Copolymers of linear and crosslinked N-isopropylacrylamide/Monoitaconates

Sıcaklığa duyarlı N-izopropilakrilamit (NIPAAm)in nötral ve, hidrofobik dimetilitakonat (DMI), hidrofilik itakonik asit (IA), hidrofilik/hidrofobik monoester komonomerlerini içeren NIPAAm/DMI, NIPAAm/IA veNIPAAm/monoitakonat hidrojelleri, çapraz bağlayıcı bileşen olarak hem hidrofilik N,N’-metilenbis(akrilamid) (BIS) hem de hidrofobik vinil sonlu poli(dimetilsiloksan) (VTPDMS) varlığında, potasyum persulfat (KPS)-N,N,N’,N’-tetrametiletilendiamin (TEMED) redoks başlatıcı çifti ve AIBN kullanılarak su/metanol karışımında ve dioksanda serbest radikal çözelti polimerizasyonu ile sentezlendi ve bunların sıcaklığa bağlı şişme özellikleri ve sıkıştırma modülleri hesaplandı. Hidrofobik makro çapraz bağlayıcı VTPDMS kullanılarak elde edilen nötral NIPAAm hidrojellerinin mekanik dayanımlarının, BIS gibi dört fonksiyonlu çapraz bağlayıcılar kullanılarak elde edilen jellere göre yaklaşık 10 kat daha fazla olduğu gözlendi. Hidrofobik komonomerler (monobutil itakonat (MBuI), mono oktil itakonat (MOcI) ve mono setil itakonat (MCeI) ile iki farklı çapraz bağlayıcı BIS konsantrasyonunda NIPAAm hidrojelleri sentezlendi ve bunların mekanik dayanım deneyleri yapıldı. BIS kullanılarak sentezlenen NIPAAm hidrojellerinin sıkıştırma modülleri ve çapraz bağ yoğunlukları, alkil zincirlerinin uzunluğunun artmasına paralel olarak MCeI>MOcI>MBuI sıralamasına göre beklendiği şekilde artış gösterdi. Elde edilen bu sonuçlar doğrultusunda ilaç salımında kullanılmak için çapraz bağlayıcı olarak BIS ve VTPDMS kullanılarak sentezlenen NIPAAm, NIPAAm/IA, NIPAAm/monoitakonat homopolimer ve kopolimer hidrojelleri seçildi. IA, DMI, MMI, MBuI, MOcI ve MCeI komonomerlerini kullanılarak, AIBN ve KPS/TEMED redoks başlatıcı çifti eşliğinde 1,4-dioksan ve metanol/su çözücü karışımında toplam monomer konsantrasyunu 0.7 mol/L sabit tutularak, NIPAAm in doğrusal kopolimer ve terpolimerleri serbest radikal çözelti polimerizasyonu ile sentezlendi ve bu kopolimerlerin alt kritik çözelti sıcaklıkları incelendi. Anahtar Kelimeler: Poli(NIPAAm) jelleri, NIPAAm/IA, LCST, poli(dimetilsiloksan), mekanik dayanım, sıkıştırma modülü, kontrollü ilaç salınımı.Poly(N-isopropyl acrylamide) (PNIPAAm) has become the most popular member of a class of polymers that exhibits inverse solubility in aqueous solutions. This property is contrary to the solution behavior of most polymers in organic solvents under atmospheric pressure near room temperature. Its macromolecular transition from a hydrophilic to a hydrophobic structure occurs at a temperature which is known as the Lower Critical Solution Temperature (LCST). This temperature, being a function of the micro-structure of the polymer chains lies between 30oC and 35oC. PNIPAAm has been used in many forms including single chains, macroscopic gels, micro gels, latexes, thin films, membranes, coatings and fibers. Moreover, wide ranges of disciplines have examined PNIPPAm, encompassing chemistry, physics, rheology, biology and photography. PNIPAAm has been synthesized by a variety of techniques. Free radical initiation in organic solvents and aqueous media is only one of these experimental methods. Various initiators and solvents such as potassium persulfate (KPS), Ammonium persulfate (APS), azobis(isobutyronitrile) (AIBN), benzoylperoxide, laurylperoxide and water, methanol, benzene, 1,4-dioxane, tetrahydrofuran (THF), respectively, have been used in free radical polymerization produced in organic solvents and in aqueous media.Redox polymerization of NIPAAm typically uses APS or KPS as the initiator and either N,N,N?,N? tetramethylethylenediamine (TEMED) as the accelerator. In this study, taking into account the above literature results, we have attempted to investigate the effect of initiator type and concentration, hydrophobic and ionizable comonomers, and synthesis-solvent composition on the swelling behaviour of NIPAAM gels. For this purpose, NIPAAM gels, initiated with two different initiator concentrations, in water, and NIPAAM/DMI (dimethyl itaconate) and NIPAAM/ IA and NIPAAm/monoesters of IA copolymer gels in water/methanol mixtures and 1,4-dioxane were synthesized and their volume phase transitions were examined. Conventional swelling theory is used to characterize the interactions between the polymer and solvent molecules. Monoitaconates containing methyl, butyl, octyl and cetyl groups were synthesized. The copolymers containing these monoitaconates, IA and DMI were obtained by free-radical solution polymerization of NIPAAm. Hydrogels composed of NIPAAm, BIS, vinyl terminated poly(dimethyl siloxane) (VTPDMS) (commercial product) and IA as hydrophobic monomer, hydrophilic crosslinker, hydrophobic crosslinker and weakly ionizable comonomer, respectively, were prepared to investigate the effect of hydrophobic component, i.e., VTPDMS on the compression moduli of the samples attained equilibrium swollen state in distilled-deionized water at 25oC. For the NIPAAm/monoitaconate copolymer hydrogels crosslinked with BIS, the effects of hydrophobic component i.e., monobutyl itaconate (MBuI), monooctyl itaconate (MOcI) and monocetyl itaconate (MCeI) on the compression moduli of the samples attained equilibrium swollen state in distilled-deionized water at 25oC were investigated. Compression moduli and crosslinking densities of NIPAAm hydrogels containing 2.50 and 5.0 mole % of monoesters of IA in the feed and crosslinked with BIS increased with alkyl chain length in the order of MCeI > MOcI > MBuI. Theophylline was used as a drug for controlled-release of PNIPAAm, NIPAAm/IA and NIPAAm/ monoitaconate copolymer hydrogels crosslinked with BIS and VTPDMS. PNIPAAm hydrogel crosslinked with VTPDMS has the lowest drug release capacity because of the unresemble structures to each other. The presence of hydrophilic and ionizable IA molecules in the structures of NIPAAm hydrogels increases the release capacities and rates of hydrogels crosslinked with BIS or VTPDMS because repulsive forces between the ?COO- groups controls the shrinking rate at 37oC and so the drug molecules do not trap in the polymeric network. PNIPAAm, poly(dimethyl itaconate) (PDMI) and, copolymers of NIPAAm with IA, DMI, MMI, MBuI, MOcI and MCeI were obtained by free radical solution polymerization using AIBN and KPS/TEMED redox pair, as initiator, in 1,4-Dioxane and in MetOH/DDW with a total monomer concentration of 0.7  mol/L. The sensitivity of NIPAAm copolymers to change in pH and temperature suggest that they could be useful in biotechnology and drug delivery applications where small changes in pH and temperature. Keywords: poly(NIPAAm) gels, poly(NIPAAm-co-IA), LCST, Poly(dimethylsiloxane), mechanical strength, compression module, drug delivery systems

The Immunohistochemical Evaluation of Kidney An Experimentally Induced Hypertensive And Diabetic Rat Model

AMAÇ: Bu çalışmada, deneysel olarak ayrı ayrı ve birlikte diyabet ve hipertansiyon modeli oluşturulan sıçanlarda, lipoik asidin hipertansif ve diyabetik böbrek üzerindeki tedavi edici/hasar önleyici etkisinin araştırılması amaçlandı. YÖNTEMLER: Çalışmamızda Wistar cinsi ratlar 8 gruba ayrıldı (n=7). I. grup; Kontrol, II. Grup; Diabetes Mellitus, III. grup; 5/6 Nefrektomi, IV. Grup; Lipoik asit, V. Grup; 5/6 Nefrektomi+Diyabet, VI. grup, Diyabet+Lipoik asit VII. Grup; 5/6 Nefrektomi+Lipoik asit ve VIII. Grup; 5/6Nefrektomi+Diyabet+Lipoik asit. Diyabet modeli 45mg/kg STZ enjeksiyonu ile oluşturuldu ve hipertansiyon modeli için 5/6 nefrektomi modeli uygulandı. dl-α-Lipoik asit 30mg/kg/gün olacak şekilde 8 hafta oral gavaj yöntemi ile deneklere uygulandı. Böbrek dokuları rutin ışık mikroskobik doku takip işlemlerinden geçirilip parafin bloklara gömüldü. İmmünohistokimyasal olarak AT1 (Anjiyotensin II tip I reseptörü), VEGF (Vasküler Endotelial Büyüme Faktörü) ve ET1 (Endotelin 1) antikorları işaretlendi. BULGULAR: Diyabet ve nefrektomi modellerinin ayrı ayrı ve birlikte uygulandığı deneysel gruplarda (Grup 2, 3, 5), glomerüloskleroz, mononükleer hücre infiltrasyonu, intersitisiyel fibrozis, damarlarda ve tübüllerde dilatasyon ve hiyalin materyal birikimi ile tübüler yapıların dejenerasyonu gözlendi. Aynı gruplarda tübülointersitisiyel ve glomerüler AT1 azalırken, VEGF ve ET1 artış göstermişti. Lipoik asit tedavi gruplarında ise AT1'de artış, VEGF ve ET1'de ise Kontrol ve Lipoik asit grubuna benzer şekilde azalma gözlendi. SONUÇ: Diyabet ve hipertansiyonun birlikte gözlenmesinin böbrek hasarının hızlı ilerlemesine neden olduğu, lipoik asidin bu hastalıklara karşı böbrek üzerinde tedavi edici etkisinin olduğu sonucuna varıldı. OBJECTIVE: In this study, experimental diabetes and nephrectomy have been applied separately and together in order to investigate possible therapeutic/damage prevention effects of Lipoic acid on hypertensive and diabetic rat kidneys. METHODS: Wistar rats were divided into 8 groups (n=7); Group 1; Control, Group 2; Diabetes Mellitus, Group 3; 5/6 Nephrectomy, Group 4; Diabetes Mellitus+5/6 Nephrectomy, Group 5; Lipoic acid administration, Group 6; Diabetes Mellitus+Lipoic acid, Group 7; 5/6 Nephrectomy+Lipoic acid, Group 8; Diabetes Mellitus+5/6 Nephrectomy+Lipoic acid groups respectively. Diabetes was formed by 45mg/kg STZ injection and for hypertension nephrectomy 5/6 model was applied. dl-α-Lipoic acid 30mg/kg/day was fed by oral gavage for 8 weeks. Kidney tissues were embedded into paraffin block after routine light microscopic preparation. AT1 (Angiotensinojen II type 1 receptor), VEGF (Vascular Endothelial Growth Factor) and ET1 (Endothelin) antibodies were labelled immunohistochemically in same group. RESULTS: In groups where diyabetes and nephrectomy were applied separately and together, glomerulosclerosis, mononuclear cell infiltration, interstitial fibrosis, vascular and tubular dilatation and hyalin deposition and degeneration of tubular structures were seen in glomerules. In the same group: tubulointerstitial and glomerular AT1 was decreased but VEGF and ET1 were increased. In Lipoic acid treatment groups, AT1 was increased and VEFG and ET1 were decreased similar to Control and Lipoic acid group. CONCLUSION: We have come to the conclusion that diabetes nd hypertension together increases the rate of renal injury and lipoic acid has therapeutic effect on kidney

The effects of resveratrol against trifluralin toxicity in the urinary tract of rats

The herbicide itself and the degradation products are highly toxic on biological systems. The aim of this study is to investigate the potential toxic effects of trifluralin (TRF) on the urinary system of male rats and to investigate the protective effects of resveratrol (RSV) in TRF-induced urinary system damage. A total of 35 male Wistar rats were randomly divided into: (1) control group, (2) sham group, (3) low dose TRF group (0.8g/kg/day), (4) high dose TRF group (2g/kg/day) and (5) high dose TRF + RSV group 10mg/kg/day. RSV was administered for 21 days by intragastric gavage at a dose of 10mg/kg/day after induction of TRF. Kidney, ureter and urinary bladder tissue was examined using light microscopy and ultrastructurally. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling was performed to detect apoptosis. Superoxide dismutase (SOD), glutathion peroxidase (GPx) and malondialdehyde (MDA) levels were also evaluated biochemically for oxidative stress parameters. Histological evaluation showed that TRF increases apoptosis and oxidative stress, causes histological tissue damages and biochemical changes in the kidneys but does not cause any damage to the ureter and bladder. Treatment with RSV significantly attenuated tissue damage in the urinary system of rats. Apopitotic cells were significantly decreased in the treatment group. Additionally, treatment with RSV decreased SOD and GPx levels and increased MDA levels in the kidney tissue of animals subjected to TRF. These results show that RSV can significantly minimize histological damage and biochemical differences in treating TRF-induced kidney injury in rats

The effects of selenium against cerebral ischemia-reperfusion injury in rats

It is known that the brain tissue is extremely sensitive to ischemia-reperfusion (IR) injury and therefore, brain ischemia and consecutive reperfusion result in neural damage and apoptosis. The proinflammatory cytokines such as tumor necrosis factor alfa (TNF-alpha) and interleukin-1 beta (IL-1 beta) are produced during neurological disorders including cerebral ischemia. On the other hand, nerve growth factor (NGF), which is essential for the differentiation, survival and functions of neuronal cells in the central nervous system, regulate neuronal development through cell survival and cell death signaling. In the present study, we aimed to investigate the effect of selenium (Se) on prefrontal cortex and hippocampal damage in rats subjected to cerebral IR injury. Selenium was injected intraperitoneally at the doses of 0.625 mg/(kg day) after induction of IR injury. Prefrontal cortex and hippocampal damage was examined by cresyl-violet staining. Apostain and caspase-3 immune staining were used to detect apoptosis. TNF-alpha, IL-1 beta and NGF levels were also evaluated. Histopathological evaluation showed that treatment with selenium after ischemia significantly attenuated IR-induced neuronal death in prefrontal cortex and hippocampal CAI regions of rats. Apoptotic cells stained with apostain and caspase-3 were significantly decreased in treatment group when compared with the IR group. Additionally, treatment with selenium decreased the TNF-alpha, and IL-1 beta levels and increased the NGF levels in prefrontal cortex and hippocampal tissue of animals subjected to IR. The present results suggest that selenium is potentially a beneficial agent in treating IR-induced brain injury in rats. (c) 2008 Published by Elsevier Ireland Ltd

Effect of ferulic acid on testicular damage caused by torsion-detorsion in rats

Testicular torsion is twisting of the spermatic cord around its axis, which impairs blood flow and causes ischemia and formation of free radicals. Ferulic acid is a phenolic acid of the hydroxycinnamic family that is found in the seeds and leaves of plants; it is present in substantial amounts in fruits and vegetables. We investigated the protective effect of ferulic acid on experimental testicular torsion in rats. Animals were divided randomly into five groups: control, ethyl alcohol, torsion, torsion-detorsion, and torsion-detorsion + ferulic acid. Histopathology was assessed using hematoxylin and eosin, and periodic acid-Schiff staining. Tissues were assessed using TUNEL, active caspase-3, myeloperoxidase and inducible nitric oxide synthase immunostaining. Biochemical changes were assessed using assays for superoxide dismutase, malondialdehyde, glutathione peroxidase and glutathione. Ferulic acid reduced the levels of free radicals and increased the levels of antioxidants. Ferulic acid also reduced histopathological changes and germ cell differentiation in the testis following torsion-detorsion. Ferulic acid should be investigated further as a potential treatment for sequelae of torsion-detorsion injury