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.

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.

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.

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.

Immunohistochemical Analysis of Anti-phospholipase A2 Receptor Antibody on Renal Biopsies: A Single Tertiary Care Center Study.

Membranous nephropathy (MN) is one of the common cause of nephrotic syndrome. The discrimination between primary MN (iMN) and secondary MN is essential because of treatment implications. Immunohistochemical (IHC) evaluation with the help of anti-phospholipase A2 receptor (PLA2R) antibody helps in tissue evaluation of iMN, which is an easy, cost-effective, and pathologist-friendly technique. The study included 82 cases of MN over a period of 3 years. IHC using PLA2R antibody was performed on iMN and secondary cases with adequate tissue. Cases of minimal change disease (MCD) were included as control. Granular staining along the basement membrane in the absence of staining of podocytes was considered positive. Medical records were verified for clinical information, baseline biochemical parameters, details of viral markers, connective tissue disease profile, and basic imaging workup. Of the 82 cases of MN, 51 were iMN and 31 secondary MN (sMN). Thirteen MCD cases were included as control. IHC with PLA2R antibody showed a sensitivity of 91.8% and specificity of 95.1%, positive predictive value of 95.7%, and negative predictive value of 90.7% in the diagnosis of iMN. The other parameters, either clinical or laboratory, did not show significant differences between iMN and sMN groups. The results of PLA2R staining by IHC were comparable with other studies and showed a higher sensitivity (91.8%) and specificity (95.1%). IHC with anti-PLA2R antibody can be considered as the standard diagnostic approach to identify iMN and offer scope for individualized treatment.

N-acetyl cysteine versus allopurinol in the prevention of contrast nephropathy in patients with chronic kidney disease: A randomized controlled trial.

Contrast media administration can lead to acute deterioration in renal function particularly in patients with pre-existing chronic kidney disease. This prospective, randomized controlled open-label parallel group study was undertaken at Nizam's Institute of Medical Sciences, Hyderabad, from June to December 2015. A total of 95 patients were included, of which 35 received n-acetylcysteine (NAC) + normal saline (NS), 30 patients received allopurinol (ALL) + NS, and 30 patients received placebo. In our study, the overall incidence of CIN was 24%. Incidence of CIN in NAC + NS, ALL + NS, and placebo group were 20%, 16%, and 36%, respectively. The major finding of this study was there was no significant difference between NAC and allopurinol in the prevention of contrast nephropathy. However, only allopurinol was superior to placebo. In our study, hyperuricemia and baseline serum creatinine were the only risk factors associated with CIN.

Canine transmissible venereal tumour: a review.

Canine transmissible venereal tumour (CTVT) is a contagious venereal tumour of dogs, commonly observed in dogs that are in close contact with one another, or in stray and wild dogs that exhibit unrestrained sexual activity. CTVT represents a unique, naturally transmissible, contagious tumour, where the mutated tumour cell itself is the causative agent and perpetuates as a parasitic allograft in the host. Clinical history, signalment and cytological features are often obvious for establishing a diagnosis though biopsy and histological examination may be needed in atypical cases. Most cases are curable with three intravenous injections of vincristine sulphate at weekly intervals. The role of stray and wild dogs makes the disease difficult to control and necessitates sustained animal birth control in stray dogs along with prompt therapy of the affected dogs. This review captures the manifold developments in different areas embracing this fascinating tumour, including its biology, diagnosis and therapeutic alternatives.

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.

Naringin inhibits gamma radiation-induced oxidative DNA damage and inflammation, by modulating p53 and NF-κB signaling pathways in murine splenocytes.

The adverse effects of ionizing radiation occur due to the generation of reactive oxygen species (ROS). The aim of this study was to identify the protective effects of naringin (NG), a citrus flavonoid, on ionizing radiation (IR)-induced differential stress response, with an exploration of the mechanisms involved in this process. Isolated murine splenocytes were incubated in the presence and in the absence of different concentrations of NG (50 and 100 µM) for 1 h prior to 6 Gy γ-irradiation, and the molecular mechanisms of action were determined through biochemical, immunoblot, flow cytometric, and immunofluorescence studies. Pretreatment with NG significantly prevented IR-induced intracellular ROS generation, thereby preventing the formation of cellular TBARS and the development of cellular nitrite. NG significantly reduced nuclear DNA damage with respect to the irradiated splenocytes, through the inhibition of DNA-PKcs and p-γH2AX. The reduced cell viability as a result of irradiation was recovered by NG through modulation of the redox-regulated cell signaling system. NG pretreatment resulted in significant inhibition of IR-induced G1/S phase cell cycle arrest through the modulation of p53-dependent p21/WAF1, cyclin E, and CDK2 activation. The results also demonstrated that NG blocked the IR-induced p38 function and reversed IR-mediated differential stress response through inhibition of the NF-κB pathway. Thus, the p38/NF-κB pathway participated in the IR-induced inflammatory development, leading to upregulation of CRP, MCP-1, and iNOS2 gene expression. However, NG pretreatment reversed the inflammatory development through downregulation of NF-κB, and regulated the expression of CRP, MCP-1, and iNOS2. The above results provide a theoretical basis for the preventive use of NG against radiation-induced multiple cellular anomalies.

No Scalpel Vasectomy (NSV) with Ligation and Excision: A Single Centre Experience.

No scalpel vasectomy (NSV) has proved to be a safe and simple procedure for permanent sterilization for men. Ligation and excision of the vas deferens followed by fascial interposition is the procedure of choice. It is believed that vas excision without fascial interposition has a risk of failure. The objective of this study was to evaluate the technique of NSV with ligation and excision only. No scalpel vasectomy performed in an urban centre was taken for this prospective study. Only ligation and excision procedure was applied in its execution. It was demonstrated and performed under the supervision of an expert. Information regarding early and late complications including failure was gathered. A total number of 3,392 NSVs were performed in an urban training centre between Apr' 2009 to Mar' 2013. The procedure applied was only excision and ligation of the vas deferens. The fascial interposition was not included in the procedure. Haematoma (1), bleeding (3), foreign body granuloma (1), scrotal pain (3), epididymitis (1) and sinus formations (1) were encountered. There was only one failure in the whole group of acceptors. NSV with ligation and excision is a simple and easy procedure to learn and perform. Complications and failures are negligible. The additional fascial interposition needs more surgical skill and is time-consuming, hence can be avoided where a large number of acceptors need to undergo NSV in a rural camp.

A study of triple negative breast cancer at a tertiary cancer care center in southern India.

BACKGROUND: Triple negative breast cancers (TNBCs) are a diverse and heterogeneous group of tumors that by definition lack estrogen and progesterone receptors and amplification of the HER-2 gene. The majority of the tumors classified as TNBCs are highly malignant, patients are usually young and only a subgroup of patients responds to conventional chemotherapy with a favorable prognosis. Various studies have been reported in western literature on TNBCs, all highlighting the poor prognosis of this subtype. However, extensive data from India is lacking. AIM: The aim of this study was to analyze the epidemiological and clinical profile of TNBCs at our institute. MATERIALS AND METHODS: This was the retrospective study carried out in Tertiary Cancer Care Center in South India. Case files of all breast cancer patients were reviewed from the hospital database registered in 1 year and TNBC patients were selected for the study. Patient's characteristic, treatment, and histological features were analyzed. RESULTS: A total of 322 patients were registered during the period of 1 year and 26% (84/322) of total patients were TNBC. Median age of presentation was 44.5 years. About 94% (79/84) of patients had first full-term delivery before the age of 30 years. The most common presenting symptom was left sided breast lump. Locally advanced and early breast cancer (EBC) was 51% (43/84) and 42% (36/84), respectively. Metastatic breast cancer was seen in five patients. The highest numbers of patients were node negative disease (36.9%) [31/84], followed by N1 30.95% (26/84). Most of the patients had high-grade tumor. 94% (34/36) of cases of EBC had undergone upfront modified radical mastectomy. Invasive ductal carcinoma was the predominant histology except one who had medullary carcinoma. Twenty-four patients received neoadjuvant chemotherapy (NACT). There was no pathological complete remission, but all patients responded to NACT. Metastatic disease was seen in five patients. All patients had bone metastasis. CONCLUSIONS: TNBCs are highly aggressive subtype, with high grade with limited treatment options and very poor prognosis. Incidence is more in our country than the western literature. Even in our country also the incidence is varies in different region. TNBCs are significantly associated with young aged patients. There was a lack of association between tumor size and lymph node positivity.

The unexpected formation of [M - H]+ species during MALDI and dopant-free APPI MS analysis of novel antineoplastic curcumin analogues.

Unusual ionization behavior was observed with novel antineoplastic curcumin analogues during the positive ion mode of matrix-assisted laser desorption ionization (MALDI) and dopant-free atmospheric pressure photoionization (APPI). The tested compounds produced an unusual significant peak designated as [M - H](+) ion along with the expected [M + H](+) species. In contrast, electrospray ionization, atmospheric pressure chemical ionization and the dopant-mediated APPI (dopant-APPI) showed only the expected [M + H](+) peak. The [M - H](+) ion was detected with all evaluated curcumin analogues including phosphoramidates, secondary amines, amides and mixed amines/amides. Our experiments revealed that photon energy triggers the ionization of the curcumin analogues even in the absence of any ionization enhancer such as matrix, solvent or dopant. The possible mechanisms for the formation of both [M - H](+) and [M + H](+) ions are discussed in this paper. In particular, three proposed mechanisms for the formation of [M - H](+) were evaluated. The first mechanism involves the loss of H2 from the protonated [M + H](+) species. The other two mechanisms include hydrogen transfer from the analyte radical cation or hydride abstraction from the neutral analyte molecule.

Cognitive and motor perturbations in elderly with longstanding diabetes mellitus.

Type 2 diabetes mellitus is a chronic disease characterized by insulin resistance; inflammation; oxidative stress; vascular damage; and dysfunction of glucose, protein, and lipid metabolisms. However, comparatively less attention has been paid to neurologic alterations seen in elderly individuals with type 2 diabetes. We review clinical, metabolic, and biochemical aspects of diabetic encephalopathy (DE) and propose that quality of dietary lipids is closely linked to DE. This implies that preventive nutritional interventions may be designed to improve DE.

Dental anxiety prediction using Venham Picture test: a preliminary cross-sectional study.

Anxiety or fearfulness affects a child's behavior, and to a large extent, determines the success of a dental treatment. It is essential to identify anxious children at the earliest age possible rather than simply deal with them later. It is crucial that every effort be made to ensure a positive experience for each child patient. Appropriate acknowledgment of patient's anxiety can solidify their confidence and allows the pediatric dentist an informed review of potential management options specific to every individual. In the present cross-sectional study, Venham Picture, a psychometric test, was used to estimate the prevalence of dental anxiety among children in the age group 6-10 years, with and without previous dental experience.

Prenatal counseling beyond the threshold of viability.

OBJECTIVE: It is common clinical practice to counsel parents expecting an early-moderate premature birth. The aim of the current study was to assess maternal knowledge of potential problems of prematurity after counseling. STUDY DESIGN: Prospective study of 49 participants admitted between 23 and 33 weeks gestation with threatened premature birth; a prematurity knowledge questionnaire and the State-Trait Anxiety Inventory were administered after counseling but before delivery. RESULT: Across all gestational-ages, participants were more aware of short-term problems than long-term problems. With increasing gestational age the knowledge of long-term problems decreased (P=0.01). Maternal knowledge was 82% for gestational ages where clear guidelines exist regarding goal of counseling and information that should be provided to the parents. CONCLUSION: Most mothers of early-moderate premature infants are not aware of the potential for long-term problems. Guidelines, which outline the information that should be provided to parents, may improve maternal knowledge after counseling.