A supernumerary tooth is that which is present additionally to the normal series and can be found in any region of the dental arch. An impacted tooth is defined as the one which is embedded in the alveolus, so that its eruption is prevented, or the tooth is locked in position by bone or the adjacent teeth. The occurrence of multiple supernumerary teeth in only one patient in the absence of an associated systemic condition or syndrome is considered as a rare phenomenon. The occurrence of supernumerary teeth in the lower molar region is rare. A prevalence of less than 2% of cases occurring in this region has been estimated. Their occurrence presents a clinical problem for orthodontists and oral surgeons. The cause, frequency, complications, and surgical operation of impacted teeth are always interesting subjects for study and research. An impacted tooth can result in caries, pulp disease, periapical and periodontal disease, temporomandibular joint disorder, infection of the fascial space, root resorption of the adjacent tooth, and even oral and maxillofacial tumours. The management of impacted wisdom teeth has changed over the past 20 years from removal of nonsymptomatic third molars to simple observation. The aim of this paper is to present a rare case of bilateral multiple impacted supernumerary mandibular third molars.
Giant cell granuloma (GCG) is an uncommon bony lesion in the head and neck region, most commonly affecting the maxilla and mandible and has a female predilection. The clinical behavior of central GCG ranges from a slowly growing asymptomatic swelling to an aggressive lesion. The clinical, radiological, histological features and management of an aggressive GCG of maxilla in an 18-year-old female patient are described and discussed. It is emphasized that surgery is the traditional and still the most accepted treatment for GCG. Le Fort I osteotomy has been advocated as one of the access osteotomy for the surgical management of aggressive and extensive GCG involving the maxilla. The postoperative morbidity and recurrence have been discussed.
Giant cell granuloma; Le Fort I access osteotomy; maxillary sinus tumor
The puzzle piece-shaped Arabidopsis leaf pavement cells (PCs) with interdigitated lobes and indents is a good model system to investigate the mechanisms that coordinate cell polarity and shape formation within a tissue. Auxin has been shown to coordinate the interdigitation by activating ROP GTPase-dependent signaling pathways. To identify additional components or mechanisms, we screened for mutants with abnormal PC morphogenesis and found that cytokinin signaling regulates the PC interdigitation pattern. Reduction in cytokinin accumulation and defects in cytokinin signaling (such as in ARR7-over-expressing lines, the ahk3cre1 cytokinin receptor mutant, and the ahp12345 cytokinin signaling mutant) enhanced PC interdigitation, whereas over-production of cytokinin and over-activation of cytokinin signaling in an ARR20 over-expression line delayed or abolished PC interdigitation throughout the cotyledon. Genetic and biochemical analyses suggest that cytokinin signaling acts upstream of ROPs to suppress the formation of interdigitated pattern. Our results provide novel mechanistic understanding of the pathways controlling PC shape and uncover a new role for cytokinin signaling in cell morphogenesis.
Arabidopsis; pavement cells; cytokinin; cell morphogenesis
Palatal swellings are rare in children and the incidence differs from that of the adult counterparts. When the palatal swellings do arise in children, they usually are palatal abscess from periapical region, and few cases like pleomorphic adenoma in young adults have also been reported. But inflammatory fibrosis of palate in children is a rare occurrence. Inflammatory fibrosis is formation of excess fibrous connective tissue in an organ or tissue, as a reparative or reactive process. This report describes an unusual case of iatrogenic inflammatory fibrosis on the palate due to extraction of tooth number 22 in a 13-year-old female patient. The patient presented with a single large well-circumscribed oval palatal swelling that was soft, fluctuant, not fixed, and nontender. Surgical excision of the lesion was done and it was sent for histopathological assessment. The biopsy showed fibrous tissue with collagen fibers, spindle shaped fibroblasts, neovascularization, RBCs, chronic inflammatory cells, and traces of salivary gland and nerve tissue.
The asymmetric unit of the title compound, C30H46N6O4, contains one half-molecule. The C(benzene)—C(CH2)—N—C(—Me) torsion angle is −79.89 (13)° suggesting a synclinal orientation of the nitrobenzene ring with respect to the macrocycle. The conformation of the macrocycle is stabilized by intramolecular N—H⋯N hydrogen bonds.
A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2′ ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central hydroxyl group showed low nM inhibitory activities against wild-type HIV-1 protease. Selected compounds were further evaluated for their inhibitory activities against a panel of multidrug-resistant protease variants and for their antiviral potencies in MT-4 cells. The crystal structures of lopinavir (LPV) and two new inhibitors containing phenyloxazolidinone-based ligands in complex with wild-type HIV-1 protease have been determined. A comparison of the inhibitor–protease structures with the LPV–protease structure provides valuable insight into the binding mode of the new inhibitors to the protease enzyme. Based on the crystal structures and knowledge of structure–activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies.
Marginal adaptation is an important factor for long term clinical success of the restoration. This study aims to evaluate and compare the marginal adaptation of zirconium coping and nickel–chromium coping using the shoulder finish line design. For the purpose of this study 30 master dies were fabricated. A total of 30 copings were fabricated in which 15 zirconia copings and 15 Ni–Cr copings were fabricated. The copings obtained were seated on the die and marginal discrepancy between the metal die and the copings were then measured with Scanning electron microscope at magnification of ×50 and the findings were statistically analyzed. Mean and standard deviation values of marginal discrepancy of cervical margins of zirconia copings were 39.32 and 2.66 μm and Ni–Cr copings were 129.98 and 2.57 μm. Higher mean marginal gap (μm) is recorded in Ni–Cr copings compared to zirconia copings. The difference in mean marginal gap (μm) between the two copings is found to be statistically significant (P < 0.001). Within the limitation of this study it was concluded that higher mean marginal gap (μm) was recorded in Ni–Cr copings compared to zirconia copings. The difference in mean marginal gap (μm) between the two copings is found to be statistically significant (P < 0.001).
Marginal adaptation; Coping; Zirconia; Ni–Cr; CAD/CAM technology; Lost wax technique
Age-related cataract (ARC) is a multifactorial disease and the leading cause of visual impairment and blindness worldwide. Genetic predisposition in association with other etiological factors may contribute to ARC. Although, there is some evidence for genetic influence for development of ARC, reports on gene mutations associated with ARC are scanty. In the present work, we identified a genetic variation (F71L) in the exon-2 of CRYAA gene in three unrelated female sporadic cases among 450 ARC patients but not in 144 normal non-cataractous controls. By comparing human recombinant wild-type and F71L-αA-crystallin, further we characterized the functional significance of this missense mutation. Size exclusion chromatography studies revealed that F71L mutation had no significant effect on the apparent molecular mass of αA-crystallin oligomeric complex. Intrinsic tryptophan fluorescence and far- and near-UV CD spectra indicated that F71L missense mutation did not significantly affect the secondary and tertiary structures of αA-crystallin. The ANS fluorescence emission spectra suggested no changes in surface hydrophobicity due to the F71L substitution. While the mutant αA-crystallin displayed almost complete loss (90%) of chaperone-like activity (CLA), in thermal aggregation of carbonic anhydrase, it showed 35-50% less protection in heat-induced aggregation of βL- and γ-crystallins. This is the first report of an αA-F71L mutation being associated with ARC. The results are consistent with the hypothesis that the mechanism of ARC in individuals carrying this mutation (F71L) might be due to the overall loss of in vivo chaperone activity due to interaction with other environmental factors.
Age-related cataract; αA-crystallin; F71L-mutation; chaperone-like activity; CD-spectra; oligomeric complex
Pediatric epileptiform encephalopathies are a group of neurologically devastating disorders related to uncontrolled ictal and interictal epileptic activity, with a poor prognosis. Despite the number of pharmacological options for treatment of epilepsy, many of these patients are drug resistant. For these patients with uncontrolled epilepsy, motor and/or neuropsychological deterioration is common. To prevent these secondary consequences, surgery is often considered as either a curative or a palliative option. Magnetic resonance imaging to look for epileptic lesions that may be surgically treated is an essential part of the workup for these patients. Many surgical procedures for the treatment of epileptiform encephalopathies have been reported in the literature. In this paper the evidence for these procedures for the treatment of pediatric epileptiform encephalopathies is reviewed.
Background: Proper gingival retraction improves the prognosis of crowns and bridges with sub gingival finishlines.Use of lasers assists the operator to achieve proper retraction with good clinical results.
Aims: The present study was intended to assess the amount of lateral gingival retraction achieved quantitatively by using diode lasers.
Settings and Design: Study was carried on 20 patients attended to a dental institution that underwent root canal treatment and indicated for fabrication of crowns.
Material and Methods: Gingival retraction was carried out on 20 teeth and elastomeric impressions were obtained. Models retrieved from the impressions were sectioned and the lateral distance between finish line and the marginal gingival was measured using tool makers microscope. Retraction was measured in mid buccal, mesio buccal and disto buccal regions.
Statistical Analysis: The values obtained were used to calculate the mean lateral retraction in microns.
Results: Mean retraction values of 399.5 μm, 445.5 μm and 422.5μm were obtained in mid buccal, mesio buccal and disto buccal regions respectively.
Conclusions: Gingival Retraction achieved was closer to the thickness of sulcular epithelium and greater than the minimum required retraction of 200um.
Lasers; Gingival Retraction; Finish Line
Epidemiological studies have shown that a diet rich in fruits and cruciferous vegetables is associated with a lower risk of prostate cancer. Indole-3-carbinol (I3C) and its dimeric product 3,3′-diindolylmethane (DIM) have been shown to exhibit anti-tumor activity both in vitro and in vivo. Recently, we have reported that a formulated DIM (B-DIM) induced apoptosis and inhibited growth, angiogenesis, and invasion of prostate cancer cells by regulating Akt, NF-κB, VEGF and the androgen receptor (AR) signaling pathway. However, the precise molecular mechanism(s) by which B-DIM inhibits prostate cancer cell growth and induces apoptosis have not been fully elucidated. Most importantly, it is not known how B-DIM affects cell cycle regulators and proteasome activity, which are critically involved in cell growth and apoptosis. In this study, we investigated the effects of B-DIM on proteasome activity and AR transactivation with respect to B-DIM-mediated cell cycle regulation and induction of apoptosis in both androgen-sensitive LNCaP and androgen-insensitive C4-2B prostate cancer cells. We believe that our results show for the first time the cell cycle-dependent effects of B-DIM on proliferation and apoptosis of synchronized prostate cancer cells progressing from G1 to S phase. B-DIM inhibited this progression by induction of p27Kip1 and down-regulation of AR. We also show for the first time that B-DIM inhibits proteasome activity in S phase, leading to the inactivation of NF-κB signaling and induction of apoptosis in LNCaP and C4-2B cells. These results suggest that B-DIM could be a potent agent for the prevention and/or treatment of both hormone sensitive as well as hormone-refractory prostate cancer.
The need for quantification of cell growth patterns in a multilayer, multi-cellular tissue necessitates the development of a 3D reconstruction technique that can estimate 3D shapes and sizes of individual cells from Confocal Microscopy (CLSM) image slices. However, the current methods of 3D reconstruction using CLSM imaging require large number of image slices per cell. But, in case of Live Cell Imaging of an actively developing tissue, large depth resolution is not feasible in order to avoid damage to cells from prolonged exposure to laser radiation. In the present work, we have proposed an anisotropic Voronoi tessellation based 3D reconstruction framework for a tightly packed multilayer tissue with extreme z-sparsity (2–4 slices/cell) and wide range of cell shapes and sizes. The proposed method, named as the ‘Adaptive Quadratic Voronoi Tessellation’ (AQVT), is capable of handling both the sparsity problem and the non-uniformity in cell shapes by estimating the tessellation parameters for each cell from the sparse data-points on its boundaries. We have tested the proposed 3D reconstruction method on time-lapse CLSM image stacks of the Arabidopsis Shoot Apical Meristem (SAM) and have shown that the AQVT based reconstruction method can correctly estimate the 3D shapes of a large number of SAM cells.
Impression making is not only important but is also the most significant step in the fabrication of any fixed or removable prosthesis. Proper impression making may be hindered by certain pathologic conditions. Reduced mouth opening is one of the common mechanical obstructions for proper orientation of the impression tray in the patient's mouth. In patients with trismus induced by submucous fibrosis, the procedure may be even more difficult to carry out because of reduced tissue resiliency and obliteration of vestibular spaces. Use of sectional trays offers one of the alternatives to overcome the problem of restricted mouth opening. Fabrication of customized impression trays according to the patient dentition improves the accuracy of impression making. The present case reports describe the fabrication of sectional custom trays designed for dentulous patients with chronic tobacco-induced submucous fibrosis.
The measles virus (MeV), a member of the paramyxovirus family, is an important cause of pediatric morbidity and mortality worldwide. In an effort to provide therapeutic treatments for improved measles management, we previously identified a small, non-nucleoside organic inhibitor of the viral RNA-dependent RNA polymerase (RdRp) by means of high-throughput screening (HTS). Subsequent structure-activity relationship (SAR) studies around the corresponding pyrazole carboxamide scaffold led to the discovery of 2 (AS-136a), a first generation lead with low nanomolar potency against life MeV and attractive physical properties suitable for development. However, its poor water solubility and low oral bioavailability (F) in the rat suggested that the lead could benefit from further SAR studies to improve the biophysical characteristics of the compound. Optimization of in vitro potency and aqueous solubility led to the discovery of 2o (ERDRP-00519), a potent inhibitor of MeV (EC50 = 60 nM) with aqueous solubility of approximately 60 μg/ml. The agent shows a 10-fold exposure (AUC/Cmax) increase in the rat model relative to 2, displays near dose proportionality in the range of 10 mg/kg to 50 mg/kg, and exhibits good oral bioavailability (F = 39%) in the rat. The significant solubility increase appears linked to the improved oral bioavailability.
measles virus; RNA-dependent RNA polymerase activity inhibitor; AS-136a; ERDRP-00519; pharmacokinetics
Acute pancreatitis complicated by acute myocardial infarction has been reported very rarely. The exact mechanism of the cause of myocardial injury is not known. We report a case of 36 year old male presenting with acute pancreatitis complicated by ST elevation acute myocardial infarction (AMI). The administration of thrombolytic therapy in such patients can have deleterious effects. We report successful performance of primary angioplasty in this complicated patient.
Acute pancreatitis; Acute myocardial infarction; Primary angioplasty
Background & objectives:
Pre-clinical toxicology evaluation of biotechnology products is a challenge to the toxicologist. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed recombinant DNA anti-rabies vaccine [DRV (100 μg)] and combination rabies vaccine [CRV (100 μg DRV and 1.25 IU of cell culture-derived inactivated rabies virus vaccine)], which are intended for clinical use by intramuscular route in Rhesus monkeys.
As per the regulatory requirements, the study was designed for acute (single dose - 14 days), sub-chronic (repeat dose - 28 days) and chronic (intended clinical dose - 120 days) toxicity tests using three dose levels, viz. therapeutic, average (2x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in monkeys. The selection of the model i.e. monkey was based on affinity and rapid higher antibody response during the efficacy studies. An attempt was made to evaluate all parameters which included physical, physiological, clinical, haematological and histopathological profiles of all target organs, as well as Tiers I, II, III immunotoxicity parameters.
In acute toxicity there was no mortality in spite of exposing the monkeys to 10XDRV. In sub chronic and chronic toxicity studies there were no abnormalities in physical, physiological, neurological, clinical parameters, after administration of test compound in intended and 10 times of clinical dosage schedule of DRV and CRV under the experimental conditions. Clinical chemistry, haematology, organ weights and histopathology studies were essentially unremarkable except the presence of residual DNA in femtogram level at site of injection in animal which received 10X DRV in chronic toxicity study. No Observational Adverse Effects Level (NOAEL) of DRV is 1000 ug/dose (10 times of therapeutic dose) if administered on 0, 4, 7, 14, 28th day.
Interpretation & conclusions:
The information generated by this study not only draws attention to the need for national and international regulatory agencies in formulating guidelines for pre-clinical safety evaluation of biotech products but also facilitates the development of biopharmaceuticals as safe potential therapeutic agents.
Biotech products; combination rabies vaccine (CRV); DNA rabies vaccine (DRV); pre-clinical toxicology; PVRV; purified vero cell-derived inactivated rabies virus vaccine; safety evaluation; toxicology
The plant stem cell regulator WUSCHEL is shown to repress differentiation-promoting transcription factors. This regulatory network is analyzed with a computational model of the three-dimensional shoot stem cell niche and a combination of genetic perturbation and live imaging.
We find that the transcription factor (TF) WUSCHEL (WUS) directly binds to the promoters and represses a group of genes including key TFs involved in differentiation thus keeping them repressed in the stem cells of the plant shoot, a mechanistic logic that is similar to animal stem cell regulation.We use a three-dimensional computational model of the plant shoot stem cell niche to show that the WUS-mediated repression of the differentiation program along with the previously reported activation of its own negative regulator leads to a robust stem cell homeostasis in a dynamic growth environment.Live imaging of target genes upon transient manipulation of WUS levels is combined with model perturbations to validate the proposed network and to connect it with a large body of previous experimental work.
In animal systems, master regulatory transcription factors (TFs) mediate stem cell maintenance through a direct transcriptional repression of differentiation promoting TFs. Whether similar mechanisms operate in plants is not known. In plants, shoot apical meristems serve as reservoirs of stem cells that provide cells for all above ground organs. WUSCHEL, a homeodomain TF produced in cells of the niche, migrates into adjacent cells where it specifies stem cells. Through high-resolution genomic analysis, we show that WUSCHEL represses a large number of genes that are expressed in differentiating cells including a group of differentiation promoting TFs involved in leaf development. We show that WUS directly binds to the regulatory regions of differentiation promoting TFs; KANADI1, KANADI2, ASYMMETRICLEAVES2 and YABBY3 to repress their expression. Predictions from a computational model, supported by live imaging, reveal that WUS-mediated repression prevents premature differentiation of stem cell progenitors, being part of a minimal regulatory network for meristem maintenance. Our work shows that direct transcriptional repression of differentiation promoting TFs is an evolutionarily conserved logic for stem cell regulation.
central zone; CLAVATA3; shoot apical meristem; stem cell niche; WUSCHEL
Fibromyxoma is a rare odontogenic tumour which is benign, but locally aggressive. The etiology of these tumours is unknown, but because of its limitation to the teeth bearing areas and occasional presence of odontogenic epithelial fragments within the tumour which suggest that it is of odontogenic origin. It is a slow growing painless tumour that frequently occurs in second and third decades of life. Females are more commonly affected than males. The tumour can cause gradual expansion of the cortical plates and cause loosening and displacement of teeth, although root resorption may be rare. The surgical treatment of these tumours consists of complete enucleation or radical excision. The aim of this paper is to present the rarity of a fibromyxoma of the maxilla.
The androgen receptor (AR) plays a critical role in the proliferation of prostate cancer cells. However, its mechanism of action in proliferation remains unknown. An understanding of the mechanism of AR action in proliferation may lead to the development of effective strategies for the treatment of prostate cancer.
In this study we report that pulse treatment of synchronized LNCaP cells with Casodex, an AR-antagonist, for 4 hours in mid-G1 phase was sufficient to prevent cells from entering S phase. Since the assembly of pre-replication complex (pre-RC) in G1 is required for the progression of cells from G1 to S phase, the effect of Casodex during mid-G1 suggested that the role of AR in proliferation might be to regulate the assembly of pre-RC. To test this possibility, we investigated the interaction between AR and Cdc6, an essential component of pre-RC in LNCaP cells. AR co-localized and co-immunoprecipitated with Cdc6, and Casodex treatment disrupted this interaction. AR-immunoprecipitate (AR-IP) also contained cyclin E and cyclin A, which play a critical role in pre-RC assembly and cell cycle entry into S phase, and DNA polymerase-α, PCNA, and ribonucleotide reductase, which are essential for the initiation of DNA synthesis. In addition, in cells in S phase, AR co-sedimented with components of the DNA replication machinery of cells that entered S phase.
Together, these observations suggest a novel role of AR as a component of the pre-RC to exert control over progression of LNCaP cells from G1 to S phase through a mechanism that is independent of its role as a transcription factor.
Cataract is a key factor in the morbidity associated with diabetes. While the pathogenesis of diabetic cataract formation is poorly understood, previous research has identified aldose reductase (ALR2) as a key player. To elucidate a potential role for this enzyme in diabetic cataract formation, we created a series of transgenic mice designed for expression of human ALR2 (AKR1B1) in epithelial and outer cortical fiber cells of the lens. One of the founder lines, designated PAR39, developed an early onset cataract that involved formation of a plaque of cells at the anterior aspect of the lens. These cells appear to separate from the anterior epithelium and undergo a dramatic change that is reminiscent of the epithelial to mesenchymal transition (EMT). We characterized this phenotype in the PAR39 strain by examining rates of cell proliferation and by immunostaining for markers of EMT. Incorporation of the thymidine analog bromodeoxyuridine (BrdU) was used to estimate cell proliferation in two functional areas of the lens epithelium: the mitotically active germinative zone (GZ) and the less proliferative center zone (CZ). Staining cell nuclei with diamido 4',6-diamidino-2-phenylindole (DAPI) was used to establish a total cell count in the demarcated areas. Lens epithelium in PAR39 transgenic mice demonstrated a decrease in the percentage of BrdU/DAPI staining within the GZ as compared to nontransgenic littermate controls (8.1% vs. 10.9%). A similar decrease in BrdU/DAPI was observed in the CZ (0.6% compared to 3.3%). However, cell density was greater within the GZ of PAR39 mice as compared with nontransgenic controls, while it was not significantly different in the CZ among the two groups. Furthermore, cells associated with the epithelial plaque did not stain positive for BrdU, but were strongly positive for alpha-smooth muscle actin, a classical marker for EMT. These findings suggest that ALR2 over-expression is associated with an alteration in the balance between proliferation and apoptosis of epithelial cells in the mouse lens, and that cells associated with epithelial plaques in the PAR39 lens have features in common with cells undergoing EMT.
cataract; EMT; epithelial-to-mesenchymal transition; aldo-keto reductase; diabetes
A transformation system which is free of in vitro plant regeneration following Agrobacterium infection is established for the forage legume, Sunnhemp (Crotalaria juncea L.) where in the entire embryo axis of the germinating seed was used as the target tissue for transformation. After standardization of transformation conditions, the cotyledonary node of the embryo axis was infected with Agrobacterium host LBA 4404 harboring the recombinant vector pCAMBIA 2301. The bivalent 1D gene of the two major foot and mouth disease virus (FMDV) serotypes ‘O’ and ‘A22’ and the neomycin phosphotransferase (nptII) gene were used as the markers for optimization of the protocol. The embryo axes were pricked randomly on the cotyledonary node and co-cultivated with Agrobacterium. The germlings were then allowed to grow under standard growth room conditions in to mature fertile plants. 60 T0 plants were established from 3 separate experiments. Three hundred seeds from the 60 T0 plants were sown to raise the T1 generation of which 180 were analyzed for integration of bivalent FMDV gene 1D “O” and “A22” and the nptII gene. Eighteen out of these 180 plants amplified both the marker genes. Two independent transgenic lines 24 and 37, showed elevated levels of expression of 12 μg and 8 μg (per gm of fresh leaf) of the bivalent ID antigen “O” and “A22” . The results showed that the transformation efficiency was 3 %. To the best of our knowledge, this is the first successful attempt of Agrobacterium tumefaciens mediated transformation of Sunnhemp. The protocol can generate whole plant transformants with relative ease and should be compatible to all genotypes of Sunnhemp.
Sunnhemp; Agrobacterium tumefaciens; FMDV -1D gene; nptII gene markers; in planta transformation
Telomeres protect the ends of linear chromosomes from being recognized as damaged DNA, and telomere stability is required for genome stability. Here we demonstrate that telomere stability in androgen receptor (AR)-positive LNCaP human prostate cancer cells is dependent on AR and androgen, as AR inactivation by AR antagonist bicalutamide (Casodex), AR-knockdown, or androgen-depletion caused telomere dysfunction, and the effect of androgen-depletion or Casodex was blocked by the addition of androgen. Notably, neither actinomycin D nor cycloheximide blocked the DNA damage response to Casodex, indicating that the role of AR in telomere stability is independent of its role in transcription. We also demonstrate that AR is a component of telomeres, as AR-bound chromatin contains telomeric DNA, and telomeric chromatin contains AR. Importantly, AR inactivation by Casodex caused telomere aberrations, including multiple abnormal telomere signals, remindful of a fragile telomere phenotype that has been described previously to result from defective telomere DNA replication. We suggest that AR plays an important role in telomere stability and replication of telomere DNA in prostate cancer cells, and that AR inactivation-mediated telomere dysfunction may contribute to genomic instability and progression of prostate cancer cells.
Androgen receptor; telomeres; fragile telomeres; Casodex; DNA damage; genomic instability; prostate cancer
To compare the cancer detection rate in patients with raised serum prostate-specific antigen (PSA) or abnormal digital rectal examination (DRE) results between the 10-core and the 16-core biopsy techniques in an Indian population.
Between November 2010 and November 2012, 95 men aged >50 years who presented to the Urology Department with lower urinary tract symptoms, elevated serum PSA, and/or abnormal DRE findings underwent transrectal ultrasonography (TRUS)-guided prostate biopsy. A total of 53 patients underwent 10-core biopsy and 42 patients underwent 16-core biopsy.
Of the 53 men in the 10-core group, 8 had cancer, whereas in the 16-core biopsy group, 23 of 42 men had cancer. Detection of prostate cancer was significantly higher in patients who underwent 16-core biopsy than in those who underwent 10-core biopsy (P<0.001). Among the 95 men, 44 men had abnormal DRE findings (46.3%), of whom 23 showed cancer (52.27%). Of 51 men with normal DRE findings and elevated PSA, 8 men had malignancy with a cancer detection rate of 15.68%. Among 20 men with PSA between 4.1 and 10 ng/mL, 2 (10%) had cancer. In 31 men with PSA between 10.1 and 20 ng/mL, 3 cancers (9.67%) were detected, and in 44 men with PSA >20 ng/mL, 26 cancers were detected (59.09%).
The cancer detection rate with 16-core TRUS-guided biopsy is significantly higher than that with 10-core biopsy (54.76% vs. 15.09%, P<0.001). In patients with both normal and abnormal DRE findings, 16-core biopsy has a better detection rate than the 10-core biopsy protocol. With increasing PSA, there is a high rate of detection of prostate cancer in both 10-core and 16-core biopsy patients.
Prostate neoplasms; Prostate-specific antigen; Digital rectal examination; Transrectal ultrasonography; Prostate biopsy
Firefly luciferase-catalyzed light emission from D-luciferin is widely used as a reporter of gene expression and enzymatic activity both in vitro and in vivo. Despite the power of bioluminescence for imaging and drug discovery, light emission from firefly luciferase is fundamentally limited by the physical properties of the D-luciferin substrate. We and others have synthesized aminoluciferin analogs that exhibit light emission at longer wavelengths than D-luciferin and have increased affinity for luciferase. However, although these substrates can emit an intense initial burst of light that approaches that of D-luciferin, this is followed by much lower levels of sustained light output. We have previously postulated that this behavior is due to product inhibition. Here we describe the creation of mutant luciferases that yield improved sustained light emission with aminoluciferins in both lysed and live mammalian cells, allowing the use of aminoluciferins for cell-based bioluminescence experiments.
A report, prepared by WHO and the World Economic Forum says that India will incur an accumulated loss of $236.6 billion by 2015 on account of unhealthy lifestyles and faulty diet. The WHO and International Obesity Task Force have declared the obesity epidemic on a global scale. Though genetic factors contribute to human obesity, the nature of diet plays a key role in Medoroga. Ayurveda has given top priority to food under the three supporters of life. Among them, Yava (Hordeum vulgare) is a supplementary diet for which wide references were found in classics as preventive and curative aspects of medoroga. Keeping this in view the present study has been taken up to evaluate the efficacy of yava in medoroga.
30 clinically diagnosed cases of Medoroga were selected from O.P.D of S.V. Ayurvedic hospital, Tirupati following specific exclusion and inclusion criteria. Diagnostic criteria including laboratory investigations along with subjective and objective parameters were considered for the study. Dose Yava churna 10 gm BD with hot water. Duration 90 days.
Statistical data revealed highly significant reduction in serum cholesterol, Body weight, MI, serum triglycerides, VLDL and significant improvement in HDL levels.
Administration of yava churna has given better results. It was evident by the significant changes in the subjective and objective parameters.