Search results for: ovarian ischemia
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 206

Search results for: ovarian ischemia

56 Effect of TPA and HTLV-1 Tax on BRCA-1 and ERE Controlled Genes Expression

Authors: Azhar Jabareen, Mahmoud Huleihel

Abstract:

BRCA-1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor. The activated ERα is a transcriptional factor which activates various genes either by direct binding to the DNA at E2-responsive elements (EREs) and indirectly associated with a range of alternative non-ERE elements. Interference with BRCA-1 expression and/or functions leads to high risk of breast or/and ovarian cancer. Our lab investigated the involvement of Human T-cell leukemia Virus Type 1 (HTLV-1) in breast cancer, since HTLV-1 Tax was found to strongly inhibit BRCA-1 expression. In addition, long exposure of 12-O-tetradecanoylphorbol-13-acetate (TPA), which is one of the stress-inducing agents activated the HTLV-1 promoter. So here the involvement of TPA in breast cancer had been examined by testing the effect of TPA on BRCA-1 and ERE expression. The results showed that TPA activated both BRCA-1 and ERE expression. In the 12 hours TPA activated the tow promoters more than others time, and after 24 hours the level of the tow promoters was decreased. Tax inhibited BRCA-1 expression but did not succeed to inhibit the effect of TPA. Then the activation of the two promoters was not through ERα pathway because TPA had no effect on ERα binding to the two promoters of the BRCA-1 and ERE. Also, the activation was not via nuclear factor kappa B (NF-κB) pathway because when the inhibitory of NF-κB had been added to the TPA, it still activated the tow promoters. However, it seems that 53BP1 may be involved in TPA activation of these promoters because ectopic high expression of 53BP1 significantly reduced the TPA activity. In addition, in the presence of Bisindolylmaleimide-I (BI)- the inhibitor of Protein Kinase C (PKC)- there was no activation for the two promoters, so the PKC is agonized BRCA-1 and ERE activation.

Keywords: BRCA-1, ERE, HTLV-1, TPA

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55 Role of Hyperbaric Oxygen Therapy in Management of Diabetic Foot

Authors: Magdy Al Shourbagi

Abstract:

Diabetes mellitus is the commonest cause of neuropathy. The common pattern is a distal symmetrical sensory polyneuropathy, associated with autonomic disturbances. Less often, Diabetes mellitus is responsible for a focal or multifocal neuropathy. Common causes for non-healing of diabetic foot are the infection and ischemia. Diabetes mellitus is associated with a defective cellular and humoral immunity. Particularly, decreased phagocytosis, decreased chemotaxis, impaired bacterial killing and abnormal lymphocytic function resulting in a reduced inflammatory reaction and defective wound healing. Hyperbaric oxygen therapy is defined by the Undersea and Hyperbaric Medical Society as a treatment in which a patient intermittently breathes 100% oxygen and the treatment chamber is pressurized to a pressure greater than sea level (1 atmosphere absolute). The pressure increase may be applied in mono-place (single person) or multi-place chambers. Multi-place chambers are pressurized with air, with oxygen given via face mask or endotracheal tube; while mono-place chambers are pressurized with oxygen. Oxygen gas plays an important role in the physiology of wound healing. Hyperbaric oxygen therapy can raise tissue oxygen tensions to levels where wound healing can be expected. HBOT increases the killing ability of leucocytes also it is lethal for certain anaerobic bacteria and inhibits toxin formation in many other anaerobes. Multiple anecdotal reports and studies in HBO therapy in diabetic patients report that HBO can be an effective adjunct therapy in the management of diabetic foot wounds and is associated with better functional outcomes.

Keywords: hyperbari oxygen therapy, diabetic foot, neuropathy, multiplace chambers

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54 Effects of Some Characteristics of Gynecological Cancer Diagnosis and Treatment on Women's Sexual Life Quality

Authors: Buse Bahitli, Samiye Mete

Abstract:

The aim of the study was to evaluate the quality of sexual life of women with diagnosed gynecological cancer and receive treatment. The study was a descriptive and cross-sectional type, and it was carried out with 276 women. Information Form and Sexual Quality of Life Scale-Female (SQOL) form was used in the study. The data was evaluated using Mann-Whitney U and Kruskal-Wallis test. In the study, Sexual Quality of Life Scale-Female average score was 68.83 ± 21.17. The %43.1 of women was endometrial cancer, %30.8 was cervical cancer, %24.6 was ovarian cancer, and %1.4 was vulvar cancer. The average time to diagnosis of patients is 41.80 ± 47.64 months. There was no significant difference mean SQOL according to individual/sociodemographic characteristics like age, education. Gynecological cancer-related characteristics like gynaecological cancer type, treatment type, surgery type were found not to affect the mean score of SQOL. However, it was found that the difference was due to the higher SQOL score in the group with a diagnosis time of 25 months and over (X²KW= 6.356, p= 0.046). The reason of significant difference means SQOL according to diagnosis over time might be that women adapted to cancer diagnosis. While women with gynaecologic cancer are evaluating their sexual lives, it is necessary to evaluate them with good evaluation tools.

Keywords: gynecological cancers, sexuality, quality of sexual life, SQOL

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53 Utility of CT Perfusion Imaging for Diagnosis and Management of Delayed Cerebral Ischaemia Following Subarachnoid Haemorrhage

Authors: Abdalla Mansour, Dan Brown, Adel Helmy, Rikin Trivedi, Mathew Guilfoyle

Abstract:

Introduction: Diagnosing delayed cerebral ischaemia (DCI) following aneurysmal subarachnoid haemorrhage (SAH) can be challenging, particularly in poor-grade patients. Objectives: This study sought to assess the value of routine CTP in identifying (or excluding) DCI and in guiding management. Methods: Eight-year retrospective neuroimaging study at a large UK neurosurgical centre. Subjects included a random sample of adult patients with confirmed aneurysmal SAH that had a CTP scan during their inpatient stay, over a 8-year period (May 2014 - May 2022). Data collected through electronic patient record and PACS. Variables included age, WFNS scale, aneurysm site, treatment, the timing of CTP, radiologist report, and DCI management. Results: Over eight years, 916 patients were treated for aneurysmal SAH; this study focused on 466 patients that were randomly selected. Of this sample, 181 (38.84%) had one or more CTP scans following brain aneurysm treatment (Total 318). The first CTP scan in each patient was performed at 1-20 days following ictus (median 4 days). There was radiological evidence of DCI in 83, and no reversible ischaemia was found in 80. Findings were equivocal in the remaining 18. Of the 103 patients treated with clipping, 49 had DCI radiological evidence, in comparison to 31 of 69 patients treated with endovascular embolization. The remaining 9 patients are either unsecured aneurysms or non-aneurysmal SAH. Of the patients with radiological evidence of DCI, 65 had a treatment change following the CTP directed at improving cerebral perfusion. In contrast, treatment was not changed for (61) patients without radiological evidence of DCI. Conclusion: CTP is a useful adjunct to clinical assessment in the diagnosis of DCI and is helpful in identifying patients that may benefit from intensive therapy and those in whom it is unlikely to be effective.

Keywords: SAH, vasospasm, aneurysm, delayed cerebral ischemia

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52 Biometry and Pathology of Internal Genital Organs of Female Camel (Camelus dromedarius) in Lahore, Pakistan

Authors: Umair Riaz, Mudassar Iqbal, Umer Farooq, Farah Ali, Musadiq Idris

Abstract:

The present work was designed to establish biometrical norms for ovaries, oviducts and crevices of one humped camels (Camelus dromedarius) and the diseases associated thereof in various age groups viz. calves (< 2 years, n=15), heifers (2-4 years, n=34) and adults (> 4 years, n=81). The genitalia were attained from Lahore Abbatoir, Punjab, Pakistan. Ovaries, oviducts and cervices of experimental genitalia were assessed for their length, width, thickness and weight. Statistically, there was no difference in the length and width of both left and right ovaries which however, increased with the advancement of age of camel. Similar results were noticed regarding the width of oviducts. The mean length of cervices of female camels correlated well with the number of cervical annular rings amongst the age groups. Regarding the abnormalities of ovaries and cervices in the 3 age groups, camel calves did not have any of the abnormalities. However, ovarian hypoplasia in heifers (2.94%) and follicular cyst in adult female camels (1.23%) were revealed in the present study. Mucocervix in heifers (2.96%) and cervicitis 1.23% in adult camels was also noticed. The present work presents a preliminary data on biometrical analysis for one humped camels and envisages a broader study with increased population and sample size.

Keywords: camelus dromedarius, pathology, biometry, female genital tract

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51 Markers for Predicting Overweight or Obesity of Riding Egyptian Broodmares Mares

Authors: Amal Abo El-Maaty, Amira Mohamed, Nashwa Abu-Aita, Hisham Morgan

Abstract:

For estimating markers of overweight or obesity of brood mares used for riding and training, 17 mares of different body conditions were subjected to blood sampling and ultrasound examination to measure rump fat thickness and monitor ovulation for six consecutive weeks. Also length (L), heart girth (G) and withers height (H) were measured to estimate body weight (BW), body fat %, body fat mass (BFM) and body mass index (BMI). Mares were classified into three groups according to both body condition score (BCS) and rump back fat (BF). Overweight mares (O) were having BCS > 7 and BF thickness >7mm, moderate body condition (M) mares were having BCS >3and ≤7and BF <3and <7mm, and emaciated mares (E) were having BCS ≤3 and BF ≤3mm. glucose, triglycerides, nitric oxide, ovarian, thyroid, insulin, insulin like growth factor-I (IGF-1), and leptin hormones were measured. Results revealed that BCS, G, L, L*G*H, BW, BF, fat %, BFM were significantly (P<0.0001) decreasing linearly from O to E. T4 concentrations of E were significantly high (P=0.04) compared to M and O but T3 concentrations tended to decrease in E (P>0.05). Insulin and IGF-1 concentrations tended to be high in O (P>0.05) and decrease with the decrease of body condition. M had (P=0.007) the highest leptin, but E mares had the lowest P4 concentrations (P=0.01). Concentrations of glucose and NO decreased with the decrease of BCS and BF but triglycerides of O were insignificantly high. In conclusion, exercise could prevent the development of metabolic syndrome in horses and back fat and morphometric measurements were the easiest and simple assessment of overweight and deviation to obesity.

Keywords: body condition score, insulin, leptin, mares, rump fat

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50 Mature Cystic Teratomas of Ovary: A Series of 19 Cases with Rare Malignant Transformation in Three

Authors: Parveen Kundu, Nitika Chawla, Ruchi Agarwal, Swaran Kaur

Abstract:

Background: Mature cystic teratoma is a benign, most common tumor of the ovary occurring mostly in young and middle-aged females. This study consists of 19 cases of mature cystic teratomas which were received in the Department Of Pathology over a period of two years. There were malignant transformations observed in three cases, which makes it very important for pathologists to thoroughly examine the entire specimen of mature cystic teratomas. Material and Methods: Nineteen reported cases of mature cystic teratomas were received in Deptt. Of Pathology, BPS GMC Khanpur Kalan, Sonepat, over a two-year period from November 2020 to October 2022 and reviewed retrospectively. Data regarding age, size, laterality, gross, morphological features, and surgery performed were retrieved from pathological archives. Results: In our study, the most common age of presentation was the 20-40 year age group. The most common presenting complaint was fullness in the abdomen or abdominal distension. Four out of 19 cases studied cases presented with bilateral ovarian cysts. Tumor size ranged from 6 to 20 cm in diameter. In seven cases, cysts were greater than or equal to 10 cm in diameter. Three cases showed malignant transformation. Conclusion: It is very important to thoroughly examine the contralateral ovary to rule out bilateral presentation. A furthermost thorough examination is advised in tumors of size >10 cm and in tumors with solid areas to rule out any malignant transformation.

Keywords: teratoma, ovary, malignant, transformation

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49 Dopamine and Female Sexual Function: A Clinical and Biochemical Study

Authors: Azza Gaber Antar Farag, Eman Abd El Fatah Badr, Wesam Ahmed Tawfik Hasssan Abdel Aal, Mustafa Elsayed Elshaib

Abstract:

Background: Female Sexual Dysfunction (FSD) represents recurrent and persistent problems that distress women and/or strain their relationships with their partners. Dopamine can affect sexual function and interacts with ovarian hormones in the ventromedial area in the hypothalamus. Objective: To investigate the possible role of dopamine in FSD. Method: This prospective case-control study was carried on 100 women having FSD and 100 healthy volunteer females. They were recruited from the Al-Menoufia governorate. All included women were subjected to the questionnaire to assess their demographic and gynecological data as well as sexual function. They were investigated for serum levels of dopamine, estradiol, progesterone and DHEA hormones. Results: Dopamine serum levels were significantly lower in females having sexual dysfunction (6.68±4.14) than controls (57.97±26.26) (P>0.001). This decreased dopamine level was of a significant positive correlation with the arousal domain and significant negative correlation regarding the pain domain (r=-0.19, p=0.01). Also, estradiol serum levels were significantly lower (P>0.001), but progesterone and DHEA serum levels were significantly higher in the FSD group than controls (P>0.001). There was a significant negative correlation between dopamine and DHEA serum levels (r= -0.45, p <0.001). Conclusions: Decreased dopamine serum levels may have an active role in the pathophysiology of FSD, impacting mainly arousal and pain domains, and its targeting should be considered during FSD management.

Keywords: dopamine, estradiol, progesterone, DHEA, females sexual dysfunction

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48 Applying Cationic Porphyrin Derivative 5, 10-Dihexyl-15, 20bis Porphyrin, as Transfection Reagent for Gene Delivery into Mammalian Cells

Authors: Hajar Hosseini Khorami

Abstract:

Porphyrins are organic, aromatic compounds found in heme, cytochrome, cobalamin, chlorophyll , and many other natural products with essential roles in biological processes that their cationic forms have been used as groups of favorable non-viral vectors recently. Cationic porphyrins are self-chromogenic reagents with a high capacity for modifications, great interaction with DNA and protection of DNA from nuclease during delivery of it into a cell with low toxicity. In order to have high efficient gene transfection into the cell while causing low toxicity, genetically manipulations of the non-viral vector, cationic porphyrin, would be useful. In this study newly modified cationic porphyrin derivative, 5, 10-dihexyl-15, 20bis (N-methyl-4-pyridyl) porphyrin was applied. Cytotoxicity of synthesized cationic porphyrin on Chinese Hamster Ovarian (CHO) cells was evaluated by using MTT assay. This cationic derivative is dose-dependent, with low cytotoxicity at the ranges from 100 μM to 0.01μM. It was uptake by cells at high concentration. Using direct non-viral gene transfection method and different concentration of cationic porphyrin were tested on transfection of CHO cells by applying derived transfection reagent with X-tremeGENE HP DNA as a positive control. However, no transfection observed by porphyrin derivative and the parameters tested except for positive control. Results of this study suggested that applying different protocol, and also trying other concentration of cationic porphyrins and DNA for forming a strong complex would increase the possibility of efficient gene transfection by using cationic porphyrins.

Keywords: cationic porphyrins, gene delivery, non-viral vectors, transfection reagents

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47 Effects of Ethanolic Purslane Shoot and Seed Extracts on Doxorubicin-Induced Hepatotoxicity in Albino Rats

Authors: Osama M. Ahmed, Walaa G. Hozayen, Haidy Tamer Abo Sree

Abstract:

Doxorubicin (DOX), an anthracycline antibiotic is a broad-spectrum antineoplastic agent, which is commonly used in the treatment of uterine, ovarian, breast and lung cancers, Hodgkin's disease and soft tissue sarcomas as well as in several other cancer types. The effect of doxorubicin (4 mg/kg b.w.week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w. day) or ethanolic purslane seeds extract (50 mg/kg b.w.day) co-treatments for 6 weeks was evaluated in adult male rats. Serum ALT, AST, ALP, GGT, total bilirubin, total protein, and albumin levels were assayed. Lipid peroxidation (indexed by MDA) and antioxidants like hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT were assessed. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation. In conclusion, it can be supposed that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX hepatopathy without harmful side effects. However, further clinical studies are required to assess the safety and efficacy of these extract in human beings.

Keywords: doxorubicin, purslane, hepatotoxicity, antioxidants

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46 Proteomics Application in Disease Diagnosis and Reproduction İmprovement in Cow

Authors: Abdollah Sobhani, Hossein Vaseghi-Dodaran

Abstract:

Proteomics is defined as the study of the component of a cell, tissue and biological fluid. This technique has the potential to identify protein biomarkers of a disease states. In this study which was performed on bovine ovarian follicular cysts (BOFC), eight proteins are over expressed in BOFC that these proteins could be useful biomarkers for BOFC. The difference between serum proteome pattern cows affected by postpartum endometritis with healthy cows revealed that concentrations orosomucoid was decreased in endometritis. The comparison proteome of brucella abortus between laboratory adapted strains and clinical isolates could be useful to better understand this disease and vaccine development. Proteomics experiments identified new proteins and pathways that may be important in future hypothesis-driven studies of glucocorticoid-induced immunosuppression. Understanding the molecular mechanisms of effective parameters on male fertility is essential for obtaining high reproductive efficiency by decreasing cost and time. The investigations on proteome of high fertility spermatozoa indicated that expression of some proteins such as casein kinase 2 (CKII) prime poly peptide and tyrosine kinase in high fertility spermatozoa was higher compared to low fertility spermatozoa. Also, some evidence has indicated that variation in protein types and amounts in seminal fluid regulates fertility indexes in dairy bull. In conclusion, proteomics is a useful technique for discovering drugs, vaccine development, and diagnosis disease by biomarkers and improvement of reproduction efficiency.

Keywords: proteomics, reproduction, biomarker, immunity

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45 Communication and Management of Incidental Pathology in a Cohort of 1,214 Consecutive Appendicectomies

Authors: Matheesha Herath, Ned Kinnear, Bridget Heijkoop, Eliza Bramwell, Alannah Frazetto, Amy Noll, Prajay Patel, Derek Hennessey, Greg Otto, Christopher Dobbins, Tarik Sammour, James Moore

Abstract:

Background: Important incidental pathology requiring further action is commonly found during appendicectomy, macro- and microscopically. It is unknown whether the acute surgical unit (ASU) model affects the management and disclosure of these findings. Methods: An ASU model was introduced at our institution on 01/08/2012. In this retrospective cohort study, all patients undergoing appendicectomy 2.5 years before (traditional group) or after (ASU group) this date were compared. The primary outcomes were rates of appropriate management of the incidental findings and communication of the findings to the patient and to their general practitioner (GP). Results: 1,214 patients underwent emergency appendicectomy; 465 in the traditional group and 749 in the ASU group. 80 (6.6%) patients (25 and 55 in each respective period) had important incidental findings. There were 24 patients with benign polyps, 15 with neuro-endocrine tumour, 11 with endometriosis, 8 with pelvic inflammatory disease, 8 Enterobius vermicularis infection, 7 with low grade mucinous cystadenoma, 3 with inflammatory bowel disease, 2 with diverticulitis, 2 with tubo-ovarian mass, 1 with secondary appendiceal malignancy and none with primary appendiceal adenocarcinoma. One patient had dual pathologies. There was no difference between the traditional and ASU group with regards to communication of the findings to the patient (p=0.44) and their GP (p=0.27), and there was no difference in the rates of appropriate management (p=0.21). Conclusions: The introduction of an ASU model did not change rates of surgeon-to-patient and surgeon-to-GP communication nor affect rates of appropriate management of important incidental pathology during an appendectomy.

Keywords: acute care surgery, appendicitis, appendicectomy, incidental

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44 Cannabinoids and Terpenes as Potential Modulators of Efflux Transporters for Overcoming Drug Resistance in Epilepsy

Authors: Tomáš Nejedlý, Dominika Mrázková, Jitka Viktorová

Abstract:

The blood-brain barrier (BBB) serves as a protective shield, preventing the entry of harmful substances into the central nervous system. On the other hand, it also restricts the transport of neuroactive drugs, such as antiepileptics, which mitigate epileptic seizures. Drug-resistant epilepsy is often associated with the overexpression of efflux transporters, including P-glycoprotein (P-gp) or multidrug resistance protein 1 (MRP1), on the BBB. The aim of this work is to find P-gp and MRP1 inhibitors derived from phytocannabinoids and terpenes. The work evaluates whether these compounds interact directly with P-gp or MRP1 by rhodamine 123 or fluorescein efflux assay. The effect of phytocannabinoids on the gene expression of these transporters is also studied using qPCR and Western blot. These transporters are found in BBB cells; however, we decided to use the human ovarian cancer cell line (A2780ADR) due to its overproduction of P-gp and malignant glioma cell line (U87) due to its overproduction of MRP1. The results showed that while terpenes suppressed the activity of efflux transporters, phytocannabinoids tended to decrease their expression. Terpenes demonstrated an average inhibition of 65%, surpassing phytocannabinoids, which exhibited an average inhibition of approximately 30%. Particularly noteworthy was the modulating effect of (-)-α-bisabolol with the highest activity among the compounds tested. Based on these findings, phytocannabinoids and terpenes emerge as promising natural candidates for addressing drug resistance linked to efflux transporters. Acknowledgment: The project was funded by the Grant No 22-20860S of The Czech Science Foundation.

Keywords: drug-resistant epilepsy, efflux transporters, multidrug resistance protein 1, P-glycoprotein, phytocannabinoids, terpens

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43 Design and Synthesis of Some Oxadiazole Bearing Benzimidazole Derivatives as Potential Epidermal Growth Factor Receptor Inhibitors

Authors: Ismail Celik, Gulgun Ayhan Kilcigil, Berna Guven, Zumra Kara, Arzu Onay-Besikci

Abstract:

Epidermal Growth Factor Receptor is the cell-surface receptor of the ErbB (erythroblastic leukemia viral oncogene homologue receptors) family of tyrosine kinases. It plays a vital role in regulating the proliferation and differentiation of cells. However, a variety of mechanisms, such as EGFR expression, mutation, and ligand-dependent receptor dimerization, are associated with the development of various activated EGFR tumors. EGFR is highly expressed in most solid tumors, including breast, head and neck cancer, non-small cell lung cancer (NSCLC), renal, ovarian, and colon cancers. Thus, specific EGFR inhibition plays one of the key roles in cancer treatment. The compounds used in the treatment as tyrosine kinase inhibitors are known to contain the benzimidazole isosterium indole, pazopanib, and axitinibin indazole rings. In addition, benzimidazoles have been shown to exhibit protein kinase inhibitory activity in addition to their different biological activities.Based on these data, it was planned and synthesized of some oxadiazole bearing benzimidazole derivatives [N-cyclohexyl-5-((2-phenyl/substitutedphenyl-1H-benzo[d]imidazole-1-yl) methyl)-1,3,4-oxadiazole-2-amine]. EGFR kinase inhibitory efficiency of the synthesized compounds was determined by comparing them with a known kinase inhibitor erlotinib in vitro, and two of the compounds bearing phenyl (19a) and 3,4-dibenzyloxyphenyl (21a) ring exhibited significant activities.

Keywords: benzimidazole, EGFR kinase inhibitory, oxadiazole, synthesis

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42 Obstetric Outcome after Hysteroscopic Septum Resection in Patients with Uterine Septa of Various Sizes

Authors: Nilanchali Singh, Alka Kriplani, Reeta Mahey, Garima Kachhawa

Abstract:

Objective: Resection of larger uterine septa does improve obstetric performance but whether smaller septa need resection and their impact on obstetric outcome is not clear. We wanted to evaluate the role of septal resection of septa of various sizes in obstetric performance. Methods: This retrospective cohort study comprised of 107 patients with uterine septum. The patients were categorized on the basis of extent of uterine septum into four groups: a) Subsepta (< 1/3rd), b) Septum > 1/3 to ½, c) Septum>1/2 to whole uterine cervix, d) Septum traversing whole of uterine cavity and cervix. Out of these 107 patients, 74 could be contacted telephonically and outcomes recorded. Sensitivity and specificity of investigative modalities were calculated. Results: Infertility was seen in maximum number of cases in complete septa (100%), whereas abortions were seen more commonly, in subsepta (18%). MRI had maximum sensitivity and positive predictive value, followed by hysteron-salpingography. Tubal block, fibroid, endometriosis, pelvic adhesions, ovarian pathologies were seen in some but no definite association of these pathologies was seen with any subgroup of septa. Almost five-year follow-up was recorded in all the subgroups. Significant reduction in infertility was seen in all septal subgroup (p=0.046, 0.032 & 0.05) patients except in subsepta (< 1/3rd uterine cavity) after septum resection. Abortions were significantly reduced (p=0.048) in third subgroup (i.e. septum > ½ to upto internal os) after hysteroscopic septum resection. Take home baby rate was 33% in subsepta and around 50% in the remaining subgroups of septa. Conclusions: Septal resection improves obstetric performance in patients with uterine septa of various sizes. Whether septal resection improves obstetric performance in patients with subsepta or very small septa, is controversial. Larger studies addressing this issue need to be planned.

Keywords: septal resection, obstetric outcome, infertility, septum size

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41 Genetic Polymorphism in the Vitamin D Receptor Gene and 25-Hydroxyvitamin D Serum Levels in East Indian Women with Polycystic Ovary Syndrome

Authors: Dipanshu Sur, Ratnabali Chakravorty

Abstract:

Background: Polycystic ovary syndrome (PCOS) is the most common metabolic abnormality such as changes in lipid profile, diabetes, hypertension and metabolic syndrome occurring in young women of reproductive age. Low vitamin D levels were found to be associated with the development of obesity and insulin resistance in women with PCOS. Variants on vitamin D receptor (VDR) gene have also been related to metabolic comorbidities in general population. Aim: The aim of this case-control study was to investigate whether the VDR gene polymorphisms are associated with susceptibility to PCOS. Methods: Women with PCOS and a control group, all aged 16-40 years, were enrolled. Genotyping of VDR Fok-I (rs2228570), VDR Apa-I (rs7975232) as well as GC (rs2282679), DHCR7 (rs12785878) SNPs between groups were determined by using direct sequencing. Serum 25-hydroxyvitamin D [25(OH)] levels were measured by ELISA. Results: Mean serum 25(OH)D in the PCOS and control samples were 19.08±7 and 23.27±6.03 (p=0.048) which were significantly lower in PCOS patients compared with controls. CC genotype of the VDR Apa-I SNP was same frequent in PCOS (25.6%) and controls (25.6%) (OR: 0.9995; 95%CI: 0.528 to 1.8921; p= 0.9987). The CC genotype was also significantly associated with both lower E2 (p=0.031) and Androstenedione levels (p=0.062). We observed a significant association of GC polymorphism with 25(OH)D levels. PCOS women carrying the GG genotype (in GC genes) had significantly higher risk for vitamin D deficiency than women carrying the TT genotype. Conclusions: In conclusion, data from this study indicate that vitamin D levels are lower, and vitamin D deficiency more frequent, in PCOS than in controls. The present findings suggest that the Apa-I, Fok-I polymorphism of the VDR gene is associated with PCOS and seems to modulate ovarian steroid secretion. Further studies are needed to better clarify the biological mechanisms by which the polymorphism influences PCOS risk.

Keywords: vitamin D receptor, polymorphism, vitamin D, polycystic ovary syndrome

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40 Palliative Performance Scale Differences between Patients Referred by Specialized Cancer Center and General Hospitals to the Palliative Care Center in Kuwait

Authors: Khalid Al Saleh, Najlaa AlSayed

Abstract:

Background: Palliative care is changing from just ‘end of life care’ to care delivered earlier in the disease course. Metanalysis showed that Palliative Performance Scale (PPS) is associated with increased length of survival. The Palliative Care Center (PCC) in Kuwait is the only stand-alone center in Eastern Mediterranean Region with a capacity of 92 beds. We compared clinical characteristics between patients referred from the Specialized Cancer Center and general hospitals in Kuwait to PCC. Method: A cross Sectional survey was conducted since the opening of PCC in January 2011 to June 2013. Patients’ data on demographics, type of the cancer, PPS score and referring hospital were collected and analyzed. Results: Total number of the patients was 142. Mean age was 61.05±14.79 years, 66 patients (47.1%) were males and 74 (52.9%) were females. The most common cancers in males were lung (n=18, 27.3%) followed by head and neck cancers (n=8, 12.1%) and brain tumors (n=7, 10.6%) while in females, the most common cancers were breast cancer (n=12, 16.7%) followed by ovarian cancer (n=10, 13.9%) and Cancer Colon (n=8, 11.1%). Patients with PPS score 30% were 27.9% (n=39), 40% in 40.7% (n=57), and 50% in 17.1% (n=24) respectively. Patients referred from the Specialized Cancer Center had significantly higher portion of patients with PPS score > 30% (73.4%, n=94), compared to patients coming from general hospitals (33.3%, n=4), P value= 0.007. Conclusion: There is significant difference in PPS scores between patients referred from the Specialized Cancer Center compared to patients referred from general hospitals. We encourage that all cancer patients should be treated in Specialized Cancer Centers and earlier involvement of Palliative Care Centers to achieve better survival. Training workshops are needed for health care professionals working in general hospitals to raise awareness about earlier referral of patients to palliative care services.

Keywords: palliative care, kuwait, performance scale differences, pps score, specialized hospitals

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39 Myocardial Reperfusion Injury during Percutaneous Coronary Intervention in Patient with Triple-Vessel Disease in Limited Resources Hospital: A Case Report

Authors: Fanniyah Anis, Bram Kilapong

Abstract:

Myocardial reperfusion injury is defined as the cellular damage that results from a period of ischemia, followed by the reestablishment of the blood supply to the infarcted tissue. Ventricular tachycardia is one of the most commonly encountered reperfusion arrhythmia as one of the types of myocardial perfusion injury. Prompt and early treatment can reduce mortality, despite limited resources of the hospital in high risk patients with history of triple vessel disease. Case report, Male 53 years old has been diagnosed with NSTEMI with 3VD and comorbid disease of Hypertension and has undergone revascularization management with Percutaneous coronary intervention. Ventricular tachycardia leading to cardiac arrest occurred right after the stent was inserted. Resuscitation was performed for almost 2 hours until spontaneous circulation returned. Patient admitted in ICU with refractory cardiac shock despite using combination of ionotropic and vasopressor agents under standard non-invasive monitoring due to the limitation of the hospital. Angiography was performed again 5 hours later to exclude other possibilities of blockage of coronary arteries and conclude diagnosis of myocardial reperfusion injury. Patient continually managed with combination of antiplatelet agents and maintenance dose of anti-arrhythmia agents. The handling of the patient was to focus more on supportive and preventive from further deteriorating of the condition. Patient showed clinically improvement and regained consciousness within 24 hours. Patient was successfully discharged from ICU within 3 days without any neurological sequela and was discharge from hospital after 3 days observation in general ward. Limited Resource of hospital did not refrain the physician from attaining a good outcome for this myocardial reperfusion injury case and angiography alone can be used to confirm the diagnosis of myocardial reperfusion injury.

Keywords: limited resources hospital, myocardial reperfusion injury, prolonged resuscitation, refractory cardiogenic shock, reperfusion arrhythmia, revascularization, triple-vessel disease

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38 The Retinoprotective Effects and Mechanisms of Fungal Ingredient 3,4-Dihydroxybenzalacetone through Inhibition of Retinal Müller and Microglial Activation

Authors: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao

Abstract:

Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.

Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR

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37 Early and Mid-Term Results of Anesthetic Management of Minimal Invasive Coronary Artery Bypass Grafting Using One Lung Ventilation

Authors: Devendra Gupta, S. P. Ambesh, P. K Singh

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Introduction: Minimally invasive coronary artery bypass grafting (MICABG) is a less invasive method of performing surgical revascularization. Minimally invasive direct coronary artery bypass (MIDCAB) provides many anesthetic challenges including one lung ventilation (OLV), managing myocardial ischemia, and pain. We present an early and midterm result of the use of this technique with OLV. Method: We enrolled 62 patients for analysis operated between 2008 and 2012. Patients were anesthetized and left endobronchial tube was placed. During the procedure left lung was isolated and one lung ventilation was maintained through right lung. Operation was performed utilizing off pump technique of coronary artery bypass grafting through a minimal invasive incision. Left internal mammary artery graft was done for single vessel disease and radial artery was utilized for other grafts if required. Postoperative ventilation was done with single lumen endotracheal tube. Median follow-up is 2.5 years (6 months to 4 years). Results: Median age was 58.5 years (41-77) and all were male. Single vessel disease was present in 36, double vessel in 24 and triple vessel disease in 2 patients. All the patients had normal left ventricular size and function. In 2 cases difficulty were encounter in placement of endobronchial tube. In 1 case cuff of endobronchial tube was ruptured during intubation. High airway pressure was developed on OLV in 1 case and surgery was accomplished with two lung anesthesia with low tidal volume. Mean postoperative ventilation time was 14.4 hour (11-22). There was no perioperative and 30 day mortality. Conversion to median sternotomy to complete the operation was done in 3.23% (2 out of 62 patients). One patient had acute myocardial infarction postoperatively and there were no deaths during follow-up. Conclusion: MICABG is a safe and effective method of revascularization with OLV in low risk candidates for coronary artery bypass grafting.

Keywords: MIDCABG, one lung ventilation, coronary artery bypass grafting, endobronchial tube

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36 Lipid-Chitosan Hybrid Nanoparticles for Controlled Delivery of Cisplatin

Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin

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Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.

Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study

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35 Montelukast Doesn’t Decrease the Risk of Cardiovascular Disease in Asthma Patients in Taiwan

Authors: Sheng Yu Chen, Shi-Heng Wang

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Aim: Based on human, animal experiments, and genetic studies, cysteinyl leukotrienes, LTC4, LTD4, and LTE4, are inflammatory substances that are metabolized by 5-lipooxygenase from arachidonic acid, and these substances trigger asthma. In addition, the synthetic pathway of cysteinyl leukotriene is relevant to the increase in cardiovascular diseases such as myocardial ischemia and stroke. Given the situation, we aim to investigate whether cysteinyl leukotrienes receptor antagonist (LTRA), montelukast which cures those who have asthma has potential protective effects on cardiovascular diseases. Method: We conducted a cohort study, and enrolled participants which are newly diagnosed with asthma (ICD-9 CM code 493. X) between 2002 to 2011. The data source is from Taiwan National Health Insurance Research Database Patients with a previous history of myocardial infarction or ischemic stroke were excluded. Among the remaining participants, every montelukast user was matched with two randomly non-users by sex, and age. The incident cardiovascular diseases, including myocardial infarction and ischemic stroke, were regarded as outcomes. We followed the participants until outcomes come first or the end of the following period. To explore the protective effect of montelukast on the risk of cardiovascular disease, we use multivariable Cox regression to estimate the hazard ratio with adjustment for potential confounding factors. Result: There are 55876 newly diagnosed asthma patients who had at least one claim of inpatient admission or at least three claims of outpatient records. We enrolled 5350 montelukast users and 10700 non-users in this cohort study. The following mean (±SD) time of the Montelukast group is 5 (±2.19 )years, and the non-users group is 6.2 5.47 (± 2.641) years. By using multivariable Cox regression, our analysis indicated that the risk of incident cardiovascular diseases between montelukast users (n=43, 0.8%) and non-users (n=111, 1.04%) is approximately equal. [adjusted hazard ratio 0.992; P-value:0.9643] Conclusion: In this population-based study, we found that the use of montelukast is not associated with a decrease in incident MI or IS.

Keywords: asthma, inflammation, montelukast, insurance research database, cardiovascular diseases

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34 Association of Vitamin D Levels in Obese and Non-Obese Patients with Polycystic Ovarian Syndrome in East Indian Populations

Authors: Dipanshu Sur, Ratnabali Chakravorty

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Introduction: Polycystic ovary syndrome (PCOS) is the most common metabolic abnormality such as changes in lipid profile, diabetes, hypertension and metabolic syndrome occurring in women. Hypovitaminsis D was found to be associated with the development of obesity and insulin resistance in women with PCOS. Aim: To evaluate the association of vitamin D levels in obese and non-obese patients with PCOS in an East Indian populations. Methods: A case control study was conducted. It enrolled 100 cases of PCOS based on Rotterdam criteria and 100 ovulatory normal cases matched for their age and BMI. Vitamin D levels were compared in the obese and non-obese PCOS groups and also with the controls. Results: The mean age of subjects was 29.48 ± 3.29 years in the PCOS group and 26.24 ± 2.56 years in the control group. Hypovitaminosis D was present in 75 out of 100 PCOS women (75.0%) and 25 women (25.0%) showed sufficient 25OHD levels ≥30 ng/ml. Women with PCOS had significantly lower total serum calcium (8.4 ± 0.25 mg/dl versus 9.8 ± 0.17 mg/dl in controls), and 25 OHD (21.2 ± 2.56 ng/ml versus 32.6 ± 2.23 ng/ml in control group) than ovulatory normal women. This difference remained significant for both groups after adjustment for BMI. Obese women in both groups had significantly lower concentration of calcium and 25OHD than normal weight patients in this study. Conclusion: Our study shows majority of the patients and controls had vitamin D deficiency and there was significant difference in the vitamin D levels in PCOS group and controls as well as obese and non-obese groups. This may reflect the vitamin D deficiency status of the community. Vitamin D deficiency should demands immediate attention as it is a severe problem among the East Indian population.

Keywords: vitamin D deficiency, polycystic ovary syndrome, obese, hypovitaminsis D

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33 Serum 25-Dihydroxy Vitamin D3 Level Estimation and Insulin Resistance in Women of 18-40 Years Age Group with Polycystic Ovarian Syndrome

Authors: Thakur Pushpawati, Singh Vinita, Agrawal Sarita, Mohapatra Eli

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Polycystic ovary syndrome (PCOS) is a disease of endocrine and frequently encountered in women in their reproductive period, and it is characterized by clinical features of anovulation, clinical and biochemical features of hyperandrogenism, and PCOS morphology on ultrasonographic examination. In Indian scenario, only a few studies are available on the correlation of serum 25-dihydroxy vitamin D3 level and insulin level. The present study is a prospective case-control study and aims to estimate the concentration of serum 25-dihydroxy vitamin D3 and insulin resistance and determine the association of serum 25-dihydroxy vitamin D3 with insulin resistance in PCOS women of 18-40 years age group. In this study, the primary objective is to estimate the concentration of 25-dihydroxy vitamin D3, insulin, glycaemic status, calcium and phosphorus levels in 18-40 year age women with polycystic ovary syndrome and to compare these parameters with age and BMI matched healthy control of same age group women. The secondary objective is to determine the association between 25-dihydroxy vitamin D3 concentration and insulin resistance among PCOS cases in 18-40 years age group women. This study was carried on at outpatient Department of Obstetrics & Gynaecology, Aiims Raipur. It took one year from the date of approval. In case, 32 women were diagnosed (Diagnosed PCOS cases as per Rotterdoms criteria among women of 18-40 years of age), as control group 32 women of 18-40 years of age were diagnosed As a result, serum insulin level was elevated among PCOS women along with 25-dihydroxy vitamin D3 deficiency.Conclude up, PCOS is more common in the age group of 20-40 years. There is a strong correlation between vitamin D deficiency and insulin resistance among PCOS patients.

Keywords: vitamin D, insulin resistance, PCOS, reproductive age group

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32 Hypertensive Response to Maximal Exercise Test in Young and Middle Age Hypertensive on Blood Pressure Lowering Medication: Monotherapy vs. Combination Therapy

Authors: James Patrick A. Diaz, Raul E. Ramboyong

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Background: Hypertensive response during maximal exercise test provides important information on the level of blood pressure control and evaluation of treatment. Method: A single center retrospective descriptive study was conducted among 117 young (aged 20 to 40) and middle age (aged 40 to 65) hypertensive patients, who underwent treadmill stress test. Currently on maintenance frontline medication either monotherapy (Angiotensin-converting enzyme inhibitor/Angiotensin receptor blocker [ACEi/ARB], Calcium channel blocker [CCB], Diuretic - Hydrochlorthiazide [HCTZ]) or combination therapy (ARB+CCB, ARB+HCTZ), who attained a maximal exercise on treadmill stress test (TMST) with hypertensive response (systolic blood pressure: male >210 mm Hg, female >190 mm Hg, diastolic blood pressure >100 mmHg, or increase of >10 mm Hg at any time during the test), on Bruce and Modified Bruce protocol. Exaggerated blood pressure response during exercise (systolic [SBP] and diastolic [DBP]), peak exercise blood pressure (SBP and DBP), recovery period (SBP and DBP) and test for ischemia and their antihypertensive medication/s were investigated. Analysis of variance and chi-square test were used for statistical analysis. Results: Hypertensive responses on maximal exercise test were seen mostly among female population (P < 0.000) and middle age (P < 0.000) patients. Exaggerated diastolic blood pressure responses were significantly lower in patients who were taking CCB (P < 0.004). A longer recovery period that showed a delayed decline in SBP was observed in patients taking ARB+HCTZ (P < 0.036). There were no significant differences in the level of exaggerated systolic blood pressure response and during peak exercise (both systolic and diastolic) in patients using either monotherapy or combination antihypertensives. Conclusion: Calcium channel blockers provided lower exaggerated diastolic BP response during maximal exercise test in hypertensive middle age patients. Patients on combination therapy using ARB+HCTZ exhibited a longer recovery period of systolic blood pressure.

Keywords: antihypertensive, exercise test, hypertension, hyperytensive response

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31 Development and Pre-clinical Evaluation of New ⁶⁴Cu-NOTA-Folate Conjugates for PET Imaging of Folate Receptor-Positive Tumors

Authors: Norah Al Hokbany, Ibrahim Al Jammaz, Basem Al Otaibi, Yousif Al Malki, Subhani M. Okarvi

Abstract:

Objective: The folate receptor is over-expressed in a wide variety of human tumors. Conjugates of folate have been shown to be selectively taken up by tumor cells via the folate receptor. In an attempt to develop new folate radiotracers with favorable biochemical properties for detecting folate receptor-positive cancers. Methods: we synthesized ⁶⁴Cu-NOTA- and ⁶⁴Cu-NOTAM-folate conjugates using a straightforward and simple one-step reaction. Radiochemical yields were greater than 95% (decay-corrected) with a total synthesis time of less than 20 min. Results: Radiochemical purities were always greater than 98% without high-performance liquid chromatography (HPLC) purification. These synthetic approaches hold considerable promise as a rapid and simple method for ⁶⁴Cu-folate conjugate preparation with high radiochemical yield in a short synthesis time. In vitro tests on the KB cell line showed that significant amounts of the radio conjugates were associated with cell fractions. Bio-distribution studies in nude mice bearing human KB xenografts demonstrated a significant tumor uptake and favorable bio-distribution profile for ⁶⁴Cu-NOTA- and ⁶⁴Cu-NOTAM-folate conjugate. The uptake in the tumors was blocked by the excess injection of folic acid, suggesting a receptor-mediated process. Conclusion: These results demonstrate that the ⁶⁴Cu-NOTAM-folate conjugate may be useful as a molecular probe for the detection and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis, as well as monitoring tumor response to treatment.

Keywords: folate, receptor, tumor imaging, ⁶⁴Cu-NOTA-folate, PET

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30 Brain Derived Neurotrophic Factor (BDNF) Down Regulation in Peritoneal Carcinomatosis Patients

Authors: Awan A. Zaima, Tanvieer Ayesha, Mirshahi Shahsoltan, Pocard Marc, Mirshahi Massoud

Abstract:

Brain-derived neurotrophic factor (BDNF) is described as a factor helping to support the survival of existing neurons by involving the growth and differentiation of new neurons and synapses. Cancer diagnosis impacts the mental health, and in consequences, depression arise eventually hinders recovery and disrupts the quality of life and surviving chances of patients. The focus of this study is to hint upon a prospective biomarker as a promising diagnostic tool for an early indicator/predictor of depression prevalence in cancer patients for better care and treatment options. The study aims to analyze peripheral biomarkers from neuro immune axis (BDNF, IL21 as a NK cell activator) using co-relation approach. Samples were obtained from random non cancer candidates and advanced peritoneum carcinomatosis patients with 25% pseudomyxoma, 21% Colon cancer,19% stomach cancer, 10% ovarian cancer, 8% appendices cancer, and 10% other area of peritoneum cancer patients. Both groups of the study were categorized by gender and age, with a range of 18 to 86 years old. Biomarkers were analyzed in collected plasma by performing multiplex sandwich ELISA system. Data were subjected to statistical analysis for the assessment of the correlation. Our results demonstrate that BNDF and IL 21 down regulated significantly in patient groupas compared to non-cancer candidates (ratio of patients/normalis 2.57 for BNDF and 1.32 for IL21). This preliminary investigation suggested that the neuro immune biomarkers are down regulated in carcinomatosis patients and can be associated with cancer expansion and cancer genesis. Further studies on larger cohort are necessary to validate this hypothesis.

Keywords: biomarkers, depression, peritoneum carcinoma, BNDF, IL21

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29 Role of Onion Extract for Neuro-Protection in Experimental Stroke Model

Authors: Richa Shri, Varinder Singh, Kundan Singh Bora, Abhishek Bhanot, Rahul Kumar, Amit Kumar, Ravinder Kaur

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The term ‘neuroprotection’ means preserving/salvaging function and structure of neurons. Neuroprotection is an adjunctive treatment option for neurodegenerative disorders. Oxidative stress is considered a major culprit in neurodegenerative disorders; hence, management strategies include use of antioxidants. Our search for a neuroprotective agent began with Allium cepa L. or onions, (family Amaryllidaceae) - a potent antioxidant. We have investigated the neuroprotective potential of onions in experimental models of ischemic stroke, diabetic neuropathy, neuropathic pain, and dementia. In pre and post-ischemic stroke model, the methanol extract of outer scales of onion bulbs (MEOS) prevented memory loss and motor in-coordination; reduced oxidative stress and cerebral infarct size. This also prevented and ameliorated diabetic neuropathy in mice. The MEOS was fractionated to yield a flavonoid rich fraction (FRF) that successfully reversed ischemia-reperfusion induced neuronal damage, thereby demonstrating that the flavonoids are responsible for the activity. The FRF effectively ameliorated chronic constriction induced neuropathic pain in rats. The FRF was subjected to bioactivity-guided fractionated. It was seen that FRF is more effective as compared to the isolated components probably due to synergism among the constituents (i.e., quercetin and quercetin glucosides) in the FRF. The outer scales of onion bulbs have great potential for prevention as well as for treatment of neuronal disorders. Red onions, with higher amounts of flavonoids as compared to the white onions, produced more significant neuroprotection. Thus, the standardized FRF from the waste material of a commonly used vegetable, especially the red variety, may be developed as a valuable neuroprotective agent.

Keywords: Allium cepa, antioxidant activity, flavonoid rich fraction, neuroprotection

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28 The Endocrinology of Obesity and Dejenerative Joint Disease

Authors: Kebret Kebede, Anthony Scinta

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Obesity is the most prevalent global problem that continues to rise at alarming rates both in the industrialized and developing countries. Adipose tissue is an endocrine tissue that secretes numerous chemical signals, hormones, lipids, cytokines and coagulation factors as well as prompting insulin resistance which is a primary contributor to Type II Diabetes- one of its most common adverse effects on health. Other hormones whose levels are linked to obesity and nutritional state are leptin, IGF-1, and adiponectin. Several studies indicate that obesity is the leading cause of high levels of cholesterol that leads to fatty liver disease, gallstones, hypertension, increased risk for cancer and degenerative joint disease that primarily affects the weight bearing joints of the lower extremities. The activation of inflammatory pathways promotes synovial pathology that results in accelerated degeneration of the joints. The study examines the prevalence of obesity in the US female population in comparison to that of the developing world and its emergence as a significant and potentially modifiable risk factor in degenerative disease of the hip and knee joints that has resulted in staggering healthcare cost. Studies have shown that as the prevalence of obesity rises, we continue to see a rise in degenerative joint disease. The percentage of arthritis cases linked directly to obesity has risen from 3 percent in 1971 to 18 percent in 2002. A person with obesity is around 60 percent more likely to develop arthritis than someone of normal body weight. In women, obesity is associated with increased mortality from breast, cervical, endometrial and ovarian cancer that may accompany debilitating joint diseases and restricted mobility.

Keywords: obesity, endocrine, degenerative, mortality, joint diseases, cancer, debilitating, mobility

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27 Pyrroloquinoline Quinone Enhances the Mitochondrial Function by Increasing Beta-Oxidation and a Balanced Mitochondrial Recycling in Mice Granulosa Cells

Authors: Moustafa Elhamouly, Masayuki Shimada

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The production of competent oocytes is essential for reproductivity in mammals. Maintenance of mitochondrial efficiency is required to supply the ATP necessary for granulosa cell proliferation during the follicular development process. Treatment with Pyrroloquinoline quinone (PQQ) has been reported to increase the number of ovulated oocytes and pups per delivery in mice by maintaining healthy mitochondrial function. This study aimed to elucidate how PQQ maintains mitochondrial function during ovarian follicle growth. To do this, both in vitro and in vivo experiments were performed with granulosa cells from superovulated immature (3-week-old) mice that were pretreated with or without PQQ. The effects of PQQ on beta-oxidation, mitochondrial function, mitophagy, and mitochondrial biogenesis were examined. PQQ increased beta-oxidation-related genes and CPT1 protein content in granulosa cells and this was associated with a decreased phosphorylation of P38 signaling protein. Using the fatty acid oxidation assay on the flux analyzer, PQQ increased the reliance of beta-oxidation on the endogenous fatty acids and was associated with a mild UCP-dependant mitochondrial uncoupling, ATP production, mitophagy, and mitochondrial biogenesis. PQQ also increased the expression of endogenous antioxidant enzymes. Thus, PQQ induced beta-oxidation in growing granulosa cells relying on endogenous fatty acids. And reduced the Reactive oxygen species (ROS) production by inducing a mild mitochondrial uncoupling with keeping high mitochondrial function. Damaged mitochondria were recycled by the induced mitophagy and replaced by the increased mitochondrial biogenesis. Collectively, PQQ may enhance reproductivity by maintaining the efficiency of mitochondria to produce enough ATP required for normal folliculogenesis.

Keywords: granulosa cells, mitochondrial uncoupling, mitophagy, pyrroloquinoline quinone (PQQ), reactive oxygen species (ROS).

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