Entrapped appendicitis in post TAPP mesh repair.

Transabdominal preperitoneal (TAPP) repair is a common laparoscopic inguinal hernia repair technique performed worldwide. A rare long-term complication of TAPP is mesh-induced appendicitis, of which only four cases have been described in the literature to date. We report a case of appendicitis due to appendix entrapped in the TAPP mesh.

Radiotherapy for Oropharyngeal Carcinoma With an Uninvolved Contralateral Neck: The Safety of Omission of Contralateral High Level II and Retropharyngeal Lymph Nodes From Elective Target Volumes.

AIMS: To analyse outcomes and patterns of failure in patients with oropharyngeal carcinoma (OPC) treated with definitive volumetric modulated arc therapy with omission of contralateral high level II lymph nodes (HLII) and retropharyngeal lymph nodes (RPLN) in the contralateral uninvolved neck. MATERIALS AND METHODS: Patients with OPC treated between January 2016 and July 2019 were retrospectively identified. In the absence of contralateral neck disease, institutional protocols allowed omission of contralateral HLII and contralateral RPLN in the additional absence of ipsilateral RPLN, soft palate/posterior pharyngeal wall primary. RESULTS: In total, 238 patients with OPC and an uninvolved contralateral neck received definitive (chemo)radiotherapy with bilateral neck treatment. The median follow-up was 30.6 months. Two-year local control, regional control and overall survival were 91.0, 91.6 and 86.5%, respectively. Contralateral HLII were omitted in 159/238 (66.8%) patients; this included 106 patients in whom the primary tumour was at/crossed the midline. The contralateral RPLN region was omitted from elective target volumes for 175/238 (73.5%); this included 114 patients with a primary tumour at/crossed the midline. The mean contralateral parotid dose when contralateral HLII and RPLN were both omitted was 24.4 Gy, compared with 28.3 Gy without HLII/RPLN omission (P < 0.001). Regional progression occurred in 18/238 (7.6%) patients, all involving the ipsilateral neck with one bilateral. There were no recurrences in the contralateral HLII or RPLN regions. CONCLUSION: In patients with OPC and an uninvolved contralateral neck receiving bilateral (chemo)radiotherapy, the omission of contralateral RPLN and HLII from elective target volumes was safe and could lead to reduced contralateral parotid doses.

Evaluation of Locoregional Recurrence Patterns Following Adjuvant (Chemo)Radiotherapy for Oral Cavity Carcinoma.

AIMS: To evaluate patterns of locoregional recurrence following adjuvant (chemo)radiotherapy for oral cavity squamous cell carcinomas. MATERIALS AND METHODS: One hundred and one patients who received adjuvant radiotherapy ± chemotherapy for oral cavity squamous cell carcinoma between 2013 and 2016 were analysed. For documented locoregional recurrence, recurrence imaging was deformably co-registered to the planning computed tomography scan. The volume of recurrence was delineated (Vrec). Vrec coverage by 95% of the corresponding planning target volume prescription dose was determined and the location compared with planning target volumes. Sites of recurrence were classified using a combined volume and centroid-based method: (A) central high dose, (B) peripheral high dose, (C) central low dose, (D) central peripheral dose, (E) extraneous. RESULTS: The median follow-up was 36 months. Forty-three per cent and 53% of patients received radiotherapy to the ipsilateral neck only and bilateral neck, respectively. Three-year overall survival, disease-free survival, local control, regional control and distant metastases-free survival were 63.0, 65.6, 88.0, 85.1 and 85.3%, respectively. Of 10 episodes of primary site recurrences, five were type A, four type B and one was type E. Of 14 episodes of regional recurrence, five were type A, two type C, two type D and five type E. Five of 21 (24%) patients with oral tongue carcinoma with an undissected/unirradiated contralateral neck had a type E contralateral neck recurrence, including 2/11 with pN0, 1/4 with pN1 and 2/6 with pN2 disease. CONCLUSIONS: Marginal and out-of-field recurrences remain a significant pattern of failure. We advocate generous target delineation postoperatively and, for oral tongue carcinomas, a comprehensive approach with bilateral neck irradiation.

Paediatric cataract surgery in Hospital Kuala Lumpur - A 5-year review of visual outcomes.

INTRODUCTION: Paediatric cataract surgery is challenging with reported post-operative visual acuity (VA) of 0.3LogMar or better varying between 33% to 68% of patients. OBJECTIVE: The aim is to document the post-operative refraction, VA and complications of non-traumatic pediatric cataract surgery performed in a tertiary referral center in Malaysia. METHODOLOGY: This retrospective study reviewed case notes of all consecutive patients aged 12 years and below who underwent cataract surgery from January 2010 to December 2015. Patients were recruited if they had a minimum of six months post-operative follow-up. Exclusion criteria included traumatic cataract, central nervous system abnormalities, incomplete medical records or pre-existing ocular pathology. Subjects were divided into two groups based on refraction at one month. Subjects with refraction within 1- dioptre of the targeted spherical equivalent were in the success group and the rest were in the failure group. RESULTS: A total of 111 subjects were recruited (65 subjects in success group and 46 subjects in the failure group). Mean age at surgery was 33.14 (SD: 33.47) months. The success group had significantly longer axial length (p:0.0045, CI: 0.566-0.994, OR: 0.750). At final review, 44.1%(49/111) subjects had visual acuity of 0.3LogMar or better. The success group had better final mean VA in comparison to the failure group (p:0.034, CI:1.079-7.224, OR: 2.791). CONCLUSION: The outcome of non-traumatic paediatric cataract surgery was acceptable with 58.6% achieved targeted refractive correction at 1-month post-operative period. Longer axial length was associated with better refractive outcome. Capsule related complications was the most common intra-operative complication.

Quality Assurance Peer Review of Head and Neck Contours in a Large Cancer Centre via a Weekly Meeting Approach.

AIMS: To assess the impact of weekly scheduled peer review of head and neck contours for definitive and adjuvant radiotherapy cases based on rates of recommended changes. MATERIALS AND METHODS: Retrospective analysis of a prospective database. Recommended changes were prospectively classified as 'major' (change in gross tumour volume and/or high-dose clinical target volume, dose/fractionation) or 'minor' (change in intermediate or elective dose clinical target volumes or organs at risk). Univariate analysis to explore associations between recommended changes and tumour site/stage and radical/adjuvant indication. RESULTS: In total, 307/375 (82%) head and neck cases treated with volumetric-modulated arc therapy were prospectively peer reviewed over a 12-month period; 195 (64%) cases received definitive and 112 (36%) received adjuvant radiotherapy. Overall, 43/307 (14.0%) changes were recommended within the peer review meetings. This comprised 27/307 (8.8%) major changes and 16/307 (5.2%) minor changes; 33/43 (77%) changes were in the clinical target volume. Rates of recommended changes were significantly higher for adjuvant versus definitive radiotherapy (odds ratio 2.26, P = 0.014) and for larynx compared with oropharynx (odds ratio 3.02, P = 0.02). There was no overall correlation between clinician experience and rates of change (P = 0.62). CONCLUSION: Routine weekly meeting contour-based peer review resulted in a number of major and minor changes to treatment. Compliance was high. Peer review was potentially beneficial for all tumour sites/stages/indications and any degree of clinician experience.

Juvenile primary extranasopharyngeal angiofibroma, presenting as cheek swelling.

Angiofibroma is a locally advancing immensely vascular tumor that essentially arises from the nasopharynx. The clinical characteristics of extranasopharyngeal angiofibroma (ENA) do not accord to that of nasopharyngeal angiofibroma and can present a diagnostic confront. We describe a case of primary juvenile ENA in a 19-year-old patient who presented with a rapidly enlarging mass of the cheek region. The case is unusual because of its anatomic location. The diagnostic and management particulars are sketched.

Postoperative (Chemo)Radiotherapy for Oral Cavity Squamous Cell Carcinomas: Outcomes and Patterns of Failure.

AIMS: To determine outcomes after adjuvant radiotherapy for squamous cell carcinoma of the oral cavity and to correlate locoregional recurrence patterns with radiotherapy target volumes. MATERIALS AND METHODS: All patients receiving adjuvant radiotherapy±chemotherapy after surgery with curative intent for oral cavity squamous cell carcinoma between 2007 and 2012 were retrospectively analysed. Locoregional recurrences were reconstructed on the planning computed tomography scan by both deformable image co-registration and by visual assessment. Recurrences were categorised as in-field, marginal or out-of-field if >95%, 20-95%, and <20% of the recurrence volume was encompassed by 95% of the prescription isodose, respectively. RESULTS: In total, 106 patients with a median follow-up of 42 months were included. Oral cavity subsites included oral tongue (54%) and floor of mouth (32%). Thirty (28%) patients received concurrent chemotherapy. Fifty-five (52%) patients received bilateral neck radiotherapy. Two year overall, disease-free, local disease-free, regional disease-free and distant metastases-free survival were 72, 83, 92, 89, 94%, respectively. On multivariate analysis, extracapsular nodal spread was the only factor significantly associated with inferior overall survival. Fourteen (13%) patients have experienced locoregional failure. Of the eight local recurrences at the primary tumour site, four, three and one were classified as in-field, marginal and out-of-field, respectively. Of 10 regional recurrences, one, one and eight were in-field, marginal and out-of-field. There were 7/21 (33%) contralateral regional recurrences in patients with pN2a/b disease who did not receive contralateral neck irradiation; there were 0/21 (0%) and 0/9 (0%) contralateral regional recurrences in patients with pN0 or pN1 disease, respectively, who did not receive contralateral neck irradiation. CONCLUSION: Marginal recurrences highlight the need for generous target volume delineation. Based upon rates of contralateral regional recurrences, a comprehensive approach to target volume selection should be advised for tumour subsites with bilateral lymphatic drainage in the presence of pN2a/b disease.

Superiority of Deformable Image Co-registration in the Integration of Diagnostic Positron Emission Tomography-Computed Tomography to the Radiotherapy Treatment Planning Pathway for Oesophageal Carcinoma.

AIMS: To investigate the use of image co-registration in incorporating diagnostic positron emission tomography-computed tomography (PET-CT) directly into the radiotherapy treatment planning pathway, and to describe the pattern of local recurrence relative to the PET-avid volume. MATERIALS AND METHODS: Fourteen patients were retrospectively identified, six of whom had local recurrence. The accuracy of deformable image registration (DIR) and rigid registration of the diagnostic PET-CT and recurrence CT, to the planning CT, were quantitatively assessed by comparing co-registration of oesophagus, trachea and aorta contours. DIR was used to examine the correlation between PET-avid volumes, dosimetry and site of recurrence. RESULTS: Positional metrics including the dice similarity coefficient (DSC) and conformity index (CI), showed DIR to be superior to rigid registration in the co-registration of diagnostic and recurrence imaging to the planning CT. For diagnostic PET-CT, DIR was superior to rigid registration in the transfer of oesophagus (DSC=0.75 versus 0.65, P<0.009 and CI=0.59 versus 0.48, P<0.003), trachea (DSC=0.88 versus 0.65, P<0.004 and CI=0.78 versus 0.51, P<0.0001) and aorta structures (DSC=0.93 versus 0.86, P<0.006 and CI=0.86 versus 0.76, P<0.006). For recurrence imaging, DIR was superior to rigid registration in the transfer of trachea (DSC=0.91 versus 0.66, P<0.03 and CI=0.83 versus 0.51, P<0.02) and oesophagus structures (DSC=0.74 versus 0.51, P<0.004 and CI=0.61 versus 0.37, P<0.006) with a non-significant trend for the aorta (DSC=0.91 versus 0.75, P<0.08 and CI=0.83 versus 0.63, P<0.06) structure. A mean inclusivity index of 0.93 (range 0.79-1) showed that the relapse volume was within the planning target volume (PTVPET-CT); all relapses occurred within the high dose region. CONCLUSION: DIR is superior to rigid registration in the co-registration of PET-CT and recurrence CT to the planning CT, and can be considered in the direct integration of PET-CT to the treatment planning process. Local recurrences occur within the PTVPET-CT, suggesting that this is a suitable target for dose-escalation strategies.

Stereotactic Ablative Radiotherapy (SABR) in Patients with Medically Inoperable Peripheral Early Stage Lung Cancer: Outcomes for the First UK SABR Cohort.

AIMS: To report outcomes for the first UK cohort treated for early stage peripheral lung cancer using stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: Patients were included who received SABR between May 2009 and May 2012. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. Patients were treated according to the UK SABR Consortium Guidelines. Univariate and multivariate Cox regression was used to determine factors that influenced overall survival and local control. RESULTS: In total, 273 patients received SABR for 288 lesions in the time period examined. The median follow-up was 19.7 months. The median overall survival for all patients was 27.3 months, with 1, 2 and 3 year overall survival of 78.0, 54.9 and 38.6%, respectively. The 1, 2 and 3 year rates of local control were 98.2, 95.7 and 95.7%, respectively. All patients completed the planned course of treatment and rates of Common Toxicity Criteria grade 3+ toxicity were low. On multivariate analysis, patients with Medical Research Council (MRC) breathlessness scores of 3-5 had worse overall survival compared with patients with scores of 1-2 (hazard ratio: 2.10; 95% confidence interval: 1.25-3.59) and the presence of histological diagnosis conferred improved overall survival (hazard ratio: 0.54; 95% confidence interval: 0.31-0.93), probably reflecting that patients who are considered well enough to undergo biopsy are generally fitter overall. No factors were identified that significantly influenced local control. CONCLUSIONS: SABR is an effective and well-tolerated treatment option for patients with early stage peripheral lung cancer who are not suitable for surgery. No patient cohort was identified in whom SABR was considered inappropriate. This series adds to the existing positive data that support SABR for this patient group.

Risk of recurrent venous thromboembolism and major hemorrhage in cancer-associated incidental pulmonary embolism among treated and untreated patients: a pooled analysis of 926 patients.

UNLABELLED: ESSENTIALS: We performed a pooled analysis of 926 patients with cancer-associated incidental pulmonary embolism (IPE). Vitamin K antagonists (VKA) are associated with a higher risk of major hemorrhage. Recurrence risk is comparable after subsegmental and more proximally localized IPE. Our results support low molecular weight heparins over VKA and similar management of subsegmental IPE. BACKGROUND: Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on computed tomography scanning not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management. METHODS: Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major hemorrhage, and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization, and management were performed. RESULTS: In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major hemorrhage and mortality were 5.8% (95% confidence interval [CI] 3.7-8.3%), 4.7% (95% CI 3.0-6.8%), and 37% (95% CI 28-47%). VTE recurrence risk was comparable under low molecular weight heparins (LMWH) and vitamin K antagonists (VKAs) (6.2% vs. 6.4%; hazard ratio [HR] 0.9; 95% CI 0.3-3.1), while 12% in untreated patients (HR 2.6; 95% CI 0.91-7.3). Risk of major hemorrhage was higher under VKAs than under LMWH (13% vs. 3.9%; HR 3.9; 95% CI 1.6-10). VTE recurrence risk was comparable in patients with an subsegmental IPE and those with a more proximally localized IPE (HR 1.1; 95% CI 0.50-2.4). CONCLUSION: These results support the current recommendation to anticoagulate cancer-associated IPE with LMWH and argue against different management of subsegmental IPE.

Assessment of outcomes with delayed (18)F-FDG PET-CT response assessment in head and neck squamous cell carcinoma.

OBJECTIVE: To assess the accuracy of a 4-month post-(chemo)radiotherapy 18-fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)-CT for head and neck squamous cell carcinoma (HNSCC). METHODS: 105 patients who underwent a baseline and response assessment (18)F-FDG PET-CT scan between 2008 and April 2013 were identified. (18)F-FDG PET-CT outcomes were analysed with reference to clinicopathological outcomes. RESULTS: 79 of 105 (75%) (18)F-FDG PET-CT scans demonstrated a complete metabolic response; 19 of 101 (19%) for assessable primary tumours were positive; and 19 of 93 (20%) for patients with nodal disease were equivocal (n = 10) or positive (n = 9). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for primary and nodal disease were 90%, 89%, 47%, 99% and 91%, 89%, 53% and 99%, respectively. Eight of nine patients with a positive nodal response scan had clinicopathological evidence of residual nodal disease (PPV, 89%). 2 of 10 patients with equivocal nodal responses had clinicopathological evidence of residual nodal disease (PPV, 20%). CONCLUSION: (18)F-FDG PET-CT 4 months post treatment has a very high NPV. A positive (18)F-FDG PET-CT has a high PPV for residual nodal disease. By contrast, patients who have an equivocal nodal response have a low PPV. ADVANCES IN KNOWLEDGE: Response assessment (18)F-FDG PET-CT is a valuable tool in guiding the selective use of neck dissection following (chemo)radiotherapy for HNSCC. An equivocal lymph node response has a limited predictive value for persistent disease, and optimal management remains a clinical challenge.

Impact of HMG-CoA reductase inhibitors on the incidence of polyomavirus-associated nephropathy in renal transplant recipients with human BK polyomavirus viremia.

BACKGROUND: Up to 20% of renal transplant recipients (RTR) will develop human BK polyomavirus (BKPyV) viremia. BKPyV viremia is a pre-requisite of polyomavirus-associated nephropathy (PyVAN). Risk of BKPyV infections increases with immunosuppression. Currently, the only effective therapy against PyVAN is reductions in immunosuppression, but this may increase the risk of rejection. In vitro data have shown that pravastatin dramatically decreased caveolin-1 expression in human renal proximal tubular epithelial cells (HRPTEC) and suppressed BKPyV infection in these cells. Based on these data, we postulated that statin therapy may prevent the progression of BKPyV viremia to PyVAN. PATIENTS AND METHODS: A multicenter, retrospective study was conducted in adult RTR transplanted between July 2005 and March 2012. All patients with documented BKPyV viremia (viral load >500 copies/mL on 2 consecutive tests) were included. Group I consisted of patients taking a statin before the BKPyV viremia diagnosis (n = 32), and Group II had no statin exposure before or after the BKPyV viremia diagnosis (n = 36). The primary endpoint was the incidence of PyVAN. RESULTS: Demographic data, transplant characteristics, and the degree of immunosuppression (i.e., induction/maintenance therapies, rejection treatment) were similar between the groups, with the exception of more diabetics in Group I. The incidence of PyVAN was comparable between the 2 groups (Group I = 28.1% vs. Group II = 41.7%; P = 0.312). CONCLUSIONS: Despite the proven in vitro effectiveness of pravastatin preventing BKPyV infection in HRPTEC, statins at doses maximized for cholesterol lowering, in RTR with BKPyV viremia, did not prevent progression to PyVAN.

Understanding and improving the use of allopurinol in a teaching hospital.

BACKGROUND: An emphasis on renal function in deciding maintenance doses of allopurinol to prevent allopurinol hypersensitivity has resulted in ineffective prevention of attacks of gout. New therapeutic guidelines for gout have shifted the focus back to titrating maintenance doses to reach a serum uric acid (SUA) concentration target of ≤ 0.36 mmol/L. AIMS: To examine trends in the prescribing of allopurinol in a teaching hospital and their concordance with the new guidelines for gout management, and to explore prescribers' approaches and attitudes to the use of allopurinol. METHODS: An audit was conducted of all inpatients prescribed allopurinol at a teaching hospital between January 2008 and December 2012. Allopurinol dose, SUA, serum creatinine concentrations and estimated glomerular filtration rates were extracted from the hospital databases. Doctors from medical units who regularly prescribed allopurinol were interviewed. RESULTS: The allopurinol dose prescribed in gout patients most commonly was a continuation of the pre-admission dosage. Dosage change during admission was rarely observed. Dosages reflected a consideration of renal function. SUA concentrations were measured in only 21% (n = 269) of gout patients. Prescriber interviews (n = 12) reflected adequate knowledge regarding allopurinol use, but most maintained that the primary care setting was more suitable for the management of dose titration in gout. CONCLUSIONS: SUA concentrations were not routinely measured in the majority of admitted gout patients taking allopurinol. Without SUA measurements and allopurinol dose titration, patients with SUA > 0.36 mmol/L are at increased risk for acute attacks of gout in hospital.

In vitro and in vivo anticancer activity of surface modified paclitaxel attached hydroxyapatite and titanium dioxide nanoparticles.

Targeted drug delivery using nanocrystalline materials delivers the drug at the diseased site. This increases the efficacy of the drug in killing the cancer cells. Surface modifications were done to target the drug to a particular receptor on the cell surface. This paper reports synthesis of hydroxyapatite and titanium dioxide nanoparticles and modification of their surface with polyethylene glycol (PEG) followed by folic acid (FA). Paclitaxel, an anticancer drug, is attached to functionalized hydroxyapatite and titanium dioxide nanoparticles. The pure and functionalised nanoparticles are characterised with XRD, TEM and UV spectroscopy. Anticancer analysis was carried out in DEN induced hepatocarcinoma animals. Biochemical, hematological and histopathological analysis show that the surface modified paclitaxel attached nanoparticles have an higher anticancer activity than the pure paclitaxel and surface modified nanoparticles without paclitaxel. This is due to the targeting of the drug to the folate receptor in the cancer cells.

De Novo transcriptome assembly (NGS) of Curcuma longa L. rhizome reveals novel transcripts related to anticancer and antimalarial terpenoids.

Herbal remedies are increasingly being recognised in recent years as alternative medicine for a number of diseases including cancer. Curcuma longa L., commonly known as turmeric is used as a culinary spice in India and in many Asian countries has been attributed to lower incidences of gastrointestinal cancers. Curcumin, a secondary metabolite isolated from the rhizomes of this plant has been shown to have significant anticancer properties, in addition to antimalarial and antioxidant effects. We sequenced the transcriptome of the rhizome of the 3 varieties of Curcuma longa L. using Illumina reversible dye terminator sequencing followed by de novo transcriptome assembly. Multiple databases were used to obtain a comprehensive annotation and the transcripts were functionally classified using GO, KOG and PlantCyc. Special emphasis was given for annotating the secondary metabolite pathways and terpenoid biosynthesis pathways. We report for the first time, the presence of transcripts related to biosynthetic pathways of several anti-cancer compounds like taxol, curcumin, and vinblastine in addition to anti-malarial compounds like artemisinin and acridone alkaloids, emphasizing turmeric's importance as a highly potent phytochemical. Our data not only provides molecular signatures for several terpenoids but also a comprehensive molecular resource for facilitating deeper insights into the transcriptome of C. longa.

Next generation sequencing and de novo transcriptome analysis of Costus pictus D. Don, a non-model plant with potent anti-diabetic properties.

BACKGROUND: Phyto-remedies for diabetic control are popular among patients with Type II Diabetes mellitus (DM), in addition to other diabetic control measures. A number of plant species are known to possess diabetic control properties. Costus pictus D. Don is popularly known as "Insulin Plant" in Southern India whose leaves have been reported to increase insulin pools in blood plasma. Next Generation Sequencing is employed as a powerful tool for identifying molecular signatures in the transcriptome related to physiological functions of plant tissues. We sequenced the leaf transcriptome of C. pictus using Illumina reversible dye terminator sequencing technology and used combination of bioinformatics tools for identifying transcripts related to anti-diabetic properties of C. pictus. RESULTS: A total of 55,006 transcripts were identified, of which 69.15% transcripts could be annotated. We identified transcripts related to pathways of bixin biosynthesis and geraniol and geranial biosynthesis as major transcripts from the class of isoprenoid secondary metabolites and validated the presence of putative norbixin methyltransferase, a precursor of Bixin. The transcripts encoding these terpenoids are known to be Peroxisome Proliferator-Activated Receptor (PPAR) agonists and anti-glycation agents. Sequential extraction and High Performance Liquid Chromatography (HPLC) confirmed the presence of bixin in C. pictus methanolic extracts. Another significant transcript identified in relation to anti-diabetic, anti-obesity and immuno-modulation is of Abscisic Acid biosynthetic pathway. We also report many other transcripts for the biosynthesis of antitumor, anti-oxidant and antimicrobial metabolites of C. pictus leaves. CONCLUSION: Solid molecular signatures (transcripts related to bixin, abscisic acid, and geranial and geraniol biosynthesis) for the anti-diabetic properties of C. pictus leaves and vital clues related to the other phytochemical functions like antitumor, anti-oxidant, immuno-modulatory, anti-microbial and anti-malarial properties through the secondary metabolite pathway annotations are reported. The data provided will be of immense help to researchers working in the treatment of DM using herbal therapies.

Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation.

H2S is highly toxic and selectively inhibits butyrate oxidation in colonocytes. Ineffective detoxification may result in mucosal insult, inflammation, and ultimately in colorectal cancer (CRC). Rhodanese can detoxify H2S and is comprised of two isoenzymes: thiosulfate sulfurtransferase (TST) and mercaptopyruvate sulfurtransferase (MST). Using specific antisera to discriminate TST from MST, we found that only TST could detoxify H2S. In sections of normal colon, both enzymes were located on the luminal mucosal surface, and they were expressed in the colonocytes but not in the mucin-secreting goblet cells. Expression of both enzymes was focally lost in ulcerative colitis and markedly reduced in advanced colon cancer, the disease progression correlating with the decreased expression of MST and TST. In HT-29 cells, a human colon cancer cell line, TST activity and expression were significantly increased by butyrate and by histone deacetylase inhibition, agents that promote HT-29 cell differentiation. Sulfide (0.1 mM) also increased TST activity, but higher sulfide concentrations (0.3-3 mM) were toxic. Preincubation in butyrate to increase TST expression, decreased sensitivity of the cells to sulfide toxicity. We conclude that decreased expression of TST (or MST) is a tumor marker for CRC. TST expression is increased in colonocyte differentiation. Dysregulation of TST expression and activity resulting in inability to effectively detoxify could be a factor in the cell loss and inflammation that accompany ulcerative colitis and ultimately then in CRC.

The effects of phytochemical pesticides on the growth of cultured invertebrate and vertebrate cells.

A range of cultured cells of invertebrate and vertebrate origin was grown in the presence of a number of phytochemical pesticides to test the effect of the latter on cell proliferation. The main observation was that azadirachtin was a potent inhibitor of insect cell replication, with an EC50 of 1.5 x 10(10) M against Spodoptera cells and of 6.3 x 10(9) M against Aedes albopictus cells, whilst affecting mammalian cells only at high concentrations (> 10(-4) M). As expected, the other phytochemical pesticides, except for rotenone, had little effect on the growth of the cultured cells. Rotenone was highly effective in inhibiting the growth of insect cells (EC50:10(-8) M) but slightly less toxic towards mammalian cells (EC50:2 x 10(-7) M). Neem terpenoids other than azadirachtin and those very similar in structure significantly inhibited growth of the cell cultures, but to a lesser degree. The major neem seed terpenoids, nimbin and salannin, for example, inhibited insect cell growth by 23% and 15%, respectively.