Thyroid function status evaluation in patient post-radiotherapy for nasopharyngeal carcinoma: A retrospective study.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is among the most common malignancy in Malaysia. Radiationinduced hypothyroidism has been reported in other countries. However, in Malaysia, no studies were ever done to determine the effect of radiation on hypothyroidism. The objective of this study is to evaluate the practice of taking thyroid function test (TFT) and determine hypothyroidism post-radiation in patients with NPC. MATERIALS AND METHODS: A retrospective study on the symptoms and results of TFT according to the dosage of intensity-modulated radiotherapy (IMRT) given to patients with NPC. Data were traced and analysed. RESULTS: A total of 78 patients were identified. All patients received IMRT with 33-35 fractions of radiotherapy (RT) with total dosage of 66-70 Gray given. Not all patients had their thyroid function status measured routinely. Twelve patients did have symptoms of hypothyroidism. TFT were obtained in this group but the results were normal. No correlation was found between RT and hypothyroidism. CONCLUSION: There was no correlation between IMRT and the development of hypothyroidism. A prospective study with better control of inclusion and exclusion criteria, and longer follow-up period with TFT, is needed to demonstrate the consistency of these findings.

Mysterious Case of Drooling Infant - Hidden Foreign Body over Hard Palate.

Foreign body over the hard palate is a rare clinical entity that happen almost exclusively in young pediatric age group with only about 40 odd cases ever reported. Most cases in the literature are described as incidental findings of hard palate mass causing heightened anxiety to parents and clinicians alike during routine oral cavity examination. Owing to its rarity and lackluster presenting symptoms, this simple condition are often overlooked but has high propensity to develop into life threatening condition if dislodged into the airway.

A comprehensive review on Nepalese wild vegetable food ferns.

Ferns are used as traditional and fascinating foods in many countries. They are also considered to possess important ethnomedicinal values; however, ferns are one of the underutilized plant resources by both scientific and local communities. Pharmagonostical studies reveal that ferns and fern-allies possess several biological activities including antibacterial, antiviral, antifungal, antimalarial, antidiarrheal, anthelmintic, analgesic, anti-inflammatory, antidiabetic, anticancer, neuroprotective, nephroprotective, hepatoprotective, antifertility, etc. Flavonoids and terpenoids are major secondary metabolites present in ferns. Ugonins, particularly isolated from Helminthostachys zeylanica, have found diverse bioactivities. Ptaquiloside, a norsesquiterpene glucoside, found in Pteridium revolutum, Dryopteris cochleata and Polystichum squarrosum, is one of the hazardous metabolites of ferns which is responsible for the toxic effect. Alkaloids are reported to be present in the ferns; however, the qualitative data are uncertain. Some fern metabolites, such as cyanogenic glycosides and terpenoids, are considered to possess defensive activity against animal attacks. Some ferns are also used for manuring as biological alternative to pesticides. Nepalese have consumed at least 33 species of ferns and fern-allies belonging to 13 families, 20 genera as cooked vegetable foods. The aim of this review is compilation of information available on their distribution, ethnomecinal values, pharmcognosy, pharmacology and phytochemistry.

The reliability of a rapid molecular detection method in determining the prevalence of rifampicin-resistant Mycobacterium tuberculosis in an urban district health facility in Malaysia.

INTRODUCTION: Rifampicin is a key first-line antimycobacterial agent employed for the treatment of pulmonary tuberculosis (PTB). This study sought to obtain prevalence data on rifampicin-resistant Mycobacterium tuberculosis among smear-positive PTB patients in the Klang District of Malaysia. MATERIALS AND METHODS: A total of 103 patients from the Chest Clinic of Hospital Tengku Ampuan Rahimah with sputum smears positive for acid-fast bacilli were included in this cross-sectional study. All sputa were tested using Xpert MTB/RIF to confirm the presence of M. tuberculosis complex and detect rifampicin resistance. Sputa were also sent to a respiratory medicine institute for mycobacterial culture. Positive cultures were then submitted to a reference laboratory, where isolates identified as M. tuberculosis complex underwent drug susceptibility testing (DST). RESULTS: A total of 58 (56.3%) patients were newly diagnosed and 45 (43.7%) patients were previously treated. Xpert MTB/RIF was able to detect rifampicin resistance with a sensitivity and specificity of 87.5% and 98.9%, respectively. Assuming that a single resistant result from Xpert MTB/RIF or any DST method was sufficient to denote resistance, a total of 8/103 patients had rifampicinresistant M. tuberculosis. All eight patients were previously treated for PTB (p<0.05). The overall prevalence of rifampicin resistance among smear-positive PTB patients was 7.8%, although it was 17.8% among the previously treated ones. CONCLUSION: The local prevalence of rifampicin-resistant M. tuberculosis was particularly high among previously treated patients. Xpert MTB/RIF can be employed in urban district health facilities not only to diagnose PTB in smear-positive patients, but also to detect rifampicin resistance with good sensitivity and specificity.

A randomized phase 2 study of MK-2206 versus everolimus in refractory renal cell carcinoma.

Background: Activation of the phosphoinisitide-3 kinase (PI3K) pathway through mutation and constitutive upregulation has been described in renal cell carcinoma (RCC), making it an attractive target for therapeutic intervention. We performed a randomized phase II study in vascular endothelial growth factor (VEGF) therapy refractory patients to determine whether MK-2206, an allosteric inhibitor of AKT, was more efficacious than the mammalian target of rapamycin inhibitor everolimus. Patients and methods: A total of 43 patients were randomized in a 2:1 distribution, with 29 patients assigned to the MK-2206 arm and 14 to the everolimus arm. Progression-free survival (PFS) was the primary endpoint. Results: The trial was closed at the first futility analysis with an observed PFS of 3.68 months in the MK-2206 arm and 5.98 months in the everolimus arm. Dichotomous response rate profiles were seen in the MK-2206 arm with one complete response and three partial responses in the MK-2206 arm versus none in the everolimus arm. On the other hand, progressive disease was best response in 44.8% of MK2206 versus 14.3% of everolimus-treated patients. MK-2206 induced significantly more rash and pruritis than everolimus, and dose reduction occurred in 37.9% of MK-2206 versus 21.4% of everolimus-treated patients. Genomic analysis revealed that 57.1% of the patients in the PD group had either deleterious TP53 mutations or ATM mutations or deletions. In contrast, none of the patients in the non-PD group had TP53 or ATM defects. No predictive marker for response was observed in this small dataset. Conclusions: Dichotomous outcomes are observed when VEGF therapy refractory patients are treated with MK-2206, and MK-2206 does not demonstrate superiority to everolimus. Additionally, mutations in DNA repair genes are associated with early disease progression, indicating that dysregulation of DNA repair is associated with a more aggressive tumor phenotype in RCC.

Antileishmanial diterpenoid alkaloids from Aconitum spicatum (Bruhl) Stapf.

The crude extracts of tubers of Aconitum spicatum (Bruhl) Stapf were investigated for in vitro antileishmanial activity against Leishmania major. The dichloromethane extract at pH 2.5 showed antileishmanial activity with IC50 value of 27.10 ± 0.0 µg/mL. Chromatographic purification of the dichloromethane extract led to isolation of three C-19 norditerpenoid alkaloids indaconitine (1), chasmaconitine (2) and ludaconitine (3). Compounds 3 and 2 showed antileishmanial activity with IC50 = 36.10 ± 3.4 and 56.30 ± 2.1 µg/mL, respectively. Compound 1 was less effective (IC50 > 100 µg/mL). The cytotoxicity of compounds 1, 2 and 3 studied against MCF7, HeLa and PC3 cancer cell lines and 3T3 normal fibroblast cell line did not show cytotoxicity at 30 µM.

Diversity, pharmacology and synthesis of bergenin and its derivatives: potential materials for therapeutic usages.

Bergenin, a natural secondary metabolite, has been isolated from different parts of a number of plants. It is one of active ingredients in herbal and Ayurvedic formulations. It exhibits antiviral, antifungal, antitussive, antiplasmodial, antiinflammatory, antihepatotoxic, antiarrhythmic, antitumor, antiulcerogenic, antidiabetic and wound healing properties. It has been analyzed and estimated in different plant extracts, blood and drug samples using chromatographic techniques, and pharmacokinetic studies have been made. Several bergenin derivatives were isolated and/or synthesized and were found to possess pharmacological activities. Total synthesis of bergenin and its derivatives were reported. This review article covers literature on bergenin and its derivatives until 2013. Ethnomedicinal value of bergenin containing plant materials is also highlighted. This comprehensive review provides information on the potentiality of bergenin and its derivatives for therapeutic usages.

The FoxO-BNIP3 axis exerts a unique regulation of mTORC1 and cell survival under energy stress.

Normal cells possess adaptive mechanisms to couple energy availability with cell growth (cell size increase) and survival, and imbalances are associated with major diseases such as cancer. Inactivation of critical regulators involved in energy stress response, including adenosine monophosphate-activated protein kinase (AMPK), liver kinase B1 (LKB1), tuberous sclerosis complex 1 (TSC1) and tuberous sclerosis complex 2 (TSC2), leads to uncontrolled cell growth yet increased apoptosis under energy stress. These energy stress regulators are also important in tumor suppression and metabolism. Here, we show that forkhead box O (FoxO) transcription factor, a central regulator of tumor suppression and metabolism, plays a unique role in energy stress response. FoxOs inhibit the mammalian target of rapamycin complex 1 (mTORC1), a key regulator of cell growth, under energy stress, and inactivation of FoxOs alleviates energy stress-mediated mTORC1 repression. Surprisingly, unlike AMPK-, Lkb1- or Tsc1/2-deficient cells, FoxO-deficient cells exhibit decreased apoptosis under energy stress. FoxOs operate to inhibit mTORC1 signaling and cell survival independent of AMPK and TSC. Integrated transcriptomic and functional analyses identified BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)-a negative regulator of both Rheb and Bcl2 prosurvival family members-as a key downstream target of FoxOs to inhibit mTORC1 function and promote apoptosis in response to energy stress. We show that p38ß, but not AMPK, is likely to function upstream of FoxO-BNIP3 to mediate energy stress response. Finally, we reveal that low expression of FoxO or BNIP3 correlates with poor clinical outcomes in renal cancer patients. Together, our study uncovers a novel signaling circuit functioning to mediate cellular energy responses to control cell growth and survival. These findings also have important implications to human cancers.

Fatty acid profile of yak milk from the Qinghai-Tibetan Plateau in different seasons and for different parities.

Yaks are the most important grazing livestock for milk production on the Qinghai-Tibetan plateau because these animals are adapted to the high elevations and extremes of cold and can graze throughout the year. In the present study, 30 yaks were selected and the fatty acid (FA) profile of yak milk at different seasons and parities was investigated using gas chromatography. The concentrations of cis-9 C18:1, cis-11 C18:1, cis-9,trans-11 C18:2, and C18:3 n-3 in yak milk were higher in summer (25.26, 1.50, 1.46, and 0.33 g/100 g of total FA, respectively) than in winter (22.17, 0.77, 1.27, and 0.28 g/100 g of total FA, respectively). The contents of monounsaturated and polyunsaturated FA in milk fat of multiparous (parities 2 to 5) yaks (31.61 and 4.20 g/100 g of total FA, respectively) were higher than those in primiparous yaks (29.61 and 3.80 g/100g of total FA, respectively). These results suggest (1) that the potential exists to improve the FA composition of yak milk by developing local supplement resources during the winter and (2) that multiparous yaks have a more favorable FA profile than primiparous yaks.

Pd-catalyzed 5-endo-trig-type cyclization of ß,γ-unsaturated carbonyl compounds: an efficient ring closing reaction to give γ-butenolides and 3-pyrrolin-2-ones.

The 5-endo-trig-type cyclization has been performed using a Pd-bis(isoxazoline) catalyst. The present cyclization of ß,γ-unsaturated carbonyl compounds gave γ-butenolides and 3-pyrrolin-2-ones in good to excellent yields.

Primitive neuroectodermal tumour metastases mimicking neurofibromatosis type 2.

Bilateral vestibular schwannomas are the diagnostic features of neurofibromatosis type 2 (NF-2), and are the most common findings associated with the disorder. We report a three-year-old boy who presented with left facial nerve palsy and weight loss with bilateral large cerebellopontine (CP) angle masses that extended into the internal auditory canal on magnetic resonance imaging. The patient also had synchronous tumours in the lateral ventricle and intradural extramedullary spinal canal. The above findings were misinterpreted as NF-2 with bilateral vestibular schwannomas, ventricular meningioma and spinal schwannomas/meningiomas. However, histological examination of the spinal masses revealed a primitive neuroectodermal tumour. Although bilateral CP angle masses are characteristic of NF-2, the possibility of diffuse craniospinal malignancy should be considered in a very young child who presents with weight loss and extensive tumours.

First Report of Corynespora Leaf Spot on Patchouli Caused by Corynespora cassiicola in China.

Patchouli (Pogostemon cablin (Blanco) Benth.) is mainly cultivated in Southeast Asia as a medicinal shrub and a source of patchouli oil used in perfumery. In 2008, a leaf spot disease was observed on patchouli plants grown on most farms (some farms had 99% incidence) in Wanning, the predominant cultivation location in the Hainan Province of China. The disease usually began at the tip of leaves, the main veins, or small veinlets. Severely irregular-shaped dark brown leaf spots expanded over 5 to 10 days, eventually causing infected leaves to abscise. The time from initial leaf lesions to abscission usually took 1 month. The disease was usually most severe in April and May, causing significant economic losses along with quality losses to patchouli oil extracted from leaves. To isolate the causal pathogen, diseased leaves were collected in August 2008 from a farm of the Hainan Branch Institute of Medicinal Plant Development in Wanning, surface sterilized in 75% ethanol for 1 min, transferred to potato dextrose agar (PDA), and incubated at 28°C for 14 days. Single-spore cultures of three isolates were obtained and identified as Corynespora cassiicola (Berk. & Curt.) Wei. on the basis of morphological and physiological features (1). Genomic DNA was extracted from all the cultures. The internal transcribed spacer (ITS) region of the rDNA was amplified using primers ITS1 (5'-TCCGATGGTGAACCTGCGG-3') and ITS4 (5'-TCCTCCGCTTATTGATATGC-3'). Amplicons were 546 bp (GenBank Accession No. HM145960) and had 99% nucleotide identity with the corresponding sequence (GenBank Accession No. GU138988) of C. cassiicola isolated from cassava (Manihot esculenta Crantz). To satisfy Koch's postulates, 50-day-old potted plants in a tent were sprayed until runoff with a spore suspension (1 × 106 spores/ml) prepared from 10-day-old cultures. Using this spray method, one isolate was inoculated separately onto nine leaves of three potted plants. The potted plants were covered with plastic bags to maintain high humidity for 48 h and then placed outside under natural environmental conditions (temperature 20 to 28°C). Another nine leaves of three potted plants, sprayed only with sterile water, served as noninoculated control plants. Leaf spot symptoms similar to those on diseased field plants appeared after 7 days on all inoculated plants. C. cassiicola was reisolated from all inoculated test plants. No symptoms were observed on the control plants. To our knowledge, this is the first report of C. cassiicola causing a leaf spot disease on patchouli in China. Other previous reports of this disease were from Cuba (2). This pathogen has also been reported previously to be economically important on a number of other hosts. On patchouli plants, more attention should be given to prevention and control measures to help manage this disease. References: (1) M. B. Ellis. Dematiaceous Hyphomycetes. Commonwealth Mycological Institute: Kew, Surrey, England, 1971. (2) I. Sandoval et al. Cienc. Tec. Agric., Prot. Plant. 10:21, 1987.

Direct transition-metal-free intramolecular arylation of phenols.

Direct transition-metal-free, base-mediated intramolecular arylation of phenols with aryl halides has been developed. In the presence of 2.5 equiv of t-BuOK in dioxane at 140 degrees C, the intramolecular cyclization of 3-(2-halobenzyloxy)phenols affords 6H-benzo[c]chromenes in high yields. This reaction proceeds by an initial formation of a benzyne intermediate followed by an aromatic sp(2) C-H functionalization (a formal C-H activation) to form the carbon-carbon bond.

Plasma immersion ion implantation treatment of polyethylene for enhanced binding of active horseradish peroxidase.

Robust attachment of active proteins to synthetic surfaces underpins the development of biosensors and protein arrays. This paper presents the results of experiments in which energetic ions, extracted from an inductively coupled nitrogen plasma, are used to modify the surface of ultrahigh molecular weight polyethylene (UHMWPE). The ability of the surface to bind active horseradish peroxidase (HRP) is significantly enhanced by the plasma treatment. The amide signal in infrared spectroscopy indicates an increased quantity of surface-attached protein on the modified surface. The activity of the bound HRP remains high compared with that of protein attached to the untreated surface, after repeated washing in buffer solution. Although Tween 20 was an effective blocking agent for the unmodified polyethylene surface, binding of HRP to the modified surface is not inhibited by its presence. We propose that the treatment produces new binding sites on the surface and that the function of the HRP is retained because the treated surface is substantially more hydrophilic.

Comparison of protein surface attachment on untreated and plasma immersion ion implantation treated polystyrene: protein islands and carpet.

Surface attachment of the enzyme horseradish peroxidase (HRP) was studied on untreated and ion beam implanted polystyrene (PS) films. The PS films of 100 nm thickness on a silicon wafer were treated using the plasma immersion ion implantation (PIII) technique, with argon ions of energy 20 keV and fluences of up to 2 x 10(16) ions/cm2. Differential transmittance Fourier transform infrared (FTIR) spectra confirmed the presence of proteins on the PS surfaces by detection of the amide A, I, and II protein vibrations. Spectroscopic ellipsometry over the UV-vis spectral region provided the optical constants and thickness of the protein layer, while tapping mode atomic force microscopy (AFM) was used to image the protein distribution on the surface. The combination of AFM, ellipsometry, and FTIR analysis showed that, on the untreated PS surface, HRP formed islands 8 nm in height and 30 nm in lateral size, covering approximately 27% of the PS surface. After PIII modification of the PS surface, the protein covered 100% of the surface area.

PtBr2-catalyzed transformation of allyl(o-ethynylaryl)carbinol derivatives into functionalized indenes. Formal sp3 C-H bond activation.

The PtBr2-catalyzed reaction of 1-ethynyl-2-(1-alkoxybut-3-enyl)benzenes at 120 degrees C in CH3CN gave functionalized indenes in good to allowable yields. Most probably, the hydrogen at the terminal alkyne is transferred to the adjacent internal beta-carbon to form an (eta2-vinylidene)platinum carbene intermediate, which activates the sp3 C-H bond at the benzylic carbon. This reaction pathway is supported by DFT calculations which suggest that the formation of the Pt-vinylidene complex is the rate-limiting stage for the whole transformation.

Lactam synthesis via the intramolecular hydroamidation of alkynes catalyzed by palladium complexes.

The palladium complexes catalyzed intramolecular hydroamidation reaction of amidoalkynes gives the corresponding lactams in good to high yields. For example, in the presence of 10 mol % of Pd(PPh3)4 and 20 mol % of PhCOOH, the reaction of the amidoalkyne 3a in 1,4-dioxane at 100 degrees C proceeded smoothly to give the corresponding lactam 4a in 92% yield.

Dural sinus thrombosis after minor head injury in a child.

INTRODUCTION: Dural sinus thrombosis following minor head injury is rare. We report such a case in a child after mild head injury. CLINICAL PICTURE: A 4-year-old child presented with giddiness and vomiting after a fall. Clinical examination was unremarkable. Magnetic resonance venogram revealed thrombosis of the right sigmoid and transverse sinuses. TREATMENT: The patient was managed conservatively. OUTCOME: Repeat scans 10 weeks after injury showed recanalisation of the thrombosis. CONCLUSION: Dural sinus thrombosis should be excluded in children presenting with persistent giddiness and vomiting after minor head injury.

Intramolecular hydroamination of alkynes catalyzed by Pd(PPh3)4/triphenylphosphine under neutral conditions.

The intramolecular hydroamination of alkynes tethered with amino group 1 in the presence of catalytic amounts of Pd(PPh3)4 and PPh3 in benzene at 100 degrees C proceeded smoothly without the use of any additional acid source to afford five- and six-membered nitrogen heterocycles 2 in good to excellent yields. A compulsory addition of carboxylic acid as a cocatalyst was not needed, and the reaction could be carried out under essentially neutral conditions.

PtBr2-catalyzed consecutive enyne metathesis-aromatization of 1-(1-methoxy-but-3-enyl)-2-(1-alkynyl)benzenes: dual role of the Pt catalyst.

1,7-Enynes 1, connected through an aromatic ring and bearing a leaving methoxy group at the 4-position, underwent the PtBr(2)-catalyzed enyne metathesis followed by aromatization in one pot to afford vinyl naphthalenes 3 in good to acceptable yields. The cyclobutene intermediate 11a and another intermediate 2a were isolated, indicating that PtBr(2) acts as a dual role catalyst: (1) as a transition metal catalyst, it induces the enyne metathesis to produce 11a starting from 1a, and (2) as a Lewis acid catalyst, it facilitates elimination of MeOH from 2a to give the aromatized product 3a.