towards src-kinase, which was coupled with cell cycle arrest, and apoptotic and autophagic interference, in colorectal cancer cells. This report introduces a novel category of PAP derivatives with promising kinase inhibitory and anticancer effects against colon cancer.

A new series of phenylaminopyrimidine (PAP) derivatives was designed and synthesized to act against tyrosine kinases for the treatment of cancer.     

Local inflammation influences oestrogen metabolism in prostatic tissue

What's known on the subject? and What does the study add? The role of oestrogen in prostatic inflammation has been extensively shown. The catechol oestrogens are known to be more potent oestrogenic moieties that not only aggravate the inflammatory response in situ, but are also believed to have oxidative stress and genotoxic effects. The present study highlights a significant role of inflammation in oestrogen metabolism and, particularly, in generating ‘bad’ oestrogen metabolites. This finding may pave the way for new therapeutic methods for the treatment and/or prevention of prostate diseases.

OBJECTIVE

• ? To investigate the impact of experimentally induced inflammation on oestrogen metabolism in rat prostate.

MATERIALS AND METHODS

• ? Prostatitis was induced in normal and oestrogen‐treated male rats by injecting 2% carrageenan solution into the ventral prostate. After 48 h, the rats were killed and the ventral prostate was collected.
• ? Prostatic inflammation and proliferation were confirmed by gross visual evidence, histology and elevated tumour necrosis factor‐α, prostaglandin E₂ and cyclin‐D₁.
• ? Expression of oestrogen‐metabolizing enzymes was assessed using capillary electrophoresis, and oestrogen metabolites within prostate tissue were assayed using liquid chromatography mass spectrometry.

RESULTS

• ? Animals exposed to carrageenan insult combined with oestrogen treatment showed the most prominent inflammatory and proliferative response.
• ? Treatment of animals with oestrogen alone induced moderate inflammation and proliferation.
• ? Oestrogen‐metabolizing enzymes were overexpressed in animals with experimental prostatitis with sequential accumulation of catechol oestrogens within prostatic tissues.
• ? Oestrogen receptor‐α was underexpressed in the prostatitis with oestrogen group, while oestrogen receptor‐β was overexpressed.

CONCLUSIONS

• ? The present work provides experimental evidence that local inflammation enhances oestrogen synthesis and directs oestrogen metabolism to generate catechol oestrogens within prostatic tissues.
• ? This may contribute, at least partly, to enhanced prostatic cell proliferation.

     

A simple HPLC method for doxorubicin in plasma and tissues of nude mice

Doxorubicin is a cytotoxic anthracycline that has been used for the treatment of several malignancies. Several HPLC methods have been reported for the quantification of doxorubicin in biological samples. Tissue matrix effect and sample size requirements, however, have been remaining issues for simple and easy-to-adapt analytical methods in small animal experiments. The present study established a simple HPLC method for doxorubicin in plasma and tissues (tumor, heart, spleen, liver, gastrointestinal tract, brain, lung, and kidney) of nude mice. Our method required a small sample volume (100 μL plasma and 10 mg tissue), which made it possible to use each blank tissue for calibration curves. The limit of quantification was 25 ng/mL in plasma and 0.1 to 0.4 μg/mg in other tissues with recovery rates ranging from 52.4 to 95.2%. The linearity, accuracy and precision in all tissues, except gastrointestinal tract (GIT), were found to be acceptable in the range of 25–2000 ng/mL plasma and 0.1–4 ng/mg tissue. This method was used successfully to determine the drug concentration in plasma and tissues of human tumor xenograft-bearing nude mice given intratumoral doxorubicin in a polymeric drug delivery system designed for sustained release. In conclusion, the present method may be useful as a simple and easy-to-adapt, yet, sensitive analytical method of doxorubicin for plasma and tissue pharmacokinetic studies in small animals such as nude mice.     

Effect of finasteride particle size reduction on its pharmacokinetic,tissue distribution and cellular permeation

Finasteride (FSD), a specific competitive inhibitor of the steroid type-II 5α-reductase enzyme, is used in treatment of benign prostate hyperplasia (BPH) and male pattern baldness. The drug is of limited solubility that affect its dissolution and bioavailability. The aim was to study the effect of FSD particle size reduction on the pharmacokinetic, tissue distribution and cellular permeation. An optimized drug micro- and nano-particles were developed, characterized, administered to group of rats, and systemic pharmacokinetic and tissue distribution within target and not-target organs were determined using near-infrared (NIR) spectroscopy technique. Moreover, the cellular permeation of the prepared formulations through normal prostate epithelial cells was assessed and compared to pure FSD. The developed micro- and nano-particles were of 930 and 645?nm, respectively. Plasma maximum drug levels (C_max) and overall exposure (AUC) of both formulations were not significantly higher than unformulated drug. However, micronized FSD achieved significant higher concentration within the target tissue (prostate) within the current study compared to pure drug and nano-sized formulation as well. Yet, this is explained by the higher sequestration ability of spleen tissue to the nano-sized formula compared to micro-sized FSD. At the cellular level, permeation of nano-sized FSD through prostate epithelial cells was superior to the unformulated FSD as well as the micro-sized drug formulation. FSD particle size reduction significantly influences its cellular permeation and to a lesser extend affect its systemic pharmacokinetics and tissue distribution after oral administration.     

Novel application of multicellular layers culture for in situ evaluation of cytotoxicity and penetration of paclitaxel

Limited drug penetration into tumor tissue is one of the major factors causing clinical drug resistance in human solid tumors. The multicellular layers (MCL) of human cancer cells have been successfully used to study tissue pharmacokinetics of anticancer drugs. The purpose of this study was to develop a direct and simple method to evaluate vitality changes in situ within MCL using calcein-AM. Human colorectal (DLD-1, HT-29) and bladder (HT-1376, J-82) cancer cells were grown in Transwell inserts to form MCL and subjected to paclitaxel exposure. The drug distribution was evaluated using paclitaxel-rhodamine. Photonic attenuation and limited penetration of calcein-AM prevented cellular vitality evaluation on optical sections under confocal microscopy in DLD-1 MCL. However, direct measurement of the fluorescence intensity on frozen sections of MCL allowed successful vitality assessment in more than 80% depth for HT-29 and J-82 MCL and in the upper 40% depth for DLD-1 and HT-1376 MCL. The penetration of paclitaxel-rhodamine was greater in HT-29 than DLD-1 and its distribution pattern was correlated to the spatial profile of vitality deterioration in both MCL, suggesting that tissue penetration may be an important determinant of drug effect in tumors. In conclusion, a novel method for vitality evaluation in situ within MCL was developed using calcein-AM. This method may provide clinically relevant data regarding the spatial pharmacodynamics of anticancer agents within avascular regions of solid tumors. ( Cancer Sci 2008; 99: 423–431)     

Design, synthesis, and evaluation of anti-inflammatory and ulcerogenicity of novel pyridazinone derivatives

A series of pyridazinone-containing compounds were designed and synthesized as congeners for diclofenac, the most potent and widely used NSAID. The target compounds were evaluated for their anti-inflammatory activity on rat paw edema inflammation model against diclofenac as a reference compound. Seven of the tested compounds demonstrated more than 50% inhibition of carrageenan-induced rat paw edema at a dose 10?mg/kg. The compounds, 6-(2-bromophenylamino)pyridazin-3(2H)-one 2a and 6-(2,6-dimethylphenylamino)pyridazin-3(2H)-one 2e, displayed 74 and 73.5% inflammation-inhibitory activity, respectively, which is comparable to diclofenac (78.3%) at the same dose level after 4?h. The most active compounds as anti-inflammatory agents, 2a, 2e, and 6a, displayed fewer number of ulcers and milder ulcer score than indomethacin in ulcerogenicity screening.