Parental Feeding Practices and Child-Related Factors are Associated with Overweight and Obesity in Children and Adolescents with Autism Spectrum Disorder

Journal of Autism and Developmental Disorders - Atypical eating behaviors displayed by children with autism spectrum disorder (ASD) predispose them to unhealthy weight gain. We determined the...     

Recombinant human alpha fetoprotein synergistically potentiates the anti-cancer effects of 1′-S-1′-acetoxychavicol acetate when used as a complex against human tumours harbouring AFP-receptors

Purpose

Previous in vitro and in vivo studies have reported that 1′-S-1′-acetoxychavicol acetate (ACA) isolated from rhizomes of the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) induces apoptosis-mediated cell death in tumour cells via dysregulation of the NF-κB pathway. However there were some clinical development drawbacks such as poor in vivo solubility, depreciation of biological activity upon exposure to an aqueous environment and non-specific targeting of tumour cells. In the present study, all the problems above were addressed using the novel drug complex formulation involving recombinant human alpha fetoprotein (rhAFP) and ACA.

Experimental Design

To study the synergistic effect of both agents on human cancer xenografts, athymic nude (Nu/Nu) mice were used and treated with various combination regimes intraperitoneally. Serum levels of tumour markers for carcinoembryonic antigen (CEA) and prostate specific antigen (PSA) were assessed using sandwich ELISA. IHC and Western blotting were also conducted on in vivo tumour biopsies to investigate the involvement of NF-κB regulated genes and inflammatory biomarkers. Quantification and correlation between drug efficacies and AFP-receptors were done using IF-IC and Pearson''s correlation analysis.

Results

Mice exposed to combined treatments displayed higher reductions in tumour volume compared to stand alone agents, consistent with in vitro cytotoxicity assays. Milder signs of systemic toxicity, such as loss in body weight and inflammation of vital organs were also demonstrated compared to stand alone treatments. Tumour marker levels were consistent within all rhAFP/ACA treatment groups where levels of CEA and PSA were initially elevated upon commencement of treatment, and consecutively reduced corresponding to a decrease in tumour bulk volume. Both IHC and Western blotting results indicated that the combined action of rhAFP/ACA was not only able to down-regulate NF-κB activation, but also reduce the expression of NF-κB regulated genes and inflammatory biomarkers. The efficacy of rhAFP/ACA complex was also found to be weakly negatively correlated to the level of surface AFP-receptors between tumour types.

Conclusions

This drug complex formulation shows great therapeutic potential against AFP-receptor positive tumours, and serves as a basis to overcome insoluble and non-specific anti-neoplastic molecules.     

Leech Therapeutic Applications

Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproductive system problems, inflammation, and dental problems. Recently, extensive researches on leech saliva unveiled the presence of a variety of bioactive peptides and proteins involving antithrombin (hirudin, bufrudin), antiplatelet (calin, saratin), factor Xa inhibitors (lefaxin), antibacterial (theromacin, theromyzin) and others. Consequently, leech has made a comeback as a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20^th century, leech therapy has established itself in plastic and microsurgery as a protective tool against venous congestion and served to salvage the replanted digits and flaps. Many clinics for plastic surgery all over the world started to use leeches for cosmetic purposes. Despite the efficacious properties of leech therapy, the safety, and complications of leeching are still controversial.     

Laboratory evaluation of four commercial repellents against larval Leptotrombidium deliense (Acari: Trombiculidae)

Four commercial repellents were evaluated in the laboratory against Leptotrombidium deliense chiggers. Both in vitro and in vivo methods were used to determine repellency of the compounds. The repellents were Kellis (containing citronella oil, jojoba oil and tea tree oil), Kaps (containing citronella oil), BioZ (containing citronella oil, geranium oil and lemon grass oil) and Off (containing DEET). The combination of three active ingredients: citronella oil, geranium oil, lemon grass oil gave the highest repellency (87%) followed by DEET (84%). In vitro repellencies ranged from 73% to 87%. There was no significant difference between the four products. All the repellents had 100% in vivo repellency compared to 41-57% for the controls.     

Ethnicity association of Helicobacter pylori virulence genotype and metronidazole susceptibility

AIM:To characterise the cag pathogenicity island in Helicobacter pylori(H.pylori) isolates by analysing the strains’ vacA alleles and metronidazole susceptibilities in light of patient ethnicity and clinical outcome.METHODS:Ninety-five H.pylori clinical isolates obtained from patients with dyspepsia living in Malaysia were analysed in this study.Six genes in the cagPAI region(cagE,cagM,cagT,cag13,cag10 and cag67) andvacA alleles of theH.pylori isolates were identified by polymerase chain reaction.The isolates’ metronidazole susceptibility was also determined using the E-test method,and the resistant gene was characterised by sequencing.RESULTS:More than 90% of the tested isolates had at least one gene in the cagPAI region,and cag67 was predominantly detected in the strains isolated from the Chinese patients,compared with the Malay and Indian patients(P < 0.0001).The majority of the isolates(88%) exhibited partial deletion(rearrangement) in the cagPAI region,with nineteen different patterns observed.Strains with intact or deleted cagPAI regions were detected in 3.2% and 8.4% of isolates,respectively.The prevalence of vacA s1m1 was significantly higher in the Malay and Indian isolates,whereas the isolates from the Chinese patients were predominantly genotyped as vacA s1m2(P = 0.018).Additionally,the isolates from the Chinese patients were more sensitive to metronidazole than the isolates from the Malay and Indian patients(P = 0.047).Although we attempted to relate the cagPAI genotypes,vacA alleles and metronidazole susceptibilities to disease outcome,no association was observed.The vacA alleles were distributed evenly among the strains with intact,partially deleted or deleted cagPAI regions.Interestingly,the strains exhibiting an intact cagPAI region were sensitive to metronidazole,whereas the strains with a deleted cagPAI were more resistant.CONCLUSION:Successful colonisation by different H.pylori genotypes is dependent on the host’s genetic makeup and may play an important role in the clinical outcome.     

p63 cytoplasmic aberrance is associated with high prostate cancer stem cell expression

Introduction: Prostate cancer in Indonesia is the 3rd ranking cancer among males and the 5th rank for theircancer mortality. Prognostic markers that can identify aggressive prostate cancer in early stages and helpselect appropriate therapy to finally reduce the mortality are therefore urgently needed. It has been suggestedthat stem cells in the prostate gland have a role in initiation, progression, and metastasis of cancer, althoughcontroversy continues to exist. Maintenance of normal stem cell or reserve cell populations in several epitheliaincluding prostate has been shown to be regulated by p63 and alteration of p63 expression is considered to havean oncogenic role in prostate cancer. We hypothesize that the expression of cytoplasmic aberrance of p63 isassociated with high ALDH1A1 expression as a cancer stem cell marker, thus leading to progression of prostatecancer. Methods: Using a cross-sectional study during two years (2009-2010), a total of 79 paraffin embeddedtissues of benign prostatic hyperplasia, PIN prostatic intraepithelial neoplasia, low and high Gleason scoreprostate cancer were investigated using immunohistochemistry. Associations between cytoplasmic p63 andALDH1A1, as well as with pathological diagnosis, were analyzed by Chi-Square test using SPSS 15.0. Links ofboth markers with cell proliferation rate (KI-67) and apoptotic rate (cleaved caspase 3) were also analyzed byKruskal-Wallis test. Results: The mean age of patient at the diagnosis is 70.0 years. Cytoplasmic aberrance ofp63 was associated with ALDH1A1 expression (p<0.001) and both were found to have significant relationshipswith pathological diagnosis (including Gleason score), (p=0.006 and p<0.001 respectively). Moreover, it was alsofound that higher levels of cytoplasmic p63 were significantly associated with the frequency of proliferatingcells and cells undergoing apoptosis in prostate cancers (p=0.001 and p=0.016 respectively). Conclusion: p63cytoplasmic aberrance is associated with high ALDH1A1 expression. These components are suggested to havean important role in prostate cancer progression and may be used as molecular markers.