Quality by design (QbD) and process analytical technology (PAT) applications in pharmaceutical industry

Quality by Design (QbD) for the pharmaceutical industry includes the design, development and production control of products and production processes from the beginning to the end of the product development phase for ensuring the consistent quality of a pharmaceutical product. The QbD is a systematic scientific approach aimed at meeting the needs of the patient in the desired and targeted quality and aiming to produce the same quality pharmaceutical product in this direction. Process Analytical Technology, which is assessed in that regard, is part of a design quality approach that is used to design, analyze, and control real-time measurements of quality and performance criteria for raw and processed materials to achieve the desired final product. This scientific and systematic approach to pharmaceutical product development, which is also acknowledged and supported by the health authorities, serves to the changing and developing pharmaceutical sector

Gökçeada Uğurlu-Zeytinlik yerleşimi neolitik dönem bezemeli çanak çömleğinin bağlamsal olarak değerlendirilmesi

Neolitik ve Kalkolitik Dönem’de iskan görmüş Uğurlu-Zeytinlik, M.Ö 6800-4300 aralığına tarihlenmektedir. Yerleşim, Çanakkale’ye bağlı olan Gökçeada’nın Uğurlu Köyüne 1 km uzaklıkta bulunmaktadır. Uğurlu-Zeytinlik Höyük Neolitik Dönem bezemeli çanak çömlekleri V. ve IV. Kültür Katlarında görülmektedir ve Uğurlu Höyük neolitik çanak çömlek toplululuğu içerisinde %1’den daha az bir orana sahiptir. En erken bezemeli çanak çömlekler V. Kültür Katında M.Ö 6200’de ortaya çıkmıştır ve IV. Kültür Katında M.Ö 5700’lere kadar devamlılık göstermektedir. Bahsedilen iki kültür katına ait bezemeli çanak çömlekler, teknolojik ve sosyal öğelerin bir parçası iken aynı zamanda diğer yerleşimler arasındaki etkileşimin takip edilmesinde aracıdır. Etkileşim konusunda, boya bezeme, İmpresso ve diğer bezeme türleri ele alındığında, Kuzey Batı Anadolu, Batı Anadolu, Göller Bölgesi, İç Anadolu, Doğu Akdeniz, Balkanlar, Makedonya, Kıta Yunanistan gibi birçok bölgeyle Uğurlu’nun etkileşime geçmiş olabileceği düşünülmektedir. Diğer yandan Uğurlu Neolitik Dönem bezemeli çanak çömleklerinin işlevsel yapıdan uzak amaçlar için de kullanılmış olabileceği ve onların sembolik, ritüel ve sosyal açıdan toplum arasında birer metafor olarak kullanıldığı öngörülmektedir. Bu tez çalışmasında Uğurlu Yerleşimi Neolitik Dönem bezemeli çanak çömleklerinin teknik özellikleri ayrıntılı olarak incelenmiş ve bezeme stilleri üzerinden analojik değerlendirmesi yapılmıştır. Diğer yandan kullanım amaçlarının daha iyi anlaşılması için etnoarkeolojik, teorik ve bağlamsal verilerden yararlanılmıştır.Uğurlu-Zeytinlik, inhabited in the Neolithic and Chalcolithic periods, is dated to between 6800-4300 BC. The settlement is located at a distance of 1 km from Uğurlu village in the island of Gökçeada, administratively a part of the Çanakkale province. Decorated ceramics from the Neolithic period in Uğurlu-Zeytinlik Höyük are encountered in Phases V and IV, amounting to less than 1% of the entire Neolithic pottery assemblage. The earliest decorated ceramics are known from c. 6200 BC in Phase V, and show continuity until c. 5700 BC in Phase IV. Decorated ceramics from these aforementioned phases, which are constituents of technological and social elements, also allow for an investigation of interaction between other settlements. Based on decorative styles including painted decoration, impresso, and others, it can be inferred that Uğurlu could have interacted with numerous regions such as Northwest Anatolia, West Anatolia, Lakes Region, Central Anatolia, Eastern Mediterranean, Balkans, Macedonia, and continental Greece. On the other hand, apart from functional purposes, it is predicted that the society of the Neolithic Uğurlu Höyük also utilized decorated ceramics as symbolic, ritual, and social metaphors. In this study, technical properties of decorated ceramics dating to the Neolithic period from Uğurlu Höyük were examined in detail and analogical assessments were made based on decorative styles. Meanwhile, ethnoarchaeological, theoretical, and contextual data were employed to reach a better understanding of the functions of these objects

An assessment of metal pollution in surface sediments of Seyhan dam by using enrichment factor, geoaccumulation index and statistical analyses

The aim of this study was to determine if high concentrations of any heavy metals exist in the sediment of Seyhan Dam reservoir to be considered toxic to the aquatic environment. Surface sediment samples from five stations in the Seyhan dam were collected quarterly from 2004 to 2005 and examined for metal content (Cr, Zn Cu, Mn, Cd, Fe, Ca, K, and Na), organic matter, and grain size. Correlation analyses showed that metal content of Seyhan dam sediment was affected by organic matter and grain size. The results have been compared with values given in the literature. The evaluation of the metal pollution status of the dam was carried out by using the enrichment factor and the geoaccumulation index. A comparison with sediment quality guideline values has also been made. Based on the enrichment factor, dam sediments were treated as a moderately severe enrichment with Cd and minor enrichment with Cr and Mn. The results of geoaccumulation index reveal that sediments of Seyhan Dam were strongly polluted in stations 1, 2, 4, and 5, and were moderately polluted in station 3 with Cd. Moreover, Cd and Cr concentrations in the sediments were above TECs except ERL for Cd.This work was supported (SÜF 2004 BAP 4) by the research fund of Çukurova University, Turke

Cytotoxic and antioxidant effects of grape seed oil on the treatment of leukemia with methotrexate

Methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by its severe toxicity. Regarding the mechanisms of its adverse effects, several hypotheses have been put forward, among which oxidative stress is highly noticeable. Additive effect of oxidative damage caused by MTX to oxidative stress induced by cancer makes the situation dramatically bad. In order to reduce the damage, several approaches have been suggested. Grape seed is one of the most significant prophylactic agents due to its antioxidant and bioflavonoids composition. The aim of this study was to investigate the protective effect of grape seed oil against MTX-induced oxidative stress in K-562 human chronic myeloid leukemia cell lines. Cells were divided into groups as following control, GSOH (tumor cells treated with 200 mg/mL of grape seed oil), GSOL (tumor cells treated with 100 mg/mL of grape seed oil), MTX (tumor cells treated with 50 nM methotrexate) and MTX + GSOH ( tumor cells treated with 200 mg/mL of grape seed oil and methotrexate). For antioxidant statue; superoxide dismutase (SOD), catalase (CAT), paraoxonase (PON) and aryl esterase (ARE) activities, for lipid peroxidation; malondialdehyde (MDA) level and also for cytotoxicity; cell viability were detected in 24th and 48th hours of the cell culture incubation. Based on the data, 200 mg/mL of grape seed oil indicates synergic effects with MTX on K562 regarding cytotoxicity especially in 48th hour. In case of GSOH + MTX combined treatment for 24 hours, antioxidant system take part preventing lipid peroxidation and a possible oxidative damage. Upon 48 hour-GSOH treatment, antioxidant parameters show significant increase and hence, prevent lipid peroxidation in cancer cells. In conclusion, GSOH complimentary treatment may be suggested for leukemia therapy with MTX to reduce side effects and enhance the cytotoxicity of MTX

Which out-of-office measurement technique should be used for diagnosing hypertension in prehypertensives?

Hypertension (HT) is diagnosed with high office blood pressure (BP), although confirmation with the addition of out-of-office measurements is currently recommended. However, insufficient data are available concerning the use of out-of-office BP measurement techniques for the diagnosis of HT in the prehypertensive population. The aim of the present study was to determine which out-of-office measurements yielded earlier and more frequent detection of development of HT in prehypertensive patients. Two hundred seven prehypertensive patients under monitoring in the Cappadocia cohort were included in the study. Office BP was measured five times at 1-min intervals, followed by 24-h ambulatory BP monitoring (24-h ABPM). Home BP measurement (HBPM) was performed five times, at the same times in the morning and evening, at 1-min intervals for 1 week. The same procedure was carried out at 4-6-month intervals for ~2 years. HT was diagnosed in 25.6% of subjects, masked HT in 11.1%, and white coat HT in 2.9%, while 23.7% remained prehypertensive and 36.7% became normotensive. Briefly, 56.6% of the patients with HT were diagnosed with office plus 24-h ABPM, 13.2% with office plus HBPM, and 30.2% with office plus HBPM and 24-h ABPM. Office with 24-h ABPM yielded statistically significantly more diagnoses (p < 0.001). In conclusion, our prospective observational study evaluated the usefulness of out-of-office BP measurements in confirming diagnosis of HT in prehypertensive patients. The findings show that 24-h ABPM detected HT earlier and more frequently in this high-risk population

Sigmoid Diverticular Perforation in a 23-year-old patient: A Case Report

Introduction: Diverticulitis is inflammation of one or more adjacent diverticulums and the surrounding colon. Patients with diverticulitis typically present acute or subacute abdominal pain in the left lower quadrant. Most patients with diverticulitis are over 50; however, diverticulitis is increasingly common in the younger. Diverticulitis may present with acute abdomen by causing intra-abdominal perforation. Although it is infrequent, diverticulitis perforation should be considered in the differential diagnosis of young patients with acute abdomen.Case Presentation: In this case, we present the acute abdomen secondary to diverticulitis perforation in a 23-year-old male patient. The patient's physical examination and computed tomography scan were interpreted as perforation. We performed explorative laparotomy. In the operation, the stomach and other lumen organs were intact. It was observed that there were diverticula in the sigmoid colon, intense inflammation in the colon serosa in the region of the diverticula, and a perforation area of 1 cm in diameter.Conclusions: Diverticulitis usually presents with abdominal pain in the left lower quadrant of the elderly patient. However, it may present with acute abdomen by causing intra-abdominal perforation. Although it is infrequent, diverticulitis perforation should be kept in mind in the differential diagnosis of young patients presenting with acute abdomen

First record of Phyllorhiza punctata von Lendenfeld, 1884 (Scyphozoa: Rhizostomeae: Mastigiidae) from Turkey

Abstract The Australian spotted jellyfish Phyllorhiza punctata has been reported from several locations in the Mediterranean, but the present report is the first record from Turkish waters. Juveniles of the Erythrean alien shrimp scad, Alepes djedaba, were observed nestling among its tentacles. Possible vectors are mentioned

First Video Case Report of Chronic Retrograde Jejunojejunal Intussusception after Subtotal Gastrectomy with Braun’s Anastomosis

Intussusception, which is seen rarely in adults, is defined as the pulling or invagination of a part of the intestine into another segment of the intestine. In this case report we present chronic retrograde jejunojejunal intussusception following gastric surgery with Braun’s anastomosis in adult with video presentation. A 66-year-old woman, who had undergone gastric surgery 39 years ago and cholecystectomy 20 years ago, was admitted to our clinic with the complaints about weight loss, abdominal pain, nausea, and vomiting. Upper gastrointestinal endoscopy (UGISE) was applied, and patient was treated with surgery. This case report indicates that intussusception should be considered in the presence of clinical complaints following gastric surgery, as well as importance of endoscopy in diagnosis

Acute free perforation of gall bladder encountered at initial presentation in a 51 years old man: a case report

Introduction: Gallbladder perforation is a rare but life threatening event. We describe a case of gallbladder perforation encountered at initial presentation. Case Presentation: A 51 years old male, without any known medical co-morbidity, presented with a 1-day history of sudden-onset abdominal pain and abdominal distension. On examination, his abdomen was distended with generalized tenderness on palpation. Abdominal x-ray showed no signs of intestinal obstruction or pneumoperitoneum. Computed tomography scan of the abdomen showed appearance suggestive of gallbladder perforation. The Patient was taken to the operating room and a diagnostic laparoscopy was performed revealing yellowish green fluid in the peritoneum. Difficulty in visualization of the anatomy led to conversion of the procedure to an open laparotomy. Intra-operative findings included a perforation near the neck of the gall bladder in association with a 2 x 1 cm gall stone. Near-total cholecystectomy was performed and a single large gall stone was retrieved. The peritoneal cavity was washed with normal saline and a drain was placed. The rectus sheath was closed but the wound was kept open for healing by delayed primary closure. The Patient\u27s hospital course was uneventful and he was discharged from the hospital on the 3rd post-operative day. He returned to the clinic after one week whereby his drain was removed and his wound closed. Conclusion: Gallbladder perforation is an unusual initial presentation of gallbladder disease. Early diagnosis of gallbladder perforation and immediate surgical intervention are of prime importance in decreasing morbidity and mortality associated with this condition