Biological activity of synthesized 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-mercapto-1, 3, 4-oxadiazole derivatives demonstrated by in silico and BSA binding studies

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

Aberrant Promoter Methylation at CpG Cytosines Induce the Upregulation of the E2F5 Gene in Breast Cancer / 한국유방암학회지

PURPOSE: The promoter methylation status of cell cycle regulatory genes plays a crucial role in the regulation of the eukaryotic cell cycle. CpG cytosines are actively subjected to methylation during tumorigenesis, resulting in gain/loss of function. E2F5 gene has growth repressive activities; various studies suggest its involvement in tumorigenesis. This study aims to investigate the epigenetic regulation of E2F5 in breast cancer to better understand tumor biology. METHODS: The promoter methylation status of 50 breast tumor tissues and adjacent normal control tissues was analyzed. mRNA expression was determined using SYBR® green quantitative polymerase chain reaction (PCR), and methylation-specific PCR was performed for bisulfite-modified genomic DNA using E2F5-specific primers to assess promoter methylation. Data was statistically analyzed. RESULTS: Significant (p<0.001) upregulation was observed in E2F5 expression among tumor tissues, relative to the control group. These samples were hypo-methylated at the E2F5 promoter region in the tumor tissues, compared to the control. Change in the methylation status (Δmeth) was significantly lower (p=0.022) in the tumor samples, indicating possible involvement in tumorigenesis. Patients at the postmenopausal stage showed higher methylation (75%) than those at the premenopausal stage (23.1%). Interestingly, methylation levels gradually increased from the early to the advanced stages of the disease (p<0.001), which suggests a putative role of E2F5 methylation in disease progression that can significantly modulate tumor biology at more advanced stage and at postmenopausal age (Pearson's r=0.99 and 0.86, respectively). Among tissues with different histological status, methylation frequency was higher in invasive lobular carcinoma (80.0%), followed by invasive ductal carcinoma (46.7%) and ductal carcinoma in situ (20.0%). CONCLUSION: Methylation is an important epigenetic factor that might be involved in the upregulation of E2F5 gene in tumor tissues, which can be used as a prognostic marker for breast cancer.

N-acetyl cysteine inhibits endothelin-1-induced ROS dependent cardiac hypertrophy through superoxide dismutase regulation

Oxidative stress down regulates antioxidant enzymes including superoxide dismutase [SOD] and contributes to the development of cardiac hypertrophy. N-Acetyl cysteine [NAC] can enhance the SOD activity, so the aim of this study is to highlight the inhibitory role of NAC against endothelin-1 [ET-1]-induced cardiac hypertrophy. In this experimental study at QAU from January, 2013 to March, 2013. ET-1 [50 microg/kg] and NAC [50 mg/kg] were given intraperitoneally to 6-day old neonatal rats in combination or alone. All rats were sacrificed 15 days after the final injection. Histological analysis was carried out to observe the effects caused by both drugs. Reactive oxygen species [ROS] analysis and SOD assay were also carried out. Expression level of hypertrophic marker, brain natriuretic peptide [BNP], was detected by western blotting. Our findings showed that ET-1-induced cardiac hypertrophy leading towards heart failure was due to the imbalance of different parameters including free radical-induced oxidative stress and antioxidative enzymes such as SOD. Furthermore NAC acted as an antioxidant and played inhibitory role against ROS-dependent hypertrophy via regulatory role of SOD as a result of oxidative response associated with hypertrophy. ET-1-induced hypertrophic response is associated with increased ROS production and decreased SOD level, while NAC plays a role against free radicals-induced oxidative stress via SOD regulation

Evaluation of flexural strength of composite by addition of dental amalgam powder: a pilot study

Dental composites are showing versatility in the field of restorative dentistry. Strength is main issue for their use especially in stress bearing area. Present study was aimed to evaluate the flexural strength of dental amalgam incorporated nano filled hybrid composite. Mechanical incorporation of a commercially available dental amalgam powder in nano filled hybrid composite was performed through amalgamator. Specimens were prepared and analyzed according to ISO standard No. 4049. Specimens analyzed were six [n=3] for each group. Null hypothesis for the study was no difference in the flexural strength of a commercially available dental composite and the prepared one which was rejected by the test statistics. Flexural strength of the control material was 90 Mpa while for the test material was 106.12 Mpa. Results showed a marked difference in the values of flexural strength of both the materials. Flexural strength can be increased by incorporating dental amalgam powder. Dental amalgam powder is a potential candidate for a high flexural strength and antibacterial composite. The study needs more trials on different aspects and evaluation of mechanical properties

Knowledge of dentists about epilepsy and their attitude toward the dental treatment of epileptic patients: a survey of dentists in Peshawar - Pakistan

The relationship of epilepsy with society, knowledge of people, attitude, and how may it affect the access of people with epilepsy to dental care. A questionnaire that explored facts about the knowledge, attitude and willingness to provide dental care to people with epilepsy was delivered to 129 dentists personally in the city of Peshawar [KPK], Pakistan. Of the 129 respondents, 10.9% were general dentists. Knowledge was patchy about the epidemiology, causes, treatment and recognition of epilepsy. 44% of dentists did not think that they could safely treat patient of epilepsy in their offices. Lack of knowledge and negative attitude towards epilepsy may affect the access to dental care for people with epilepsy

Dimensional stability of vinylsiloxanether impression material after autoclave sterilization - an in vitro study

Dental impressions are often neglected in clinical practice as a source of spread of infectious diseases. In Pakistan more than fifty percent of the clinicians do not disinfect impressions. Blood and saliva contaminated impressions should be either disinfected or sterilized before further handling. Aim of this study was to determine effect of autoclave sterilization on the time dependent dimensional stability of vinylsiloxanether impression material. Impressions of stainless steel die [ADA/ANSI specification No. 19], were made of Vinylsiloxanether. Out of 40 specimens, half were allotted to group A and were autoclaved at 134°C AND 20 psi for 5 minutes. Rest of the specimens [Group B] served as a control. Dimensional changes were calculated for two time intervals i.e. after one hour and after twenty-four hours. Samples were scanned and images were analyzed by using Adobe reader XI [AcroRd 32] software. Paired t-test showed significant difference [p = 0.007] between readings at first hour [-0.047%] and twenty fourth hour [0.084%] in group A. Whereas independent t-test showed no significant difference in group A and B for both time intervals i.e. at first hour [p = 0.162] and twenty fourth hour [p = 0.148]. It was concluded that Vinylsiloxanether can be sterilized in an autoclave without any deleterious change in dimensions

Missing teeth among school going children in a Peshawar sample

Congenitally missing teeth is the most common craniofacial malformation. It is present either individually or associated with syndrome. Hypodontia occur as a result of multifactorial trait, influenced by a combination of gene function, environmental interaction, hence vary among different ethnic regions. This study aims to determine the prevalence of missing teeth among the school going children in Peshawar, its occurrence rate among male and female and distribution of missing teeth in upper and lower jaw. This was a cross sectional study conducted with 780 school going children from age ranged 13 to 15 years. The data were recorded on a structured check list, analyzed by using SPSS version 15 and Micro Soft Excel. Out of total only 30 students were diagnosed as having missing teeth and accounted for 3.8% prevalence [3.0% in female, and 1.5% in male]. Left mandibular site accounted highest frequency 10[33.3%]. Mandibular 2nd premolar was the most commonly observed missing tooth among the sampled students. Hypodontia was more prevalent in females, though not significantly differ

interface of glass ionomer sealer and conditioned elephant tusk dentine: a scanning electron microscopy study

The purpose of this in vitro study was to characterize the interface of glass ionomer sealer and dentine conditioned with common endodontic irrigants through scanning electron microscope. The interface between Ketac-Cem radiopaque glass ionomer sealer and elephant tusk dentine conditioned with distilled water, citric acid and phosphoric acid was investigated. Cylinder of glass ionomer sealer was formed on the conditioned dentine surface and allowed to set for 60 minutes. The specimens were first shear tested to failure to determine their adhesive bond strength. Three debonded dentine specimens from each group were then processed for scanning electron microscopic study. The test failed surface of the strongest, intermediate and weakest bond strength specimens were examined. The specimens were cross sectioned and the interface was examined. The microscopic detail of the debonded interfaces between glass ionomer sealer and dentine was assessed in this study. Failures in all of the specimens were found to be mainly cohesive in nature

Duodenal perforation among patients of acid peptic disease

Introduction: Duodenal ulcer [DU] perforation is one of the severe complications of duodenal ulcer. Although, antiulcer drugs reduce the risk of duodenal ulcer perforations but perforation may occur in 2-10% patients taking antiulcer drugs. In elderly patients of duodenal ulcer perforation, the mortality remains 30-50% in-spite of optimal management

Objective: To find out the frequency and characteristics of patients with duodenal ulcer perforation on regular anti ulcer drugs, on irregular therapy and in those not taking medications for acid peptic disease

Study Design: Cross sectional study[Hospital based]

Study Setting: Department of Surgery, Bahawal Victoria Hospital, Bahawalpur

Duration of Study: From 11-02-2009 to 10-01-2010

Subjects and Methods: Fifty five patients of Duodenal Ulcer perforation diagnosed on clinical ground and Laparoscopy/Laparotomy with known history of peptic ulcer, whether taking antiulcer drugs [complete or incomplete course] or not, were included in this study. All the data was recorded on pre-designed Proforma and results were analyzed using SPSS 13.0 version

Results: 55 patients were operated for perforated duodenal ulcer during the study period in the surgical department of Bahawal Victoria Hospital, Bahawalpur. This consisted of 50 males [91%] and 05 females [09%]. The male/female ratio was 10:1; the patients were aged 20-60 years. The peak incidence was in the 5th decade. Duration of acute symptoms before presentation was a few hours to 5 days. None of the perforations was associated with recent ingestion of non steroidal anti-inflammatory drugs [NSAIDS]. There was a history of chronic peptic ulcer disease in 39[71%] patients. Abdominal tenderness and classical signs of peritonitis were demonstrable in 49[89.1%] and 46[83.6%] patients respectively. Plain abdominal and chest x-rays were carried out for all these patients, with free gas under the diaphragm demonstrated in 70% percent of cases. A total of 49 patients [89%] had anterior pyloroduodenal perforations with serous peritoneal fluid in 29 [53%], cloudy/opalescent peritoneal fluid in 13 [24%] and frank peritoneal pus with fibrinoid adhesions in 13 [24%] patients. Six of the perforations were found to be sealed. Five of the perforations were of size 10mm in size. Only six patients out of fifty five [11%] during or after a course of the antiulcer drugs developed Duodenal Ulcer Perforation

Conclusion: Duodenal ulcer perforation may occur in patients who were taking antiulcer drugs. Duodenal ulcer perforation is more common in patients with acid peptic disease who were not taking antiulcer drugs

Effect of bleaching on shear bond strength of orthodontic brackets

The purpose of this in vitro study was to determine the effect of bleaching on shear bond strength of orthodontic brackets. This randomized control trial was performed over a period of 6 months in the department of orthodontics, de,Montmorency College of Dentistry, Lahore. A total of one hundred and forty extracted premolar teeth were included which were further divided into two groups. Group A was assigned as control group without bleaching and Group B as study group with bleaching. The teeth in both groups were embedded individually in acrylic placed in rubber moulds using a mounting jig so that the labial surfaces would be parallel to the applied force during the shear test. Group B was bleached with Pola office advanced tooth whitening system and were stored in a solution of 0.9% saline till they were bonded. The bonding process for both groups was then performed in a standard manner. After bonding bracket was properly positioned on its respective tooth. An occluso-gingival load was applied to the bracket producing a shear force at the bracket tooth interface using a computerized shear bonding testing machine. The results showed that there was no statistically significant difference between the shear bond strength of unbleached teeth and that of bleached teeth following a two weeks interval after bleaching

Comparison of working length in curved mesial canals of mandibular molar between pre-flared and non-flared group

The aim of this study was to compare the working length in the curved mesial canals of mandibular molars between pre-flared and non-flared groups. It was a comparative study which was carried out at Dental Department of PIMS [Pakistan Institute of Medical Sciences] Islamabad from 2003 to 2004. A total of 60 patients were divided equally into pre-flared and non-flared groups. In both groups a 15 # K file was used for the measurement of working length but in the pre-flared group the coronal portion of the canal was flared with Hedstrom files [25-55] or Gates Glidden Drills from # 02 to # 05 before inserting the # 15 K file. Then the tooth was radiographed at this moment and the distance between the tip of the file and the radiographic apex. The location of the tip was classified as a] within 1 mm of the radiographic apex b] more than 1 mm of radiographic apex c] over extended, beyond the radiographic apex. In the non-flared group 33.3% of the cases belonged to group [a], 40% to group [b] and 26.7% to group [c]. In the pre-flared group 73.3% of the cases belonged to group [a], 10% to group [b] and 16.7% to group [c]. It was concluded that when the coronal portion of the canal is constricted, then the clinicians cannot discern the accuracy of what they feel apically because quite often the file bends or stucks more coronally than apically. When the coronal portion of the curved canal is pre-flared or prepared then it greatly improves the access to apical portion of curved canal and thus to the apical constriction, which is an apical reference for correct working length determination, by removing the dentinal hindrances in the coronal portion of the curved canals. Thus pre-flaring is a highly recommended procedure, especially in curved canal for correct working length determination

shear bond strength of glass ionomer root canal sealer to elephant tusk dentine conditioned with common endodontic irrigants

The purpose of this in vitro study was to evaluate the shear bond strength of glass ionomer sealer to dentine exposed to common endodontic irrigants in both well and poorly prepared dentine surface. In the methodology four groups of elephant dentine sample were used. Each group was well cleaned and prepared with different irrigants for the effective removal of smear layer. One group was treated with distilled water with smear layer retained. All the dentine used for the experiment was cut in form of disks of about 2.4mm thickness with a hole in the centre and subjected to root canal preparation. All the prepared dentine samples were filled with Ketac-Cem sealer and metal pin was inserted. The shear bond strength of metal pin and sealer was tested using Instron universal testing machine. The observations of bond strength in the four sample groups were analysed statistically through ANOVA test. It was found statistically that shear bond strength with phosphoric acid treated samples was quite higher than the other samples

Effect of mechanical modification of acrylic resin denture teeth bonded to acrylic denture base

Techniques for bonding denture teeth to acrylic resin denture base remains empirical, with little consensus from the literature, among clinicians or among dental laboratories. Despite of this great variation, the data available regarding effectiveness of various methods used are sparse. The study was carried out to compare the effect of different surface treatments of ridge lap area of acrylic resin denture teeth on bond strength of acrylic resin denture teeth with acrylic resin denture base. 180 Maxillary central incisors were divided into 6 groups of 30 each according to surface preparations. First group served as the control with no surface preparation; other groups included horizontal grooves, vertical grooves, diatorics, sand blasting and roughened surfaces. Compressive shear force was applied to incisal edge of each tooth until fracture occurred, the force recorded and teeth visually inspected to determine adhesive or cohesive failure. Significant increase in failure load ranged for diatoric 274 +/- 78N. Significant decrease in failure mode was observed after sand blasting 157 +/- 79N. Remaining groups showed non-significant increase in force required for bond failure

Comparison of shear bond strength of metal castings luted to dentine using resin cements

The purpose of this study was to investigate the shear bond strength of metal discs luted to dentine. In this study three resin luting cements i.e. Panavia F [Group I], Variolink II [Group II] and Superbond C and B [Group III] were compared to demonstrate which material was more superior to bond sandblasted cobalt chromium alloy to dentine. Groups I, II and III were compared using ANOVA, P < 0.05. Panavia F demonstrated significantly higher bond strengths than Variolink II or SuperBond C and B. SuperBond C and B had significantly higher shear bond strength than Variolink II. Thus, there were significant differences among the tested resin luting cements for bonding metal discs. Panavia F was found to give the highest shear bond strength within the limitations of this study followed by Superbond C and B and Variolink II

Smear layer and sealing ability of three root canal sealers

The purpose of this study was to determine the sealing ability of three individual sealers and to compare the sealing ability of these sealers in the presence and absence of smear layer. Total of sixty single rooted mandibular first premolar teeth were used. The crowns were removed at the cemento-enamel junction and roots prepared to # 35 K-file. The teeth were randomly divided into two equal groups A and B. The smear layer was removed from group B with EDTA [17%] and NaOCl [5.25%] but it was not removed in group A. Group A was then divided into three sub-groups, Al, A2 and A3. Group B was also divided into three sub-groups, Bl, B2 and B3. Each sub-group consisted of 10 specimens. In sub-groups Al andBl, AH Plus sealer, in sub-groups A2 and B2, Ketac-endo sealer and in sub-groups A3 and B3, Roth sealer was used and obturated withguttapercha using lateral condensation technique. After storage in 100% humidity at 37°C for one week, the root surfaces were coated with nail polish [except at the apex] and suspended in 2% methylene blue dye solution for one week. The roots were sectioned logitudinally to determine the following mean levels of dye penetration, Al -2.675 mm, Bl -2.092mm,A2-2.346mmB2endo-4.520mm,A3-4.929mm,B3-3.372mm.This study has illustrated that Ketac-Endo sealer provides significantly better seal in the presence of smear layer than in the absence of smear layer. Moreover it gave better seal than Roth 801 sealer in the presence of smear layer

effect of resin coating technique on shear bond strength

The purpose of this study was to investigate the shear bond strength of metal discs luted to dentine using Resin Coating Technique. In this study the adhesives used were dentine bonding agents, namely, Clearfil SE Bond and Syntac Sprint which were applied one week prior to cementation of Cobalt Chromium [Co-Cr] alloy discs to determine if there was any increase in the bond strengths when later luted using Panavia F and Variolink II. Thus there were four test groups with twelve teeth in each group i.e. Group I:Panavia F, Group II: Clearfil SE Bond I Panavia F, Group III: Variolink Hand Group IV: Syntac Sprint I Variolinkll. The mean shear bond strengths for the four test groups were recorded and the data were compared. It was found that the bond strengths increased significantly with the coating of the dentine bonding agents

Carcinoma caecum - a rare presentation

Caecal and right sided colonic cancers mostly present with fatigue, weakness and iron deficiency anemia. Such tumours rarely perforate posteriorly and involve the retroperitoneum. We report a case of an old Omani lady who came with insidious sign and symptoms of perforated caecum leading to retroperitoneal collection and necrotizing fasciitis of abdominal wall due to carcinoma of caecum. She underwent surgery but despite active intervention, she died because of septicemic shock

Evaluation of sealing ability of three root canal sealers

The purpose of this study was to determine the sealing ability of three different sealers and to compare the sealing ability of three sealers. Thirty single rooted mandibular first premolar teeth were used. The crowns were removed at the cemento - enamel junction and root canals were prepared to a # 35 K-file. The teeth were randomly divided into three groups, A, K and R. Each group consisted of 10 specimens. In group A, AH Plus sealer, group K, Ketac-endo sealer and group R, Roth 801 sealer were used and obturated with gutta percha using lateral condensation technique. After storage in 100% humidity at 37°C for one week, the root surfaces were coated with nail polish [except at the apex] and suspended in 2% methylene blue dye solution for one week. The roots were sectioned longitudinally to determine the following mean values of dye penetration, group A - 2.675 mm, group K - 2.346 mm, group R - 4.929 mm. This study shows that Ketac-endo gave better seal than Roth 801 sealer

Surgery for the assault patients

One hundred ninety nine patients were included in this study of one year duration. There were 177 males and 22 females. The mean length of hospital stay of the 16 most seriously injured patients [ISS scores of more than 15] was 7 days. The head was the principal area to be injured. The head region sustained 132 injuries [41% of all injuries] and four cranial operations [3% of injuries to the head] were performed. The maxillofacial region required most surgical operations. Twenty three facial operations [39% of all operations] were performed. The ratio between operations and injuries was highest for the lower limb and the lowest for the cranium. There were 14 injuries to the lower extremity and 10 lower limb operations [72% of injuries to lower limb] were performed. Fifty three patients [26.6% of total] required operations. There was one death of a woman of 88 years of age with an ISS score of 9 and her death was largely due to post operative complications

Skin manifestations amongst diabetic patients admitted in a general medical ward for various other medical problems

To calculate prevalence of incidental skin manifestations in patients with diabetes mellitus admitted for treatment of various other medical problems in a general medical ward of a teaching hospital, Lahore, Pakistan. Design: Cross-sectional study. Setting: Hospital based study on admitted patients in a medical ward, Mayo Hospital, Lahore. Subjects: One hundred consecutive adult diabetic patients of any age and either sex admitted for various other diseases/problems. Main Outcome Measures: Skin manifestations. Out of 100 patients, 60% were males, and 40% females. Skin manifestations were seen in 90% of patients. Diabetic neuropathy was seen in 65.6%, cutaneous infections in 62.2%, pruritus in 46.7%, Diabetic dermopathy in 33.3%, skin tags in 21.1%, acanthosis nigricans in 16.7%, eruptive xanthomas in 8.9%, vitiligo in 6.7%, diabetic bullae in 5.6%, diabetic rubeosis in 5.6%, lichen planus in 4.4%, erysipelas like erythema in 4.4%, trophic ulcers in [3.3%], wet gangrene foot in 2.2% and necrobiosis lipodica, granuloma annulare and reacting perforating collagenosis in 1.1% each. Conclusions: There are many skin manifestations amongst diabetics who are also suffering from various other medical problems. Patients in routine do not give much importance to these lesions because they appear harmless to them. They do not seek advice of physician/surgeon/dermatologist unless they develop serious skin and soft tissue infections like carbuncles, trophic ulcers or gangrene