Are the Cytotoxic Properties of Conjugated Unsaturated Ketones Inactivated by Thiols?

The focus of this study was to examine whether the conversion of cytotoxic conjugated unsaturated ketones (or enones) into the corresponding thiol adducts leads to a reduction or abolition of cytotoxic potencies. A number of enones and related thiol adducts were evaluated against human HCT116 and HT29 colon cancer cells. Some 63% of the IC50 values are less than 10 µM and several compounds are more toxic than 5-FU. The thiol adducts are either more potent or are equipotent with the corresponding enones. A number of compounds are far more toxic to HCT116 and HT29 neoplasms than non-malignant CRL1790 cells leading to impressive Selectivity Index figures. An additional positive feature of these compounds is that they have favorable ADME properties.

Cytotoxic benzylidene hydrazides of terephthalic acid and related compounds.

The present investigation involved the synthesis of a number of novel benzylidene hydrazides as candidate cytotoxic agents. The preparation of these compounds from terephthalic acid and isophthalic acid proceeded satisfactorily. However, the reaction of phthalic acid hydrazide with various aryl aldehydes was unsuccessful in general. Some of the unexpected products were identified. The shapes and also the distances between the centers of the aryl rings designated B and C of three representative compounds 1b, 2b and 3b were determined. The compounds designated 1a-e, 2a-e and 3b were screened against human HCT116 and HT29 colon cancer cells as well as human CRL1790 non-malignant colon cells which revealed the tumor-selective toxicity displayed by these compounds.

Establishment of tandem mass spectrometric fingerprint of novel antineoplastic curcumin analogues using electrospray ionization.

RATIONALE: Curcumin analogues are antineoplastic agents, designed based on the structure of the spice turmeric with structural modifications aiming at enhancing potency. The goal is to identify the common tandem mass spectrometric (MS/MS) behavior of 13 novel curcumin analogues. Such knowledge is critical for their biological assessment, including metabolite identification and pharmacokinetic evaluation. METHODS: Both detection of the protonated molecules [M + H](+) of the synthesized compounds and determination of their exact molecular masses were achieved with hybrid quadrupole orthogonal time-of-flight mass spectrometry (QqTOF-MS). Low-energy collision-induced dissociation (CID)-MS/MS analysis was performed using triple quadrupole linear ion trap mass spectrometry (QqLIT-MS). Both instruments were equipped with an electrospray ionization (ESI) source. MS(3) and neutral loss experiments were performed using QqLIT-MS to confirm the genesis of the observed product ions. RESULTS: Abundant [M + H](+) molecules were formed using the QqTOF-MS hybrid instrument with mass accuracies below 6 ppm. CID-MS/MS dissociation studies were centered on the piperidone ring of curcumin analogues; twelve common product ions have been identified from the fission of the various bonds within the piperidone moiety. There was a tendency for the formation of highly conjugated product ions, stabilized via resonance. The variety of the side-chain substituents at the nitrogen atom resulted in side-chain-specific product ions. CONCLUSIONS: The ESI-CID-MS/MS analysis of curcumin analogues revealed a common fragmentation behavior of all tested compounds, which gave diagnostic product ions identified for each molecule. The established MS/MS behavior will be applied to determine metabolic by-products of curcumin analogues as well as to develop targeted identification/quantification methods within biological extracts.

Beta thalassemia in a tertiary care hospital with their chelation habit.

Beta-thalassemia which is one of the most common genetic disorders in Bangladesh encompasses a group of monogemic diseases that have reduced synthesis or no synthesis of one or more globin chain of haemoglobin. The defects involved are extremely heterogenous and give rise to a large phenotypic spectrum with patients that are almost asymptomatic to cases in which regular blood transfusions are required to sustain life. The aim of the study is to estimate the frequency of beta thalassemia among the blood recipients in the Day Care Centre of Transfusion Medicine Department of Mymensingh Medical College Hospital from July, 2009 to June, 2010 along with their chelation habit. Retrospective cross-sectional study with the sample size of 784, clinical and family data was collected and descriptive statistics were done in the Laboratory of Transfusion Medicine Department. Among the 784 subjects, the beta thalassemia was 521 (66.46%), among the thalassemic patients only 59(11.32%) take injection Dysferrioxamine (Dysferol), the iron chelating agent. Male are predominant than female (63.53%). Those of the affected patients 67.18% were in age group 6 to 20 years. Although beta thalassemia is one of the first monogemic diseases and represents a global health problem, only recently has the scientific community started to focus on the real molecular mechanisms that underline this disease, opening new & exciting therapeutic perspectives for thalassemic patients worldwide. It is concluded from our study that availability of blood transfusion facilities along with an orally and cheaper iron chelator is an urgent need to ensure the management of needy thalassemic patients in Bangladesh.

Effect of various concentrations of sodium hypochlorite on primary dentin: an in vitro scanning electron microscopic study.

BACKGROUND: Sodium hypochlorite solutions have been evaluated for their effects in bonding procedures as they are found to deplete or remove the organic portion of the dentin, particularly the collagen fibrils. The aim of this in vitro study was to assess and compare the efficacies of 1%, 2.5%, 5% and 10% NaOCl at 30, 60 and 120s on etched primary dentin. METHODS: 84 primary anterior teeth were ground to expose a flat dentin area on the buccal surface. The specimens were divided into fourteen groups of six each based on the dentin surface treatment (35% phosphoric acid etching for 7 seconds-AE and/or NaOCl application), NaOCl solution concentrations (1%, 2.5%, 5% and 10%) and time of application (0, 30, 60 and 120s). Specimens were prepared for SEM and photomicrographs were taken of the surface and were scored against a five point scale, based on the smear layer and amount of collagen removed. The scores were submitted to Kruskal-Wallis and Mann Whitney tests. RESULTS: This study showed the presence of smear layer in the control group. The group treated with Acid Etchant showed a demineralized pattern of dentin with exposure of dentin tubules and collagen fibrils network on the intertubular and peritubular dentin which was not significantly different from the groups treated with 1% and 2.5% NaOCl. Groups treated with 5% NaOCI were not statistically different from each other the surface was corroded but collagen fibrils were not completely depleted. Groups treated with 10% NaOCl were not statistically different from each other and showed complete removal of collagen fibrils with wider tubular apertures and several secondary tubules on peritubular and intertubular dentin. CONCLUSION: Higher concentrations of NaOCl solutions (5% and 10%) produced significant changes in the etched primary dentin. The higher the concentration of the NaOCI solution, the lower can be the time for the application of the solution for the complete removal of collagen fibrils.

Efficient passivation of n-type and p-type silicon surface defects by hydrogen sulfide gas reaction.

An efficient surface defect passivation is observed by reacting clean Si in a dilute hydrogen sulfide-argon gas mixture (<5% H2S in Ar) for both n-type and p-type Si wafers with planar and textured surfaces. Surface recombination velocities of 1.5 and 8 cm s-1are achieved on n-type and p-type Si wafers, respectively, at an optimum reaction temperature of 550 °C that are comparable to the best surface passivation quality used in high efficiency Si solar cells. Surface chemical analysis using x-ray photoelectron spectroscopy shows that sulfur is primarily bonded in a sulfide environment, and synchrotron-based soft x-ray emission spectroscopy of the adsorbed sulfur atoms suggests the formation of S-Si bonds. The sulfur surface passivation layer is unstable in air, attributed to surface oxide formation and a simultaneous decrease of sulfide bonds. However, the passivation can be stabilized by a low-temperature (300 °C) deposited amorphous silicon nitride (a-Si:NX:H) capping layer.

2-[4-(4-Methoxyphenylcarbonyloxy)benzylidene]-6-dimethylaminomethyl cyclohexanone hydrochloride: a Mannich base which inhibits the growth of some drug-resistant strains of Mycobacterium tuberculosis.

2-[4-(4-Methoxyphenylcarbonyloxy)benzylidene]-6-dime-thylaminomethyl cyclohexanone hydrochloride 1 has a MIC value of 0.78 microg/mL towards Mycobacterium tuberculosis H37Rv and displays similar or identical MIC figures towards various drug-resistant strains of this microorganism. The enone 1 along with a partial structure 2-dimethylaminomethylcyclohexanone hydrochloride 3 affected respiration in isolated rat liver mitochondria differently which may contribute to the variation in toxicity to both normal cells and M. tuberculosis.

Treatment effects produced by preorthodontic trainer appliance in patients with class II division I malocclusion.

The aim of the present study was to evaluate cephalometrically the treatment effects of preorthodontic trainer on dentoskeletal components in individuals showing class II division I malocclusion. This study comprised of 50 class II div. I patients (20 test patients and 30 controls) in the age group of 8-12 years. The test group was treated with a preorthodontic trainer for a period of 15 months. Standardized lateral cephalograms of both groups were taken before and after the treatment period. The cephalograms were then evaluated to determine the skeletal and dental changes in the course of treatment and then compared with the normative growth data to eliminate the possible growth effects. The readings were tabulated and subjected to statistical analysis. The results of the study after excluding the changes due to growth showed reduction in ANB and OP-SN values, indicating a significant reduction in the skeletal class II relationship. An upward cant of the occlusal plane in the treatment group was noted, probably due to the forward rotation of mandible. A significant increase in the vertical dimensions of the face in general and the mandible in particular was observed with the use of preorthodontic trainer. A significant reduction in the overjet and an increase in the inclination of mandibular incisor (L1-NB deg) were noted in the treatment group when compared with control group. It can be concluded that class II corrections can be achieved with the preorthodontic trainer appliance, which appears to have mostly dentoalveolar effects with smaller but significant skeletal effects.

Comparison of the effectiveness of sterilizing endodontic files by 4 different methods: an in vitro study.

Sterilization is the best method to counter the threats of microorganisms. The purpose of sterilization in the field of health care is to prevent the spread of infectious diseases. In dentistry, it primarily relates to processing reusable instruments to prevent cross-infection. The aim of this study was to investigate the efficacy of 4 methods of sterilizing endodontic instruments: Autoclaving, carbon dioxide laser sterilization, chemical sterilization (with glutaraldehyde) and glass-bead sterilization. The endodontic file was sterilized by 4 different methods after contaminating it with bacillus stearothermophillus and then checked for sterility by incubating after putting it in test tubes containing thioglycollate medium. The study showed that the files sterilized by autoclave and lasers were completely sterile. Those sterilized by glass bead were 90% sterile and those with glutaraldehyde were 80% sterile. The study concluded that autoclave or laser could be used as a method of sterilization in clinical practice and in advanced clinics; laser can be used also as a chair side method of sterilization.

Silicon induces phytochelatin and ROS scavengers facilitating cadmium detoxification in rice.

Cadmium (Cd) is detrimental to crops and the environment. This work examines the natural mechanisms underlying silicon- (Si-)directed Cd detoxification in rice plants. The addition of Si to plants under Cd stress caused significant improvements in morphological parameters, chlorophyll score, Fv /Fm and total soluble protein concentration compared to controls, confirming that Si is able to ameliorate Cd-induced damage in rice plants. This morpho-physiological evidence was correlated with decreased cell death and electrolyte leakage after Si application. The results showed no critical changes in root Cd concentration, while shoot Cd decreased significantly after Si supplementation in comparison with Cd-stressed rice. Additionally, expression of Cd transporters (OsNRAMP5 and OsHMA2) was significantly down-regulated while the concentration of phytochelatin, cysteine and glutathione, together with expression of OsPCS1 (phytochelatin synthase) in roots of Cd-stressed rice was significantly induced when subjected to Si treatment. This confirms that the alleviation of Cd stress is not only limited to the down-regulation of Cd transporters but also closely related to the phytochelatin-driven vacuolar storage of Cd in rice roots. The enzymatic analysis further revealed the role of SOD and GR enzymes in protecting rice plants from Cd-induced oxidative harm. These findings suggest a mechanistic basis in rice plants for Si-mediated mitigation of Cd stress.

Evaluation of Breast Lump - Comparison between True-cut Needle Biopsy and FNAC in MMCH: A Study of 100 Cases.

One-fourth of all women suffer from breast disease in their lifetime. World Health Organization estimated that over 508,000 women died in 2011 due to breast cancer worldwide.For several years, fine needle aspiration cytology (FNAC) was the most practiced method for the pathological diagnosis of breast lump specially differentiation of benign from malignant. The advent of core needle or True-Cut biopsy (TCB) in the new millennium has resulted in many surgeons switching to TCB since it provides a sufficient amount of tissue for pathologists to make an accurate histological diagnosis.During the study period, patients present with clinically palpable breast lump admitted in different surgicalunits of MMCH, among them 100 patients selected purposively. Then a prospective comparative study was carried out in the Department of Surgery, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from September 2017 to February 2018. Out of a total of 100 patients, who presented with suspicious breast lump, as clinically diagnosed 68 patients had benign breast lump and 32 patients had malignant breast lump. FNAC confirmed the diagnosis of breast carcinoma in 27 patients with sensitivity 89.65% and specificity 66.66%. True-cut biopsy confirmed the diagnosis of breast carcinoma in 29 patients with sensitivity 96.66% and specificity 100%. It also gave the definitive histological type and grade which correlated with the final histopathology report in 29 out of the 30 patientsTCB also provides adequate tissue for the evaluation of molecular markers which have extreme therapeutic value.

Legg-Calve-Perthes Disease: Correlation between Computed Radiography and Magnetic Resonance Imaging.

The purpose of this study is to diagnose Legg-Calve-Perthes disease by computed radiography and Magnetic resonance imaging and accurate staging and correlating the findings of these two modalities. Thirty five (35) patients complaining pain in groins and painful walking, after thorough physical examinations were sent to Department of Radiology & Imaging, Mymensingh Medical College Hospital, Mymensingh, Bangladesh for computed radiography and Magnetic Resonance Imaging examination. This cross sectional study was conducted in the Department of Radiology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July 2016 to June 2018. Legg-Calve-Perthes disease among the selected 35 cases were started at the age of 5(2.9%) and age range of the patients were 5-13 years; mean age was (9.63±1.82) years and most of them belonged to 8-10 years of age (51.4%). Patients with Legg-Calve-Perthes disease had been suffering from pain in right and left groins forvarious durations. Maximum duration was 1-2 years (~88.57%). Maximum proportion of diagnosed patients was delivered by normal delivery (60%) and maximum proportion of patients was premature (65.7%). Most of the patients were low birth weight baby (65.7%). Here chi-square test was done and found no significant relationship between delivery mode and birth weight in case of Legg-Calve-Perthesdisease (x²=1.712) (P=0.191). The result of the X-ray and MRI findings by cross table of chi square test found fair inter relationship between two diagnostic instruments. Result found fine difference in staging of the disease between X-ray and MRI findings. It can be said that MRI definitely a better tool for early diagnosis of Legg-Calve-Perthes disease and its staging but X-ray modality can be used. A primary tool for diagnosis and staging of the disease can be done where the MRI facility is not available or cost expensive for patient.

1,5-diaryl-3-oxo-1,4-pentadienes: a case for antineoplastics with multiple targets.

A number of organic molecules which contain the 1,5-diaryl-3-oxo-1,4-pentadienyl group, referred to hereafter as the dienone moiety, have antineoplastic properties. Emphasis is made on the attachment of this structural moiety to several molecular scaffolds, namely piperidines, N-acylpiperidines, cycloalkanes and 3,4-dihydro-1H-napthalenes. Many of these compounds are potent cytotoxins having micromolar and nanomolar IC(50) values towards a wide range of neoplastic and transformed cells. On occasions, greater toxicity towards neoplasms than normal cells has been demonstrated. A number of these compounds have in vivo anticancer properties and in general excellent tolerability in rodents is demonstrated. The way in which a number of physicochemical properties such as redox potentials, torsion angles, atomic charges and logP values govern cytotoxic potencies are presented. The importance of the shapes of different compounds as determined by molecular modeling in contributing to antineoplastic properties is outlined. Arguments are presented in favour of designing antineoplastics which have multiple sites of action in contrast to those bioactive molecules which have only one molecular target. A number of compounds which possess the dienone group have different modes of action some of which are chronicled in this review, such as inducing apoptosis, affecting respiration in mitochondria, inhibiting macromolecular biosynthesis and both inhibiting and stimulating certain enzymes. Other important properties of these compounds are discussed including their anti-angiogenic, MDR-revertant and antioxidant properties. It is hoped that this eulogy of the importance of the dienone group will encourage researchers to consider incorporating this structural unit into candidate cytotoxins in the future.

Exercise training decreases proinflammatory profile in Zucker diabetic (type 2) fatty rats.

OBJECTIVE: In the present study we evaluated the effect of exercise on the plasma levels of proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory molecule uric acid in the Zucker diabetic fatty (ZDF) rats that are more prone to develop type 2 diabetes mellitus. METHODS: Sixteen obese ZDF (Gmi fa/fa) rats (8 wk old, 228.40 +/- 4.05 g) were randomly assigned to one of two groups (n = 8 each): an exercise-trained group and a sedentary one. In addition, 16 lean ZDF (Gmi +/+) rats (8 wk old, 199.00 +/- 3.50 g) were subjected to identical sedentary and exercise conditioning (n = 8 each). Initially, rats swam 15 min/d (5 d/wk) in a 36 degrees C bath. The exercise protocol was gradually increased by 15 min/d until a swimming period of 1 h/d (1 wk) was attained. Thereafter, rats swam 1 h/d, 3 d/wk, for an additional period of 11 wk. Rats were sacrificed 48 h after the last training period and the blood and pancreas were collected. Circulating levels of glucose, glycosylated hemoglobin, total cholesterol, triglycerides, insulin, uric acid, IL-6, and TNF-alpha were assessed. The concentrations of proinflammatory cytokines in the pancreas were also evaluated. RESULTS: In the diabetic ZDF (fa/fa) rats, exercise decreased hyperuricemia (-37.3%) and IL-6 and TNF-alpha levels (-16.9% and -12.7% respectively) and maintained the weight of the pancreas at near normal. Immunohistochemistry revealed a marked decrease in the expression of TNF-alpha and IL-6 in the pancreatic islet cells of ZDF (fa/fa) rats. CONCLUSION: These results indicate that aerobic exercise is anti-inflammatory in nature.

Albumin and lipid enriched albumin for the critically ill.

Albumin, the principal transporter of plasma fatty acids, binds to majority of the drugs ingested, traps oxygen radicals and has potent anti-oxidant actions. Albumin binds to its specific binding sites on vascular endothelial cells and thus, prevents endothelial apoptosis. Albumin regulates the enzyme pyruvate dehydrogenase, the flux of glucose and lactate in astrocytes, and enhances the formation of anti-inflammatory lipoxins, resolvins and protectins from docosahexaenoic acid (DHA) and other polyunsaturated fatty acids that, in turn, could limit ischemia-induced neuronal damage. This may explain the beneficial action of DHA-enriched albumin in stroke and other critical diseases.

Tooth brushing skills for the children aged 3-11 years.

OBJECTIVES: The objective of this study was to evaluate tooth brushing management and ability of children in relation to age and gender. MATERIALS AND METHODS: The study population consisted of 45 children, who attended Department of Pedodontics and Preventive Dentistry at V.S Dental College and Hospital Bangalore. Children were divided into three groups according to age: Group I: 3-5 years, Group II: 6-8 years, and Group III: 9-11 years. Each child selected his/her favorite toothbrush and brushed his/her teeth under supervision of one instructor. The grip type during tooth brushing was recorded on a videotape and duration of tooth brushing also was noted. The data were analyzed in relation to the age and gender using the chi-square test. ANOVA was used to find if there is any significant difference between the mean brushing times in the different groups. RESULTS: The results of statistical analysis showed that in all cases P> 0.05 for grip preferences and P. CONCLUSION: The required manual dexterity for tooth brushing was present in younger age groups.

A comparative study to evaluate the effect of fluoride releasing sealant cured by visible light, argon lasers, and light emitting diode curing units: an in vitro study.

In Pediatric Dentistry, the use of pit and fissure sealant is one of the essential forms of prevention. Pit and fissure caries may be substantially decreased by obliteration of these developmental defects in occlusal, buccal and lingual surfaces with resin based dental sealants. Visible light-curing units, or LCUs, are an integral part of modern adhesive dentistry" They are used to cure resin based composite restoration materials, resin modified glass-ionomer and pit and fissure sealants, as well as to bond orthodontic teeth. Most recently, the argon laser has been approved for initiating the setting reaction with visible light cured-resins. Argon curing of resin materials has been show to enhance the physical properties and degree of polymerization of the resin, while reducing the polymerization time by 75 percent. The study is undertaken considering the inadequate research reports of regarding the comparison of curing ability using argon laser. LEDs and visible light as well as the resistant towards caries activity of the preventive fluoride releasing pit and fissure sealant cured by above mentioned curing units.

Effectiveness of circumoral muscle exercises in the developing dentofacial morphology in adenotonsillectomized children: an ultrasonographic evaluation.

Alterations in the functions of the facial muscle can establish changes in facial skeleton and in the development of occlusion. The effect of mouth breathing on the facial morphology is probably greatest during the growth period. Removal of nasal obstruction, adenoids, and tonsils have not given beneficial results in the reversion of the habit unless intercepted with various muscle exercises. Hence, this study was conducted to ultrasonographically evaluate the effectiveness of circumoral muscle exercises in the developing dentofacial morphology in adenotonsillectomized children.

Ankylosis of temporomandibular joint in children.

BACKGROUND: Temporomandibular joint (TMJ) ankylosis or hypomobility involves fusion of the mandibular condyle to the base of the skull. It is a major clinical problem that affects many patients suffering from facial trauma, infection, or systemic disease. The treatment of TMJ ankylosis poses a significant challenge because of technical difficulties and a high incidence of recurrence. CASE REPORT: This report describes a case of a 4-year-old boy with inability to open mouth, diagnosed with unilateral right bony TMJ ankylosis. The surgical approach consisted of gap arthroplasty followed by vigorous physiotherapy. CONCLUSION: A detailed history, clinical and functional examination, radiographic examination facilitating correct diagnosis followed by immediate surgical intervention, and physiotherapy can help us to restore physical, psychological, and emotional health of the child patient.

Motor Outcome of Stroke Patients with Low Dose Levodopa Therapy.

Stroke is one of the leading cause of disability worldwide. Motor function deficits due to stroke contribute to overall low quality of life. The objective was of this study is to observe functional motor outcome after stroke with low dose Levodopa therapy. This prospective follow up study was carried out in the Department of Neurology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July 2014 to June 2016 to see the effect of low dose of Levodopa (110mg) on motor outcome after stoke disability. Motor deficit was measured by Medical Research Council (MRC) grading and Rivermead Mobility Index (RMI) score. Two groups were selected by simple random method, consisted of both ischemic and hemorrhagic stroke. All the patients of both the groups were suffering from at least some post stroke motor disability and attended full course of physiotherapy. The group (L) received 110mg Levodopa with physiotherapy. On the other hand (NL) group received only physiotherapy. They were all followed up for four times within two months of time and were assessed for recovery of motor function. Mean age was 59.03±11.56 years in Levodopa (L) group and 57.10±12.41 years in the Non Levodopa (NL) group; Males were predominant in both groups. Ninety three (77.50%) cases had ischemic stroke and 27(22.50%) cases had hemorrhagic stroke. Most common risk factors were hypertension and smoking. No known risk factor was detected in 8 (6.67%) patients. Single or multiple risk factors were confirmed in 112 patients (93.33%). MRC score was significantly higher both in affected upper and lower limb in Levodopa group comparing non Levodopa group at 4th visit. RMI score was also significantly higher in Levodopa group comparing non Levodopa group at 4th visit. The Levodopa (L) group showed better recovery pattern than Non Levodopa (NL) group. It can be concluded that motor recovery was better with administration of a single low dose of Levodopa in combination with physiotherapy. Motor outcome was significantly higher in levodopa group than non-levodopa group.