Cosmeceutical Aptitudes of Azelaic Acid.

Azelaic acid (AZA) is a white crystalline dicarboxylic acid naturally found in grains, rye, and barley. AZA has substantial biological and therapeutic abilities (viz a viz) its anti-inflammatory, anti-oxidant, anti-keratinizing, anti-microbial properties, etc., which contribute to its applicability in the management of mild to harsh dermatological complications (acne, rosacea, dermatitis, hyper-pigmentation, carcinomas, etc.). AZA has shown its effectiveness against varied non-inflammatory and inflammatory lesions by normalizing hyper-keratinization state and attenuating the increased levels of microbial content. Topically AZA, either alone or in conjunction with other active moieties, has proved to effectively prevent acne and several other hyper-pigmentary conditions. Chronic applicability of AZA has been evidenced with the effects like itching, burning, stinging, redness, etc. To deal with the former issues, research is being conducted to substitute the conventional formulations with novel preparations (liposome's, niosomes, micro sponges, lipid nanocarriers, etc.), which could enhance the overall pharmaceutical and pharmacological profile of the drug. This article is an attempt to highlight the basic physiochemical properties of AZA, its physiological role (especially in dermatology), various commercial preparations and recent novel approaches that are in research with an aim to augment the therapeutic and safety profile of AZA.

Near complete resolution of COVID-19 pneumonia lesions in a patient of carcinoma lung treated with volumetric modulated arc therapy.

A 49-year-old male presented with non-small cell lung cancer in right upper lobe lung with solitary brain metastasis. He developed COVID-19 infection and received domiciliary treatment for 3 weeks. Three weeks after testing negative for RT-PCR test, he received stereotactic radiosurgery (SRS) to brain metastasis. He then presented in emergency with pain in the epigastrium and was detected with amoebic liver abscess. Subsequently, he developed recurrent hemoptysis for which he was planned for palliative radiation to right lung mass. Planning CT scan showed COVID-19 pneumonia lesions involving bilateral lungs in addition to right upper lobe tumour. Palliative radiation 8 Gy/1 fraction was delivered to lung tumour with VMAT technique. He showed near total resolution of COVID-19 lesions with low-dose scatter radiation and relief of haemoptysis.

Expanding the Arsenal Against Huntington's Disease-Herbal Drugs and Their Nanoformulations.

Huntington's disease (HD) is an autosomal fatal genetic disease in which degeneration of neuronal cells occurs in the central nervous system (CNS). Commonly used therapeutics are cludemonoamine depletors, antipsychotics, antidepressants, and tranquilizers. However, these drugs cannot prevent the psychotic, cognitive, and behavioral dysfunctions associated with HD. In addition to this, their chronic use is limited by their long-term side effects. Herbal drugs offer a plausible alternative to this and have shown substantial therapeutic effects against HD. Moreover, their safety profile is better in terms of side effects. However, due to limited drug solubility and permeability to reach the target site, herbal drugs have not been able to reach the stage of clinical exploration. In recent years, the paradigm of research has been shifted towards the development of herbal drugs based nanoformulations that can enhance their bioavailability and blood-brain barrier permeability. The present review covers the pathophysiology of HD, available biomarkers, phytomedicines explored against HD, ongoing clinical trials on herbal drugs exclusively for treating HD and their nanocarriers, along with their potential neuroprotective effects.

Stereotactic ablative radiotherapy (SABR) for recurrent and previously irradiated head and neck cancers.

OBJECTIVE: To assess the response and toxicity of stereotactic ablative radiotherapy (SABR) in patients with recurrent head and neck cancer (HNC), who had previously received radiation for their primary tumor. METHODS: Between 2014 and 2018, patients who received SABR to recurrent HNC within the previously irradiated region were retrospectively reviewed. Mean age was 60 years (range 30-78 Years). Histology was confirmed in all patients. MRI and /or CT-positron emission tomography were done to evaluate local extent and to rule out metastasis. Response was assessed as per RECIST/PERCIST Criteria. Cox proportional hazards regression and the Kaplan-Meier methods were used for statistical analysis. RESULTS: 32 patients received SABR. RPA Class II, III patients were 20 and 12 respectively. 87% patients received a dose of ≥30 Gy/5 fractions. Median follow-up was 12 months. Estimated 1 year and 2 years local control was 64.2 and 32% and 1 year and 2 years overall survival was 67.5 and 39.5% respectively. Acute Grade 2 skin and Grade 3 mucosal toxicity was seen in 31.3 and 28% patients respectively. Late Grade 3 toxicity was seen in 9.3% patients. CONCLUSION: Re-irradiation with SABR yields high local control rates and is well tolerated. It compares favorably with other treatment modalities offered to patients with recurrent HNC. It is also suitable for patients of RPA Class II and III. There is need for novel systemic agents to further improve the survival. ADVANCES IN KNOWLEDGE: Treatment of patients with recurrent HNC is challenging and is more difficult in previously radiated patient. More than 50% patients are unresectable. Other options of salvage treatment like re-irradiation and chemotherapy are associated with poor response rates and high incidence of acute and late toxicity (Gr ≥3 toxicity 50-70%). SABR is a novel technology to deliver high dose of radiation to recurrent tumor with high precision. It yields high local control rates with less toxicity compared to conventionally fractionated radiation.

Development and Validation of a MATLAB Software Program for Decoding the Treatment Errors in Real-time Position Management™ Gating-generated Breathing Trace.

INTRODUCTION: The Real-time Position Management™ (RPM) is used as a motion management tool to reduce normal tissue complication. However, no commercial software is available to quantify the "beam-on" errors in RPM-generated breathing traces. This study aimed to develop and validate an in-house-coded MATLAB program to quantify the "beam-on" errors in the breathing trace. MATERIALS AND METHODS: A graphical user interface (GUI) was developed using MATLAB (Matrix Laboratory Ra2016) software. The GUI was validated using two phantoms (Varian-gated phantom and Brainlab ET gating phantom) with three regular motion profiles. Treatment time delay was calculated using regular sinusoidal motion profile. Ten patient's irregular breathing profiles were also analyzed using this GUI. RESULTS: The beam-on comparison between the recorded reference trace and irradiated trace profile was done in two ways: (1) beam-on time error and (2) beam-on displacement error. These errors were ≤1.5% with no statistical difference for phase- and amplitude-based treatments. The predicated amplitude levels of reference phase-based profiles, and the actual amplitude levels of amplitude-based irradiated profiles were almost equal. The average treatment time delay was 47 ± 0.003 ms. The irregular breathing profile analysis showed that the amplitude-based gating treatment was more accurate than phase based. CONCLUSION: The developed GUI gave the same and acceptable results for all regular profiles. These errors were due to the lag time of the linear accelerator with gating treatment. This program can be used as to quantifying the intrafraction "beam-on" errors in breathing trace with both mode of gating techniques for irregular breathing trace, and in addition, it is capable to convert phase-based gating parameters to amplitude-based gating parameters for treatment.

The Composite Planning Technique in Left Sided Breast Cancer Radiotherapy: A Dosimetric Study.

OBJECTIVE: The aim of this retrospective study is to reduce the dose of heart, both lung and opposite breast and left anterior descending artery (LAD) and avoid long term complication and radiation induced secondary malignancies in radiotherapy left breast/chest wall without losing homogeneity and conformity of the Planning Target Volume (PTV), contoured using Radiotherapy Oncology Group (RTOG 1005) guideline. MATERIALS AND METHODS: The treatment plans were generated retrospectively by TFIF, VMAT and Composite techniques for 30 patients. Dose-Volume Histograms (DVHs) were evaluated for PTV and organs at risk (OAR's) and analyzed in two groups BCS and MRM using Wilcoxon signed rank test. RESULTS: The homogeneity index (HI) was improved in Composite technique by 32.72% and 21.81% of VMAT, 50.66% and 49.41% of TFIF in BCS and MRM group respectively. The Conformity Index (CI) for composite plan was statistically same as VMAT and superior by 27.94% and 41.37% of TFIF in BCS and MRM group respectively. The low dose volume V5Gy and V10Gy of the heart were improved in Composite plan by 47.9% and 26.1% of VMAT respectively in BCS group and in MRM group, improved by 21.2% and 45.6% of VMAT. The V5Gy and V10Gy of ipsilateral lung were improved in Composite plan by 16% and 13.7% of VMAT respectively in BCS and 8.4% and 3% of VMAT respectively in MRM group. CONCLUSION: The Composite plan consisting of VMAT and TFIF plan with an optimum selection of fractions can achieve lower low dose exposure to the OAR's without compromising coverage compared to VMAT.

Stereotactic ablative body radiotherapy (SABR) for inoperable, chemorefractory retroperitoneal lymph node relapse from non seminomatous germ cell tumour of testis: a case report.

We describe a case of non-seminomatous germ cell tumour (NSGCT) of the testis with oligorecurrence in para-aortic nodal mass, which was inoperable and chemorefractory. Conventionally fractionated radiotherapy in this setting is generally believed to achieve poor results, because the dose is limited by the tolerance of surrounding normal tissues. Use of stereotactic ablative body radiotherapy (SABR) for para-aortic nodal recurrence from a few sites has been reported; its application in NSGCT has not been described in literature to our knowledge. SABR allowed us to deliver highly precise, ablative dose of radiation to the recurrent para-aortic nodal mass with long-term disease control (more than 6 years). The ablative dose delivered with SABR proved to be effective in NSGCT, traditionally considered radioresistant. While, in the present case SABR was delivered due to the inoperability of the lesion, further data on its successful use in NSGCT recurrences is warranted.

Plasma fibronectin stabilizes Borrelia burgdorferi-endothelial interactions under vascular shear stress by a catch-bond mechanism.

Bacterial dissemination via the cardiovascular system is the most common cause of infection mortality. A key step in dissemination is bacterial interaction with endothelia lining blood vessels, which is physically challenging because of the shear stress generated by blood flow. Association of host cells such as leukocytes and platelets with endothelia under vascular shear stress requires mechanically specialized interaction mechanisms, including force-strengthened catch bonds. However, the biomechanical mechanisms supporting vascular interactions of most bacterial pathogens are undefined. Fibronectin (Fn), a ubiquitous host molecule targeted by many pathogens, promotes vascular interactions of the Lyme disease spirochete Borrelia burgdorferi Here, we investigated how B. burgdorferi exploits Fn to interact with endothelia under physiological shear stress, using recently developed live cell imaging and particle-tracking methods for studying bacterial-endothelial interaction biomechanics. We found that B. burgdorferi does not primarily target insoluble matrix Fn deposited on endothelial surfaces but, instead, recruits and induces polymerization of soluble plasma Fn (pFn), an abundant protein in blood plasma that is normally soluble and nonadhesive. Under physiological shear stress, caps of polymerized pFn at bacterial poles formed part of mechanically loaded adhesion complexes, and pFn strengthened and stabilized interactions by a catch-bond mechanism. These results show that B. burgdorferi can transform a ubiquitous but normally nonadhesive blood constituent to increase the efficiency, strength, and stability of bacterial interactions with vascular surfaces. Similar mechanisms may promote dissemination of other Fn-binding pathogens.

Significance of perineural invasion in locally advanced bucco alveolar complex carcinomas treated with surgery and postoperative radiation ± concurrent chemotherapy.

BACKGROUND: The purpose of this study was to evaluate prognostic factors, locoregional control, and survival in locally advanced bucco-alveolar complex cancers. METHODS: A retrospective review of 83 patients treated between January 2009 and December 2012 with bucco-alveolar complex cancers was conducted. All patients had surgery and adjuvant radiotherapy with intensity-modulated radiotherapy (IMRT) with/without concurrent chemotherapy. Survival analysis was performed using Kaplan-Meier and multivariable Cox regression model. RESULTS: On univariate and multivariate analysis, perineural invasion (PNI) was found to be an independent adverse risk factor. Patients with PNI-positive disease had significantly worse 2-year disease-free survival (DFS), locoregional failure free survival, and overall survival (OS) as compared to patients with PNI-negative disease (P < 0. 001, 0.001 and < 0. 001) respectively. CONCLUSION: Compared with patients with PNI-negative disease, patients with PNI-positive disease had much worse outcome despite aggressive adjuvant treatment. It warrants escalation of therapy and modification in radiation portals to cover neural pathways in patients with PNI-positive disease.

Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet-induced obesity.

Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high-fat diet-induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil- and macrophage-based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B. burgdorferi-infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high-fat diet, toll-like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow-derived macrophages from obese, B. burgdorferi-infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice.

The Lyme Disease Pathogen Borrelia burgdorferi Infects Murine Bone and Induces Trabecular Bone Loss.

Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice. In mice inoculated with B. burgdorferi or vehicle (mock infection), we measured the presence of B. burgdorferi DNA in bones, bone mineral density (BMD), bone formation rates, biomechanical properties, cellular composition, and two- and three-dimensional features of bone microarchitecture. B. burgdorferi DNA was detected in bone. In the long bones, increasing B. burgdorferi DNA copy number correlated with reductions in areal and trabecular volumetric BMDs. Trabecular regions of femora exhibited significant, copy number-correlated microarchitectural disruption, but BMD, microarchitectural, and biomechanical properties of cortical bone were not affected. Bone loss in tibiae was not due to increased osteoclast numbers or bone-resorbing surface area, but it was associated with reduced osteoblast numbers, implying that bone loss in long bones was due to impaired bone building. Osteoid-producing and mineralization activities of existing osteoblasts were unaffected by infection. Therefore, deterioration of trabecular bone was not dependent on inhibition of osteoblast function but was more likely caused by blockade of osteoblastogenesis, reduced osteoblast survival, and/or induction of osteoblast death. Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption.

Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

A patient-based dosimetric study of intracavitary and interstitial brachytherapy in advanced stage carcinoma of the cervix.

Intracavitary brachytherapy (ICBT) and interstitial brachytherapy (IB) techniques are commonly practiced for treating carcinoma of the cervix, either alone or in combination with external beam radiotherapy. Both these brachytherapy techniques have their own advantages and limitations in terms of tumor coverage and normal tissue sparing. Limited studies have been reported comparing the dosimetric features of these two techniques, especially from a single institution. We carried out a prospective clinical dosimetric comparison between ICBT and IB for patients treated at one center to bring out the inherent dosimetric features of these to two techniques. The study was carried out on 26 patients treated with ICBT and 55 with IB using CT-based planning. Of the 55 patients treated with IB, 27 included tandem source loading (IBT) and 28 without the tandem loading (IBWT). The high-dose volumes covered by 200% and 180% isodose surfaces were considerably larger in ICBT as compared to IB, whereas the treated volume was larger in IB as compared to ICBT. The bladder and rectal doses were the highest in ICBT and IBWT, respectively. The larger treated volume in IB as compared to ICBT was mainly because patients with larger tumor volumes were generally considered for IB. The results also indicated that in interstitial brachytherapy, better rectal sparing was achieved by including the tandem for treatment delivery.

Fractionated stereotactic radiosurgery with volumetric modulated arc therapy (Rapid Arc) for reradiation in recurrent high grade gliomas.

BACKGROUND: To evaluate 'Rapid Arc (RA)' technique for delivering fractionated stereotactic radiosurgery (FSRS) in patients with recurrent high grade gliomas (HGGs) for minimizing the dose to previously radiated high dose brain volume. MATERIALS AND METHODS: Between April 2010 and February 2011, 16 consecutive patients with recurrent HGGs and previously treated with intensity modulated radiation therapy (IMRT) and Temozolamide received FSRS. The median time between IMRT and FSRS was 10.72 months. FSRS to a dose of 30 Gy in a median of 5 fractions was delivered to the recurrent tumor (gross tumor volume [GTV]). Brain volume around the GTV and previously treated to a mean dose >50 Gy was delineated as "Avoidance Volume (AV)." Patients were planned with both RA and Dynamic Conformal Arc (DCA) to achieve minimum dose to AV. Dose received by GTV, AV, rest of the normal brain (brain minus PTV) and conformity index (CI) and heterogenecity index (HI) were compared by the two techniques. RESULTS: At a median follow up of 7.33 months, median progression free and overall survival was 6.4 and 9.3 months, respectively. Mean dose to AV was significantly lower with RA as compared with DCA (10.8 Gy vs. 15.5 Gy, P - 0.0001) with no significant difference in the dose delivered to GTV. No patient developed radiation necrosis. CONCLUSION: As compared with DCA, RA delivered significantly less dose to previously radiated high dose brain volume. It may contribute to minimizing the risk of radionecrosis with stereotactic radiosurgery (SRS) in patients with recurrent HGG.

A phantom study on bladder and rectum dose measurements in brachytherapy of cervix cancer using FBX aqueous chemical dosimeter.

The ferrous sulphate-benzoic acid-xylenol orange (FBX) chemical dosimeter, due to its aqueous form can measure average volume doses and hence may overcome the limitations of point dosimetry. The present study was undertaken to validate the use of FBX dosimeter for rectum and bladder dose measurement during intracavitary brachytherapy (ICBT) and transperineal interstitial brachytherapy (TIB). We filled cylindrical polypropylene tubes (PT) and Foley balloons (FB) with FBX solution and used them as substitutes for rectum and bladder dose measurements respectively. A water phantom was fabricated with provision to place the Fletcher-type ICBT and MUPIT template applicators, and FBX filled PT and FB within the phantom. The phantom was then CT scanned for treatment planning and subsequent irradiation. Our results show that the average difference between DVH derived dose value and FBX measured dose is 3.5% (PT) and 13.7% (FB) for ICBT, and 9% (PT) and 9.9% (FB) for TIB. We believe that the FBX system should be able to provide accuracy and precision sufficient for routine quality assurance purposes. The advantage of the FBX system is its water equivalent composition, average volume dose measuring capability, and energy and temperature independent response as compared to TLD or semiconductor dosimeters. However, detailed studies will be needed with regards to its safety before actual in-vivo dose measurements are possible with the FBX dosimeter.

Celiac G+ antibody assay for the detection of autoantibodies in celiac disease.

Celiac disease (CD) affects approximately 1% of the population and may present with varied symptomatic as well as asymptomatic clinical manifestations. Simple methods of detecting CD such as serum antibody tests have helped in the early identification of the disease thus preventing serious complications of the disorder. Our objective is to develop specific and sensitive immunoassays that are reliable in the detection of CD. To this end, immunoassays were developed for the detection of IgG and IgA antibodies to gliadin using synthetic peptides. Over 200 serum samples were included in the study from individuals with CD submitted for endomysial (EMA) and tissue transglutaminase (tTG) antibody tests as well as from disease controls and healthy normals. To examine the reliability of the Celiac G+ antibody test in comparison with EMA, a test with higher sensitivity and specificity, samples with low and high EMA titers were included in the study. Comparative evaluations of the Celiac G+ antibody assay were made with EMA and another commercially available gliadin peptide assay along with tTG antibody assays. The data show that as the EMA levels increased the sensitivity of detection of antibodies to synthetic peptides on both systems increased, reaching 100% at EMA titers greater than 160. The diagnostic performance of the newly developed Celiac G+ synthetic gliadin peptide assay is significantly superior in comparison with another available gliadin peptide immunoassay. Overall, the diagnostic performance of the Celiac G+ assay for IgA and IgG reached a sensitivity of 80% and 90% respectively in comparison with EMA. Similar comparison of the EMA positivity to the other available synthetic peptide immunoassay yielded sensitivities of 59% (IgA) and 75% (IgG). The specificity of the Celiac G+ antibody assay for IgA and IgG was 90-95% as compared to the other similar assay with specificity of 88-90%. In conclusion, the performance of the recently developed Celiac G+ ELISA is superior in both its sensitivity and specificity in comparison with other available synthetic gliadin peptide immunoassays. Furthermore, the IgG Celiac G+ antibody test and IgA tTG antibody test used in combination is an excellent screening algorithm for suspected cases of celiac disease.

Characterisation of the constitutive over-expression of AJ18 in a novel rat stromal bone marrow cell line (D8-SBMC).

OBJECTIVE: The elucidation of the molecular pathways involved in osteoblast proliferation and differentiation has been greatly enhanced by the availability of cell culture model systems. However, many of the current bone cell culture systems suffer from disadvantages such as the inability to generate mineralised bone-like nodules, a transformed genetic background, cell heterogeneity, and a relatively long time frame from cell seeding to mineralisation, often in the order of several weeks. Here we describe the establishment and characterisation of a novel bone cell line named D8-SBMC. As a first demonstration of their potential value, D8-SBMC was utilised to further support a role for AJ18 during osteogenesis. DESIGN: D8-SBMC was established from a single cell suspension of the previously characterised long term rat stromal bone marrow cells [Kotev-Emeth S, Pitaru S, Pri-Chen S, Savion N. Establishment of a rat long-term culture expressing the osteogenic phenotype: dependence on dexamethasone and FGF-2. Connect Tissue Res 2002;43(4):606-12; Pitaru S, Kotev-Emeth S, Noff D, Kaffuler S, Savion N. Effect of basic fibroblast growth factor on the growth and differentiation of adult stromal bone marrow cells: enhanced development of mineralized bone-like tissue in culture. J Bone Miner Res 1993;8(8):919-29]. AJ18 was constitutively and stably over-expressed in D8-SBMC and analysed. RESULTS: D8-SBMC possesses the ability to form robust mineralised bone-like nodules within 8 days proceeding cell confluency. Interestingly, a cement line-like matrix is also generated between the culture dish and a basal monolayer of cells. Constitutive and stable over-expression of AJ18 resulted in an increase in cell proliferation and mineralisation. Expression of bone marker genes, such as bone sialoprotein, osteopontin, osteocalcin, collage type 1, and osteonectin, was up-regulated by AJ18 over-expression. CONCLUSION: A novel bone cell line, D8-SBMC, was established and characterised. D8-SBMC may be a valuable model system for biomineralisation studies. D8-SBMC was utilised to further understand the role of AJ18 in cell proliferation and differentiation during osteogenesis.

FBX aqueous chemical dosimeter for measurement of virtual wedge profiles.

We investigated the ferrous sulfate-benzoic acid-xylenol orange (FBX) aqueous chemical dosimeter for measurement of virtual (dynamic) wedge profiles on a linear accelerator. The layout for irradiation of the FBX-filled tubes mimicked a conventional linear detector array geometry. A comparison of the resulting measurements with film-measured profiles showed that, in the main beam region, the difference between the FBX system and the film system was within +/-2% and that, in the penumbra region, the difference varied from +/-1 mm to +/-2.5 mm in terms of positional equivalence, depending on the size of the dosimeter tubes. We thus believe that the energy-independent FBX dosimetry system can measure virtual wedge profiles with reasonable accuracy at reasonable cost. However, efficiency improvement is required before this dosimetry system can be accepted into routine practice.

Role of vitamin E in mitigating methomyl induced acute toxicity in blood of male Wistar rats.

The present study was designed to evaluate the protective potential of vitamin E, if any, in attenuating the toxic effects induced by acute methomyl treatment in rats. Male Wistar rats, weighing between 230 and 250 g, received either a single oral dose of 9 mg/kg of methomyl, vitamin E alone injected intraperitoneally on alternate days (4 injections) at 50 mg/kg body for 1 week prior to methomyl treatment, or both methomyl plus vitamin E given in a similar manner. The effects of different treatments were studied on lipid peroxidation (LPO), reduced glutathione (GSH) and antioxidant enzymes, which included superoxide dismutase (SOD), glutathione-s-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GSHPx) and catalase and various hematological parameters, including total leucocytes count (TLC), differential leukocyte count (DLC), hemoglobin, platelets counts, red cell counts, and scanning electron microscopy (SEM). Acute 24-h treatment to rats resulted in a significant increase in the LPO. GSH levels and the activities of catalase, GST, and GSHPx were found to be significantly decreased following methomyl treatment. A significant elevation in the activity of SOD and in TLC was also observed after 24 h of methomyl treatment. Further, a significant increase in the neutrophils and eosinophil counts was also observed. However, lymphocytes showed a significant decrease following methomyl treatment. SEMs showed significant morphological changes following methomyl treatment. Vitamin E pretreatment to methomyl-treated rats effectively normalized the levels of LPO and GSH. Vitamin E could also significantly elevate the activity of catalase, increase platelets counts and TLC, and normalized the activities of SOD and GSHPx. Vitamin E pretreatment improved the morphology of the red blood cells. The study concludes that vitamin E affords protection in methomyl-induced toxicity in the rat.

Role of osteopontin in neutrophil function.

Osteopontin (OPN) is important for the function of fibroblasts, macrophages and lymphocytes during inflammation and wound healing. In recent studies of experimental colitis we demonstrated exacerbated tissue destruction in OPN-null mice, associated with reduced tumour necrosis factor-alpha expression and increased myeloperoxidase activity. The objective of this investigation therefore was to determine the importance of OPN expression in neutrophil function. Although, in contrast to macrophages, neutrophils expressed low levels of OPN with little or no association with the CD44 receptor, intraperitoneal recruitment of neutrophils in OPN-null mice was impaired in response to sodium periodate. The importance of exogenous OPN for neutrophil recruitment was demonstrated by a robust increase in peritoneal infiltration of PMNs in response to injections of native or recombinant OPN. In vitro, OPN(-/-) neutrophils exhibited reduced chemokinesis and chemotaxis towards N-formyl methionyl leucyl phenylalanine (fMLP), reflecting a reduction in migration speed and polarization. Exogenous OPN, which was chemotactic for the neutrophils, rescued the defects in polarization and migration speed of the OPN(-/-) neutrophils. In contrast, the defensive and cytocidal activities of OPN(-/-) neutrophils, measured by assays for phagocytosis, generation of reactive oxygen species, cytokine production and matrix metalloproteinase-9, were not impaired. These studies demonstrate that, while exogenous OPN may be important for the recruitment and migration of neutrophils, expression of OPN by neutrophils is not required for their destructive capabilities.